Extreme Fluctuations in Wnt/beta-Catenin Signaling as an Approach for Colon Cancer Prevention and Therapy

Abstract: Mutations in the Wnt/beta-catenin (Wnt) signaling pathway initiate most cases of sporadic colon cancers (CC); therefore one approach for CC prevention and therapy is to suppress Wnt activity. However, the prolonged suppression of the signaling pathway is detrimental to the intestinal stem cells that rely on Wnt signaling for survival. Furthermore, CC cells exposed for an extended period of time to a single Wnt signaling -modulating agent may develop resistance to it. A possible solution is suggested by our findings that: (a) butyrate, a colonic metabolite of dietary fiber, and synthetic histone deacetylase inhibitors that mimic the effects of butyrate, hyperactivate Wnt transcriptional activity in CC cells with mutations in the pathway, and (b) high fold changes of Wnt signaling induce high apoptotic levels in the mutated cells. Therefore, diet-and drug-based regimens that result in alternating periods of suppressed and hyper-activated Wnt signalling may become powerful anti-CC preventive and therapeutic approaches. The hypothesis can be tested by (1) evaluating the effects of drug-and dietbased regimens, which induce maximal fluctuations in Wnt signaling, on the adenoma burden of Apc/min mice, an established in vivo model of intestinal cancer, (2) epidemiological studies analyzing the dietary habits, such as daily fasting hours and fiber intake, of healthy individuals and patients with positive colonoscopies, and 352 D. L. Lazarova and M. Bordonaro (3) examining the ability of different diets to produce colonic lumen content with apoptotic and Wnt-modulatory functions

Evidence of the Boyer Model of Scholarship in Counselor Education

This study delineated how the Boyer (1990) model of scholarship has been implemented in counselor education. The taxonomy of scholarship was delineated: Scholarship of Discovery, Scholarship of Teaching, Scholarship of Application, and Scholarship of Integration. The Journal of Counseling and Development and Counselor Education and Supervision were examined from 2000 to 2008. Examples of scholarship from each journal were identified. Evidence of the Boyer model in premier counseling journals suggests a consistency of approach between this model and scholarly activities in counselor education. An expanded view of scholarship may have positive implications for scholarly activity in graduate education and pretenured faculty

Fossils of San Juan province

Se mencionan los principales fósiles que se hallan en el actual territorio de la provincia de San Juan, agrupados según las Eras Paleozoica, Mesozoica y Cenozoica. Se describen brevemente las características morfológicas de los fósiles más representativos, indicando su lugar de hallazgo, su edad y el ambiente sedimentario que lo caracteriza. También se definen y describen algunos conceptos y procesos geológicos utilizados en las ciencias paleontológicas.The main fossils of San Juan province are mentioned. They are grouped into the Paleozoic, Mesozoic and Cenozoic Eras. The morphological features of the most representative fossils are briefly described, with indication of their ages, localities and characteristic sedimentary environments. Also defined are some concepts and geological processes used in paleontological sciences.Fil: Bordonaro, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Raviolo, Mariana M.. No especifíca

genetic diversity and relationship among the three autochthonous sicilian donkey populations assessed by microsatellite markers

AbstractIn the developed countries donkey has lost its main function as draft animal because of the mechanization in agri-culture; as a consequence donkey population was greatly reduced. According to SAVE monitoring institute, three of the eight Italian endangered donkey breeds are native of Sicily (Ragusano, Pantesco, Grigio Siciliano). Urgent safeguard plans are required. The aim of this work is to investigate the distribution of genetic diversity and the relationships among the three Sicilian autochthonous donkey breeds using a set of microsatellite markers. A total of 116 blood samples (61 Ragusano, 39 Pantesco, 16 Grigio Siciliano) were collected in 9 herds all over Sicily. Representative samples of Ragusano and Grigio donkey populations consist of unrelated individuals, whereas the sample of Pantesco represents nearly the entire studbook-registered population managed by "Ispettorato Ripartimentale delle Foreste di Erice (TP)" in the "Azienda S. Matteo". Genomic DNA was amplified at 11 microsatellite..

Genetic diversity and admixture analysis of Sanfratellano and three other Italian horse breeds assessed by microsatellite markers.

Sanfratellano is a native Sicilian horse breed, mainly reared in the north east of the Island, developed in the 19th century from local dams and sires with a restricted introgression of Oriental, African and, more recently, Maremmano stallions. In this study, the genetic relationships and admixture among Sanfratellano, the other two Sicilian autochthonous breeds and Maremmano breed were assessed using a set of microsatellites. The main goals were to infer the impact of Maremmano breed in the current Sanfratellano horse and to provide genetic information useful to improve the selection strategies of the Sanfratellano horse. The whole sample included 384 horses (238 Sanfratellano, 50 Sicilian Oriental Purebred, 30 Sicilian Indigenous and 66 Maremmano), chosen avoiding closely related animals. A total of 111 alleles from 11 microsatellite loci were detected, from four at HTG7 to 15 at ASB2 locus. The mean number of alleles was the lowest in Oriental Purebred (6.7), the highest in Sanfratellano (8.3). All the breeds showed a high level of gene diversity (He) ranging from 0.71 ± 0.04 in Sicilian Oriental Purebred to 0.81 ± 0.02 in Sicilian Indigenous. The genetic differentiation index was low; only about 6% of the diversity was found among breeds. Nei's standards (DS) and Reynolds' (DR) genetic distances reproduced the same population ranking. Individual genetic distances and admixture analysis revealed that: (a) nowadays Maremmano breed does not significantly influence the current Sanfratellano breed; (b) within Sanfratellano breed, it is possible to distinguish two well-defined groups with different proportions of Indigenous blood

Mitochondrial DNA control region variation in Sanfratellano horse and two other Sicilian autochthonous breeds

Mitochondrial D-loop hypervariable region was analysed in 20 Sanfratellano and two other Sicilian autochthonous horse breeds (20 Sicilian Oriental Purebred and 20 Sicilian Indigenous) in order to investigate matrilineal genetic diversity. A total of 20 different haplotypes were identified sequencing a fragment of 397 bp; overall, haplotypes showed 31 polymorphic sites (7.8%). High diversity was detected in Sanfratellano (11 haplotypes) and Sicilian Indigenous (13 haplotypes), whereas only one haplotype was found in Sicilian Oriental Purebred. Sanfratellano sequences were compared with those belonging to the other Sicilian autochthonous horses and 118 sequences selected from the GenBank database in order to calculate the statistics of molecular diversity. Six haplotypes were exclusive of Sanfratellano which shares haplotype C, D, H, and O with the Sicilian Indigenous and haplotype U with the Sicilian Oriental Purebred; not significant differentiation was found between Sanfratellano and Sicilian Indigenous. BLAST search showed Sicilian haplotypes overlap with the database sequences but for three. Phylogenetic analysis did not show monophyletic group for Sanfratellano samples or the other breeds included in this analysis

Protein fraction heterogeneity in donkey's milk analysed by proteomic methods

Donkey's milk is often well tolerate by patients affected by cow's milk protein allergy, probably thanks to its protein composition. This empiric evidence, confirmed by some clinical trials, needs to be better investigated. A preliminary survey on the protein fraction of donkey's milk was carried out: fifty-six individual milk samples have been collected and analysed by IEF and SDS-PAGE. Five different IEF patterns have been identified, showing a marked heterogeneity both in casein and whey protein fractions. A single IEF pattern showed an apparent reduced amount of casein fraction highlighted by SDS. Three of the five IEF patterns have been further investigated by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)

Accuracy of a Wrist-Worn Heart Rate Sensing Device during Elective Pediatric Surgical Procedures

The reliability of wearable photoplethysmography (PPG) sensors to measure heart rate (HR) in hospitalized patients has only been demonstrated in adults. We evaluated the accuracy of HR monitoring with a personal fitness tracker (PFT) in children undergoing surgery. HR monitoring was performed using a wrist-worn PFT (Fitbit Charge HR) in 30 children (8.21 \ub1 3.09 years) undergoing laparoscopy (n = 8) or open surgery (n = 22). HR values were analyzed preoperatively and during surgery. The accuracy of HR recordings was compared with measurements recorded during continuous electrocardiographic (cECG) monitoring; HRs derived from continuous monitoring with pulse oximetry (SpO2R) were used as a positive control. PFT-derived HR values were in agreement with those recorded during cECG (r = 0.99) and SpO2R (r = 0.99) monitoring. PFT performance remained high in children < 8 years (r = 0.99), with a weight < 30 kg (r = 0.99) and when the HR was < 70 beats per minute (bpm) (r = 0.91) or > 140 bpm (r = 0.99). PFT accuracy was similar during laparoscopy and open surgery, as well as preoperatively and during the intervention (r > 0.9). PFT-derived HR showed excellent accuracy compared with HRs measured by cECG and SpO2R during pediatric surgical procedures. Further clinical evaluation is needed to define whether PFTs can be used in different health care settings

Revisión estratigráfica y litofacial de la Formación La Silla (Ordovícico Inferior) en la Precordillera Oriental de San Juan, Argentina

La Formación La Silla (Cámbrico Superior - Ordovícico Inferior) fue definida en 1994 por Keller et al. a partir de los niveles inferiores de la Formación San Juan. Esta Formación consiste en una sucesión distintiva de calizas claras, con escasos fósiles y muy explotadas por su alta pureza. Basados en estudios detallados en la sección tipo cercana a Jáchal y siete secciones en el área sur cercana a la ciudad de San Juan, proponemos una subdivisión formal para la Formación La Silla en tres miembros. La división de la unidad está basada en la ubicación preferencial de bancos dolomíticos en el sector central de la Formación mientras que el sector superior e inferior son calizas monótonas. Los miembros se denominan, de base a techo: Miembro Río del Agua, Miembro Río Blanco y Miembro Río Salado (85, 140 y 81 m, respectivamente). Las dolomías en el Miembro Río Blanco son de dos tipos: macizas, potentes y generalmente asociadas a chert; y dolomías con laminación planar y/o entrecruzada, ambas fácilmente distinguibles a simple vista, otorgándole a este Miembro un aspecto bandeado debido a la alternancia entre calizas y dolomías. Esto contrasta con el aspecto macizo y monótono de los Miembros restantes con estratificación tabular y a veces suavemente ondulante. Se reconocen las facies de grainstone peloidal, grainstone oolítico, rudstone intraclástico, packstone peloidal, mudstone, microbiales laminadas y trombolíticas. Además se describen las nuevas facies de dolomías laminadas y dolomías macizas. De la misma manera que lo observado por Keller et al. (1994), la Formación La Silla representa una fase distinta en la sucesión cambro-ordovícica, con las dolomías perimareales de la Formación La Flecha por debajo y las calizas fosilíferas de plataforma abierta de la Formación San Juan por encima

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study

Càncer colorectal metastàtic; Oxaliplatina; Trifluridina/TipiracilCáncer colorrectal metastásico; Oxaliplatino; Trifluridina/TipiracilMetastatic colorectal cancer; Oxaliplatin; Trifluridine/tipiracilBackground In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. Patients and methods In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. Results In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. Conclusion FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.The study was funded jointly by Servier, France and Taiho Pharmaceutical, Japan