Attentional modulation of interhemispheric (a)symmetry in children with developmental language disorder

Publisher Copyright: © 2022, The Author(s).The nature of auditory processing problems in children with developmental language disorder (DLD) is still poorly understood. Much research has been devoted to determining the extent to which DLD is associated with general auditory versus language-specific dysfunction. However, less emphasis has been given to the role of different task conditions in these dysfunctions. We explored whether children with DLD demonstrate atypical interhemispheric asymmetry during the auditory processing of speech and non-speech sounds and whether this interhemispheric balance is modulated by attention. Magnetoencephalography was used to record auditory evoked fields in 18 children (9 to 10 years old), 9 with DLD and 9 with language typical development, during active or passive listening to speech and non-speech sounds. A linear mixed model analysis revealed a bilateral effect of attention in both groups. Participants with DLD demonstrated atypical interhemispheric asymmetry, specifically in the later (185–600 ms) time window but only during the passive listening condition. During the active task, the DLD group did not differ from the typically developed children in terms of hemispheric balance of activation. Our results support the idea of an altered interhemispheric balance in passive auditory response properties in DLD. We further suggest that an active task condition, or top–down attention, can help to regain leftward lateralization, particularly in a later stage of activation. Our study highlights the highly dynamic and interhemispheric nature of auditory processing, which may contribute to the variability in reports of auditory language processing deficits in DLD.Peer reviewe

Predictors of postoperative urinary retention after posterior spinal fusion for adolescent idiopathic scoliosis

Purpose To determine predictors for postoperative urinary retention in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. Postoperative urinary retention affects almost every third adolescent after spinal fusion for idiopathic scoliosis. There are limited data regarding the risk factors of postoperative urinary retention in this patient group.Methods A retrospective study with prospectively collected urinary retention data from paediatric spine register with 159 consecutive patients (114 females, mean age 15.6 years, range 10-21 years) undergoing pedicle screw instrumentation for adolescent idiopathic scoliosis at a university hospital between May 2010 and April 2020. Postoperative urinary retention was defined as an inability to void after catheter removal and documented residual over 300 mL as confirmed using an ultrasound or by catheterization.Results Postoperative urinary retention was diagnosed in 33% (53 of 159) of the patients during hospital stay. Opioid amount on the day of catheter removal (OR 6.74 [95% CI: 2.47, 18.36], p Conclusions Higher total opioid consumption, opioid amount on the day of catheter removal, higher weight, and male gender increases the risk of postoperative urinary retention in adolescents with idiopathic scoliosis undergoing posterior spinal fusion.</p

Kannattava ja ympäristöystävällinen sianlihan tuotantoketju : Eläinaineksen tehokas hyödyntäminen sikatiloilla

Eläinaineksen tehokas hyödyntäminen sikatiloilla -hankkeessa selvitettiin kahden Suomessa yleisesti käytetyn, jalostusstrategioiltaan erilaisen emakkohybridin, DanAvl ja Topigs Norsvin, jälkeläisten tuotanto-ominaisuuksia ja tuotannon kannattavuutta. Nelivuotinen hanke (1.8.2016–31.7.2020) koostui neljästä työpaketista. Kolmen ensimmäisen työpaketin tavoitteena oli löytää ratkaisuja eläinaineksen käyttöön ja kannattavuuteen porsas-, välikasvatus- ja lihasikatuotannossa. Neljäs työpaketti keskittyi hankkeen hallinnointiin ja tiedotustoimintaan. Hanke kehitti sianlihan tuotantoketjun toimijoille uusia, käytännönläheisiä toimintatapoja tiloilla tehtävään eläinaineksen valintaan, tuotanto-ominaisuuksien vertailuun ja tuotannon kannattavuuden arviointiin. Hanke lisäsi sikalaverkostojen yhteistyötä ja tiedon saannin avoimuutta taloudellisesti kannattavan sika-alan hyväksi ja kehitti uusia toimintatapoja, joilla tiloilla tehtävän seurannan ja testaustoiminnan tulokset saadaan nopeasti käyttöön yritysten kehittämiseksi. Hankkeen tulosten perusteella tiineyden kesto oli noin kaksi päivää pidempi DanAvl emakoilla kuin Topigs Norsvin emakoilla. Pahnuekoko oli suurempi ja kasvoi nopeammin porsimiskerroittain DanAvl emakoilla kuin Topigs Norsvin emakoilla. Topigs Norsvin emakoiden jälkeläisillä oli välikasvatusvaiheessa erittäin merkitsevästi parempi päiväkasvu kuin DanAvl emakoiden jälkeläisillä. Lihasikavaiheen kasvussa tai rehuhyötysuhteessa ei ollut tilastollisesti merkitseviä eroja DanAvl ja Topigs Norsvin emakoiden jälkeläisten välillä. Topigs Norsvin emakoiden jälkeläisillä oli kuitenkin merkitsevästi korkeampi lihaprosentti kuin DanAvl emakoiden jälkeläisillä. Taloudellisessa tarkastelussa hankkeessa kerätyn tuotosaineiston ja teurastamoiden suuremman tuotantoaineiston sekä talouden tunnuslukujen avulla eri hybridilinjoille tehtiin vertailuskenaariot sekä laskelmia, joiden avulla vertailtiin hybridilinjojen sikojen tuotantokustannuksia ja taloudellista tuottoa. Laskelmien perusteella Topigs Norsvin hybridillä porsaan tuotantokustannus oli hieman korkeampi kuin DanAvl hybridillä, mutta Topigs Norsvin hybridin jälkeläisillä lihasian tuotantokustannus jäi kuitenkin alemmaksi ja myös ruhon arvo oli myös hieman korkeampi kuin DanAvl jälkeläisillä. Ruhon osien painon mukaan laskettuna DanAvl jälkeläisillä oli kuitenkin hieman korkeampi ruhon arvo (€/kg), mutta erot eivät olleet tilastollisesti merkitseviä. Hanke sai rahoitusta Manner-Suomen maaseudun kehittämisohjelmasta ja sen toteuttaja oli Satafood Kehittämisyhdistys ry yhdessä Finnpig Oy:n ja Luonnonvarakeskuksen kanssa ja se toteutettiin Satakunnan, Varsinais-Suomen, Pirkanmaan ja Etelä-Pohjanmaan ELY -keskusten alueella. Hankkeen käytännön toteutus tehtiin yhteistyössä kohdealueen sikayrittäjän kanssa.202

Keratins Are Altered in Intestinal Disease-Related Stress Responses

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery.</p

The amount of keratins matters for stress protection of the colonic epithelium

Keratins (K) are important for epithelial stress protection as evidenced by keratin mutations predisposing to human liver diseases and possibly inflammatory bowel diseases. A role for K8 in the colon is supported by the ulcerative colitis-phenotype with epithelial hyperproliferation and abnormal ion transport in K8-knockout (K8-/-) mice. The heterozygote knockout (K8+/-) colon appears normal but displays a partial ion transport-defect. Characterizing the colonic phenotype we show that K8+/- colon expresses ~50% less keratins compared to K8 wild type (K8+/+) but de novo K7 expression is observed in the top-most cells of the K8+/- and K8-/- crypts. The K8+/- colonic crypts are significantly longer due to increased epithelial hyperproliferation, but display no defects in apoptosis or inflammation in contrast to K8-/-. When exposed to colitis using the dextran sulphate sodium-model, K8+/- mice showed higher disease sensitivity and delayed recovery compared to K8+/+ littermates. Therefore, the K8+/- mild colonic phenotype correlates with decreased keratin levels and increased sensitivity to experimental colitis, suggesting that a sufficient amount of keratin is needed for efficient stress protection in the colonic epithelia

Keratins Are Altered in Intestinal Disease-Related Stress Responses

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery

Structure in stress management : Keratins in intestinal stress protection

Intermediate filaments (IFs), a major constituent of the cellular cytoskeleton, contribute mainly to the mechanical stability of the cell. Simple epithelial keratins (SEKs) are IF proteins expressed in the single-layered and glandular epithelia of organs that involve secretion and absorption. In the colon, the main keratins (K) expressed are K7, K8, K18, K19 and K20. A new emerging role of SEKs in stress protection has been described for epithelial organs such as the liver, pancreas and kidney, where also the phosphorylation of K8 has been used as a marker of stress. The role of K8 in intestinal stress protection was examined by studying the stress response of the K8 wild type (K8+/+), K8 heterozygous (K8+/-) and K8 knock out (K8-/-) mice. K8+/+ mice were subjected to human disease-related stresses, while K8+/- mice were examined in regards of stress protection by investigating their stress susceptibility to colitis. The stress response in K8-/- mice was studied by investigating their impaired energy metabolism in response to ketogenic situations. As demonstrated by murine intestinal stress models, colonic keratins act as stressresponsive proteins, which are upregulated in stress and recovery. Depletion of the in vivo colonic microbiota upregulated protein levels of the main colonic keratin-pair, K8-K19, confirmed by the lipopolysaccharide (LPS)-mediated in vitro inflammational stress model. Another inflammational stress-induced keratin pair identified was the K7-K20 pair, upregulated by the experimental dextran sulphate sodium (DSS) colitis model. Except for the K7-K20 upregulation on protein level, this stress model also affected the keratin distribution by showing a wider crypt distribution of both K7 and K20 in response to stress. The role of keratins in colonic stress protection was confirmed by examining the stress susceptibility of the K8+/- mouse. The K8+/- mouse, which has 50 % less K8 compared to the K8+/+ mouse, displays hyperproliferation, longer crypts and a higher susceptibility to DSS-induced colitis when compared to K8+/+ mice, suggesting a protective role for K8 in colonic stress. In addition, by examining the K8-/- mouse in regards of stress protection, the role of K8 in colonic energy homeostasis was investigated. K8 was found to modulate the energy metabolism in colonocytes by affecting the amount of the ketogenic control enzyme, 3-hydroxy-3-methylglutaryl-CoA-synthase (HMGCS2). As a consequence of the deletion of K8 filaments, murine HMGCS2 levels were downregulted in the K8-/-mouse, together with the downregulation of the upstream short chain fatty acid (SCFA) transporter, monocarboxylate transporter isoform 1 (MCT1). Therefore, elevated K8-/- colonocyte luminal SCFAs that feed into the ketogenic pathway cannot enter the K8-/- colonocytes in sufficient amounts, leading to a decreased ketogenesis and overall ketogenic energy metabolism, contributing to the inflammatory K8-/-phenotype. When the impaired K8-/- ketogenesis was challenged with ketogenic conditions, the K8-/- mouse showed a blunted response, suggesting a protective role of K8 in the overall decreased K8-/- energy metabolism. In conclusion, these data, as shown by the K8+/+ stress-responsive behavior, the increased DSS-susceptibility of the K8+/- mice and the blunted K8-/- ketogenesis, indicate that colonic keratins likely play an important role in the protection from intestinal stress

Predictors of postoperative urinary retention after posterior spinal fusion for adolescent idiopathic scoliosis

Purpose To determine predictors for postoperative urinary retention in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. Postoperative urinary retention affects almost every third adolescent after spinal fusion for idiopathic scoliosis. There are limited data regarding the risk factors of postoperative urinary retention in this patient group. Methods A retrospective study with prospectively collected urinary retention data from paediatric spine register with 159 consecutive patients (114 females, mean age 15.6 years, range 10-21 years) undergoing pedicle screw instrumentation for adolescent idiopathic scoliosis at a university hospital between May 2010 and April 2020. Postoperative urinary retention was defined as an inability to void after catheter removal and documented residual over 300 mL as confirmed using an ultrasound or by catheterization. Results Postoperative urinary retention was diagnosed in 33% (53 of 159) of the patients during hospital stay. Opioid amount on the day of catheter removal (OR 6.74 [95% CI: 2.47, 18.36], p < 0.001), male gender (OR 2.26 [95% CI: 1.01, 5.05], p = 0.048), and increasing weight (OR 1.04 [95% CI: 1.01, 1.07], p = 0.014) were associated with postoperative urinary retention. Mean opioid consumption on the day of catheter removal was 0.81 mg/kg (95% CI: 0.66, 0.96) in the retention group vs 0.57 mg/kg (95% CI: 0.51, 0.64) in the non-retention group, p < 0.001. Conclusions Higher total opioid consumption, opioid amount on the day of catheter removal, higher weight, and male gender increases the risk of postoperative urinary retention in adolescents with idiopathic scoliosis undergoing posterior spinal fusion.Peer reviewe

Kannattava ja ympäristöystävällinen sianlihan tuotantoketju -hanke

202

Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors &alpha; and &beta; and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds