"Role of long non-coing RNAs in the stressed heart". Wisper : a novel cardiac fibroblast-enriched IncRNA that modulate fibrosis in the failing heart

LncRNAs are transcripts greater than 200 nucleotides in length with no apparent coding potential. They exert important regulatory functions in the genome. Their role in cardiac fibrosis is however unexplored. To identify IncRNAs that could modulate cardiac fibrosis, we profiled the long non-coding transcriptome in the infarcted mouse heart, and identified 1500 novel IncRNAs. These IncRNAs have unique characteristics such as high tissue and cell type specificity. Their expression is highly correlated with parameters of cardiac dimensions and function. The majority of these novel IncRNAs are conserved in human. Importantly, human IncRNAs appear to be differentially expressed in heart disease. Using a computational pipeline, we identified a super-enhancer-associated IncRNA, which is dynamically expressed after myocardial infarction. We named this particular transcript Wisper for «Wisp2 super-enhancer- derived IncRNA ». Interestingly, Wisper expression is overexpressed in cardiac fibroblasts as compared to cardiomyocytes or to fibroblasts isolated from other organs than the heart. The importance of Wisper in the biology of fibroblasts was demonstrated in knockdown experiments. Differentiation of cardiac fibroblast into myofibroblasts in vitro is significantly impaired upon Wisper knockdown. Wisper downregulation in cardiac fibroblasts results in a dramatic reduction of fibrotic gene expression, a diminished cell proliferation and an increase in apoptotic cell death. In vivo, depletion of Wisper during the acute phase of the response to infarction is detrimental via increasing the risk of cardiac rupture. On the other hand, Wisper knockdown following infarction in a prevention study reduces fibrosis and preserves cardiac function. Since WISPER is detectable in the human heart, where it is associated with severe cardiac fibrosis, these data suggest that Wisper could represent a novel therapeutic target for limiting the extent of the fibrotic response in the heart. -- Les long ARN non-codants (IncRNAs) sont des ARN de plus de 200 nucléotides qui ne codent pas pour des protéines. Ils exercent d'importantes fonctions dans le génome. Par contre, leur importance dans le développement de la fibrose cardiaque n'a pas été étudiée. Pour identifier des IncRNAs jouant un rôle dans ce processus, le transcriptome non-codant a été étudié dans le coeur de'souris après un infarctus du myocarde. Nous avons découverts 1500 nouveaux IncRNAs. Ces transcrits ont d'uniques caractéristiques. En particulier ils sont extrêmement spécifiques de sous-populations de cellules cardiaques. Par ailleurs, leur expression est remarquablement corrélée avec les paramètres définissant les dimensions du coeur et la fonction cardiaque. La majorité de ces IncRNAs sont conservés chez l'humain. Certains sont modulés dans des pathologies cardiaques. En utilisant une approche bioinformatique, nous avons identifié un IncRNA qui est associé à des séquences amplificatrices et qui est particulièrement enrichi dans les fibroblastes cardiaques. Ce transcrit a été nommé Wisper pour «Wisp2 super-enhancer-derived IncRNA ». L'importance de Wisper dans la biologie des fibroblastes cardiaques est démontrée dans des expériences de déplétion. En l'absence de Wisper, l'expression de protéines impliquées dans le développement de la fibrose est dramatiquement réduite dans les fibroblastes cardiaques. Ceux-ci montrent une prolifération réduite. Le niveau d'apoptose est largement augmenté. In vivo, la déplétion de Wisper pendant la phase aiguë de l'infarctus rehausse le risque de rupture cardiaque. Au contraire, la réduction de l'expression de Wisper pendant la phase chronique diminue la fibrose cardiaque et améliore la fonction du coeur. Puisque Wisper est exprimé dans le coeur humain, ce transcrit représente une nouvelle cible thérapeutique pour limiter la réponse fibrotique dans le coeur.

Psychosocial Quality-of-Life, Lifestyle and Adiposity: A Longitudinal Study in Pre-schoolers (Ballabeina Study).

PURPOSE: In obesity prevention, understanding psychosocial influences in early life is pivotal. Reviews reported contradictory results and a lack of longitudinal studies focusing on underlying lifestyle factors. This study tested whether psychosocial Quality-Of-Life (QOL) was associated with pre-schoolers' lifestyle and adiposity changes over one school year and whether lifestyle moderated the latter. It was hypothesised that QOL might not impact adiposity in everybody but that this might depend on preceding lifestyle. METHOD: Longitudinal data from 291 Swiss pre-schoolers (initially 3.9-6.3 years) was available. The following measures were used in longitudinal regressions: psychosocial QOL by PedsQL, adiposity (BMI z-score, waist, fat%), diet (food frequency), sedentary time and accelerometer-based activity. RESULTS: Concerning lifestyle, low psychosocial QOL was only related to unfavourable changes in diet (less fruit β = 0.21 and more fat intake β = -0.28) and lower physical activity (β = 0.21). Longitudinal QOL-adiposity relations appeared only after moderation by lifestyle factors (beta-range 0.13-0.67). Low psychosocial QOL was associated with increased adiposity in children with an unhealthy diet intake or high sedentary time. By contrast, low psychosocial QOL was associated with decreasing adiposity in high fruit consumers or more physically active pre-schoolers. CONCLUSION: Results emphasise the need for testing moderation in the QOL-adiposity relation. An unhealthy diet can be a vulnerability factor and high physical activity a protective factor in QOL-related adiposity. Consequently, QOL and lifestyle should be targeted concurrently in multi-factorial obesity prevention. The environment should be an 'activity encouraging, healthy food zone' that minimises opportunities for stress-induced eating. In addition, appropriate stress coping skills should be acquired.

A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study)

Background: Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. Methods: Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients" satisfaction with treatment. Adverse events were also recorded. Results: Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (−0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. Conclusions: The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion.

Early adversity and 5-HTT-BDNF genes: New evidences of Gene-Environment interactions on depressive symptoms in a general population

Background Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene×environment (G×E) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. Method A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. Results Total childhood adversity (β=0.27, p<0.001), childhood sexual abuse (CSA; β=0.17, p<0.001), childhood emotional abuse (β=0.27, p<0.001) and childhood emotional neglect (β=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001). Conclusions Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

Nuorisorikollisuuden esiintyvyys, taustatekijät ja sovittelu

Tausta Vaikka nuorisorikollisuus on kriminologisen tutkimuksen perinteinen kohde, on edelleen tarvetta pitkittäistutkimuksille, joissa on laaja, koko väestöä edustava otos. Kriminaalipolitiikan alalla puolestaan rikosten sovittelu ja muut restoratiivisen oikeuden muodot ovat nousseet Suomessakin haastamaan perinteiset rikoskontrollin paradigmat, rangaistuksen ja hoidon. Tutkimuskysymykset Tutkimuksen pääkysymyksenä oli, mitkä lapsuudessa (8 v.) ja nuoruudessa (18 v.) mitatut psykososiaaliset tekijät ovat yhteydessä nuorisorikollisuuden (16-20 v.) määrään ja lajiin. Lisäksi yhtenä kysymyksenä oli, miten varusmiespalvelun aikaiset psykiatriset diagnoosit liittyvät nuorisorikollisuuteen. Lisäksi tutkimme nuorisorikollisuuden esiintyvyyttä ja palvelujen käyttöä, ja vertailimme eri informanttien (tutkimushenkilöt itse, vanhemmat ja opettajat) vastausten ennusvoimaa lasten tulevan rikollisuuden suhteen. Rikosten sovittelun osalta kysymyksenä oli, miten suomalainen sovittelukäytäntö vastaa restoratiivisen oikeuden teoriaa ja miten sovittelua pitäisi kehittää. Aineisto ja metodit Pitkittäistutkimuksemme aineistona oli valtakunnallisesti edustava satunnaisotos, joka vastasi 10% vuonna 1981 Suomessa syntyneistä suomenkielisistä pojista. Ensimmäinen tiedonkeruu tapahtui 1989, kun pojat olivat 8-vuotiaita. Tietoa kerättiin lomakekyselyin pojilta itseltään sekä heidän vanhemmiltaan ja opettajiltaan. Tietoja saatiin 2946 pojasta. Lasten lomakkeena oli Children’s Depression Inventory, vanhemman lomakkeena Rutter A2 ja opettajan lomakkeena Rutter B2. Toinen tiedonkeruu järjestettiin, kun pojat osallistuivat kutsuntoihin 1999. Tietoja saatiin 2330 pojasta. Lomakkeena oli Young Adult Self-Report . Puolustusvoimien rekisteristä saatiin tiedot poikien kutsunnoissa ja palvelusaikana (vuosina 1999-04) saamista psykiatrisista diagnooseista, jotka luokiteltiin kuuteen luokkaan: antisosiaalinen persoonallisuushäiriö, päihdehäiriöt, psykoottiset häiriöt, ahdistuneisuushäiriöt, masennustilat ja sopeutumishäiriöt. Tieto mahdollisesta diagnoosista saatiin 2712 pojasta. Rikollisuus operationalisoitiin poliisin ns. RIKI-rekisteriin vuosina 1998-2001 rekisteröityjen tekojen avulla, kun pojat olivat pääasiassa 16-20-vuotiaita. Rikosten määrän mukaan pojat jaettiin neljään ryhmään: ei rikoksia, 1-2 rikosta (satunnainen rikollisuus), 3-5 rikosta (uusintarikollisuus) ja yli 5 rikosta (aktiivinen uusintarikollisuus). Rikoslajeista muodostettiin viisi kategoriaa: huume-, väkivalta-, omaisuus-, liikenne- ja rattijuopumusrikollisuus. Analyysivaiheessa rekisteridatasta poistettiin liikennerikkomukset. Kaikkiaan tiedot mahdollisista poliisikontakteista saatiin 2866 pojasta. Sovitteludata koostui 16 sovittelujutun havainnoinnista Turussa vuosina 2001- 2003. Tulokset Kaikkiaan 23% pojista oli rekisteröity rikoksesta (poissulkien liikennerikkomukset) nelivuotisen tutkimusperiodin aikana 16-20-vuotiaana. Satunnaisia rikoksentekijöitä oli 15%, uusijoita 4% ja moninkertaisia uusijoita 4%. Rikokset kasautuivat moninkertaisille uusijoille: tämä 4%:n ryhmä teki 72% kaikista rikoksista . Omaisuus- ja liikennerikollisia oli eniten (kumpiakin 11%), ja huumerikollisia vähiten (4%). Kaikki rikoslajit korreloivat keskenään tilastollisesti merkitsevästi. Nuorisorikollisuuden itsenäisiä ennustekijöitä lapsuudessa olivat rikkinäinen perherakenne, vanhempien alhainen koulutustaso, lapsen käytösongelmat ja hyperaktiivisuus. Kun verrattiin eri informantteja (lapset itse ja heidän vanhempansa ja opettajansa), etenkin opettajien vastaukset ennustivat lasten tulevaa rikollisuutta. Nuoruudessa rikollisuuden itsenäisiä korrelaatteja olivat pienellä paikkakunnalla asuminen, vanhempien ero, seurustelu, itse ilmoitettu antisosiaalisuus ja säännöllinen tupakointi ja humalajuominen. Ennus- ja taustatekijöille oli tyypillistä se, että ne olivat lineaarisessa yhteydessä rikosten määrään (ongelmat ja rikosten määrä lisääntyivät käsi kädessä) ja että ne liittyivät useaan rikoslajiin yhtä aikaa. Huumerikollisuudella oli kuitenkin vähemmän itsenäisiä ennus- ja taustatekijöitä kuin muilla rikoslajeilla. Joka kymmenes poika kärsi psykiatrisista häiriöistä. Tämä ryhmä teki noin puolet kaikista rikoksista, ja lähes joka toinen poika, jolla oli psykiatrinen häiriö, oli rekisteröity rikoksista. Rikolliseen käytökseen liittyivät etenkin antisosiaalinen persoonallisuushäiriö ja päihdehäiriöt. Masennustilat olivat kuitenkin ainoa diagnoosiryhmä, joka ei ollut yhteydessä rikollisuuteen. Myös psykiatristen häiriöiden esiintyvyys kasvoi lineaarisesti rikosten määrän kanssa; aktiivisista uusintarikollisista yli puolella (59%) oli psykiatrinen diagnoosi. Rikollisuuden lisäksi erilaiset psykososiaaliset ongelmat kasautuivat pienelle vähemmistölle. Aktiivisten uusijoiden ryhmään olivat tilastollisesti merkitsevästi yhteydessä lähes kaikki ongelmat mitä tutkimme. Kuitenkin tästä ryhmästä vain alle 3% oli käyttänyt mielenterveyspalveluja viimeisen vuoden aikana. Rikossovittelun havainnointitutkimuksen perusteella sovittelussa monet perusasiat ovat kunnossa, ja toiminta on mielekästä niin asianosaisten kuin yhteiskunnankin kannalta. Useimmiten osapuolet kohtasivat ja saivat aikaan sopimuksen, johon he vaikuttivat tyytyväisiltä. Rikoksentekijät olivat motivoituneita korvaamaan aiheuttamansa vahingot. Osapuolet saivat kertoa tarinansa omin sanoin, heitä kuunneltiin ja he ymmärsivät mitä sovittelussa puhutaan ja sovitaan. Sovittelun kuluessa jännitys väheni ja asiat saatiin loppuunkäsiteltyä. Asianosaiset saivat vaikuttaa prosessiin ja sopimukseen, ja uhrin oikeudet olivat sovittelussa keskeisellä sijalla. Restoratiivisen teorian perusteella sovittelussa havaittiin myös kehittämisen varaa: Etenkin nuoria rikoksentekijöitä oli hankala saada osallistumaan tosissaan, ja aikuiset helposti hallitsivat keskustelua. Etukäteistapaamisia ja tukihenkilöitä ei juuri hyödynnetty. Sovitteluja hallitsi puhe sopimuksesta ja rahasta. Työkorvauksia ei käytetty eikä rehabilitaatiota käsitelty. Sekä sovitteluun pääsy että sovittelumenettely riippuivat yksittäisistä henkilöistä. Johtopäätökset Rikosten tekeminen nuoruudessa on melko yleistä ja monimuotoista. Rikokset ja psykososiaaliset ongelmat kasautuvat pienelle ryhmälle ja kulkevat käsi kädessä. Myös psykiatriset häiriöt ovat lineaarisessa yhteydessä rikosten määrään. Rikosriskiä voidaan ennustaa jo lapsuudessa, ja etenkin opettajat ovat tarkkanäköisiä lasten ongelmien suhteen. Eri rikoslajeilla on varsin samanlaisia taustatekijöitä. Aktiiviset rikoksentekijät vastaavat suuresta osasta kokonaisrikollisuutta, tarvitsevat eniten apua, mutta eivät kuitenkaan hakeudu psykososiaalisten palvelujen piiriin. Rikosten sovittelu tarjoaa keinon puuttua ongelmiin varhaisessa vaiheessa ilman leimaamista. Sovittelun kehitystehtävät liittyvät etenkin dialogiin, valmisteluihin, tukihenkilöihin, työkorvauksiin, palveluunohjaukseen ja sovittelun sovellusalaan. Sovittelua ja muita restoratiivisia menettelyjä on kehitettävä ja laajennettava esimerkiksi niin, että niitä voitaisiin käyttää palveluunohjauksen välineenä.

Personality and Depression

The aim of this study was to illustrate the associations of personality variables and depression. The first study population consisted of 50 patients with DSM-IV defined major depressive disorder. Subjects were randomized to receive either fluoxetine medication or short-term psychodynamic psychotherapy. The Hamilton Depression Rating Scale was completed at the baseline and in the follow-up at four months. Baseline mature defense style measured with the Defense Style Questionnaire predicted favourable outcome in the fluoxetine treatment group, whereas no associations were found in psychotherapy group. The Psychological Mindedness Scale scores were not predictive for recovery in patients receiving psychotherapy or medication. The Psychological Mindedness Scale seems not to be useful in selecting optimal treatment in major depressive disorder. Harm Avoidance measured with the Temperament and Character Inventory associated with the baseline severity of the depressive state. In the fluoxetine treatment group high Reward Dependence, high Self-Directedness and high Cooperativeness were predictive for more severe depression in the four months follow-up, whereas no associations were found in the psychotherapy treatment group. It is possible that the result reflects the differences in the placebo response. The second data were derived from the Finnish Public Sector Study. These prospective studies with four years follow-up focused on the predictive value of optimism and pessimism, first, to work disability with a diagnosis of depression lasting at least 90 days and returning to work (N= 38214) , and second, to the likelihood of initiating antidepressant medication treatment lasting at least 100 days and ending the treatment (N= 29930). Results show that low optimism associates with the elevated risk of work disability and higher likelihood of antidepressant use. High pessimism associated with higher likelihood starting at least 100 days antidepressant medication and not stopping medication during the follow up. High pessimism did not seem to predict the entering to depression related work disability, but in the case of disability period it associated with the lower likelihood of returning to work. The thesis shows that personality features play a role as a vulnerability factor, and influence the onset and course of depression. Taking these factors into account more than is currently done may increase the possibilities to enhance the treatment results in depression.

Identifying first graders at risk of reading and writing difficulties : creating a group-based screening tool in kiswahili in Tanzania

Early identification of beginning readers at risk of developing reading and writing difficulties plays an important role in the prevention and provision of appropriate intervention. In Tanzania, as in other countries, there are children in schools who are at risk of developing reading and writing difficulties. Many of these children complete school without being identified and without proper and relevant support. The main language in Tanzania is Kiswahili, a transparent language. Contextually relevant, reliable and valid instruments of identification are needed in Tanzanian schools. This study aimed at the construction and validation of a group-based screening instrument in the Kiswahili language for identifying beginning readers at risk of reading and writing difficulties. In studying the function of the test there was special interest in analyzing the explanatory power of certain contextual factors related to the home and school. Halfway through grade one, 337 children from four purposively selected primary schools in Morogoro municipality were screened with a group test consisting of 7 subscales measuring phonological awareness, word and letter knowledge and spelling. A questionnaire about background factors and the home and school environments related to literacy was also used. The schools were chosen based on performance status (i.e. high, good, average and low performing schools) in order to include variation. For validation, 64 children were chosen from the original sample to take an individual test measuring nonsense word reading, word reading, actual text reading, one-minute reading and writing. School marks from grade one and a follow-up test half way through grade two were also used for validation. The correlations between the results from the group test and the three measures used for validation were very high (.83-.95). Content validity of the group test was established by using items drawn from authorized text books for reading in grade one. Construct validity was analyzed through item analysis and principal component analysis. The difficulty level of most items in both the group test and the follow-up test was good. The items also discriminated well. Principal component analysis revealed one powerful latent dimension (initial literacy factor), accounting for 93% of the variance. This implies that it could be possible to use any set of the subtests of the group test for screening and prediction. The K-Means cluster analysis revealed four clusters: at-risk children, strugglers, readers and good readers. The main concern in this study was with the groups of at-risk children (24%) and strugglers (22%), who need the most assistance. The predictive validity of the group test was analyzed by correlating the measures from the two school years and by cross tabulating grade one and grade two clusters. All the correlations were positive and very high, and 94% of the at-risk children in grade two were already identified in the group test in grade one. The explanatory power of some of the home and school factors was very strong. The number of books at home accounted for 38% of the variance in reading and writing ability measured by the group test. Parents´ reading ability and the support children received at home for schoolwork were also influential factors. Among the studied school factors school attendance had the strongest explanatory power, accounting for 21% of the variance in reading and writing ability. Having been in nursery school was also of importance. Based on the findings in the study a short version of the group test was created. It is suggested for use in the screening processes in grade one aiming at identifying children at risk of reading and writing difficulties in the Tanzanian context. Suggestions for further research as well as for actions for improving the literacy skills of Tanzanian children are presented.

Administration of Bifidobacterium animalis subsp. lactis BB-12 and xylitol with a novel pacifier in early childhood

Probiotic bifidobacteria are used in the prevention and treatment of childhood diseases. On the other hand, these bacteria are also connected to dental caries. The purpose of the present work was to test a food supplement containing Bifidobacterium animalis subsp. lactis BB-12 (B. lactis BB-12) and xylitol, and to investigate its health effects, properties and safety when used in a novel pacifier in early childhood. In a double-blind, placebo-controlled trial, newborn infants (n=163) were assigned randomly to receive B. lactis BB-12, xylitol, or sorbitol from the age of 1– 2 monthsto 2 years with a pacifier or a spoon. Children were followed up to four years of age. A part of the parents participating in the clinical trial evaluated the feasibility of the novel administration method. The pattern of tablet release from the pouch of the pacifier was tested in adults. The food supplement tablet containing B. lactis BB-12 and xylitol could be delivered in a safe and controlled way with the novel pacifier. The early administration of B. lactis BB-12 did not result in permanent oral colonization of this probiotic or affect the colonization of mutans streptococci in early childhood. Moreover, B. lactis BB-12 did not increase the occurrence of caries. Controlled administration of B. lactis BB-12 significantly reduced the incidence of respiratory infections during the first eight months of life in a Finnish population with breastfed infants. To conclude, administration of B. lactis BB-12 in early childhood is safe with regard to the future dental health of the child. In addition, B. lactis BB-12 may add to the protection against respiratory infections provided by human breast milk in infancy.

The Use of Nervous System Drugs and the Risk of Fractures in Old Adults

Hermostoon vaikuttavien lääkkeiden käyttö on yleistä iäkkäässä väestössä. Erityisen yleistä käyttö on pitkäaikaisessa laitoshoidossa asuvilla iäkkäillä. Hermostoon vaikuttavien lääkkeiden haittavaikutuksia on tutkittu paljon, ja useat hermostoon vaikuttavat lääkeaineryhmät on tunnistettu murtumien riskitekijöiksi. Aikaisemmin ei ole kuitenkaan tutkittu usean hermostoon vaikuttavan lääkkeen yhteiskäytön yhteyksiä murtuman riskiin 65 vuotta täyttäneillä. Väitöskirjatutkimuksessa havaittiin, että usean hermostoon vaikuttavan lääkeaineen yhtäaikainen käyttö oli hyvin yleistä Porin kaupunginsairaalan viidellä pitkäaikaisen laitoshoidon osastolla (n = 154) vuosien 2004 ja 2005 vaihteessa. Kolmasosa tutkituista käytti säännöllisesti kolmea tai useampaa hermostoon vaikuttavaa lääkettä samanaikaisesti. Kun huomioitiin myös tarvittaessa otettavat lääkkeet, vastaava luku oli 53 %. Tutkimuksessa havaittiin myös viitteitä lääkkeiden epäasianmukaisesta käytöstä, kun potilaiden käyttämiä lääkkeitä verrattiin heidän kognitiiviseen ja fyysiseen suorituskyynsä sekä asetettuihin diagnooseihin. Liedon kunnassa 1990-luvulla toteutettuun väestöpohjaiseen Liedon Iäkkäät -seurantatutkimukseen osallistui 1177 lietolaista 65 vuotta täyttänyttä. Lääkitystietoja sekä seuranta-aikana tapahtuneita murtumia analysoimalla havaittiin, että kahden tai useamman bentsodiatsepiinin sekä kahden tai useamman psykoosilääkkeen käyttö oli yhteydessä murtuman riskiin 65 vuotta täyttäneillä miehillä. Opioidin ja psykoosilääkkeen yhteiskäyttö sekä opioidin ja bentsodiatsepiinin yhteiskäyttö oli yhteydessä iäkkäiden miesten murtuman riskiin. Naisilla vastaavia tilastollisesti merkitseviä yhteyksiä ei havaittu. Väitöskirjatutkimuksen uusin osa-aineisto perustui Porissa vuosina 2009–2010 toteutetun Satauni-tutkimuksen aineistoon. Tutkimuksessa osoitettiin 89 potilaan aineistossa, että hallittu, yhden kuukauden aikana lääkärin ja hoitajan tuella toteutettu bentsodiatsepiinivieroitus paransi merkitsevästi 55 vuotta täyttäneiden naisten käden puristusvoimaa kuuden kuukauden seuranta-aikana. Vastaavaa yhteyttä ei havaittu miehillä. Bentsodiatsepiinivieroituksella ei ollut yhteyttä osallistujien tasapainotestin tulosten paranemiseen kuuden kuukauden seurantaaikana. Murtumilla on vakavia seurauksia sekä yksilötasolla että yhteiskunnallisesti iäkkäässä väestössä. Murtumien ehkäisy on hyvin tärkeää. Siinä tulee kiinnittää huomiota potilaan käyttämään lääkitykseen ja arvioida erityisesti usean hermostoon vaikuttavan lääkkeen yhteiskäytön tarpeellisuutta.

Reproductive biology of Pseudolaelia corcovadensis Porto & Brade (Orchidaceae): melittophyly and self-compatibility in a basal Laeliinae

The floral biology, mating systems and phenology of Pseudolaelia corcovadensis (Orchidaceae), in the "Estação de Pesquisa e Desenvolvimento Ambiental de Peti", São Gonçalo do Rio Abaixo, Minas Gerais state was studied. This species flowers from April to September, with a higher availability of flowers in June and July. The flowers are dark-pink, strongly zygomorphic, and have osmophores and nectar-guides absorbing ultraviolet light. However, the flowers of P. corcovadensis do not present nectar and are pollinated by Bombus (Fervidobombus) atratus Franklin, 1913 (Hymenoptera: Apidae) by deceit. Apparently, the flowers do not form a model-mimic pair with other species in the community, but mimic a generalized melittophilous food-flower. As a consequence, visits are very rare and fruit set is low (18%). Pseudolaelia corcovadensis is self-compatible and presents inbreeding depression in the early stages of development. The phylogenetic position of the genus Pseudolaelia and studies on floral biology in related genera suggest that melittophyly and self-compatibility are basal characters in the subtribe Laeliinae, with subsequent adaptive radiation to pollination by hummingbirds, Lepidoptera, Diptera and other Hymenoptera.

Prenatal and postnatal depression among low income Brazilian women

Postnatal depression is a significant problem affecting 10-15% of mothers in many countries and has been the subject of an increasing number of publications. Prenatal depression has been studied less. The aims of the present investigation were: 1) to obtain information on the prevalence of prenatal and postnatal depression in low income Brazilian women by using an instrument already employed in several countries, i.e., the Edinburgh Postnatal Depression Scale (EPDS); 2) to evaluate the risk factors involved in prenatal and postnatal depression in Brazil. The study groups included 33 pregnant women interviewed at home during the second and third trimesters of pregnancy, and once a month during the first six months after delivery. Questions on life events and the mother's relationship with the baby were posed during each visit. Depressed pregnant women received less support from their partners than non-depressed pregnant women (36.4 vs 72.2%, P<0.05; Fisher exact test). Black women predominated among pre- and postnatally depressed subjects. Postnatal depression was associated with lower parity (0.4 ± 0.5 vs 1.1 ± 1.0, P<0.05; Student t-test). Thus, the period of pregnancy may be susceptible to socio-environmental factors that induce depression, such as the lack of affective support from the partner. The prevalence rate of 12% observed for depression in the third month postpartum is comparable to that of studies from other countries.

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Health in early adulthood: the contribution of the 1978/79 Ribeirão Preto birth cohort

The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with alpha = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.