Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF ␤, NFB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.cdc42 ͉ runx2 ͉ thyroid cancer ͉ vimentin T hyroid carcinoma is the most common classical endocrine malignancy, and its incidence is rising rapidly, due almost entirely to an increase in papillary thyroid carcinoma (PTC) diagnoses (1). Patients diagnosed with PTC at an early stage have an excellent prognosis; however, individuals with large, invasive tumors and/or distant metastases have a 5-year survival rate of Ϸ40% (2, 3). Thus, there is a need to better understand the molecular causes of thyroid cancer progression to develop new treatment options.The genetic defects believed to be responsible for PTC initiation have been identified in the majority of cases; these include genetic rearrangements involving the tyrosine kinase domain of RET and activating mutations of BRAF and RAS (3-5). Although some correlation studies support an association between specific genetic alterations and aggressive cancer behavior (6-9), there are a number of events that are found nearly exclusively in aggressive PTCs, including mutations of P53 (10, 11), dysregulated ␤-catenin signaling (12), up-regulation of cyclin D1 (13), and overexpression of metastasis-promoting, angiogenic, and/or cell adhesion-related genes (14-20). We have determined that invasive regions of primary PTCs are frequently characterized by enhanced Akt activity and cytosolic p27 localization (21, 22). We, and others, have also demonstrated functional roles for PI3 kinase, Akt, and p27 in PTC cell invasion in vitro (16,23,24). However, the correlation between increased Akt activity and invasion was not found for PTCs with activating BRAF mutations. Most importantly, these focused s...

Travelers’ diarrhea (TD) is the most common ailment affecting travelers, including deployed U.S. military. Continuing Promise 2011 was a 5-month humanitarian assistance/disaster response (HA/DR) military and non-governmental organization training mission aboard the hospital ship USNS Comfort, which deployed to Central and South America and the Caribbean between April and September 2011. Enhanced TD surveillance was undertaken during this mission for public health purposes. Passive surveillance (clinic visits), active surveillance (self-reported questionnaires), and stool samples were collected weekly from shipboard personnel. Descriptive statistics and multivariate-logistic regression methods were used to estimate disease burden and risk factor identification. Two polymerase chain reaction methods on frozen stool were used for microbiological identification. TD was the primary complaint for all clinic visits (20%) and the leading cause of lost duties days due to bed rest confinement (62%), though underreported, as the active self-reported incidence was 3.5 times higher than the passive clinic-reported incidence. Vomiting (p = 0.002), feeling lightheaded or weak (p = 0.005), and being a food handler (p = 0.017) were associated with increased odds of lost duty days. Thirty-eight percent of self-reported cases reported some amount of performance impact. Based on the epidemiological curve, country of exercise and liberty appeared to be temporally associated with increased risk. From the weekly self-reported questionnaire risk factor analysis, eating off ship in the prior week was strongly associated (adjusted odds ratio [OR] 2.4, p<0.001). Consumption of seafood increased risk (aOR 1.7, p = 0.03), though consumption of ice appeared protective (aOR 0.3, p = 0.01). Etiology was bacterial (48%), with enterotoxigenic Escherichia coli as the predominant pathogen (35%). Norovirus was identified as a sole pathogen in 12%, though found as a copathogen in an additional 6%. Despite employment of current and targeted preventive interventions, ship-board HA/DR missions may experience a significant risk for TD among deployed US military personnel and potentially impact mission success.

Differentiated thyroid cancers, including papillary and follicular variants, are a useful model with which to examine interactions between cancer and the immune system. Differentiated thyroid cancers are detected in only 20,000 individuals annually in the USA, but thyroid microcarcinomas (< 1 cm in diameter) are far more common. This suggests that the immune system might restrain the growth of these microcarcinomas. On the clinical level, patients with lymphocytes that infiltrate into papillary thyroid cancer have improved survival, supporting the notion that immune system activation might improve this. Together, these observations suggest that the growth and distant spread of thyroid carcinoma are suppressed by mechanisms of immune surveillance, possibly involving lymphocytes, macrophages and their secreted products. In this review, we examine the general hypothesis of immune surveillance and the data pertaining to the roles of lymphocytes, dendritic cells and cytokines in the immune response against thyroid cancers.

The paired box-8 protein (Pax-8) has been observed in the nucleus of normal adult thyroids, follicular adenomas, follicular thyroid cancers, and papillary thyroid cancers (PTC) but not undifferentiated thyroid cancers. To our knowledge, Pax-8 has not been studied in pediatric thyroid cancer. Because of the more favorable prognosis for PTC in children compared to young patients, we hypothesized that Pax-8 expression might be different in pediatric thyroid cancers. To test this, we stained 47 thyroid lesions from children and young patients for Pax-8. Pax-8 was located in the cytoplasm (cPAX) or nucleus (nPAX) in the majority of samples. There was no significant difference in nPAX between benign and malignant lesions. However, cPAX was more commonly seen in PTC than autoimmune diseases (p = 0.01) and the intensity of cPAX staining correlated with tumor size (p = 0.041), metastasis, age, completeness of resection, local invasion, and tumor size (MACIS) scores (p = 0.045), and the presence of invasion, metastasis, recurrence, or persistence (p = 0.012). Disease-free survival was significantly reduced for cancers with intense cPAX staining (p = 0.0003). These data show that cPAX is common in PTC, and although limited by small sample size, suggest an association with higher MACIS scores, an aggressive clinical course, and an increased risk of clinically evident recurrence for children and young patients.

BackgroundDisease and non-battle injury (DNBI) are a leading cause of morbidity in deployments and can compromise operational mission performance. No study to date has examined DNBI incidence and impact aboard humanitarian aid/disaster response (HADR) mission ships.MethodsFrom April to September 2011, US military and civilian personnel participated in Continuing Promise 2011, a HADR training mission aboard USNS COMFORT (T-AH 20). Health surveillance was conducted for the purpose of assessing DNBI trends and improving force health protection during the deployment through passive surveillance, collection of DNBI data among those seeking care at the ship’s clinic, and actively through use of an anonymous weekly, self-report questionnaire. Categorical and total DNBI incidence rates were calculated per 100 person-weeks and incidence rate ratios (IRR) were calculated utilizing a negative binomial model to assess potential risk factors.ResultsThe leading syndrome-specific cause of weekly visits to the ship’s clinic was gastrointestinal (GI) followed by dermatologic and respiratory conditions (2.22, 1.97, and 1.46 cases per 100 person-weeks, respectively). The top three categorical DNBI were similarly represented by the questionnaire, with respiratory conditions having the highest reported rate followed by dermatologic and GI (11.79, 8.71, and 7.38 cases per 100 person-weeks, respectively). GI had the highest morbidity measures accounting for 61.9 % of lost work days and 27.3 % of reported moderate/severe impact to mission performance. Several factors were also associated with increased DNBI rates including personnel ages 26–36 (IRR = 1.23), officers (IRR = 1.23), days-off-ship (IRR = 1.09), and affiliation with nursing services (IRR = 1.48), naval mobile construction battalion (IRR = 3.17), and security (IRR = 1.71).ConclusionsDNBI can significantly impact mission performance on HADR missions, and establishing baseline rates and identifying risk factors can help improve force health protection in future HADR missions.

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The overall incidence of OS/MH complaints was low in participants of CP11 but was under-estimated by clinic-based reporting. The OS/MH complaints increased as the mission progressed, were more prevalent in certain groups, and appeared to be related to ship's movement. These findings document the pattern of operational stress in a ship-based medical humanitarian mission and confirm unique ship-based stressors. This information may be used by planners of similar missions to develop mitigation strategies for known stressors and by preventive medicine, behavioral health specialists, and mission leaders to develop sensitive surveillance tools to better detect and manage operational stress while on mission. Scouten WT , Mehalick ML , Yoder E , McCoy A , Brannock T , Riddle MS . The epidemiology of operation stress during Continuing Promise 2011: a humanitarian response and disaster relief mission aboard a US Navy hospital ship. Prehosp Disaster Med. 2017;32(4):393-402.

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