Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma

BACKGROUND Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data. METHODS Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. RESULTS Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05). CONCLUSIONS Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.

Simple Estimation of Incident HIV Infection Rates in Notification Cohorts Based on Window Periods of Algorithms for Evaluation of Line-Immunoassay Result Patterns

Background Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. Methods We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship ‘Prevalence = Incidence x Duration’ in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship ‘incident = true incident + false incident’ and also to the IIR derived from the BED incidence assay. Results Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R2 = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. Conclusions IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Capability of E-Bike Tourism in Switzerland

AIM OF PAPER AND RESEARCH QUESTIONS The primary aim of this investigation was to examine, if tourism in Switzerland can be stimulated by focusing on e-bike offers. Switzerland is an attractive and manifold country for bike tourism. However, there are plenty of hilly and steep areas, where the topography is quite demanding and cycling is predestined to ambitious sportsperson. Less performance-oriented bike tourists are possibly discouraged by the challenges of the landscape. E-bikes seem to be a reasonable alterna-tive to enable less trained person to attend bike tours in steeper regions as well as to keep heterogeneous groups together. E-bikes are already popular in Switzerland for daily routes as the journey to work, but they are not very common in the tour-istic context. The presented investigation evaluates the current standing of supply and demand for e-bike tourism and asks for opportunities and threats in the future development. LITERTURE REVIEW The existing frameworks to analyse capability in the field of sport tourism are limited, because of the broad variation of sports and tourism types. Still several conceptions are valuable to evaluate the opportunities of e-bike tourism in Switzer-land. According to Higham and Hinch (2009) the potential of touristic products and destinations always depends on the interaction among the factors place, people and activity. Standeven and de Knop (1999) support this position by identify-ing the experience of place as a key component of the sport tourism experience. Bull (2005) assumes that place not only affects experience. In his opinion, the specific spatially located resources are even crucial for the existence of nature sports. He identifies four factors determining the attraction of touristic products or destination, as physical characteristics, accessibility and infrastructural arrangements, political and economic resources as well as cultural and perceptual aspects. Concerning the demand side (people) the contemporary research is guided by an individual psychological focus delivering mainly results about motives and the decision making process (e.g. Görtz & Hürten, 2011). RESEARCH DESIGN AND DATA ANALYSIS The presented study is based on a between method triangulation, consisting of qualitative interviews with important stake-holders on the supply side and a cross sectional survey on the demand side. Qualitative interviews were conducted with the first provider of touristic e-bike routes and with the manager of the leading e-bike rental company in Switzerland. The interviews were evaluated by qualitative content analysis according to Mayring (2008). The survey covered a randomized sample of 748 adult persons and focused on interests and needs of potential consumers. The concluding potentials analy-sis combined the results of the interviews and the survey with the findings of literature research. As central outcome the strengths, weaknesses, opportunities and threats were evaluated and presented by SWOT-analysis. RESULTS Results showed that the development of e-bike tourism in Switzerland was not initiated by tourism promoter, but by an innovative e-bike producer. However, also for the manufacturer the fit between landscape (place), product (activity) and visitors (people) was the crucial criterion. The first e-bike tours were offered in a demanding and rural region, in order that the experience of place was able to promote a positive overall experience. Due to the success of the first touristic e-bike products, several tourism regions started to extend their portfolio with e-bike offers. To date a nationwide network for signalised e-bike tours, rental stations and changing stations for rechargeable batteries is established. Despite the attractive offer, the demand is only moderate. The obtained results of the consumer survey pointed at a certain barrier to use e-bikes for tourism activities. The most substantial barrier is the missing affinity for bike tourism in general. Another notable group considering themselves as “fit enough for normal bike tourism”. Nevertheless 55% of the respondent are interested in tour-istic e-bike products. Looking only at people with e-bike tourism experience, even 92% are interested in further activities. DISCUSSION AN CONCLUSION The current study findings are encouraging because they suggest a superior suitability and an attractive level of e-bike tourism products in Switzerland. The results of the consumer survey indicate an increasing demand for e-bike tourism. The investigation also points at some risks, as the rivalry for bike tourism or the raised safety hazard because of the increased driving speed. Summing up, the results support the conclusion, that e-bike tourism will become more important in the com-ing years. However, to reach the goal relevant trends as the requirement for customised offers must be considered and marketing activities are supposed to be extended. REFERENCES Bull, C. (2005). Sport tourism resource analysis. In J. Higham (Ed.), Sport tourism destination: Issues, opportunities and analysis (pp. 25-38). Amsterdam: Elsevier Butterworth-Heinemann. Görtz, M., & D. Hürten (2011). Motive der Radurlauber, psychografische Merkmale und Reiseverhalten. In A. Dreyer, E. Miglbauer & R. Mühlnickel (Hrsg.), Radtourismus. Entwicklungen, Potenziale, Perspektiven (S. 36-43). München: Olden-bourg. Higham, J., & Hinch, T. (2009). Sport and Tourism. Globalization, Mobility and Identity. Amsterdam: Butterworth-Heinemann. Mayring, P. (2008). Qualitative Inhaltsanalyse. Grundlagen und Techniken (10. Aufl.). Weinheim: Beltz Verlag. Standeven, J., & De Knop, P. (1999). Sport Tourism. Campaign: Human Kinetics.

Increased endothelial microparticles and oxidative stress at extreme altitude.

PURPOSE Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed. METHODS 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol. RESULTS 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group. CONCLUSION Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.

Effect of tympanic cavity evacuation and flushing on microbial isolates during total ear canal ablation with lateral bulla osteotomy in dogs.

OBJECTIVE To evaluate differences in bacterial numbers, identity, and susceptibility in samples obtained from the tympanic cavity on entry (preflush) and after evacuation and lavage (postflush) and assess perioperative and empiric antimicrobial selection in dogs that underwent total ear canal ablation (TECA) with lateral bulla osteotomy (LBO) or reoperation LBO. DESIGN Prospective clinical study. ANIMALS 34 dogs. PROCEDURE TECA with LBO or reoperation LBO was performed on 47 ears. Pre- and postflush aerobic and anaerobic samples were obtained from the tympanic cavity. Isolates and antimicrobial susceptibility patterns were compared. RESULTS Different isolates (31/44 [70%] ears) and susceptibility patterns of isolate pairs (6/44 [14%] ears) were detected in pre- and postflush samples from 84% of ears. Evacuation and lavage of the tympanic cavity decreased the number of bacterial isolates by 33%. In 26% of ears, bacteria were isolated from post-flush samples but not preflush samples. Only 26% of isolates tested were susceptible to cefazolin. At least 1 isolate from 53% of dogs that received empirically chosen antimicrobials postoperatively was resistant to the selected drugs. Anaerobic bacteria were recovered from 6 ears. CONCLUSIONS AND CLINICAL RELEVANCE Accurate microbiologic assessment of the tympanic cavity should be the basis for selection of antimicrobials in dogs undergoing TECA with LBO. Bacteria remain in the tympanic cavity after evacuation and lavage. Cefazolin was a poor choice for dogs that underwent TECA with LBO, as judged on the basis of culture and susceptibility testing results.