Risk of basal cell carcinoma after Hodgkin's disease

Background: Basal cell cancer is a common skin cancer, yet studies of second tumors after Hodgkin's disease tend to exclude basal cell cancers as second malignant tumors from analysis. Basal cell carcinomas (BCC) are possibly more common in immunosuppressed patients and were recently implicated as indicators of subsequent malignancies. Materials and Methods: Our database of 1,120 patients with Hodgkin's disease (derived from the tumor registry) was investigated for the occurrence of later BCCs. Kaplan-Meier curves were calculated. Results: A total of 9 cases of BCC were observed 0-20 years after the diagnosis of Hodgkin's disease, One case relapsed after excision. The probability of second BCC was 2.1% after 15 years of follow-up and 7.1% after 20 years. Statistically, the risk for second BCC was increased only in younger patients and with prolonged follow-up, but not in the total group of patients with Hodgkin's disease. Conclusion: BCC is not a major threat: for the survivors of Hodgkin's disease, but continued follow-up is necessary

Unexpected earthquake hazard revealed by Holocene rupture on the Kenchreai Fault (central Greece): Implications for weak sub-fault shear zones

High-resolution elevation models, palaeoseismic trenching, and Quaternary dating demonstrate that the Kenchreai Fault in the eastern Gulf of Corinth (Greece) has ruptured in the Holocene. Along with the adjacent Pisia and Heraion Faults (which ruptured in 1981), our results indicate the presence of closely-spaced and parallel normal faults that are simultaneously active, but at different rates. Such a configuration allows us to address one of the major questions in understanding the earthquake cycle, specifically what controls the distribution of interseismic strain accumulation? Our results imply that the interseismic loading and subsequent earthquakes on these faults are governed by weak shear zones in the underlying ductile crust. In addition, the identification of significant earthquake slip on a fault that does not dominate the late Quaternary geomorphology or vertical coastal motions in the region provides an important lesson in earthquake hazard assessment.This work forms part of the NERCand ESRC-funded project ‘Earthquakes Without Frontiers’, and was partly funded by the NERC grant ‘Looking Inside the Continents from Space’

Validation of a statistical shape model-based 2D/3D reconstruction method for determination of cup orientation after THA

Purpose: The aim of this study was to validate the accuracy and reproducibility of a statistical shape model-based 2D/3D reconstruction method for determining cup orientation after total hip arthroplasty. With a statistical shape model, this method allows reconstructing a patient-specific 3D-model of the pelvis from a standard AP X-ray radiograph. Cup orientation (inclination and anteversion) is then calculated with respect to the anterior pelvic plane that is derived from the reconstructed model. Materials and methods: The validation study was conducted retrospectively on datasets of 29 patients (31 hips). Among them, there were 15 men (15 hips) and 14 women (16 hips). The average age of the patients was 69.4±8.5(49−82) years. Each dataset has one postoperative X-ray radiograph and one postoperative CT scan. The postoperative CT scan for each patient was used to establish the ground truth for the cup orientation. The cup anteversion and inclination that were calculated from the 2D/3D reconstruction method were compared to the associated ground truth. To validate reproducibility and reliability, two observers performed measurements for each dataset twice in order to measure the reproducibility and the reliability of the 2D/3D reconstruction method. Results: Our validation study demonstrated a mean accuracy of 0.4 ± 1.8°(−2.6° to 3.3°) for inclination and a mean accuracy of 0.6±1.5°(−2.0° to 3.9°) for anteversion. Through the Bland-Altman analysis, no systematic errors in accuracy were detected. The method showed very good consistency for both parameters. Conclusions: Our validation results demonstrate that the statistical shape model-based 2D/3D reconstruction-based method is an accurate, consistent, and reproducible technique to measure cup orientation from postoperative X-ray radiographs. The best results were achieved with radiographs including the bilateral anterior superior iliac spines and the cranial part of non-fractured pelvise

High-Dose Hydrocortisone Treatment Does Not Affect Serum C-Reactive Protein (CRP) Concentrations in Healthy Dogs

Measuring C-reactive protein (CRP) in serum is a useful surrogate marker for assessing disease progression and treatment response in dogs with autoinflammatory diseases. Affected dogs often receive high-dose glucocorticoid treatment, but the effect of such treatment alone on serum CRP concentrations is unknown. We evaluated serum CRP concentrations via immunoassay (sandwich enzyme-linked immunosorbent assay and particle-enhanced turbidimetric immunoassay) in 12 healthy beagle dogs administered high-dose hydrocortisone (8 mg/kg q12 h) per os vs. placebo over 28 days (days 0, 1, 5, and 28) in a randomized parallel study design. Serum CRP concentrations slightly decreased during treatment or placebo but without a significant association with hydrocortisone administration (p = 0.761). Compared to baseline, serum CRP concentrations were decreased by >2.7-fold (minimum critical difference) in three hydrocortisone-treated dogs and two dogs in the placebo group on day 28, whereas an increase to >2.7-fold was seen in one dog receiving placebo. These results suggest a lack of confounding effects of high-dose hydrocortisone administration on serum CRP concentrations in healthy dogs. This might also hold in dogs with autoinflammatory conditions and/or administration of other high-dose corticosteroids, suggesting that CRP presents a suitable biomarker to monitor inflammatory disease processes. However, this needs confirmation by further studies evaluating corticosteroid-induced cellular (e.g., hepatic) transcriptome and proteome changes

Loss of genes implicated in gastric function during platypus evolution

Several genes implicated in food digestion have been deleted or inactivated in platypus. This loss perhaps explains the anatomical and physiological differences in the gastrointestinal tract between monotremes and other vertebrates and provides insights into platypus genome evolution

Overexpression of piRNA pathway genes in epithelial ovarian cancer

The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and MAEL have a repressive effect on cell invasiveness.Shu Ly Lim, Carmela Ricciardelli, Martin K. Oehler, Izza M. D. De Arao Tan, Darryl Russell, Frank Grützne

Transcriptome and translatome co-evolution in mammals.

Gene-expression programs define shared and species-specific phenotypes, but their evolution remains largely uncharacterized beyond the transcriptome layer <sup>1</sup> . Here we report an analysis of the co-evolution of translatomes and transcriptomes using ribosome-profiling and matched RNA-sequencing data for three organs (brain, liver and testis) in five mammals (human, macaque, mouse, opossum and platypus) and a bird (chicken). Our within-species analyses reveal that translational regulation is widespread in the different organs, in particular across the spermatogenic cell types of the testis. The between-species divergence in gene expression is around 20% lower at the translatome layer than at the transcriptome layer owing to extensive buffering between the expression layers, which especially preserved old, essential and housekeeping genes. Translational upregulation specifically counterbalanced global dosage reductions during the evolution of sex chromosomes and the effects of meiotic sex-chromosome inactivation during spermatogenesis. Despite the overall prevalence of buffering, some genes evolved faster at the translatome layer-potentially indicating adaptive changes in expression; testis tissue shows the highest fraction of such genes. Further analyses incorporating mass spectrometry proteomics data establish that the co-evolution of transcriptomes and translatomes is reflected at the proteome layer. Together, our work uncovers co-evolutionary patterns and associated selective forces across the expression layers, and provides a resource for understanding their interplay in mammalian organs

Hyperhomocysteinemia in greyhounds and its association with hypofolatemia and other clinicopathologic variables

Background: Folate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy. Objectives: To evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds. Animals: Data and serum samples from 559 Greyhounds. Methods: Nested case-control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea. Results: Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (q = -0.28; P = .0386) and were positively associated with serum albumin concentration (q = 0.66; P = .0022). Conclusions and Clinical Relevance: Hyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans

Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy

A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.Vincent J. Lynch, Mauris C. Nnamani, Aurélie Kapusta, Kathryn Brayer, Silvia L. Plaza, Erik C. Mazur, Deena Emera, Shehzad Z. Sheikh, Frank Grützner, Stefan Bauersachs, Alexander Graf, Steven L. Young, Jason D. Lieb, Francesco J. DeMayo, Cédric Feschotte, Günter P. Wagne