Familial colorectal cancer, omics and all that jazz....

Notwithstanding the hereditary colorectal cancer (CRC) syndromes where the underlying genetic defects have been characterized, for the vast majority of familial cases (15-20%) the disease-causing genes remain unknown, posing serious problems for genetic counselling and patient management of individuals at risk. Aiming to improve the molecular classification of familial CRC, an omics-based approach employing BAC (aCGH), cDNA microarrays and distinct in silico analytical strategies were used to study both the genomic and expression profiles generated from a large collection of colorectal adenomatous polyps. Though the overall results showed a high degree of similarity shared by genomic and expression profiles of familial colonic adenomas, which casts several serious doubts on the classification of hereditary CRC syndromes by omics technologies, the presented findings also argue in favour of a common molecular basis for CRC formation and contribute to the elucidation of the early events associated with colorectal tumorigenesis, namely the early occurrence of CIN and of the complex cross-talk between signalling pathways, in hereditary and in sporadic CRC and even across-species, and additionally in highlighting the power of integrated approaches in the discovery and prioritization of putative targets involved in colorectal tumorigenesis.LUMC, Humane GeneticaKWF (Dutch Cancer Society)Tumorgenetic

Fatigue Evaluation through Machine Learning and a Global Fatigue Descriptor

Research in physiology and sports science has shown that fatigue, a complex psychophysiological phenomenon, has a relevant impact in performance and in the correct functioning of our motricity system, potentially being a cause of damage to the human organism. Fatigue can be seen as a subjective or objective phenomenon. Subjective fatigue corresponds to a mental and cognitive event, while fatigue referred as objective is a physical phenomenon. Despite the fact that subjective fatigue is often undervalued, only a physically and mentally healthy athlete is able to achieve top performance in a discipline. )erefore, we argue that physical training programs should address the preventive assessment of both subjective and objective fatigue mechanisms in order to minimize the risk of injuries. In this context, our paper presents a machine-learning system capable of extracting individual fatigue descriptors (IFDs) from electromyographic (EMG) and heart rate variability (HRV) measurements. Our novel approach, using two types of biosignals so that a global (mental and physical) fatigue assessment is taken into account, reflects the onset of fatigue by implementing a combination of a dimensionless (0-1) global fatigue descriptor (GFD) and a support vector machine (SVM) classifier. )e system, based on 9 main combined features, achieves fatigue regime classification performances of 0.82 ± 0.24, ensuring a successful preventive assessment when dangerous fatigue levels are reached. Training data were acquired in a constant work rate test (executed by 14 subjects using a cycloergometry device), where the variable under study (fatigue) gradually increased until the volunteer reached an objective exhaustion state

Dataset supporting the proteomic differences found between excretion/secretion products from two isolates of Fasciola hepatica newly excysted juveniles (NEJ) derived from different snail hosts

Here we present the proteomic profile datasets of two Fasciola hepatica NEJ isolates derived from different snail hosts: Lymnaea viatrix and Pseudosuccinea columella. The data used in the analysis are related to the article ‘A proteomic comparison of excretion/secretion products in Fasciola hepatica newly excysted juveniles (NEJ) derived from Lymnaea viatrix or Pseudosuccinea columella’ (Di Maggio et al., 2019

Barrier Distributions as a Tool to Investigate Fusion and Fission

The recent availability of precisely measured fusion cross-sections has enabled the extraction of a representation of the distribution of barriers encountered during fusion. These representations, obtained from a variety of reactions, provide a direct observation of how the structure of the fusing nuclei changes the inter-nuclear potential landscape, thus affecting the fusion probability. Recent experiments showing the effects of static quadrupole and hexadecapole deformation, single-- and double-phonon states, transfer of nucleons between two nuclei, and high lying excited states are reviewed. The application of these concepts to the explanation of the anomalous fission-fragment anisotropies observed following reactions with actinides is discussed.Comment: 12 pages, To be published in the Proceedings of the NN 97 Conference, Gatlinburg, Tennessee, June 1997 (Nucl. Phys. A

Across intra-mammalian stages of the liver f luke Fasciola hepatica: a proteomic study

Fasciola hepatica is the agent of fasciolosis, a foodborne zoonosis that affects livestock production and human health. Although flukicidal drugs are available, re-infection and expanding resistance to triclabendazole demand new control strategies. Understanding the molecular mechanisms underlying the complex interaction with the mammalian host could provide relevant clues, aiding the search for novel targets in diagnosis and control of fasciolosis. Parasite survival in the mammalian host is mediated by parasite compounds released during infection, known as excretory/secretory (E/S) products. E/S products are thought to protect parasites from host responses, allowing them to survive for a long period in the vertebrate host. This work provides in-depth proteomic analysis of F. hepatica intra-mammalian stages, and represents the largest number of proteins identified to date for this species. Functional classification revealed the presence of proteins involved in different biological processes, many of which represent original findings for this organism and are important for parasite survival within the host. These results could lead to a better comprehension of host-parasite relationships, and contribute to the development of drugs or vaccines against this parasite

Monitorização do vale e pico sérico de vancomicina em recém-nascidos de termo: comparação entre as técnicas de cromatografia líquida de alta eficácia e imunoensaio por fluorescência polarizada

INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower.INTRODUÇÃO: Foi realizada monitorização dos níveis séricos de vancomicina em recém-nascidos de termo com sepse ou suspeita de sepse Staphylococcus sp., através da cromatografia líquida de alta eficácia (HPLC) e imunoensaio por fluorescência polarizada (FPIA). OBJETIVO: Verificar a existência de correlação estatística entre os resultados obtidos pelas duas técnicas. MÉTODO E CASUÍSTICA: Foram obtidas dezoito e vinte concentrações séricas de vancomicina no pico e vale respectivamente, em recém-nascidos de termo, no período de outubro de 1995 a outubro de 1997. RESULTADO: O coeficiente de correlação linear para pico sérico foi de 0,27, p=0,110 e para vale sérico 0,26, p= 0,1045 não sendo estatisticamente significativo, não sendo estatisticamente significativo. CONCLUSÃO: Apesar da pequena casuística, não houve correlação estatisticamente significante entre os resultados obtidos pelos duas técnicas

Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation : Experience of the Spanish Group of Hematopoietic Stem Cell Transplant

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Romiplostim and eltrombopag are the currently available thrombopoietin receptor agonists (TPO-RAs), and some studies with very small numbers of cases have reported their potential efficacy in the allo-SCT setting. The present retrospective study evaluated the safety and efficacy of TPO-RAs in 86 patients with persistent thrombocytopenia after allo-HSCT. Sixteen patients (19%) had isolated thrombocytopenia (PT), and 71 (82%) had secondary failure of platelet recovery (SFPR). TPO-RA therapy was started at a median of 127 days (range, 27 to 1177 days) after allo-SCT. The median initial and maximum administered doses were 50 mg/day (range, 25 to 150 mg/day) and 75 mg/day (range, 25 to 150 mg/day), respectively, for eltrombopag and 1 µg/kg (range, 1 to 7 µg/kg) and 5 µg/kg (range, 1 to 10 µg/kg), respectively, for romiplostin. The median platelet count before initiation of TPO-RA therapy was 14,000/µL (range, 1000 to 57,000/µL). Platelet recovery to ≥50,000/µL without transfusion support was achieved in 72% of patients at a median time of 66 days (range, 2 to 247 days). Eighty-one percent of the patients had a decreased number of megakaryocytes before treatment, showing a slower response to therapy (P =.011). The median duration of treatment was 62 days (range, 7 to 700 days). Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the patients. At last follow-up, 81% of patients had discontinued TPO-RAs and maintained response, and 71% were alive. To our knowledge, this is the largest series analyzing the use of TPO-RAs after allo-SCT reported to date. Our results support the efficacy and safety in this new setting. Further prospective trials are needed to increase the level of evidence and to identify predictors of response

Recent experimental results in sub- and near-barrier heavy ion fusion reactions

Recent advances obtained in the field of near and sub-barrier heavy-ion fusion reactions are reviewed. Emphasis is given to the results obtained in the last decade, and focus will be mainly on the experimental work performed concerning the influence of transfer channels on fusion cross sections and the hindrance phenomenon far below the barrier. Indeed, early data of sub-barrier fusion taught us that cross sections may strongly depend on the low-energy collective modes of the colliding nuclei, and, possibly, on couplings to transfer channels. The coupled-channels (CC) model has been quite successful in the interpretation of the experimental evidences. Fusion barrier distributions often yield the fingerprint of the relevant coupled channels. Recent results obtained by using radioactive beams are reported. At deep sub-barrier energies, the slope of the excitation function in a semi-logarithmic plot keeps increasing in many cases and standard CC calculations over-predict the cross sections. This was named a hindrance phenomenon, and its physical origin is still a matter of debate. Recent theoretical developments suggest that this effect, at least partially, may be a consequence of the Pauli exclusion principle. The hindrance may have far-reaching consequences in astrophysics where fusion of light systems determines stellar evolution during the carbon and oxygen burning stages, and yields important information for exotic reactions that take place in the inner crust of accreting neutron stars.Comment: 40 pages, 63 figures, review paper accepted for EPJ