Search

Michael J Hall,1 Julie Innocent,2 Christina Rybak,1 Colleen Veloski,3 Walter J Scott,4 Hong Wu,5 John A Ridge,4 John P Hoffman,4 Hossein Borghaei,2 Aruna Turaka,6 Mary B Daly1 1Department of Clinical Genetics, 2Department of Medical Oncology, 3Department of Internal Medicine, 4Department of Surgical Oncology, 5Department of Pathology, 6Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA Introduction: Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report: A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). Discussion: Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion: To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described. Keywords: menin gene, ovarian tumors, hyperparathyroidism

Traditional instruction is adaptive-that is, instructor-driven, face-to-face and/or online training to teach skills and knowledge and convey information, policies, and procedures. In contrast, generative learning is learner-driven, collaborative, and problem-focused. Web 2.0 technologies can support both types of learning but are especially valuable for generative learning. This article reviews learning processes and Web 2.0 capabilities, describes two case examples, outlines ways to design Web 2.0 training applications, and discusses the changing role of learning professionals from delivering structured, one-way adaptive learning to designing and facilitating generative learning opportunities. The article concludes with ideas for corporate education and research on Web 2.0-based learning processes, including utilizing the technology to track and improve learning. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 testing in high-risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease-associated) mutations in non-white populations. In this study, the authors examined the prevalence of BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing.Methods: In this cross-sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non-Ashkenazi Jewish women who underwent genetic testing.Results: From 1996 to 2006, 46,276 women who met study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non-European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; P < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1-1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1-1.4]) ancestries had a significantly higher prevalence of deleterious BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 mutations in those 2 groups. Non-European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%-->5.9%), and women of African ancestry experienced the largest decline (58%).Conclusions: Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high-risk women. [ABSTRACT FROM AUTHOR]

Ossur Kristinsson first developed the Icelandic roll-on silicone socket (ICEROSS) in the mid 1980s. This type of socket interface was quickly popularized in the prosthetic community and has become the standard of treatment for transtibial amputees. Multiple manufacturers of roll-on liners, of various materials, now exist. These companies claim that liners offer superior comfort, suspension, and relief of dermatological problems compared with previous prosthetic options. A review of relevant literature reveals studies that are limited by the lack of diagnoses made by dermatologists (Cluitman et al., Prosthet Orthot Int. 1994;18:78-83; Lake and Supan, J Prosth Orthot. 1997;9:97-106; and Hachisuka et al., Arch Phys Med Rehabil. 2001;82:1286-1289) and a failure to identify the frequency of these problems (Levy, Prosthet Orthot Int. 1980;4:37-44 and Dudek, et al. Arch Phys Med Rehabil. 2005;86:659-663). The purpose of this cross-sectional study is to determine the prevalence of dermatological problems in transtibial amputee subjects who use a roll-on liner with their prosthesis. A questionnaire determined demographic information, skin type, hygiene and prosthetic habits, comorbidities, and reported skin problems. All participants were offered a free examination by the dermatologist to verify medical history and document current skin problems. A [chi]2, trend, and rank-sum test were used. Results indicated that 90.9% of subjects reported a history of skin problems, whereas 78% presented with a problem during the exam with the dermatologist. Specific correlations between habits and reported skin problems are also reported in this article. However, a direct correlation between amputee habits and skin problems is not clear. Because of high gasoline prices in rural Iowa, few participated in the skin exam. In this study, a greater number of transtibial amputees using roll-on liners had dermatological problems than previously reported. [ABSTRACT FROM AUTHOR]

Detailed family history is a critical element of cancer risk assessment. The relative importance of pancreatic cancer (PC) in a close family member, particularly in hereditary breast-ovarian syndrome (HBOS), is not clearly defined. We use a case-control design to investigate the importance of a family history of PC to cancer risk assessment. Case and control families were identified from the University of Chicago Cancer Risk database (1994-2005). Pedigrees were analyzed for personal and familial clinical cancer data. Cases included all new subjects (probands) reporting a close relative (first or second degree) with PC. Controls included the probands enrolled in the database immediately prior to and subsequent to each case (i.e. two controls for each case). From 1,231 pedigrees, 103 PC were reported by the proband in 87 unique families. Many probands reported multiple or early-onset PCs: one third (28/87) of case families met criteria for a familial PC syndrome [> or =2 first-degree relatives with PC (n = 10) or PC diagnosed < or =50 (n = 18)]. Of these families, the majority (75%) concurrently met criteria suggestive of hereditary breast-ovarian syndrome (HBOS). Because of a family history consistent with HBOS, at least one individual from each of 29 case and 55 control families underwent genetic testing for BRCA1/2. Among case families, 19 of 29 (66%) had a BRCA1/2 mutation compared with 16 of 55 (29%) controls. A significant association between family history of PC and a BRCA1/2 mutation was seen (OR 3.78, 1.32-10.9). This point estimate was strengthened but less precise in the non-Ashkenazi Jewish subset of tested families (OR 6.03, 1.68-22.14). In a high-risk population, a family history of PC, though infrequently reported, is nonetheless clinically meaningful. In risk assessment for HBOS, identifying a family history of PC should strongly raise the suspicion of an unrecognized BRCA1/2 mutation. [ABSTRACT FROM AUTHOR]

Background. There has been a shift towards research with children and the adoption of the concept of child-centred research. However, the majority of oral health research is conducted on children, rather than with them. Objective. This study aimed to provide an overview of contemporary approaches to research with children. Considerations. The methodological considerations of such research include: the power relationship between the adult researcher and the child participant, with important factors of language use, the setting for the research, appropriate analysis, and quality of the data; ethical factors such as the purpose and risks of the research, confidentiality, recruitment, funding, information to children and parents, consent, and dissemination; and appropriate methods. Methods suitable for oral health research with children include quantitative techniques such as questionnaires and qualitative approaches including interviews individually or in groups and participatory techniques such as time-lines/life grids, drawings, and vignettes. Conclusion. There is considerable scope to access children's perspectives of their oral health and care through actively involving them in research. To conduct such research, however, requires training or collaboration with colleagues from other disciplines. [ABSTRACT FROM AUTHOR]

Planning for the public's psychological and behavioral reactions to a bioterrorist attack must address individual and community preparedness, response, and recovery. Bioterrorism raises issues requiring skilled risk communication and education including isolation, quarantine, administering vaccinations and distributing medications. The United States anthrax attacks, the international outbreak of Severe Acute Respiratory Syndrome (SARS), and the U.S. smallpox vaccination program offer useful lessons. The Iraqi missile attacks on Israel and the Tokyo sarin gas attacks highlight challenges of emergency medical evaluation and triage. Early public health interventions should identify symptoms and behaviors linked to psychological distress and suggest strategies to restore well-being. [ABSTRACT FROM AUTHOR]

Kindness can be the key to delivering better care. [ABSTRACT FROM AUTHOR]