Forprófun á íslenskri útgáfu Sjálfsmatskvarða Becks fyrir börn og unglinga

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenGerð var forprófun á Sjálfsmatskvörðum Becks fyrir börn á aldrinum 7-14 ára til þess að athuga próffræðilega eiginleika íslenskrar útgáfu af kvörðunum. Þátttakendur voru 293 úr 12 grunnskólum í Reykjavík. Próffræðilegir eiginleikar reyndust sambærilegir við erlendar rannsóknir. Innri áreiðanleiki var hár og fylgni atriða við heildarskor hvers kvarða viðunandi. Samleitni kvarða var athugað með þáttagreiningu og niðurstöður sýndu að þunglyndi, kvíði og hegðunarvandi voru einsleitir kvarðar en atriði sjálfsmyndar og reiði mynduðu tvo þætti. Gerð var þáttagreining á öllum 100 atriðum kvarðanna. Niðurstöður sýndu þrjá þætti sem skýrðu 38,6% dreifingar. Fyrsti þáttur samanstóð af þunglyndi, reiði og kvíða. Á annan þátt lögðust þrjú atriði reiði og 18 atriði hegðunarvanda og á þriðja þátt lögðust 18 atriði sjálfsmyndar. Há fylgni reyndist vera milli kvíða, þunglyndis og reiði en það er sambærilegt niðurstöðum erlendra rannsókna. Réttmæti kvarðanna var athugað með þremur spurningum um líðan í skóla og stríðni. Spurning um líðan í frímínútum hafði hæstu fylgni við þunglyndi sem bendir til þess að nemendur sem sýna þunglyndiseinkenni líður frekar illa í frímínútum. Spurning um líðan í kennslustundum hafði hæstu fylgni við hegðunarvanda og reiði og loks var hæst fylgni milli hegðunarvanda og stríðni. Enginn kynja- eða aldursmunur kom fram á kvörðum fyrir þunglyndi, reiði og kvíða. Hins vegar var meðaltal eldri hóps og drengja hærra á kvarða fyrir hegðunarvanda en hjá yngri hóp og stúlkum. Meðaltal á sjálfsmyndarkvarða var lægra í hópi eldri þáttakenda og meiri munur var á milli yngri og eldri stúlkna sem bendir til að sjálfsmynd verði neikvæðari á unglingsárum og sérstaklega hjá stúlkum. Próffræðilegir eiginleikar reyndust í megindráttum góðir en safna þarf meiri gögnum um áreiðanleika og réttmæti kvarðanna áður en hægt er að mæla með almennri notkun þeirra hér á landi.A pilot study of the Beck Youth Inventories (BYI) for children 7-14 years was undertaken to evaluate the psychometric properties of the Icelandic version. Participants were 293 from 12 elementary schools in Reykjavík. Psychometric properties revealed similar findings as other studies abroad have revealed. The internal consistency reliability was high and item total correlation acceptable. A principal axis factor analysis was conducted to evaluate the homogeneity of the BYI. Depression, anxiety and disruptive behavior were unidimensional but self-concept and anger revealed two factors. Additionally a principal axis factor analysis of all items of the inventories indicated three factors explaining 38,6% of variance. Items of depression, anxiety and anger loaded on the first factor. Disruptive behavior and 3 items of anger loaded on the second factor. Items of self-concept loaded on the third factor. Depression, anxiety and anger correlated highly, consistent with studies abroad and the factor analysis results. The scales´ validity was evaluated by three items assesing emotional well being in school and teasing other pupils. The highest correlation was between emotional well being in school breaks and depression, emotional well being in classrooms and disruptive behavior and anger, and between teasing other pupils and disruptive behavior. No significant age and gender differences were found on depression, anxiety and anger. Mean score for boys was higher than for girls on disruptive behavior and older students scored higher than younger students. Older students´ mean score was lower than younger students´ mean on self-concept and this difference was greater for girls than boys. Psychometric properties were good, but additonal studies need to be undertaken on the scales´ reliability and validity before we can recommend general use of the scales for clinical purposes in Iceland

TAT-dextran-mediated mitochondrial transfer enhances recovery from models of reperfusion injury in cultured cardiomyocytes

Acute myocardial infarction is a leading cause of death among single organ diseases. Despite successful reperfusion therapy, ischaemia reperfusion injury (IRI) can induce oxidative stress (OS), cardiomyocyte apoptosis, autophagy and release of inflammatory cytokines, resulting in increased infarct size. In IRI, mitochondrial dysfunction is a key factor, which involves the production of reactive oxygen species, activation of inflammatory signalling cascades or innate immune responses, and apoptosis. Therefore, intercellular mitochondrial transfer could be considered as a promising treatment strategy for ischaemic heart disease. However, low transfer efficiency is a challenge in clinical settings. We previously reported uptake of isolated exogenous mitochondria into cultured cells through co-incubation, mediated by macropinocytosis. Here, we report the use of transactivator of transcription dextran complexes (TAT-dextran) to enhance cellular uptake of exogenous mitochondria and improve the protective effect of mitochondrial replenishment in neonatal rat cardiomyocytes (NRCMs) against OS. TAT-dextran-modified mitochondria (TAT-Mito) showed a significantly higher level of cellular uptake. Mitochondrial transfer into NRCMs resulted in anti-apoptotic capability and prevented the suppression of oxidative phosphorylation in mitochondria after OS. Furthermore, TAT-Mito significantly reduced the apoptotic rates of cardiomyocytes after OS, compared to simple mitochondrial transfer. These results indicate the potential of mitochondrial replenishment therapy in OS-induced myocardial IRI

Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice

Runt-related transcription factor 2 (Runx2)-deficient mice can be used to model congenital tooth agenesis in humans. Conversely, uterine sensitization-associated gene-1 (Usag-1)-deficient mice exhibit supernumerary tooth formation. Arrested tooth formation can be restored by crossing both knockout-mouse strains; however, it remains unclear whether topical inhibition of Usag-1 expression can enable the recovery of tooth formation in Runx2-deficient mice. Here, we tested whether inhibiting the topical expression of Usag-1 can reverse arrested tooth formation after Runx2 abrogation. The results showed that local application of Usag-1 Stealth small interfering RNA (siRNA) promoted tooth development following Runx2 siRNA-induced agenesis. Additionally, renal capsule transplantation of siRNA-loaded cationized, gelatin-treated mouse mandibles confirmed that cationized gelatin can serve as an effective drug-delivery system. We then performed renal capsule transplantation of wild-type and Runx2-knockout (KO) mouse mandibles, treated with Usag-1 siRNA, revealing that hindered tooth formation was rescued by Usag-1 knockdown. Furthermore, topically applied Usag-1 siRNA partially rescued arrested tooth development in Runx2-KO mice, demonstrating its potential for regenerating teeth in Runx2-deficient mice. Our findings have implications for developing topical treatments for congenital tooth agenesis

FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche

Both glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are bona fide self-renewal factors for spermatogonial stem cells, whereas retinoic acid (RA) induces spermatogonial differentiation. In this study, we investigated the functional differences between FGF2 and GDNF in the germline niche by providing these factors using a drug delivery system in vivo. Although both factors expanded the GFRA1+ subset of undifferentiated spermatogonia, the FGF2-expanded subset expressed RARG, which is indispensable for proper differentiation, 1.9-fold more frequently than the GDNF-expanded subset, demonstrating that FGF2 expands a differentiation-prone subset in the testis. Moreover, FGF2 acted on the germline niche to suppress RA metabolism and GDNF production, suggesting that FGF2 modifies germline niche functions to be more appropriate for spermatogonial differentiation. These results suggest that FGF2 contributes to induction of differentiation rather than maintenance of undifferentiated spermatogonia, indicating reconsideration of the role of FGF2 in the germline niche

Efficacy and safety of micafungin in empiric and D-index-guided early antifungal therapy for febrile neutropenia ; A subgroup analysis of the CEDMIC trial

Objectives: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. Methods: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. Results: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2–79.4) and 79.6% (71.0–86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2–80.9%) and 78.0% (65.3–87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. Conclusions: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT

Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10⁴/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients

サイボウ ノ イデンシ ドウニュウ ト サイボウ チリョウ ノ タメ ノ イデンシ カイヘン オ メザシタ タトウ カラ ナル ヒウイルスセイ キャリア ノ ソウセイ ト ヒョウカ

京都大学0048新制・課程博士博士(工学)甲第14644号工博第3112号新制||工||1463(附属図書館)26996UT51-2009-D356京都大学大学院工学研究科高分子化学専攻(主査)教授 田畑 泰彦, 教授 岩田 博夫, 教授 木村 俊作学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDFA

A gene transfection for rat mesenchymal stromal cells in biodegradable gelatin scaffolds containing cationized polysaccharides.

The objective of this study was to design three-dimensional scaffolds of bone marrow-derived stem cells capable of their gene transfection and evaluate the transfection extent. Three-dimensional scaffolds of gelatin and β-tricalcium phosphate (β-TCP) were prepared. Spermine-introduced pullulan (spermine-pullulan) was prepared as the non-viral carrier of gene transfection. The spermine-pullulan was mixed with a luciferase plasmid DNA to prepare their polyion complex. The scaffolds were treated with succinylated gelatin (suc-gel) at different concentrations, treated in different methods of freeze-drying and dehydrothermal treatment, and placed in the aqueous of complexes to prepare various scaffolds containing the complex. When the stem cells were seeded into the scaffolds to evaluate the gene transfection of cells, the level of plasmid DNA transfection depended on the method of complex containing scaffolds preparation. The complexes were released with time from the scaffolds although the release profile depended on the type of scaffolds. The order of gene transfection for the stem cells in the scaffolds was in good accordance with that of plasmid DNA released. It is possible that cells were transfected with the complexes released from the scaffolds