Comparative evaluation of sealing ability, penetration and adaptation of a self etching pit and fissure sealant- stereomicroscopic and scanning electron microscopic analyses

Background: The efficacy of pit and fissure sealants in preventing occlusal caries is a well-established fact. Considering the difficulty in achieving strict isolation for a longer duration while treating the pediatric patients, a simplified procedure of sealant application is desirable. While, a self-etching sealant, Prevent Seal offers a quick procedure, the physical properties of this material haven?t been studied yet. Thus, this study was aimed to comparatively evaluate sealing ability, penetration and adaptation of a self-etching pit and fissure sealant and a conventional resin sealant. Material and Methods: This was an in vitro intergroup comparative study, which consisted of 2 groups- Group I (Conventional acid etch sealant, Clinpro) and Group II (Self etching sealant, Prevent Seal). Out of 32 selected teeth 16 were used to study microleakage, with the help of dye penetration test using Övrebö and Raadal criteria. Remaining 16 were used to evaluate sealant penetration and adaptation viz bubbles in the bottom of fissure, debris in the fissure, tags in the bottom of the fissure and tags at cuspal slopes and fissure entrance was done using stereomicroscope. Post stereomicroscopic evaluation 4 samples each were randomly chosen from both the groups and checked for etching pattern using Scanning electronic microscope. Results: The comparison of tested properties between the groups was done using Chi square test. There was no statistically significant difference observed when microleakage and sealant penetration / adaptation properties were compared between two groups (p=0.63 and p= 0.131, 0.131, 0.302, 0.106 respectively). No conclusive results could be withdrawn while etching patterns were compared between the groups (p=0.717). Conclusions: The self-etching sealant Prevent seal was found to have similar microleakage, sealant penetration and adaptation properties as conventional acid etch sealant

Well-differentiated papillary mesothelioma of the peritoneum is genetically defined by mutually exclusive mutations in TRAF7 and CDC42.

Well-differentiated papillary mesothelioma is an uncommon mesothelial neoplasm that most frequently arises in the peritoneal cavity of women of reproductive age. Whereas malignant mesothelioma is an aggressive tumor associated with poor outcome, well-differentiated papillary mesothelioma typically exhibits indolent behavior. However, histologically differentiating between these two entities can be challenging, necessitating the development of distinguishing biomarkers. While the genetic alterations that drive malignant mesothelioma have recently been determined, the molecular pathogenesis of well-differentiated papillary mesothelioma is unknown. Here we performed genomic profiling on a cohort of ten well-differentiated papillary mesothelioma of the peritoneum. We identified that all tumors harbored somatic missense mutations in either the TRAF7 or CDC42 genes, and lacked alterations involving BAP1, NF2, CDKN2A, DDX3X, SETD2, and ALK that are frequent in malignant mesothelioma. We recently identified that another mesothelial neoplasm, adenomatoid tumor of the genital tract, is genetically defined by somatic missense mutations in the TRAF7 gene, indicating a shared molecular pathogenesis between well-differentiated papillary mesothelioma and adenomatoid tumors. To the best of our knowledge, well-differentiated papillary mesothelioma is the first human tumor type found to harbor recurrent mutations in the CDC42 gene, which encodes a Rho family GTPase. Immunohistochemistry demonstrated intact BAP1 expression in all cases of well-differentiated papillary mesothelioma, indicating that this is a reliable marker for distinguishing well-differentiated papillary mesothelioma from malignant mesotheliomas that frequently display loss of expression. Additionally, all well-differentiated papillary mesothelioma demonstrated robust expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation, similar to that observed in adenomatoid tumors. In contrast, we have previously shown that L1CAM staining is not observed in normal mesothelial cells and malignant mesotheliomas of the peritoneum. Together, these studies demonstrate that well-differentiated papillary mesothelioma is genetically defined by mutually exclusive mutations in TRAF7 and CDC42 that molecularly distinguish this entity from malignant mesothelioma

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.

Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation.

Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs). These mutations all clustered into one of five recurrent hotspots within the WD40 repeat domains at the C-terminus of the protein. Functional studies in vitro revealed that expression of mutant but not wild-type TRAF7 led to increased phosphorylation of nuclear factor-kappa B (NF-kB) and increased expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation. Immunohistochemistry demonstrated robust L1CAM expression in adenomatoid tumors that was absent in normal mesothelial cells, malignant peritoneal mesotheliomas and multilocular peritoneal inclusion cysts. Together, these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation that drives aberrant NF-kB pathway activation

Prophets vs. profits: How market competition influences leaders' disciplining behavior towards ethical transgressions

We investigate how market competition influences the way organizational leaders discipline moral transgressions of employees. In a cross-sectional study among organizational leaders at various hierarchical levels (Study 1), we find that strong market competition is related to an instrumental decision frame (business practices being perceived as focused on serving the organization’s interest). This decision frame explains why strong market competition is related to leaders’ perceptions of the evaluation of wrongdoing in terms of instrumental rather than moral concerns. In two subsequent experiments (Study 2 and 3), we find that high (relative to low) market competition makes leaders’ disciplining of moral transgressions contingent upon the instrumentality of the transgression to the organization. We find that the same transgression is punished less severely when it resulted in profit for the organization than when it resulted in loss. This research is among the first to identify conditions that determine the disciplinary responses of organization leaders to employees’ moral transgressions, and it feeds the debate on whether market competition - a fundamental characteristic of capitalist economies - promotes the display of moral or immoral behavior within organization

Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry.

Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutan

A Psittacine bite and subcutaneous basidiobolomycosis: A case with a therapeutic challenge

Basidiobolus ranarum is a saprophyte that can be found in soil, rotting vegetables, and frogs' digestive tracts. Clinically, basidiobolomycosis presents as a persistent infection of subcutaneous tissue affecting the trunk and extremities in an immunocompetent host. We describe a case of subcutaneous basidiobolomycosis in a 56-year-old immunocompetent woman farmer by occupation residing at remote part of central India. This study highlights the traumatic implantation and zoonotic potential of fungal species. Clinical suspicion of fungal etiology and timely mycology laboratory diagnostic support is key to address such cases. This case is documented to emphasize the problems of compliance to treatment specially in remote and poor patients challenging the treatment with complete cure. 2012 Elsevier Ltd. All rights reserved

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.

Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies