Understanding depressive symptoms through psychological traits and physiological stress reactivity

Peer reviewe

Gender- and age-stratified analyses of ADHD medication use in children and adolescents in Finland using population-based longitudinal data, 2008-2018

Aims: This study examined medication use for attention-deficit/hyperactivity disorder (ADHD) among children and adolescents by gender in Finland during 2008-2018. Methods: Aggregated data on medication use for ADHD from 2008 to 2018 were extracted from the nationwide register on reimbursed prescriptions. The annual prevalence of ADHD medication use was calculated as the number of children (6-12 years) and adolescents (13-17 years) per calendar year with at least one ADHD medication purchase divided by the number of children and adolescents in the population. Population prevalence for children was also examined by birth month. Results: In 2008, the prevalence rates for males were 1.26% in children and 0.93% in adolescents, and for females 0.21% and 0.14%, respectively. In 2018, the prevalence rates for males were 4.42% in children and 4.21% in adolescents, and for females 0.99% and 1.28%, respectively. Male-to-female ratios decreased during the study period from 6.0:1 to 4.5:1 (children) and from 6.6:1 to 3.3:1 (adolescents). ADHD medication use was more common among males and females (aged 6-12 years) born in May-August or September-December than among males and females born in January-April. Conclusions: The prevalence of ADHD medication use has continued to increase in Finland. Although use has increased more rapidly among females resulting in lower male-to-female ratios, medication use among females is considerably lower compared with males. Consequently, gender discrepancy in 2018 was relatively large, particularly among children. Future studies should also consider reporting annual prevalence by children's birth month

Children's Relative Age and ADHD Medication Use : A Finnish Population-Based Study

Using population-based register data, we examine the association between children's birth month and ADHD medication use in a single jurisdiction (Finland). OBJECTIVES: The youngest children in a classroom are at increased risk of being medicated for attention-deficit/hyperactivity disorder (ADHD). We examined the association between children's birth month and ADHD medication rates in Finland. METHODS: Using a population-based study, we analyzed ADHD medication use among children born in 2005 to 2007. Cases (n= 7054) were identified from the first purchase of medication for ADHD. Cox proportional hazard models and hazard ratios (HRs) were examined by birth month and sex. Finnish children start first grade in the year of their seventh birthday. The cutoff date is December 31. RESULTS: Risk of ADHD medication use increased throughout the year by birth month (ie, January through April to May through August to September through December). Among boys born in September to December, the association remained stable across cohorts (HR: 1.3; 95% confidence interval [CI]: 1.1-1.5). Among girls born in September to December, the HR in the 2005 cohort was 1.4 (95% CI: 1.1-1.8), whereas in the 2007 cohort it was 1.7 (95% CI: 1.3-2.2). In a restricted follow-up, which ended at the end of the year of the children's eighth birthday, the HRs for boys and girls born in September to December 2007 were 1.5 (95% CI: 1.3-1.7) and 2.0 (95% CI: 1.5-2.8), respectively. CONCLUSIONS: Relative immaturity increases the likelihood of ADHD medication use in Finland. The association was more pronounced during the first school years. Increased awareness of this association is needed among clinicians and teachers.Peer reviewe

Aktiivisuuden ja tarkkaavuuden häiriön (ADHD) lääkkeiden käyttö on yleistynyt

English summaryPeer reviewe

Chronic Comorbidities Contribute to the Burden and Costs of Persistent Asthma

Background. We aimed to study the prevalence of chronic comorbidities in asthma patients and the costs of health care use associated with asthma with comorbidities. Material and Methods. We analysed the prevalence of the four most common chronic diseases in asthma patients in 2008-2014 in Finland. Prevalence of coronary artery disease, diabetes and dyslipidaemia, hypertension, epilepsy, inflammatory bowel disease, rheumatic diseases, and severe psychiatric disease was studied by register of the Social Insurance Institution of Finland. The costs of health care services were collected from the registries maintained by the National Institute for Health and Welfare (THL). Results. Prevalence of asthma was 4.6% in 2014. Diabetes was among the four most common comorbidities in all the age groups. The other common comorbidities were hypertension (>= 46 years; 12.9-37.6%), severe psychiatric disorders (age groups of 16-59 years; 1.4-3.5%), and ischaemic heart disease (>= 60 years; 10-25%). In patients with both asthma and diabetes, the costs of hospitalization were approximately 169% compared with patients with asthma alone. Conclusions. Prevalence of asthma increases by tenfold when aging. The comorbidity diversity and rate are age-dependent. Prevalence of diabetes as comorbidity in asthma has increased. Costs of hospitalizations in asthma approximately double with chronic comorbidities.Peer reviewe

Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.Peer reviewe

SH3 Domain-Mediated Recruitment of Host Cell Amphiphysins by Alphavirus nsP3 Promotes Viral RNA Replication

Among the four non-structural proteins of alphaviruses the function of nsP3 is the least well understood. NsP3 is a component of the viral replication complex, and composed of a conserved aminoterminal macro domain implicated in viral RNA synthesis, and a poorly conserved carboxyterminal region. Despite the lack of overall homology we noted a carboxyterminal proline-rich sequence motif shared by many alphaviral nsP3 proteins, and found it to serve as a preferred target site for the Src-homology 3 (SH3) domains of amphiphysin-1 and -2. Nsp3 proteins of Semliki Forest (SFV), Sindbis (SINV), and Chikungunya viruses all showed avid and SH3-dependent binding to amphiphysins. Upon alphavirus infection the intracellular distribution of amphiphysin was dramatically altered and colocalized with nsP3. Mutations in nsP3 disrupting the amphiphysin SH3 binding motif as well as RNAi-mediated silencing of amphiphysin-2 expression resulted in impaired viral RNA replication in HeLa cells infected with SINV or SFV. Infection of Balb/c mice with SFV carrying an SH3 binding-defective nsP3 was associated with significantly decreased mortality. These data establish SH3 domain-mediated binding of nsP3 with amphiphysin as an important host cell interaction promoting alphavirus replication

Intravenously Administered Alphavirus Vector VA7 Eradicates Orthotopic Human Glioma Xenografts in Nude Mice

VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that VA7 exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose of this study was to determine if intravenously administered VA7 would be effective against human glioma.In vitro, U87, U251, and A172 human glioma cells were infected and killed by VA7-EGFP. In vivo, antiglioma activity of VA7 was tested in Balb/c nude mice using U87 cells stably expressing firefly luciferase in subcutaneous and orthotopic tumor models. Intravenously administered VA7-EGFP completely eradicated 100% of small and 50% of large subcutaneous U87Fluc tumors. A single intravenous injection of either VA7-EGFP or VA7 expressing Renilla luciferase (VA7-Rluc) into mice bearing orthotopic U87Fluc tumors caused a complete quenching of intracranial firefly bioluminescence and long-term survival in total 16 of 17 animals. In tumor-bearing mice injected with VA7-Rluc, transient intracranial and peripheral Renilla bioluminescence was observed. Virus was well tolerated and no damage to heart, liver, spleen, or brain was observed upon pathological assessment at three and ninety days post injection, despite detectable virus titers in these organs during the earlier time point.VA7 vector is apathogenic and can enter and destroy brain tumors in nude mice when administered systemically. This study warrants further elucidation of the mechanism of tumor destruction and attenuation of the VA7 virus

Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.</p

Koneoppimisen hyödyntäminen ohjelmistorobotiikassa

Insinöörityössä oli tavoitteena luoda ohjelmistorobotiikalla ratkaisu, joka toimii ihmisen rinnalla tiedostojen ja niiden sisältämän datan keräämiseen. Samalla ratkaisu nopeuttaa työprosessin sulavuutta ja tehokkuutta. Ohjelmistorobotiikan lisäksi työssä perehdyttiin koneoppimiseen ja siihen, sitä voitaisiin hyödyntää osana ohjelmistorobotiikan toteutusta. Koneoppimista päädyttiin hyödyntämään neuroverkkoihin perustuvaan tekstintunnistukseen kuvatiedostoista, joiden kopioiminen ei onnistu tavallisilla ohjelmistorobotiikan sisältämillä työkaluilla. Insinöörityön lopputuloksena oli toimiva ohjelmistorobotti, joka suoritti työprosessin niin kuin sen oli tarkoitus. Se nopeutti tiedostojen hakemista sekä niiden käsittelyä huomattavasti aiempaan avustamattomaan työprosessiin verrattuna