Identification of novel non-autonomous CemaT transposable elements and evidence of their mobility within the C. elegans genome

We describe here two new transposable elements, CemaT4 and CemaT5, that were identified within the sequenced genome of Caenorhabditis elegans using homology based searches. Five variants of CemaT4 were found, all non-autonomous and sharing 26 bp inverted terminal repeats (ITRs) and segments (152-367 bp) of sequence with similarity to the CemaT1 transposon of C. elegans. Sixteen copies of a short, 30 bp repetitive sequence, comprised entirely of an inverted repeat of the first 15 bp of CemaT4's ITR, were also found, each flanked by TA dinucleotide duplications, which are hallmarks of target site duplications of mariner-Tc transposon transpositions. The CemaT5 transposable element had no similarity to maT elements, except for sharing identical ITR sequences with CemaT3. We provide evidence that CemaT5 and CemaT3 are capable of excising from the C. elegans genome, despite neither transposon being capable of encoding a functional transposase enzyme. Presumably, these two transposons are cross-mobilised by an autonomous transposon that recognises their shared ITRs. The excisions of these and other non-autonomous elements may provide opportunities for abortive gap repair to create internal deletions and/or insert novel sequence within these transposons. The influence of non-autonomous element mobility and structural diversity on genome variation is discussed.

Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis

Purpose: To identify papillary thyroid carcinoma (PTC)-associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue. Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. The BRAF(V600E) mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling. Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAF(V600E) mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway. Conclusion: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for FTC therapy.

The interaction between N-category and N-ratio as a new tool to improve lymph node metastasis staging in gastric cancer: Results of a single cancer center in Brazil

Background: Depth of tumor invasion (T-category) and the number of metastatic lymph nodes (N-category) are the most important prognostic factors in patients with gastric cancer. Recently, the ratio between metastatic and dissected lymph nodes (N-ratio) has been established as one. The aim of this study is to evaluate the impact of N-ratio and its interaction with N-category as a prognostic factor in gastric cancer. Methods: This was a retrospective study in which we reviewed clinical and pathological data of 165 patients who had undergone curative surgery at our institution through a 9-year period. The exclusion criteria included metastases, gastric stump tumors and gastrectomy with less than 15 lymph nodes dissected. Results: The median age of the patients was 63 years and most of them were male. Total gastrectomy was the most common procedure and 92.1% of the patients had a D2-lymphadenectomy. Their 5-year overall survival was 57.7%. T-category, N-category, extended gastrectomy, and N-ratio were prognostic factors in overall and disease-free survival in accordance with univariate analysis. In accordance with TNM staging, N1 patients who have had NR1 had 5-year survival in 75.5% whereas in the NR2 group only 33% of the cases had 5-year survival. In the multivariate analysis, the interaction between N-category and N-ratio was an independent prognostic factor. Conclusion: Our findings confirmed the role of N-ratio as prognostic factor of survival in patients with gastric cancer surgically treated with at least 15 lymph nodes dissected. The relationship between N-category and N-ratio is a better predictor than lymph node metastasis staging. (C) 2010 Elsevier Ltd. All rights reserved.

Mid-humeral sentinel lymph node dissection in patients with primary cutaneous malignant melanoma

In rare cases, lymphatic drainage from the malignant melanomas in the upper extremity may follow an unpredictable pattern (outside the axillary nodes), and these aberrant sentinel nodes may represent the only site of regional lymph node metastases. The precise anatomical landmarks and technical aspects of surgical exploration of these aberrant sentinel lymph nodes are rarely described in the literature, including aberrant sentinel mid-humeral lymph nodes. This report describes a step-by-step dissection of the mid-humeral sentinel lymph nodes in two patients with a primary malignant melanoma in the upper extremity, identified by lymphatic mapping. Recognition of precise regional anatomy and following a special surgical technique makes the procedure safe and successful, thus avoiding local complications and allowing a prompt recovery. Melanoma Res 20:138-140 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

A low-temperature insulating phase at v=1.5 for 2D holes in high-mobility SiSi1-xGex heterostructures with Landau level degeneracy

Magneto-transport measurements of the 2D hole system (2DHS) in p-type Si-Si1-xGex heterostructures identify the integer quantum Hall effect (IQHE) at dominantly odd-integer filling factors v and two low-temperature insulating phases (IPs) at v = 1.5 and v less than or similar to 0.5, with re-entrance to the quantum Hall effect at v = 1. The temperature dependence, current-voltage characteristics, and tilted field and illumination responses of the IP at v = 1.5 indicate that the important physics is associated with an energy degeneracy of adjacent Landau levels of opposite spin, which provides a basis for consideration of an intrinsic, many-body origin.

Lymph Node Size in Rectal Cancer Following Neoadjuvant Chemoradiation-Can We Rely on Radiologic Nodal Staging After Chemoradiation?

OBJECTIVES: Local excision is currently being considered as an alternative strategy for ypT0-2 rectal cancer. However, patient selection is crucial to rule out nodal disease and is performed by radiologic studies that consider size as a surrogate marker for positive nodes. The purpose of this study was to determine the difference in size between metastatic and nonmetastatic nodes and the critical lymph node size after neoadjuvant chemoradiation therapy. METHODS: The 201 lymph nodes available from 31 patients with ypT0-2 rectal cancer were reviewed and measured. Lymph nodes were compared according to the presence of metastases and size. RESULTS: There was a mean of 6.5 lymph nodes per patient and 12 positive nodes of the 201 recovered (6%). Ninety-five percent of all lymph nodes were <5 mm, whereas 50% of positive lymph nodes were <3 mm. Metastatic lymph nodes were significantly greater in size (5.0 vs. 2.5mm; P = 0.02). Lymph nodes >4.5 mm had a greater risk of harboring metastases (P = 0.009). CONCLUSIONS: Patients with ypT0-2 rectal cancer following neoadjuvant chemoradiation have very small perirectal nodes. Individual metastatic lymph nodes are significantly larger. However, a significant number of lymph nodes after neoadjuvant chemoradiation (negative and positive) are <3 mm. Individual lymph node size is not a good predictor of nodal metastases and may lead to inaccurate radiologic staging.

Lymph Node Involvement and Not the Histophatologic Subtype Is Correlated with Outcome After Resection of Adenocarcinoma of the Ampulla of Vater

Background Intestinal and pancreaticobiliary types of Vater`s ampulla adenocarcinoma have been considered as having different biologic behavior and prognosis. The aim of the present study was to determine the best immunohistochemical panel for tumor classification and to analyze the survival of patients having these histological types of adenocarcinoma. Method Ninety-seven resected ampullary adenocarcinomas were histologically classified, and the prognosis factors were analyzed. The expression of MUC1, MUC2, MUC5AC, MUC6, CK7, CK17, CK20, CD10, and CDX2 was evaluated by using immunohistochemistry. Results Forty-three Vater`s ampulla carcinomas were histologically classified as intestinal type, 47 as pancreaticobiliary, and seven as other types. The intestinal type had a significantly higher expression of MUC2 (74.4% vs. 23.4%), CK20 (76.7% vs. 29.8%), CDX2 (86% vs. 21.3%), and CD10 (81.4% vs. 51.1%), while MUC1 (53.5% vs. 82.9%) and CK7 (79.1% vs. 95.7%) were higher in pancreatobiliary adenocarcinomas. The most accurate markers for immunohistochemical classification were CDX2, MUC1, and MUC2. Survival was significantly affected by pancreaticobiliary type (p=0.021), but only lymph node metastasis, lymphatic invasion, and stage were independent risk factors for survival in a multivariate analysis. Conclusion The immunohistochemical expression of CDX2, MUC1, and MUC2 allows a reproducible classification of ampullary carcinomas. Although carcinomas of the intestinal type showed better survival in the univariate analysis, neither histological classification nor immunohistochemistry were independent predictors of poor prognosis.

Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly 1 higher predictive accuracy than any single biomarker (p < 0.001.). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p < 0.001) and cancer specific mortality (4.3%, p < 0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p < 0.001). Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

Role of ankle mobility in foot rollover during gait in individuals with diabetic neuropathy

Background: The purpose of this study was to investigate the ankle range of motion during neuropathic gait and its influence on plantar pressure distribution in two phases during stance: at heel-strike and at push-off. Methods: Thirty-one adults participated in this study (control group, n = 16; diabetic neuropathic group, n = 15). Dynamic ankle range of motion (electrogoniometer) and plantar pressures (PEDAR-X system) were acquired synchronously during walking. Plantar pressures were evaluated at rearfoot. midfoot and forefoot during the two phases of stance. General linear model repeated measures analysis of variance was applied to investigate relationships between groups, areas and stance phases. Findings: Diabetic neuropathy patients walked using a smaller ankle range of motion in stance phase and smaller ankle flexion at heel-strike (P = 0.0005). Peak pressure and pressure-time integral values were higher in the diabetic group in the midfoot at push-off phase when compared to heel-strike phase. On the other hand, the control group showed similar values of peak pressure in midfoot during both stance phases. Interpretation: The ankle mobility reduction observed could be associated to altered plantar pressure distribution observed in neuropathic subjects. Results demonstrated that midfoot and forefoot play a different role in subjects with neuropathy by receiving higher loads at push-off phase that are probably due to smaller ankle flexion at stance phase. This may explain the higher loads in anterior areas of the foot observed in diabetic neuropathy subjects and confirm an inadequate foot rollover associated to the smaller ankle range of motion at the heel-strike phase. (C) 2009 Elsevier Ltd. All rights reserved.

Cervical Mobility in Women With Migraine

Objective.-To contrast the cervical range of motion (CROM) in women with episodic migraine (EM), transformed migraine (TM), and controls without migraine headaches. Background.-Migraineurs often complain about neck pain. Furthermore, neck problems can worsen the headaches in individuals with migraine. Individuals with neck pain usually have reduced CROM. Nonetheless, studies assessing the CROM in migraineurs are scarce. Methods.-Our sample was selected in an outpatient headache clinic, and consisted of 45 women aged 20-54 years old, 15 per group. Cervical mobility was evaluated in movements of flexion, extension, right lateral flexion, left lateral flexion, right rotation, and left rotation using the CROM technique, and was contrasted among the groups. Migraine clinical patterns were also evaluated ( frequency, duration of migraine, pain in the moment of evaluation, pain in movement, and pain localization) as a function of CROM. Results.-Compared with controls, individuals with TM had numerically inferior CROM in all parameters, and significant reduction in 3 of them: extension (59.3 vs 68.1, P = .02), left lateral flexion (44.5 vs 49.1, P = .03), and right rotation (62.2 vs 69.6, P = .02). Compared with individuals with migraine, the TM group presented significantly reduced mobility only for extension ( 59.3 vs 68.4, P = .02). Migraineurs also had numerically inferior ROM, contrasted to controls, in 5 of the 6 parameters, although significance was seen just for right rotation (60.8 vs 68.6 P < .01). There was no correlation between cervical mobility and migraine parameters. The CROM was not reduced for the symptomatic side of migraine, in cases of unilateral pain. Conclusion.-Contrasted to controls, individuals with episodic and TM have decreased cervical range of motion.

A Century of Change in Coral Reef Status in Southeast and Central Pacific: Polynesia Mana Node, Cook Islands, French Polynesia, Kiribati, Niue, Tokelau, Tonga, Wallis and Futuna

The Polynesia Mana Node of the southeast and central Pacific contains 7 independent or autonomous countries or territories with only 6,000 km2 of land on 347 islands, but surrounded by 12 million km2 of EEZ. These seas contain 13,000 km2 of coral reefs as the main natural ecosystem providing food resources and opportunities for development, especially for tourism and pearl culture for 500,000 inhabitants. During the 19th and first half of the 20th centuries, there was major exploitation by the colonial powers of mother-of-pearl oysters for the button industry, as well as guano, sandalwood and trepang. The Polynesian people were largely involved in a subsistence economy and all coral reefs and lagoons were healthy. During the last two decades of the 20th, all countries experienced rapid development and urbanization, rising populations, and some increased agriculture. These developments were limited to a few islands of each country (i.e. 15 islands amongst the 347) with resulting degradation of the coral reefs around these sites. The other islands remained mostly uninhabited and pristine, and continued with a subsistence economy. Generally, there was more damage to the coral reefs through natural events such as cyclones and coral bleaching, than by human activities. There is however, an urgent need to combat the threats on some islands from increased sedimentation, over-fishing, dredging and nutrient pollution.