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Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

Association between resistin levels and cardiovascular disease events in older adults: The health, aging and body composition study.

OBJECTIVE: Prospective data on the association between resistin levels and cardiovascular disease (CVD) events are sparse with conflicting results. METHODS: We studied 3044 aged 70-79 years from the Health, Aging, and Body Composition Study. CVD events were defined as coronary heart disease (CHD) or stroke events. «Hard » CHD events were defined as CHD death or myocardial infarction. We estimated hazard ratio (HR) and 95% confidence intervals (CI) according to the quartiles of serum resistin concentrations and adjusted for clinical variables, and then further adjusted for metabolic disease (body mass index, fasting plasma glucose, abdominal visceral and subcutaneous adipose tissue, leptin, adiponectin, insulin) and inflammation (C-reactive protein, interleukin-6, tumor necrosis factors-α). RESULTS: During a median follow-up of 10.1 years, 559 patients had « hard » CHD events, 884 CHD events and 1106 CVD Events. Unadjusted incidence rate for CVD events was 36.6 (95% CI 32.1-41.1) per 1000 persons-year in the lowest quartile and 54.0 per 1000 persons-year in the highest quartile (95% CI 48.2-59.8, P for trend < 0.001). In the multivariate models adjusted for clinical variables, HRs for the highest vs. lowest quartile of resistin was 1.52 (95% CI 1.20-1.93, P < 0.001) for « Hard » CHD events, 1.41 (95% CI 1.16-1.70, P = 0.001) for CHD events and 1.35 (95% CI 1.14-1.59, P = 0.002) for CVD events. Further adjustment for metabolic disease slightly reduced the associations while adjustment for inflammation markedly reduced the associations. CONCLUSIONS: In older adults, higher resistin levels are associated with CVD events independently of clinical risk factors and metabolic disease markers, but markedly attenuated by inflammation.

Mechanisms of protein homeostasis in health, aging and disease.

When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.

Process variability-aware proactive reconfiguration technique for mitigating aging effects in nanos scale SRAM lifetime

Postprint (published version)

Creative thinking

Portal web d'intercanvi d'idees creatives, confeccionat en tecnología JEE i Liferay com a gestor de continguts i gestor de portlets.

Celebrating Creative Consciousness: Insights Into Oscar Wilde’s Aesthetics

Tutkielmani valottaa irlantilaisen kirjailijan Oscar Wilden (1854-1900) vähemmän tunnettua työtä ja ajattelua taidekriitikkona fin de sièclen ja modernismin välisen siirtymävaiheen estetiikassa. Wilden voidaan sanoa olleen edellä aikaansa estetiikkakäsityksensä suhteen: Hän käsittelee taidekritiikissään teemoja, jotka tulivat keskeisiksi modernismin ja postmodernismin myötä – esimerkiksi kielen pettävyyttä, sellaisten käsitteiden kuin ’todellisuus’, ’luonto’ tai ’yhteiskunta’ sattumanvaraisuutta sekä yhteisön ja yksilön identiteettien fragmentoitumista. Wilde myös kyseenalaistaa – paradoksien, kielellisten nokkeluuksien ja ironian avulla – monia länsimaisessa filosofiassa ’normatiivisina’ pidettyjä arvoja, kuten totuuteen pyrkimisen. Lisäksi hän haastaa taiteenkritiikin akateemisen tradition hylkäämällä sellaiset sen hyveinä pitämät piirteet kuin johdonmukaisuus ja ristiriidattomuus. Tarkastelen Wilden estetiikkakäsitystä pääasiassa esseekokoelman Intentions (1891), etenkin esseen Valehtelun rappio, sekä De Profundis –teoksen (1905) kautta. Tekstejä analysoimalla ja vertaamalla osoitan miten 1890-luvun alkupuolen ja vankilatuomiotaan istuvan Wilden estetiikkakäsitys muuttui ja kehittyi. Wilden kohdalla on syytä puhua taidefilosofiasta taiteenteorian sijaan. Hänen kriittiset esseensä eivät tähtää ’harmonisen’ kokonaisuuden luomiseen tai pragmaattis-loogisen mallin rakentamiseen taiteen ymmärtämiseksi vaan tulvivat ironiaa ja ristiriitaisuuksia. Wildella taideteoksen tarkasteluun liittyy aina eettisiä, ontologisia ja metafyysisiä kysymyksiä, jotka syventävät mutta myös monimutkaistavat esteettistä kokemusta. Keskeinen teema Wildelle onkin taiteen ja elämän vastakkainasettelu sekä niiden välisen yhteyden tunnistaminen ja tunnustaminen: taide on sekä autonomista että subjektiivista. Tämä paradoksi kulminoituu esteettisessä kokemuksessa. Wildelle luomistyö ja vastaanottajan elämys ovat tiedostamattomia prosesseja – tietoista luovuutta ei ole. Esteettinen kuitenkin voidaan yhdistää tietoisuuteen, mutta se edellyttää että myös tietoisuuden on oltava luovaa. Siksipä lähestyäkseen taidetta kritiikin on tultava enemmän taiteen kaltaiseksi – epänormatiiviseksi ja epäloogiseksi. Tässä prosessissa paradokseilla on merkittävä tehtävä: ne muistuttavat siitä, että puhuttaessa taiteesta ei ole oikeita vastauksia, on vain hyviä kysymyksiä.

La ramaderia de muntanya sota el canvi climàtic : estudi sobre la vulnerabilitat i la capacitat adaptativa de les explotacions ramaderes convencionals del Pallars Sobirà

La continuïtat de la ramaderia a les zones muntanyoses es troba en risc sever. El canvi climàtic és un fenomen que es suma a la ja precària situació de la ramaderia al Pallars Sobirà, castigada pel despoblament, l’envelliment de la població i la crisi econòmica. En aquest context, les entrevistes realitzades mostren com els ramaders, tot i ser conscients dels creixents fenòmens climàtics extrems, com les sequeres, a la zona, la seva capacitat adaptativa es veu reduïda per causa d’aquests estressos socioeconòmics. Entre ells, el procés d’envelliment posa en risc el manteniment del coneixement tradicional que és un dels aspectes clau en l’adaptació. Tanmateix, les estratègies d’adaptació a estressos climàtics posades en pràctica actualment pels ramaders són limitades i tenen un marcat caràcter reactiu.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer"s disease. The type of multi‐targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health‐promoting extra virgin olive oil (EVOO), might constitute a new family of plant‐produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound"s structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS‐predicted BAS of substances based on thousands of"mechanism‐ effect" and"effect‐mechanism" relationships, we illuminate hypothesis‐generating pharmacological effects, mechanisms of action, and targets that might underlie the anti‐aging/anti‐cancer activities of the gerosuppressant EVOO oleuropeins.

Factors associated with active aging in Finland, Poland, and Spain

BACKGROUND: Continuous population aging has raised international policy interest in promoting active aging (AA). AA theoretical models have been defined from a biomedical or a psychosocial perspective. These models may be expanded including components suggested by lay individuals. This paper aims to study the correlates of AA in three European countries, namely, Spain, Poland, and Finland using four different definitions of AA. METHODS: The EU COURAGE in Europe project was a cross-sectional general adult population survey conducted in a representative sample of the noninstitutionalized population of Finland, Poland, and Spain. Participants (10,800) lived in the community. This analysis focuses on individuals aged 50 years old and over (7,987). Four definitions (two biomedical, one psychosocial, and a complete definition including biomedical, psychosocial, and external variables) of AA were analyzed. RESULTS: Differences in AA were found for country, age, education, and occupation. Finland scored consistently the highest in AA followed by Spain and Poland. Younger age was associated with higher AA. Higher education and occupation was associated with AA. Being married or cohabiting was associated with better AA compared to being widowed or separated in most definitions. Gender and urbanicity were not associated with AA, with few exceptions. Men scored higher in AA only in Spain, whereas there was no gender association in the other two countries. Being widowed was only associated with lower AA in Poland and not being married was associated with lower AA in Poland and Finland but not Spain. CONCLUSIONS: Associations with education, marital status, and occupation suggest that these factors are the most important components of AA. These association patterns, however, seem to vary across the three countries. Actions to promote AA in these countries may be addressed at reducing inequalities in occupation and education or directly tackling the components of AA lacking in each country.

Creative Industries: a Preliminary Insight to their Location Determinants

This paper is about location decisions of Creative Industries and the role played by existent spatial distribution and agglomeration economies of these kinds of activities in order to analyse their location determinants. Our main statistical source is the REIC (Catalan Manufacturing Establishments Register), which has plant-level microdata on location of new plants. Using Count Data Models, our main results show that location determinants are quite similar between both industries and also both non-creative and creative firms are positively influenced by the specialisation level in Creative Industries of municipalities. Moreover, our results provide evidence that the unobserved ‘creative milieu’ has a limited impact on attracting firms. Keywords: creative industries, creative milieu, count data models, industrial location, agglomeration economies

Validation of an instrument to evaluate quality of life in the aging population: WHOQOL-AGE.

BACKGROUND: There is a need for short, specific instruments that assess quality of life (QOL) adequately in the older adult population. The aims of the present study were to obtain evidence on the validity of the inferences that could be drawn from an instrument to measure QOL in the aging population (people 50+ years old), and to test its psychometric properties. METHODS: The instrument, WHOQOL-AGE, comprised 13 positive items, assessed on a five-point rating scale, and was administered to nationally representative samples (n = 9987) from Finland, Poland, and Spain. Cronbach's alpha was employed to assess internal consistency reliability, whereas the validity of the questionnaire was assessed by means of factor analysis, graded response model, Pearson's correlation coefficient and unpaired t-test. Normative values were calculated across countries and for different age groups. RESULTS: The satisfactory goodness-of-fit indices confirmed that the factorial structure of WHOQOL-AGE comprises two first-order factors. Cronbach's alpha was 0.88 for factor 1, and 0.84 for factor 2. Evidence supporting a global score was found with a second-order factor model, according to the goodness-of-fit indices: CFI = 0.93, TLI = 0.91, RMSEA = 0.073. Convergent validity was estimated at r = 0.75 and adequate discriminant validity was also found. Significant differences were found between healthy individuals (74.19 ± 13.21) and individuals with at least one chronic condition (64.29 ± 16.29), supporting adequate known-groups validity. CONCLUSIONS: WHOQOL-AGE has shown good psychometric properties in Finland, Poland, and Spain. Therefore, considerable support is provided to using the WHOQOL-AGE to measure QOL in older adults in these countries, and to compare the QOL of older and younger adults.

Desenvolupament d'eines informàtiques per a residències geriàtriques

L’envelliment de la població demana cada cop més centres especialitzats en geriatria en els països desenvolupats. Aquests mateixos països pateixen recentment una falta de personal qualificat en infermeria. Aquests dos factors es combinen i posen en evidència la necessitat de desenvolupar eines informàtiques que modernitzin les residències geriàtriques. El projecte que s’ha desenvolupat consisteix en una aplicació de gestió d’una residència geriàtrica amb una base de dades centralitzada en un PC des de la qual s’hi pot accedir a través d’una aplicació feta per PDA. La seva funció principal és poder agilitzar tota la repartició de medicació dins la residència geriàtrica, gestionant des de les pautes de medicació corresponents a cada resident, fins a un control d’stock. Consta, per tant, d’una aplicació per PC, programada amb Visual Basic i utilitzant com a base de dades Microsoft Access, i d’una aplicació per PDA, programada amb Embedded Visual Basic i utilitzant la mateixa base de dades creada per l’aplicació per PC. L’aplicació de PC proporcionarà als usuaris una gestió ràpida i còmode i, alhora, rapidesa i estalvi de treball si es vol fer un determinat manteniment a través de l’aplicació de PDA. En el manteniment de l’aplicació, però, no s’hi inclou el manteniment dels usuaris tot i haver un control d’aquests. En aquest projecte s’estudia com es desenvolupa una aplicació per PDA i com comparteix una base de dades amb una altra aplicació a través del sistema de sincronització PC↔PDA anomenat ActiveSync.

Percepció de dificultat i esforç en la mobilització de persones dependents, en el seu entorn domiciliari, per part dels seus cuidadors, abans i després de la utilització de llençols lliscants

Les persones amb dependència necessiten ajuda en la mobilització al llit, que suposa un esforç per a la persona cuidadora. La percepció de dificultat en dur a terme aquestes tasques pot afectar negativament la qualitat de vida de les persones cuidadores i també la de les persones dependents. L’objectiu d’aquest estudi va ser investigar si la utilització de superfícies de reducció de la fricció (tipus llençols lliscants) redueix la dificultat percebuda per les persones cuidadores i les persones dependents en la mobilització al llit. Mètodes: es va dur a terme un estudi quasi experimental a domicili en una mostra seleccionada a conveniència de 12 persones amb dependència i els seus cuidadors en diverses localitats. Es va avaluar la percepció de dificultat en la mobilització per part dels cuidadors i les persones dependents abans i després d’una intervenció formativa simultània a la utilització de llençols lliscants. Resultats: el perfil del cuidador és el d’una dona de mitjana edat amb una relació filial amb la persona dependent i sense formació específica en mètodes de mobilització de persones dependents. El perfil de la persona dependent és el d’una dona major de 80 anys amb una gran dependència que necessita ajuda de la persona que la cuida en les maniobres de redreçament i trasllat al llit. En una escala de percepció de la dificultat de 0 a 10, les mitjanes de les puntuacions observades en els cuidadors abans de la intervenció van ser de 6,9 (DE: 3,1) en el redreçament cap amunt i de 7,1 (DE: 3,1) en el trasllat lateral; després de la intervenció van ser d’1,25 (DE: 1,8) en el redreçament cap amunt i d’1,45 (DE: 1,6) en la mobilització lateral. En la mateixa escala, les mitjanes de les puntuacions observades en les persones dependents abans de la intervenció van ser de 8,6 (DE: 2,3) en el redreçament cap amunt i de 8,6 (DE: 2,3) en el trasllat cap als costats, i després de la intervenció van ser de 2 (DE: 2,6) en els redreçaments cap amunt i de 2 (DE: 2,6) en els trasllats cap als costats. Comparant les puntuacions d’abans i després de la intervenció, observem que la dificultat percebuda per part dels cuidadors de les persones dependents va disminuir de manera significativa (p < 0,001); en les persones dependents també va disminuir, però la disminució no va arribar a ser significativa (p = 0,057). Conclusions: els resultats observats mostren que la utilització de llençols lliscants millora la qualitat de vida dels cuidadors, mesurada per la percepció de la dificultat en les maniobres de mobilització al llit. Així mateix, la seva utilització pot contribuir a un millor envelliment actiu. Caldria fer estudis que permetin quantificar l’esforç físic necessari i el cost-benefici que suposa la utilització d’aquests dispositius.