Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia-AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35-47% AA (specificity 98-95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals

Magnetothermal properties of molecule-based materials

We critically review recent results obtained by studying the low-temperature specific heat of some of the most popular molecular magnets. Perspectives of this field are discussed as well.Comment: 12 pages text + 14 pages figures, Submitted as "feature article" to Journal of Materials Chemistr

Cultura organizacional en estructuras en red : el caso de la mina Uchucchacua

La miner?a es el principal rubro de exportaciones del pa?s, siendo un sector con altas ventajas competitivas considerando los inmensos recursos mineros existentes. En el caso de la plata, nuestro pa?ses el primer productor y la mina Uchucchacua es una de las principales productoras en el mundo. Paradojicamente, el sector minero atraviesa por un momento cr?tico en nuestro pa?s, caracterizado por los conflictos sociales que giran en torno de una supuesta falta de aporte al desarrollo, contaminaci?n del medioambiente, desconocimiento de las costumbres de las comunidades campesinas e incumplimiento de la normatividad vigente. En este especial entorno, las empresas mineras buscan adoptar estrategias que incrementen sus vol?menes de producci?n y reduzcan sus costos, a efecto de aprovechar el alto precio que registran los minerales met?licos.Considerando el contexto descrito, se propone un modelo te?rico nuevo que comprenda la influencia de la cultura organizacional en la administraci?n estrat?gica, con un enfoque que considere la estructura organizacional en red aplicado al sector minero

Fluctuations of wave functions about their classical average

Quantum-classical correspondence for the average shape of eigenfunctions and the local spectral density of states are well-known facts. In this paper, the fluctuations that quantum mechanical wave functions present around the classical value are discussed. A simple random matrix model leads to a Gaussian distribution of the amplitudes. We compare this prediction with numerical calculations in chaotic models of coupled quartic oscillators. The expectation is broadly confirmed, but deviations due to scars are observed.Comment: 9 pages, 6 figures. Sent to J. Phys.

TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors

Background: Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than "classic" IDHwt GBM. Methods: We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data. Results: p53 was altered by gene mutation or protein overexpression in all cases, while driver IDH1, IDH2, BRAF, or H3F3A mutations were infrequent or absent. Compared to IDHwt GBMs, gcGBMs had a significant higher frequency of TP53, ATRX, RB1, and NF1 mutations, while lower frequency of EGFR amplification, CDKN2A deletion, and TERT promoter mutation. Almost all tumors had low TML values. The high TML observed in only 2 tumors was consistent with POLE and MSH2 mutations. In the histopathological review of TCGA IDHwt, TP53-mutant tumors identified giant cells in 37% of the cases. Considering our series and that of the TCGA, patients with TP53-mutant gcGBMs had better overall survival than those with TP53wt GBMs (log-rank test, P < .002). Conclusions: gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine

Longitudinal analysis on parasite diversity in honeybee colonies: new taxa, high frequency of mixed infections and seasonal patterns of variation

To evaluate the influence that parasites have on the losses of Apis mellifera it is essential to monitor their presence in the colonies over time. Here we analysed the occurrence of nosematids, trypanosomatids and neogregarines in five homogeneous colonies for up to 21 months until they collapsed. The study, which combined the use of several molecular markers with the application of a massive parallel sequencing technology, provided valuable insights into the epidemiology of these parasites: (I) it enabled the detection of parasite species rarely reported in honeybees (Nosema thomsoni, Crithidia bombi, Crithidia acanthocephali) and the identification of two novel taxa; (II) it revealed the existence of a high rate of co-infections (80% of the samples harboured more than one parasite species); (III) it uncovered an identical pattern of seasonal variation for nosematids and trypanosomatids, that was different from that of neogregarines; (IV) it showed that there were no significant differences in the fraction of positive samples, nor in the levels of species diversity, between interior and exterior bees; and (V) it unveiled that the variation in the number of parasite species was not directly linked with the failure of the colonies

Increased urinary markers of kidney damage in the institutionalized frail elderly due to recurrent urinary tract infections.

Objective: To characterize the impact on kidney injury of recurrent urinary tract infections (RUTI) in the frail elderly. Methods: Prospective observational study in 200 frail elderly subjects for 1 year. Groups: GA (n = 100): subjects without RUTI, GB (n = 100): subjects with RUTI. Variables: age, concomitant diseases, glomerular filtration rate (GFR), urine neutrophil gelatinase-associated lipocalin (NGAL) at the beginning (NGAL-1) and end (NGAL-2) of the study, urine N-acetyl glucosaminidase (NAG) at the beginning (NAG-1) and the end (NAG-2) of the study, urine transforming growth factor-beta 1 (TGFbeta-1). Descriptive statistics, Mann-Whitney test, Chi-squared test, Fisher's exact test, and multivariate analysis were used. Results: Mean age was 84.33 (65-99) years old, with no difference between GA and GB. Mean NGAL-1 was 1.29 ng/ml (0.04-8). There was lower in GA than in GB. Mean NGAL-2 was 1.41 ng/ml (0.02-9.22). NGAL-2 was lower in GA than in GB. Mean NAG-1 was 0.38 UU.II/ml (0.01-2.63. NAG-1 in GA was lower than in GB. Mean NAG-2 was 0.44 UU.II/ml (0-3.41). NAG-2 was lower in GA compared with GB. Mean TGFbeta-1 was 23.43 pg/ml (0.02-103.76). TGFbeta-1 was lower in GA than GB. There were no differences in the presence of secondary diagnoses between GA and GB. NAG-2 and NGAL-1 were the most determining factors of renal function; in GA it was NGAL-2, followed by NAG-1; in GB it was NGAL-1, followed by NAG-2. Conclusion: Frail elderly with RUTI have higher urinary levels of renal injury markers, specifically NGAL, NAG, and TGFbeta-1, chronically in periods between urinary tract infection (UTI). Urinary markers of renal injury, specifically NGAL, NAG, and TGFbeta-1, identify early deterioration of renal function, compared with serum creatinine, or albuminuria, in frail elderly with recurrent urinary infections

Holonomy from wrapped branes

Compactifications of M-theory on manifolds with reduced holonomy arise as the local eleven-dimensional description of D6-branes wrapped on supersymmetric cycles in manifolds of lower dimension with a different holonomy group. Whenever the isometry group SU(2) is present, eight-dimensional gauged supergravity is a natural arena for such investigations. In this paper we use this approach and review the eleven dimensional description of D6-branes wrapped on coassociative 4-cycles, on deformed 3-cycles inside Calabi-Yau threefolds and on Kahler 4-cycles.Comment: 1+8 pages, Latex. Proceedings of the Leuven workshop, 2002. v2: Corrected typos in equations (4)-(8

Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin

OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy