Giant Cell Tumor of the Mandible

A 53-year-old woman presented with left mandibular area pain, trismus, and facial numbness that had persisted for 4 years. Physical examination revealed a 3×5 cm, hard, non-tender, and round mass on the left mandibular area. Computed tomography and magnetic resonance imaging revealed an expansile tumor involving the left mandibular ramus and temporomandibular joint area with bone destruction, extending to the base of middle cranial fossa and left zygomatic bone. The mass at the segment of left mandible and zygomatic bone, and base of middle cranial fossa was removed. Pathological examination of the mass revealed a giant cell tumor. The defect was reconstructed with iliac bone for the mandible and temporal bone and fascia for the cranial bone and dura. The case is described along with a review of the literature

Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

BACKGROUND. During development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. METHODOLOGY/PRINCIPAL FINDINGS. We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68=89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. CONCLUSIONS/SIGNIFICANCE. Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental amniotes. Rather, we hypothesize that these membranes may share an additional unifying characteristic, steroidogenesis, across amniotes at large.Sigma Xi (G20073141634396861); National Science Foundation (2008059161); UF-Howard Hughes G.A.T.O.R. Program; Howard Hughes Medical Institute Professorshi

Preferential Localization of Human Origins of DNA Replication at the 5′-Ends of Expressed Genes and at Evolutionarily Conserved DNA Sequences

Replication of mammalian genomes requires the activation of thousands of origins which are both spatially and temporally regulated by as yet unknown mechanisms. At the most fundamental level, our knowledge about the distribution pattern of origins in each of the chromosomes, among different cell types, and whether the physiological state of the cells alters this distribution is at present very limited.We have used standard λ-exonuclease resistant nascent DNA preparations in the size range of 0.7–1.5 kb obtained from the breast cancer cell line MCF–7 hybridized to a custom tiling array containing 50–60 nt probes evenly distributed among genic and non-genic regions covering about 1% of the human genome. A similar DNA preparation was used for high-throughput DNA sequencing. Array experiments were also performed with DNA obtained from BT-474 and H520 cell lines. By determining the sites showing nascent DNA enrichment, we have localized several thousand origins of DNA replication. Our major findings are: (a) both array and DNA sequencing assay methods produced essentially the same origin distribution profile; (b) origin distribution is largely conserved (>70%) in all cell lines tested; (c) origins are enriched at the 5′ends of expressed genes and at evolutionarily conserved intergenic sequences; and (d) ChIP on chip experiments in MCF-7 showed an enrichment of H3K4Me3 and RNA Polymerase II chromatin binding sites at origins of DNA replication.Our results suggest that the program for origin activation is largely conserved among different cell types. Also, our work supports recent studies connecting transcription initiation with replication, and in addition suggests that evolutionarily conserved intergenic sequences have the potential to participate in origin selection. Overall, our observations suggest that replication origin selection is a stochastic process significantly dependent upon local accessibility to replication factors

EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine–immune interactions

EBAG9 has been recently identified as an oestrogen responsive gene in MCF-7 human breast carcinoma cells. EBAG9 is identical to RCAS1, a cancer cell surface antigen possibly involved in immune escape. In this study, we examined the expression of EBAG9/RCAS1 in human breast carcinomas using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). EBAG9 immunoreactivity was also associated with various clinicopathological parameters, including intratumoural infiltration of inflammatory cells, to examine the biological significance of EBAG9 in human breast carcinomas. EBAG9 immunoreactivity was detected in the entire surface and cytoplasm of carcinoma cells in 82 out of 91 invasive ductal carcinomas (90.1%). In non-neoplastic mammary glands, EBAG9 immunoreactivity was weakly present on the luminal surface of epithelial cells. Results from RT-PCR (n = 7) were consistent with those of immunohistochemistry. EBAG9 immunoreactivity was significantly associated with estrogen receptor (ER) α labelling index (P = 0.0081), and inversely associated with the degree of intratumoural infiltration of mononuclear cells (P = 0.0020), or CD3+ T lymphocytes (P = 0.0025). This study suggests that EBAG9 is produced via ER in carcinoma cells and inhibits the intratumoural infiltration of T lymphocytes in the context of a possible endocrine–immune interaction in human breast carcinomas. © 2001 Cancer Research Campaign http://www.bjcancer.co

A mixed methods pilot study with a cluster randomized control trial to evaluate the impact of a leadership intervention on guideline implementation in home care nursing

Abstract Background Foot ulcers are a significant problem for people with diabetes. Comprehensive assessments of risk factors associated with diabetic foot ulcer are recommended in clinical guidelines to decrease complications such as prolonged healing, gangrene and amputations, and to promote effective management. However, the translation of clinical guidelines into nursing practice remains fragmented and inconsistent, and a recent homecare chart audit showed less than half the recommended risk factors for diabetic foot ulcers were assessed, and peripheral neuropathy (the most significant predictor of complications) was not assessed at all. Strong leadership is consistently described as significant to successfully transfer guidelines into practice. Limited research exists however regarding which leadership behaviours facilitate and support implementation in nursing. The purpose of this pilot study is to evaluate the impact of a leadership intervention in community nursing on implementing recommendations from a clinical guideline on the nursing assessment and management of diabetic foot ulcers. Methods Two phase mixed methods design is proposed (ISRCTN 12345678). Phase I: Descriptive qualitative to understand barriers to implementing the guideline recommendations, and to inform the intervention. Phase II: Matched pair cluster randomized controlled trial (n = 4 centers) will evaluate differences in outcomes between two implementation strategies. Primary outcome: Nursing assessments of client risk factors, a composite score of 8 items based on Diabetes/Foot Ulcer guideline recommendations. Intervention: In addition to the organization's 'usual' implementation strategy, a 12 week leadership strategy will be offered to managerial and clinical leaders consisting of: a) printed materials, b) one day interactive workshop to develop a leadership action plan tailored to barriers to support implementation; c) three post-workshop teleconferences. Discussion This study will provide vital information on which leadership strategies are well received to facilitate and support guideline implementation. The anticipated outcomes will provide information to assist with effective management of foot ulcers for people with diabetes. By tracking clinical outcomes associated with guideline implementation, health care administrators will be better informed to influence organizational and policy decision-making to support evidence-based quality care. Findings will be useful to inform the design of future multi-centered trials on various clinical topics to enhance knowledge translation for positive outcomes. Trial Registration Current Control Trials ISRCTN0691089

Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial

Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. 284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72-86]) and presence (97% [91-99]) were significantly greater than that of ultrasound (70% [62-78] for disease extent, 92% [84-96] for disease presence); a 10% (95% CI 1-18; p=0·027) difference for extent, and 5% (1-9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85-98]) was significantly greater than that of ultrasound (81% [64-91]); a difference of 14% (1-27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86-99) with MRE and 84% (65-94) with ultrasound (difference 12% [0-25]; p=0·054). There were no serious adverse events. Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. National Institute of Health and Research Health Technology Assessment. [Abstract copyright: Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Diagnostic accuracy for the extent and activity of newly diagnosed and relapsed Crohn’s disease: a multicentre prospective comparison of magnetic resonance enterography and small bowel ultrasound –The METRIC Trial

Background Magnetic resonance enterography (MRE) and ultrasound (US) are used to image Crohn’s disease, but comparative accuracy for disease extent and activity is not known with certainty. We undertook a prospective multicentre cohort trial to address this Methods We recruited from 8 UK hospitals. Eligible patients were 16 years or older, newly diagnosed with Crohn’s disease, or had established disease with suspected relapse. Consecutive patients underwent MRE and US in addition to standard investigations. Discrepancy between MRE and US for small bowel (SB) disease presence triggered an additional investigation, if not already available. The primary outcome was difference in per patient sensitivity for SB disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). Accuracy for SB and colonic disease presence and activity were secondary outcomes. The trial is completed (ISRCTN03982913). Findings 284 patients completed the trial (133 new diagnosis, 151 relapse). MRE sensitivity (n=233) for SB disease extent (80% [95%CI 72 to 86]) and presence (97% [91 to 99]) were significantly greater than US (70% [62 to 78], 92% [84 to 96]); a 10% (1 to 18; p=0.027), and 5% (1 to 9), difference respectively. MRE specificity for SB disease extent (95% [85 to 98]) was significantly greater than US (81% [64 to 91]). Sensitivity for active SB disease was significantly greater for MRE than US (96% [92 to 99] vs. 90% [82 to 95]), difference 6% (2 to 11). Overall, there were no significant accuracy differences for colonic disease presence. Accuracy in newly diagnosed and relapse patients was similar, although US had significantly greater sensitivity for colonic disease than MRE in newly diagnosed patients (67% [49 to 81) vs. 47% [31 to 64]), difference 20% (1 to 39). There were no serious adverse events. Interpretation MRE has higher diagnostic accuracy for the extent and activity of SB Crohn’s disease than US when tested in a prospective multi centre cohort trial setting

Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization

Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice