Intermediate-onset colorectal cancer: A clinical and familial boundary between both early and late-onset colorectal cancer

Comparative studies of colorectal cancer (CRC) according to the age of onset have found differences between early-onset CRC (EOCRC) and late-onset CRC (LOCRC). Using this as a starting point, we wished to determine whether intermediate-onset CRC (IOCRC) might also be considered as an independent group within CRC. We performed a retrospective comparative study of the clinicopathological and familial features, as well as of the symptoms and their duration, of a total of 272 subjects diagnosed with CRC classified into three groups according to the age-of-onset (98 EOCRC, 83 IOCRC and 91 LOCRC). The results show that from a clinicopathological point of view, IOCRC shared certain features with EOCRC (gender, prognosis), and with LOCRC (multiple primary CRCs), whereas it also had characteristics that were specific for IOCRC (mean number of associated polyps). A gradual progression was observed from EOCRC to LOCRC from a greater family aggregation to sporadic cases, in parallel with a change of Lynch Syndrome cases to the sporadic microsatellite instability pathway, with the IOCRC being a boundary group that is more related to EOCRC. With respect to symptoms, duration and correlation with stages, IOCRC appeared more similar to EOCRC. Clinically, IOCRC behaves as a transitional group between EOCRC and LOCRC, with features in common with both groups, but also with IOCRC-specific features. Excluding cases with familial cancer history, the awareness for EOCRC diagnosis should be extended to IOCRC.Wethank the Tumor Registry of the Pathology Department of the 12 de Octubre University Hospita lfor providing the paraffinembedded tissues,and Ron Hartong for his help with the English revision of this manuscript.S

Misfolded α-Synuclein in Autosomal Dominant Alzheimer's Disease.

We analyzed Lewy body (LB) pathology in 18 autosomal dominant Alzheimer's disease (ADAD) brains via immunohistochemistry. Real-time quaking induced conversion was used to detect misfolded α-synuclein (α-syn) in 18 living ADAD cerebrospinal fluid (CSF) samples. Concomitant LB pathology was present in 44% ADAD brains. Only 6% CSF samples were positive for misfolded α-syn. In an additional AD sample, all patients with confirmed LB presented misfolded α-syn in postmortem CSF regardless of the LB staging. In conclusion, misfolded α-syn in CSF was scarce in symptomatic living ADAD individuals, in contrast to postmortem brain tissue. These results suggest late appearance of LB pathology in ADAD

Hydroxamate Titanium−Organic Frameworks and the Effect of Siderophore-Type Linkers over Their Photocatalytic Activity

The chemistry of Metal-Organic Frameworks (MOFs) relies on the controlled linking of organic molecules and inorganic secondary building units to assemble an unlimited number of reticular frameworks. However, the design of porous solids with chemical stability remains still limited to carboxylate or azolate groups. There is a timely opportunity to develop new synthetic platforms that make use of unexplored metal binding groups to produce metal-linker joints with hydrolytical stability. Living organisms use siderophores (iron carriers in greek) to effectively assimilate iron in soluble form. These compounds make use of hard oxodonors as hydroxamate or catecholate groups to coordinate metal Lewis acids like iron, aluminium or titanium to form metal complexes very stable in water. Inspired by the chemistry of these microorganisms, we report the first hydroxamate MOF prepared by direct synthesis. MUV-11 (MUV = Materials of Universidad de Valencia) is a crystalline, porous material (close to 800 m2·g-1) that combines photoactivity with good chemical stability in acid conditions. By using a high-throughput approach, we also demonstrate that this new chemistry is compatible with the formation of single crystalline phases for multiple titanium salts, thus expanding the scope of precursors accessible. Titanium frameworks are regarded as promising materials for photocatalytic applications. Our photoelectrochemical and catalytic tests suggests important differences for MUV-11. Compared to other Ti-MOFs, changes in the photoelectrochemical and photocatalytic activity have been rationalized with computational modelling revealing how the chemistry of siderophores can introduce changes to the electronic structure of the frontier orbitals, relevant to the photocatalytic activity of these solids

Higher socioeconomic status is related to healthier levels of fatness and fitness already at 3 to 5 years of age: The PREFIT project: Relation between socioeconomic status, fatness and fitness in preschoolers

This study aimed to analyse the association between socioeconomic status (SES) and fatness and fitness in preschoolers. 2, 638 preschoolers (3–5 years old; 47.2% girls) participated. SES was estimated from the parental educational and occupational levels, and the marital status. Fatness was assessed by body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). Physical fitness components were assessed using the PREFIT battery. Preschoolers whose parents had higher educational levels had lower fatness (P < 0.05). BMI significantly differed across occupational levels of each parent (P < 0.05) and WHtR across paternal levels (P = 0.004). Musculoskeletal fitness was different across any SES factor (P < 0.05), except handgrip across paternal occupational levels (P = 0.05). Preschoolers with high paternal occupation had higher speed/agility (P = 0.005), and those with high or low maternal education had higher VO2max (P = 0.046). Odds of being obese and having low musculoskeletal fitness was lower as SES was higher (P < 0.05). Those with married parents had higher cardiorespiratory fitness than single-parent ones (P = 0.010). School-based interventions should be aware of that children with low SES are at a higher risk of obesity and low fitness already in the first years of life

Growth Hormone Improves Growth Retardation Induced by Rapamycin without Blocking Its Antiproliferative and Antiangiogenic Effects on Rat Growth Plate

Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis

UV measurements at Marambio and Ushuaia during 2000–2010

Solar ultraviolet (UV) irradiances were measured with NILU-UV multichannel radiometers at Ushuaia (54°&thinsp;S) and Marambio (64°&thinsp;S) between 2000 and 2013. The measurements were part of the Antarctic NILU-UV network, which was started in cooperation between Spain, Argentina and Finland. The erythemally weighted UV irradiance time series of both stations were analysed for the first time. The quality assurance procedures included a travelling reference instrument to transfer the irradiance scale to the stations. The time series were homogenized and high quality measurements were available for the period 2000–2010. During this period UV indices of 11 or more were measured on 5 and 35 days at Marambio and Ushuaia, respectively. At Marambio, the peak daily maximum UV index of 12 and daily doses of around 7&thinsp;kJ&thinsp;m−2 were measured in November 2007. The highest UV daily doses at both stations were typically around 6&thinsp;kJ&thinsp;m−2 and occurred when the stations were inside the polar vortex, resulting in very low total ozone amount. At both stations, daily doses in late November could even exceed those in the summer. At Marambio, in some years, also daily doses in October can be as high as those during the summer. At Ushuaia, the peak daily maximum UV index of 13 was measured twice: in November 2003 and 2009. Also during those days, the station of Ushuaia was inside the polar vortex.</p

Thermal Liquid Biopsy (TLB) Focused on Benign and Premalignant Pancreatic Cyst Diagnosis

19 pags., 7 figs., 2 tabs. -- This article belongs to the Special Issue Gastrointestinal Cancers and Personalized MedicineBackground: Current efforts in the identification of new biomarkers are directed towards an accurate differentiation between benign and premalignant cysts. Thermal Liquid Biopsy (TLB) has been previously applied to inflammatory and tumor diseases and could offer an interesting point of view in this type of pathology. Methods: In this work, twenty patients (12 males and 8 females, average ages 62) diagnosed with a pancreatic cyst benign (10) and premalignant (10) cyst lesions were recruited, and biological samples were obtained during the endoscopic ultrasonography procedure. Results: Proteomic content of cyst liquid samples was studied and several common proteins in the different groups were identified. TLB cyst liquid profiles reflected protein content. Also, TLB serum score was able to discriminate between healthy and cysts patients (71% sensitivity and 98% specificity) and between benign and premalignant cysts (75% sensitivity and 67% specificity). Conclusions: TLB analysis of plasmatic serum sample, a quick, simple and non-invasive technique that can be easily implemented, reports valuable information on the observed pancreatic lesion. These preliminary results set the basis for a larger study to refine TLB serum score and move closer to the clinical application of TLB providing useful information to the gastroenterologist during patient diagnosis.This research was funded by the Spanish Ministry of Economy and Competitiveness and European ERDF Funds (MCIU/AEI/FEDER, EU) (BFU2016-78232-P to A.V.C.); Projects funded by Instituto de Salud Carlos III and co-funded by European Union (ESF, ”Investing in your future”): “PI15/00663 (FIS project to O.A)”, “PI18/00349 (FIS project to O.A. and Contract to LC)”, “FI19/00146 (PFIS contract for SHD)”, “CPII13/00017 (Miguel Servet Program to OA)”; Diputación General de Aragón (Protein Targets and Bioactive Compounds Group E45_17R to A.V.C. and Digestive Pathology Group B25_17R to O.A.); and the Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).Peer reviewe