Influence of Self-Efficacy on Cancer-Related Fatigue and Health-Related Quality of Life in Young Survivors of Childhood Cancer

This study aims to elucidate how self-efficacy influences cancer-related fatigue and health-related quality of life (HRQoL) in young survivors of childhood cancer. Forty-six young survivors (age range, 8-18 years) of childhood cancer who were currently in complete remission completed measures for self-efficacy (Pediatric General Self-Efficacy Scale (PedsSE)), cancer-related fatigue (Cancer-related Fatigue Score (CRFS)), and HRQoL (Pediatric Quality of Life Inventory 4.0 Generic Core Scale, Pediatric Quality of Life Inventory (PedsQL)). Structural relationships between the PedsSE and CRFS or PedsQL, including the effects of potential demographic or clinical confounders, were examined by machine learning random forest algorithms and structural equation modeling. According to the distribution of the PedsQL, six survivors with PedsQL < 70 were determined to have compromised HRQoL (referred to as low-PedsQL survivors). The random forest model identified six variables for the prediction of the CRFS, with the PedsSE being the most important, and eight variables for the distinction of low-PedsQL survivors, with the CRFS being the most and the PedsSE the third most important variable. The structural equation model indicated that a direct influence of the PedsSE on the PedsQL was less detectable (beta = -0.049), whereas an indirect influence of the PedsSE on the PedsQL via the CRFS was evident (beta = 0.333). The model explained 51% of the variation of the CRFS and 28% of the variation of the PedsQL. The PedsSE was strongly correlated with altered mood in the subclass of the CRFS (r = -0.470), and altered mood was strongly correlated with the PedsQL (r = 0.737). In conclusion, self-efficacy is a major determinant of cancer-related fatigue and influences HRQoL via cancer-related fatigue in survivors of childhood cancer. The main pathway from self-efficacy to HRQoL is thought to be via the emotional aspect of cancer-related fatigue. However, unlike adult survivors of cancer, self-efficacy for young survivors may not contribute much to self-management behaviors that maintain HRQoL

Screening of the Maturity Status of the Tibial Tuberosity by Ultrasonography in Higher Elementary School Grade Schoolchildren

This study aimed to obtain screening data on the maturity status of the tibial tuberosity in schoolchildren of higher elementary school grades for risk management of Osgood-Schlatter disease (OSD). The maturity stages and cartilage thicknesses at the tibial tuberosity were determined by ultrasonography on the occasion of a school-based musculoskeletal examination for 124 grade 5-6 elementary schoolchildren, and their associations with the students\u27 demographic characteristics and OSD were examined. The time-dependent changes of the maturity status of the tibial tuberosity were also examined in grade 5 students (n = 26) by a longitudinal survey. The cross-sectional survey showed that the epiphyseal stage was reached in 89% of girls and 35% of boys. The girls who had experienced menarche (n = 28) were all in the epiphyseal stage and had a decreased cartilage thickness (p = 0.004, after adjusting maturity stages). Students with OSD (n = 5) were all girls in the epiphyseal stage, and only two of them had an increased cartilage thickness. During the longitudinal survey, a marked increase in cartilage thickness from the previous measurement was observed in three boys (without clinical symptoms) and a girl who newly developed OSD. Two students with OSD without chronic pain had thin cartilage. In conclusion, for schoolchildren of higher elementary school grades, the risk of OSD is higher among girls with the epiphyseal stage. Cartilage thickness may not contribute to the diagnosis of OSD, since thick cartilage is not very common in OSD. However, cartilage thickness may reflect the status of OSD

Establishment of a Novel Fluorescence-Based Method to Evaluate Chaperone-Mediated Autophagy in a Single Neuron

Background: Chaperone-mediated autophagy (CMA) is a selective autophagy-lysosome protein degradation pathway. The role of CMA in normal neuronal functions and in neural disease pathogenesis remains unclear, in part because there is no available method to monitor CMA activity at the single-cell level. Methodology/Principal Findings: We sought to establish a single-cell monitoring method by visualizing translocation of CMA substrates from the cytosol to lysosomes using the HaloTag (HT) system. GAPDH, a CMA substrate, was fused to HT (GAPDH-HT); this protein accumulated in the lysosomes of HeLa cells and cultured cerebellar Purkinje cells (PCs) after labeling with fluorescent dye-conjugated HT ligand. Lysosomal accumulation was enhanced by treatments that activate CMA and prevented by siRNA-mediated knockdown of LAMP2A, a lysosomal receptor for CMA, and by treatments that inactivate CMA. These results suggest that lysosomal accumulation of GAPDH-HT reflects CMA activity. Using this method, we revealed that mutant cPKC, which causes spinocerebellar ataxia type 14, decreased CMA activity in cultured PCs. Conclusion/Significance: In the present study, we established a novel fluorescent-based method to evaluate CMA activity in a single neuron. This novel method should be useful and valuable for evaluating the role of CMA in various neurona

Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis

Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.Peer reviewe

Scintillator ageing of the T2K near detectors from 2010 to 2021

The T2K experiment widely uses plastic scintillator as a target for neutrino interactions and an active medium for the measurement of charged particles produced in neutrino interactions at its near detector complex. Over 10 years of operation the measured light yield recorded by the scintillator based subsystems has been observed to degrade by 0.9–2.2% per year. Extrapolation of the degradation rate through to 2040 indicates the recorded light yield should remain above the lower threshold used by the current reconstruction algorithms for all subsystems. This will allow the near detectors to continue contributing to important physics measurements during the T2K-II and Hyper-Kamiokande eras. Additionally, work to disentangle the degradation of the plastic scintillator and wavelength shifting fibres shows that the reduction in light yield can be attributed to the ageing of the plastic scintillator. The long component of the attenuation length of the wavelength shifting fibres was observed to degrade by 1.3–5.4% per year, while the short component of the attenuation length did not show any conclusive degradation

Utility of urinary presepsin in the diagnosis of pyelonephritis: a cross-sectional study

Abstract Background Presepsin is produced during the phagocytosis of bacteria by granulocytes. Presepsin increases at the site of infection; however, the significance of urinary presepsin in pyelonephritis is unknown. This study aimed to evaluate whether measuring urinary presepsin can distinguish between pyelonephritis and nonpyelonephritis. Methods A cross-sectional study of patients with suspected pyelonephritis was conducted. Urinary presepsin at admission was compared between the pyelonephritis and nonpyelonephritis groups using the Mann–Whitney test. The predictive accuracy of urinary presepsin for diagnosing pyelonephritis was evaluated by the area under the receiver operating characteristics (ROC) analysis curve. Results A total of 35 eligible participants were included in the pyelonephritis group and 25 in the nonpyelonephritis group. The median urinary presepsin level was 2232.0 (interquartile range [IQR], 1029.0–3907.0) pg/mL in the pyelonephritis group and 1348.0 (IQR, 614.5–2304.8) pg/mL in the nonpyelonephritis group. Urinary presepsin concentrations were significantly higher in the pyelonephritis group than in the nonpyelonephritis group (P = 0.023). ROC analysis of urinary presepsin revealed a cutoff value of 3650 pg/mL to distinguish between the pyelonephritis and nonpyelonephritis groups. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for the diagnosis of pyelonephritis were 0.40 (95% confidence interval [CI], 0.24–0.58), 0.96 (95% CI, 0.79–1.00), 0.93 (95% CI, 0.68–1.00), 0.52 (95% CI, 0.37–0.68), 9.60 (95% CI, 1.35–68.23), and 0.62 (95% CI, 0.47–0.83), respectively. Conclusions The measurement of urinary presepsin is useful in differentiating pyelonephritis from other diseases