Nanomolècules "computeritzades"

Molts dels materials i sistemes funcionals creats a partir de nanotecnologia estan basats en molècules, com per exemple els [2]rotaxans, que presenten unes propietats físiques i químiques potencialment útils en informàtica i en medicina. Aquesta tesi desenvolupa i utilitza una potent estratègia computacional per modelar amb molta eficàcia un [2]rotaxà que va ser sintetitzat i caracteritzat experimentalment a la University College de Dublin, a Irlanda.Gran parte de los sistemas y materiales creados a partir de la nanotecnología están basados en moléculas. Un ejemplo de éstas son los [2]rotaxanos, cuyas propiedades físicas y químicas son potencialmente útiles en informática y medicina. Esta tesis desarrolla y emplea una potente estrategia computacional para modelar con gran eficiencia un [2]rotaxano desarrollado en el University College de Dublin, en Irlanda.Most of the materials and functional systems developed by nanotechnology are based on molecules. An example of these are the [2]rotaxanes, which present physical and chemical properties potentially useful for Informatics and Medicine. In this thesis, a powerful computational strategy is outlined and tested for studying a [2]rotaxane which was synthesized at the University College Dublin, Ireland

Molecular modelling of switchable [2]Rotaxanes

Consultable des del TDXTítol obtingut de la portada digitalitzadaEn aquesta tesi s'ha desenvolupat i utilitzat una potent estrategia computacional per a l'estudi, tant estructural, dinàmic i energètic, de nous [2]rotaxanes que van ser sintetizats i caracteritzats experimentalment pel grup de recerca col·laborador del Prof. Donald Fitzmaurice de la University College Dublin, a Irlanda. Com a etapa preliminar, es van estudiar uns pseudorotaxans formats per les mateixes estacions que presentaven els nous [2]rotaxans. Es va modelitzar el comportament dels pseudorotaxans en diferents dissolvents (CH3CN i CH3OH) i amb la presència de dos tipus de contraions (PF6- i Br-). Es va voler aprofundir en el coneixement de les interaccions entre el macrocicle i les estacions. En aquesta direcció, es van determinar les energies de complexació dels complexes estació-macrocicle i també la variació energètica davant la posició del macrocicle respecte l'eix del pseudorotaxà. Els results obtinguts computacionalment van ser comparats amb els resultats obtinguts en estudis experimentals en dissolució (RMN, espectroscòpia d'absorció òptica, voltametria cíclica). Posteriorment, es va examinar el moviment traslacional del macrocicle degut a la reducció de les estacions del [2]rotaxà realitzant simulations de Perturbació d'Energia Lliure. Existeix una important contribució metodològica present en el desenvolupament de les parametritzacions per a modelitzar amb AMBER els ions PF6- i Br- i les estacions utilitzades en aquesta tesi. També s'han detectat deficiències en el mòdul RESP durant la comprovació del seu funcionament. Els [2]rotaxans estudiats són interessants ja que presenten força aplicacions pràctiques en el futur. Un dels grups bloquejador del [2]rotaxà es pot quedar unit a la superfície d'un elèctrode o alguna nanopartícula semiconductora. Així doncs, com a resultat de la col·laboració de tots dos grups es pot concloure que s'ha generat informació útil que pot ajudar a realitzar un millor disseny de [2]rotaxans i supermolècules relacionades que tinguin la capacitat de funcionar com a interrupturs bi-estables i puguin ésser utilitzats en la contrucció de futurs sistemes electrònics, en particular, com a dispositius bi-estables d'emmagatzematge d'informació.En esta tesis se ha desarrollado y utilizado una potente estrategia computacional para el estudio, tanto estructural, dinámico como energético, de nuevos [2]rotaxanos que fueron sintetizados y caracterizados experimentalmente por el grupo de investigación colaborador del profesor Donald Fitzmaurice de la University College Dublin, en Irlanda. Como etapa preliminar, se estudiaron unos pseudorotaxanos formados por las mismas estaciones que presentaban los nuevos [2]rotaxanos. Se modelizó el comportamiento de pseudorotaxanos en diferentes disolventes (CH3CN y CH3OH) y con la presencia de dos tipos de contraiones (PF6- y Br-). Se quería profundizar en el conocimiento de las interacciones entre el macrociclo y las estaciones. En esta dirección, se determinaron las energías de complejación de los complejos estación-macrociclo y también la variación energética según la posición del macrociclo respecto el eje del pseudorotaxano. Los resultados obtenidos computacionalmente fueron comparados con los resultados obtenidos en estudios experimentales en disolución (RMN, espectroscopía de absorción óptica, voltametría cíclica). Posteriormente, se examinó el movimiento traslacional del macrociclo debido a la reducción de las estaciones del [2]rotaxano realizando simulaciones de Perturbación de Energía Libre. Existe una importante contribución metodológica presente en el desarrollo de las parametrizaciones para modelizar en AMBER los iones PF6- y Br- y las estaciones utilizadas en esta tesis. También se han detectado deficiencias en el módulo RESP durante la comprobación de su funcionamento. Los [2]rotaxanos estudiados son interesantes ya que presentan numerosas aplicaciones prácticas en el futuro. Uno de los bloqueadores del [2]rotaxano se puede unir a la superficie de un electrodo o a alguna nanopartícula semiconductora. Por tanto, como resultado de la colaboración de ambos grupos se puede concluir que se ha generado información útil que puede ayudar a realizar un mejor diseño de [2]rotaxanos y supermoléculas relacionadas que tengan la capacidad de funcionar como interruptores bi-estables y puedan ser utilizados en la construcción de futuros sistemas electrónicos, en particular, como dispositivos bi-estables de almacenamiento de información.Powerful computational strategy is outlined and tested for studying the structure, dynamics and the energetics of novel modified [2]rotaxanes which were synthesized and experimentally characterized by a collaborative group of Prof. Donald Fitzmaurice from the University College Dublin, Ireland. As a first necessary step, [2]pseudorotaxanes had been examined that contain in the axles the same bipyridinyl stations of the [2]rotaxanes. The behavior of the pseudorotaxanes in two different solvents, acetonitrile and methanol is modeled at the presence of two types of counterions, PF6- and Br-. In this way an insight is gained into the interactions between the crown ether ring and the stations. Complexation energies for the viologen-crown complexes were determined, as well as the energy profiles for the movement of the crown macroring along the axle of the pseudorotaxane. The computed data for the [2]rotaxanes are compared with results from solution studies (NMR, optical absorption spectroscopy, cyclic voltametry). In addition, the shuttling of the ring in the [2]rotaxane induced by stepwise reduction of the viologen stations is examined by FEP simulations. An important methodological contribution presents the development of parameterizations for the modeling with AMBER of the hexafluorophosphate and the bromine anions and the viologens. Some deficiencies of RESP have been also noticed when testing its performance. The [2]rotaxanes studied present an interesting case with probable future practical applications. Namely, one of the bulky stoppers of the [2]rotaxane can be used to attach the rotaxane to the surface of an electrode or semiconductor nanoparticle. Thus the joint efforts of the two groups could be expected to produce useful information that can help in the rational design of [2]rotaxanes and related supermolecules capable of functioning as bi-stable switches for use in the next generation electronics, in particular as bistable devices for information storage

Multidisciplinary Prehabilitation and Postoperative Rehabilitation for Avoiding Complications in Patients Undergoing Resection of Colon Cancer: Rationale, Design, and Methodology of the ONCOFIT Study

ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary Prehabilitation and Postoperative Program (PPP) on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care. Primary and secondary endpoints will be assessed at baseline, at preoperative conditions, at the end of the PPP intervention (after 12 weeks) and 1-year post-surgery, and will include: post-surgery complications (primary endpoint); prolonged hospital length of stay; readmissions and emergency department call within 1-year after surgery; functional capacity; patient reported outcome measures targeted; anthropometry and body composition; clinical/tumor parameters; physical activity levels and sedentariness; dietary habits; other unhealthy habits; sleep quality; and fecal microbiota diversity and composition. Considering the feasibility of the present intervention in a real-life scenario, ONCOFIT will contribute to the standardization of a cost-effective strategy for preventing and improving health-related consequences in patients undergoing resection of colon cancer with an important clinical and economic impact, not only in the scientific community, but also in clinical practice.This study was funded by the University of Granada, Plan Propio de Investigación 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES). P.C. was supported by the Margarita Salas postdoctoral grant, convened by de University of the Basque Country (UPV/EHU), funded by the Ministry of Universities of Spain and the European Union-Next Generation EU

Programa sin créditos: una investigación basada en la práctica artística

Fac. de Bellas ArtesTRUEpu

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

Nanomolècules "computeritzades"

Molts dels materials i sistemes funcionals creats a partir de nanotecnologia estan basats en molècules, com per exemple els [2]rotaxans, que presenten unes propietats físiques i químiques potencialment útils en informàtica i en medicina. Aquesta tesi desenvolupa i utilitza una potent estratègia computacional per modelar amb molta eficàcia un [2]rotaxà que va ser sintetitzat i caracteritzat experimentalment a la University College de Dublin, a Irlanda.Gran parte de los sistemas y materiales creados a partir de la nanotecnología están basados en moléculas. Un ejemplo de éstas son los [2]rotaxanos, cuyas propiedades físicas y químicas son potencialmente útiles en informática y medicina. Esta tesis desarrolla y emplea una potente estrategia computacional para modelar con gran eficiencia un [2]rotaxano desarrollado en el University College de Dublin, en Irlanda.Most of the materials and functional systems developed by nanotechnology are based on molecules. An example of these are the [2]rotaxanes, which present physical and chemical properties potentially useful for Informatics and Medicine. In this thesis, a powerful computational strategy is outlined and tested for studying a [2]rotaxane which was synthesized at the University College Dublin, Ireland

Residential proximity to industrial pollution sources and colorectal cancer risk: A multicase-control study (MCC-Spain)

Background: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. Objectives: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Methods: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects’ residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. Results: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44–2.87) to 3 km (1.26; 1.00–1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77–4.00), surface treatment of metals (1.48; 1.08–2.02), glass and mineral fibers (2.06; 1.39–3.07), organic chemical industry (4.80; 3.20–7.20), inorganic chemical industry (6.74; 4.38–10.36), food/beverage sector (3.34; 2.38–4.68), and surface treatment using organic solvents (6.16; 4.06–9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91–14.28), antimony (5.30; 3.45–8.15), naphthalene (3.11; 2.16–4.49), organotin compounds (2.64; 1.76–3.98), manganese (2.53; 1.63–3.93), dichloromethane (2.52; 1.74–3.66), and vanadium (2.49; 1.59–3.91). Conclusions: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer.Scientific Foundation of the Spanish Association Against Cancer (Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC)) EVP-1178/14Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP)Instituto de Salud Carlos III FIS 12/01416Carlos III Institute of Health (ISCIII) grantsERDF funds-a way to build Europe PI08/0533 PI08/1359 PI08/1770 PS09/00773Cantabria PS09/01286-Leon PS09/01662-Granada PS09/01903Valencia PS09/02078-Huelva PI11/00226 PI11/01403 PI11/01810 PI11/01889-FEDER PI11/02213 PI12/00150 PI12/00265Fundacion Caja de Ahorros de AsturiasUniversity of OviedoJunta de Castilla y Leon LE22A10-2Regional Government of the Basque CountryConselleria de Sanitat of the Generalitat Valenciana AP_061/10Junta de Andalucia PI-0571-2009 PI-0306-2011 salud201200057018traCatalan Government DURSI grant 2014SGR647European Commission European Commission Joint Research Centre FOOD-CT-2006036224-HIWATELa Caixa Foundation 2010ACUP 00310Agency for Management of University and Research Grants (AGAUR) of the Catalan Government 2017SGR723Spanish Association Against Cancer (AECC) Scientific FoundationThe ERDF funds-a way to build Europe PI12/00488 PI12/00715 PI12/01270 PI14/00613 PI14/01219 PI15/00069 PI15/00914 PI15/01032 PI17-0009

Todani Ic cystic dilatation of the bile duct.

The congenital dilation of the bile duct is an infrequent pathology in western countries and is associated with the female sex. It is usually diagnosed clinically with complementary tests and evaluated at an early age and also appears frequently in adults. These dilatations are grouped into five types according to Todani's classification, including type Ic (Figure 1). The treatment of choice for dilatations of the biliary duct Todani type I is the complete excision of the biliary tract due to the susceptibility of malignant degeneration. A reconstruction is performed via a hepaticojejunostomy with a Roux-en-Y loop. Although in non-malignant cases, a papillotomy with prophylactic stent placement using ERCP can be performed as an alternative. We present the case of a 54-year-old female with a history of high blood pressure, she was examined due to generalized abdominal pain which was unrelated to food intake. The blood test did not identify any alterations of interest. Ultrasound identified a fusiform dilation of the common bile duct occupied by lithiasis. ERCP was attempted due to choledocholithiasis, but the procedure was abandoned as it was not feasible to channel the duodenal papilla. The study was completed with NMR cholangiography (transverse plane [Figure 2] and coronal plane [Figure 3]), identifying a diffuse fusiform dilatation of the common bile duct and common hepatic duct, compatible with congenital cystic lesion Todani type Ic. Finally, the patient underwent a hepaticojejunostomy after sectioning of the main bile duct and extraction of choledocholithiasis

Todani Ic cystic dilatation of the bile duct

The congenital dilation of the bile duct is an infrequent pathology in western countries and is associated with the female sex. It is usually diagnosed clinically with complementary tests and evaluated at an early age and also appears frequently in adults. These dilatations are grouped into five types according to Todani's classification, including type Ic (Figure 1). The treatment of choice for dilatations of the biliary duct Todani type I is the complete excision of the biliary tract due to the susceptibility of malignant degeneration. A reconstruction is performed via a hepaticojejunostomy with a Roux-en-Y loop. Although in non-malignant cases, a papillotomy with prophylactic stent placement using ERCP can be performed as an alternative. We present the case of a 54-year-old female with a history of high blood pressure, she was examined due to generalized abdominal pain which was unrelated to food intake. The blood test did not identify any alterations of interest. Ultrasound identified a fusiform dilation of the common bile duct occupied by lithiasis. ERCP was attempted due to choledocholithiasis, but the procedure was abandoned as it was not feasible to channel the duodenal papilla. The study was completed with NMR cholangiography (transverse plane [Figure 2] and coronal plane [Figure 3]), identifying a diffuse fusiform dilatation of the common bile duct and common hepatic duct, compatible with congenital cystic lesion Todani type Ic. Finally, the patient underwent a hepaticojejunostomy after sectioning of the main bile duct and extraction of choledocholithiasis

Valorisation of fish discards assisted by enzymatic hydrolysis and microbial bioconversion: Lab and pilot plant studies and preliminary sustainability evaluation

14 pages, 7 tables, 5 figuresThe new EU fishing policies (Landing Obligation) are aimed at preventing the elimination of fishing discards overboard. These new biomasses that have to be landed from 2019 force to stablish valorisation protocols since, in most cases, they cannot be used directly for human consumption. In this context, the aim of this work was to develop an integral process based on enzyme proteolysis that permitted jointly the production and recovery of fish protein hydrolysates (FPHs), oils, bioactive peptides and fish peptones. This procedure was initially applied to ten fish discards to lab scale. FPHs of high quality in terms of soluble protein and amino acid contents, digestibility and bioactivities were obtained. The growth and metabolites productions by Pediococcus acidilactici on peptones from FPHs was also evaluated with excellent results. Pilot plant trials confirmed the results of FPHs production obtained at lab scale. Finally, a comparison with the nowadays most common use of fish biomass (fish meal production) has been made as a preliminary sustainability assessment of the proposed FPHs valorisation chainThis research was funded by the projects LIFE iSEAS (LIFE+Programme, LIFE13 ENV/ES/000131), CVMar+i (0302_CVMAR_I_1_P, POCTEP 2015), GAIN (H2020 grant agreement N° 773330) and Xunta de Galicia (Grupos de Potencial Crecimiento, IN607B 2018/19)Peer reviewe