From incipient to mid-range and beyond

Peer reviewe

Efficacy of a multicomponent singing intervention on communication and psychosocial functioning in chronic aphasia: A randomized controlled crossover trial

The ability to produce words through singing can be preserved in severe aphasia, but the benefits of group-based singing rehabilitation in aphasia are largely unknown. Our aim was to determine the efficacy of a multicomponent singing intervention on communication and speech production, emotional-social functioning and caregiver well-being in aphasia. Fifty-four patients with acquired brain injury and chronic aphasia and their family caregivers (n = 43) were recruited. Using a crossover randomized controlled trial design, participants were randomized to two groups who received a 4-month singing intervention either during the first or second half of the study in addition to standard care. The intervention comprised weekly group-based training (including choir singing and group-level melodic intonation therapy) and tablet-assisted singing training at home. At baseline, 5- and 9-month stages, patients were assessed with tests and questionnaires on communication and speech production, mood, social functioning, and quality of life and family caregivers with questionnaires on caregiver burden. All participants who participated in the baseline measurement (n = 50) were included in linear mixed model analyses. Compared with standard care, the singing intervention improved everyday communication and responsive speech production from baseline to 5-month stage, and these changes were sustained also longitudinally (baseline to 9-month stage). Additionally, the intervention enhanced patients’ social participation and reduced caregiver burden. This study provides novel evidence that group-based multicomponent singing training can enhance communication and spoken language production in chronic aphasia as well as improve psychosocial wellbeing in patients and caregivers.Peer reviewe

Resistance of R-Ras knockout mice to skin tumour induction

The R-ras gene encodes a small GTPase that is a member of the Ras family. Despite close sequence similarities, R-Ras is functionally distinct from the prototypic Ras proteins; no transformative activity and no activating mutations of R-Ras in human malignancies have been reported for it. R-Ras activity appears inhibitory towards tumour proliferation and invasion, and to promote cellular quiescence. Contrary to this, using mice with a deletion of the R-ras gene, we found that R-Ras facilitates DMBA/TPA-induced skin tumour induction. The tumours appeared in wild-type (WT) mice on average 6 weeks earlier than in R-Ras knockout (R-Ras KO) mice. WT mice developed almost 6 times more tumours than R-Ras KO mice. Despite strong R-Ras protein expression in the dermal blood vessels, no R-Ras could be detected in the epidermis from where the tumours arose. The DMBA/TPA skin tumourigenesis-model is highly dependent upon inflammation, and we found a greatly attenuated skin inflammatory response to DMBA/TPA-treatment in the R-Ras KO mice in the context of leukocyte infiltration and proinflammatory cytokine expression. Thus, these data suggest that despite its characterised role in promoting cellular quiescence, R-Ras is pro-tumourigenic in the DMBA/TPA tumour model and important for the inflammatory response to DMBA/TPA treatment

Neuroanatomical correlates of speech and singing production in chronic post-stroke aphasia

A classical observation in neurology is that aphasic stroke patients with impairments in speech production can nonetheless sing the same utterances. This preserved ability suggests a distinctive neural architecture for singing that could contribute to speech recovery. However, to date, these structural correlates remain unknown. Here, we combined a multivariate lesion–symptom mapping and voxel-based morphometry approach to analyse the relationship between lesion patterns and grey matter volume and production rate in speech and singing tasks. Lesion patterns for spontaneous speech and cued repetition extended into frontal, temporal and parietal areas typically reported within the speech production network. Impairment in spontaneous singing was associated with damage to the left anterior–posterior superior and middle temporal gyri. Preservation of grey matter volume in the same regions where damage led to poor speech and singing production supported better performance in these tasks. When dividing the patients into fluent and dysfluent singers based on the singing performance from demographically matched controls, we found that the preservation of the left middle temporal gyrus was related to better spontaneous singing. These findings provide insights into the structural correlates of singing in chronic aphasia and may serve as biomarkers to predict treatment response in clinical trials using singing-based interventions for speech rehabilitation.Peer reviewe

Salmonellan leviäminen suomalaisille sika- ja nautatiloille

Hankkeen tavoitteina oli tunnistaa nauta- ja sikatilojen salmonellatartuntojen lähteitä sekä toimintatapoja, joilla saneeraus ja tartuntojen ehkäisy tiloilla parhaiten onnistuu. Lukuisista tartuntalähteistä tärkeimmiksi arvioimme yhdyskuntalinnut ja muut haittaeläimet sekä turkistuotanto mahdollisena alkulähteenä haittaeläinten välittämille tartunnoille. Viime vuosina nauta- ja sikatiloille tehtyjen saneerausten aineistosta arvioimme seikkoja, jotka johtivat saneerauksen onnistumiseen tai pitkittymiseen tai tartunnan uusimiseen. Saneeraus pitkittyi, jos tartunta oli alkutilanteessa levinnyt laajalle, tartuntalähdettä ei saatu heti selville, salmonellapositiivisia eläimiä ei poistettu ajoissa, puhdistus-, pesu- ja desinfiointitoimet eivät olleet riittäviä tai käytettävissä oleva työpanos ei riittänyt. Saneerauksen onnistumista edistivät hyvä työnjohto, systemaattisuus, saneeraussuunnitelma sekä suunnitelman ja muiden ohjeiden noudattaminen. Tarkastelimme tilan salmonellatartunnan ja sen saneerauksen vaatimuksia myös työturvallisuuden suhteen. Salmonellatartunnan ehkäisy edellyttää tilatason tautisuojausta, jonka on oltava jokapäiväistä ja kohdistuttava tilan koko toimintaan ottaen huomioon haittaeläimistä aiheutuva tartuntavaara. Hankkeessa syntyi tietopääomaa salmonellan epidemiologiseen seurantaan, saneerausneuvontaan ja suosituksia tukemaan salmonellatorjuntaa.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Enteroviruses (EVs) are common RNA viruses that cause diseases ranging from rash to paralytic poliomyelitis. For example, EV-A and EV-C viruses cause hand-foot and mouth disease and EV-B viruses cause encephalitis and myocarditis, which can result in severe morbidity and mortality. While new vaccines and treatments for EVs are under development, methods for studying and diagnosing EV infections are still limited and therefore new diagnostic tools are required. Our aim was to produce and characterize new antibodies that work in multiple applications and detect EVs in tissues and in vitro. Rats were immunized with Coxsackievirus B1 capsid protein VP1 and hybridomas were produced. Hybridoma clones were selected based on their reactivity in different immunoassays. The most promising clone, 3A6, was characterized and it performed well in multiple techniques including ELISA, immunoelectron microscopy, immunocyto- and histochemistry and in Western blotting, detecting EVs in infected cells and tissues. It recognized several EV-Bs and also the EV-C representative Poliovirus 3, making it a broad-spectrum EV specific antibody. The 3A6 rat monoclonal antibody can help to overcome some of the challenges faced with commonly used EV antibodies: it enables simultaneous use of mouse-derived antibodies in double staining and it is useful in murine models.This study was supported by TEKES – the Finnish Funding Agency for Innovation (project THERDIAB 1843/31/2014) as well as JDRF grants for the nPOD-Virus Group, JDRF 25-2012-516 to A. Pugliese and JDRF 25-2012-770 to M.A. Atkinson for the nPOD-Virus Group, the Diabetes Research Foundation in Finland, the Sigrid Juselius Foundation, Reino Lahtikari Foundation, the Academy of Finland and the European Commission (Persistent Virus Infection in Diabetes Network (PEVNET), Frame Programme 7, Contract No. 261441) and the Swedish Child Diabetes Research Foundation. Additional support was given by a Diabetes Research Wellness Foundation Non-Clinical Research Fellowship and, since 2014, a JDRF Career Development Award (5-CDA-2014-221-A-N) to S.J.R

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe