Mouse Models of Follicular and Papillary Thyroid Cancer Progression

A significant number of well-differentiated thyroid cancers progress or recur, becoming resistant to current therapeutic options. Mouse models recapitulating the genetic and histological features of advanced thyroid cancer have been an invaluable tool to dissect the mechanisms involved in the progression from indolent, well differentiated tumors to aggressive, poorly differentiated carcinomas, and to identify novel therapeutic targets. In this review, we focus on the lessons learned from models of epithelial cell-derived thyroid cancer showing progression from hyperplastic lesions to locally invasive and metastatic carcinomas

Field evaluation of a second-generation cytometer UF-100 in diagnosis of acute urinary tract infections in adult patients

AbstractAims The authors evaluated the analytical performance of the Sysmex UF-100 cytometer vs. the diagnosis of urinary tract infections (UTI).Methods We considered 2010 subjects, aged between 18 and 78, 870 males and 1140 females. The majority (90.2%) of the samples were voided urine specimens collected by using the midstream technique. Each sample was subjected to microbiological evaluation (culture + residual antibacterial activity), dipstick tests, UF-100 examination and microscopic observation. In order to obtain a final diagnosis of UTI these laboratory results were taken into consideration together with clinical data and patients' characteristics. The analytical performance of the laboratory tests was obtained by adopting this diagnosis as standard practice.Results Out of the total 2010 subjects considered a clinical diagnosis of UTI was obtained in 529 cases (26.32%). The UF-100-based screening had sensitivity, 0.94; specificity, 0.93; positive predictive value, 0.83; negative predictive value, 0.98; and correctly classified incidence, 0.93.Conclusions In our experience the results of the UF-100-based screening show a very good correlation with the diagnosis of acute UTI in adults patients

Reinitiation of protein synthesis in Escherichia coli can be induced by mRNA cis-elements unrelated to canonical translation initiation signals

AbstractIn Eubacteria, de novo translation of some internal cistrons may be inefficient or impossible unless the 5′ neighboring cistron is also translated (translational coupling). Translation reinitiation is an extreme case of translational coupling in which translation of a message depends entirely on the presence of a nearby terminating ribosome. In this work, the characteristics of mRNA cis-elements inducing the reinitiation process in Escherichia coli have been investigated using a combinatorial approach. A number of novel translational reinitiation sequences (TRSs) were thus identified, which show a wide range of reinitiation activities fully dependent on a translational coupling event and unrelated to the presence/absence of secondary structure or mRNA stability. Moreover, some of the isolated TRSs are similar to intercistronic sequences present in the E. coli genome

Determining the Moisture Content of Pre-Wetted Lightweight Aggregate: Assessing the Variability of the Paper Towel and Centrifuge Methods

Internally cured (IC) concrete is frequently produced in North America using pre-wetted lightweight aggregate (LWA). One important aspect associated with the production of quality IC concrete is the accurate determination of the moisture content, including absorbed moisture and surface moisture of the LWA. Knowledge of the moisture content enables aggregate moisture corrections to be made for the concrete mixture, thereby enabling an accurate water-to-cement ratio to be maintained. Two methods for determining the moisture content of LWA include the specified ASTM C1761-13b “paper towel method” and a method that uses a centrifuge (Miller, Barrett, Zander, & Weiss, 2014). There are limited data available on the variability associated with either of these approaches when the test is performed by multiple users. In this study, the absorption of four commercially available LWAs was tested by a single operator in a single laboratory using the centrifuge method. In addition, the absorption of three commercially available LWAs was tested by 25 users performing both experimental methods. This article provides an estimation of precision associated with both a single operator and multiple operators performing both the paper towel method and the centrifuge method to find the absorption of pre-wetted lightweight fine aggregate

Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. Despite a relatively low prevalence, it accounts for a disproportionate number of thyroid cancer-related deaths, due to its resistance to any therapeutic approach. Here we describe the first mouse model of ATC, obtained by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion, and distant metastases. Expression profiling of the murine ATCs reveals a significant overlap with genes found deregulated in human ATC, including genes involved in mitosis control. Furthermore, similar to the human tumors, [Pten, p53]thyr−/− tumors and cells are highly glycolytic and remarkably sensitive to glycolysis inhibitors, which synergize with standard chemotherapy. Taken together, our results show that combined PI3K activation and p53 loss faithfully reproduce the development of thyroid anaplastic carcinomas, and provide a compelling rationale for targeting glycolysis to increase chemotherapy response in ATC patients

Milankovitch forcing and meridional moisture flux in the atmosphere : insight from a zonally averaged ocean–atmosphere model

Author Posting. © American Meteorological Society, 2010. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 23 (2010): 4841–4855, doi:10.1175/2010JCLI3273.1.A 1-Myr-long time-dependent solution of a zonally averaged ocean–atmosphere model subject to Milankovitch forcing is examined to gain insight into long-term changes in the planetary-scale meridional moisture flux in the atmosphere. The model components are a one-dimensional (latitudinal) atmospheric energy balance model with an active hydrological cycle and an ocean circulation model representing four basins (Atlantic, Indian, Pacific, and Southern Oceans). This study finds that the inclusion of an active hydrological cycle does not significantly modify the responses of annual-mean air and ocean temperatures to Milankovitch forcing found in previous integrations with a fixed hydrological cycle. Likewise, the meridional overturning circulation of the North Atlantic Ocean is not significantly affected by hydrological changes. Rather, it mainly responds to precessionally driven variations of ocean temperature in subsurface layers (between 70- and 500-m depth) of this basin. On the other hand, annual and zonal means of evaporation rate and meridional flux of moisture in the atmosphere respond notably to obliquity-driven changes in the meridional gradient of annual-mean insolation. Thus, when obliquity is decreased (increased), the meridional moisture flux in the atmosphere is intensified (weakened). This hydrological response is consistent with deuterium excess records from polar ice cores, which are characterized by dominant obliquity cycles.A. A. thanks the Global Environmental and Climate Change Centre of McGill University for a Network Grant that made possible an enriching twoweek stay at WHOI during June 2007. O. M. acknowledges support from theU.S.National Science Foundation. Support from a Canadian NSERC Discovery Grant awarded to L.A.M. is gratefully acknowledged

A survey of clinical features of allergic rhinitis in adults

Background: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18–45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. . Conclusions: These fndings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed