This paper aims to clarify the association between various social capital components at the municipal level (community social capital) and two quality-of-life factors at the individual level ...individual self-rated life satisfaction and self-rated health (SRH) based on data from a nationwide social capital survey that the authors carried out in 2013 in Japan (N = 3406 in 99 municipalities). The survey covers residents in Japan between the ages of 20 and 79 years. We focus on both contextual social capital and household income inequality in terms of the Gini coefficient at the municipality level since, to the best of our knowledge, no paper has explicitly dealt with municipalities in Japan as the units of contextual social capital and the Gini. Our analyses show that the subjective life satisfaction of individuals, after controlling for socioeconomic status and health at the individual level, is associate with both an income gap and social capital at the municipal level. Every component of community social capital in this study except for generalized reciprocity, both cognitive (generalized trust, particularized trust, and particularized reciprocity), and structural (three types of group participation and daily contacts with neighbors, friends/acquaintances, and colleagues), and the Gini coefficient on earned income were associated with self-rated life satisfaction at the individual level with statistical significance. However, SRH is associated only with cognitive social capital at the community level. SRH has no significant association with structural components of community social capital or with a community income gap in terms of the Gini coefficient on personal income. Judging from the results of estimates in the study, most of the components of community social capital at the municipal level seem to play an important role in enhancing self-rated life satisfaction. Life satisfaction may be associated with the broad atmosphere of the municipal level where one resides, while SRH is associated with cognitive social capital rather than structural social capital. However, the difference in the impact of contextual social capital between the two QOL indices may indicate the importance of considering a proper contextual level that is suitable for the outcome.
•This paper clarifies the association between municipal SC and life satisfaction/SRH.•We also examined the impact of income gap (Gini) and the average municipal income.•Cognitive and structural SC enhance life satisfaction, while Gini deteriorates it.•As for SRH, only cognitive SC and the average income are of importance.•Neither structural SC nor Gini registered significant association with SRH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Secondary bile acids (SBAs) with high hydrophobicity are abundant in the colonic lumen. However, both aggravating and protective roles of SBAs have been proposed in the pathogenesis of inflammatory ...bowel diseases (IBDs). We observed that oral administration of hyodeoxycholic acid (HDCA), a hydrophilic bile acid, prevented the development of dextran sulfate sodium (DSS)-induced colitis in mice. We then examined the individual effects of DSS and HDCA as well as their combined effects on fecal bile acid profile in mice. HDCA treatment increased the levels of most of fecal bile acids, whereas DSS treatment had limited effects on the levels of fecal bile acids. The combined treatment with DSS and HDCA synergistically increased the levels of fecal chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) in feces, which are potent activators of the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). The overall hydrophobicity of fecal bile acids was not modified by any treatments. Our data suggest that the preventive effect of HDCA on DSS-induced colitis in mice is due to the synergism between DSS and HDCA in increasing the levels of the fecal bile acids with potencies to activate FXR and TGR5.
Introduction
Laparoscopic inguinal hernia repair has significantly reduced the incidence of postoperative acute and chronic pain compared to open repair, but it remains problematic. This study’s ...purpose was to retrospectively identify predictive factors of acute pain after laparoscopic inguinal hernia repair.
Methods
We reviewed the medical records of 193 patients. After excluding atypical cases and female patients, 156 patients were analysed. Factors affecting rescue analgesic requirements were investigated via multivariable logistic regression analysis. Independent variables included age, body mass index, analgesics used during surgery and surgical factors (unilateral/bilateral, primary/recurrent). The degree of postoperative pain and the hospital stay duration after surgery were also investigated.
Results
Of the 156 patients, 40 (25.6%) required rescue analgesics. Patients under 60 years of age were about seven times more likely to need rescue analgesics than patients over 80 years of age. Primary surgery patients were about 5.5 times more likely to need rescue analgesics than recurrent surgery patients. The maximum verbal rating scale score was less than 3 in 89% of patients. All patients were discharged by two days postoperatively.
Conclusion
Laparoscopic inguinal hernia repair results in less postoperative acute pain. However, analgesia management should be considered prudently for younger patients and primary surgery patients.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abnormalities of
PLEKHG2
gene, encoding a Rho family-specific guanine nucleotide exchange factor, are involved in microcephaly with intellectual disability. However, not only the role of PLEKHG2 in ...the developmental process but also its expression profile is unknown. In this study, we prepared a specific antibody against PLEKHG2 and carried out expression analyses with mouse tissues. In western blotting, PLEKHG2 exhibited a tissue-dependent expression profile in adult mouse and was expressed in a developmental stage-dependent manner in brain. Then, in immunohistochemical analyses, while PLEKHG2 was observed in the cortical plate and ventricular zone surface of the cerebral cortex at embryonic day 14, it came to be distributed throughout the cerebral cortex in layer II/III and V during corticogenesis. PLEKHG2 was also detected mainly in the nucleus of neurons in the hippocampal CA regions and dentate gyrus at P7. Notably, the nuclear accumulation disappeared at P30 and PLEKHG2 came to be located at the axons and/or dendrites at this time point. Moreover, in vitro immunofluorescence revealed that PLEKHG2 was at least partially localized at both excitatory and inhibitory synapses in primary cultured hippocampal neurons. These results suggest roles of PLEKHG2 in the development of the central nervous tissue and synaptic function.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray ...matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin β1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.
The temporal resolution in scanning transmission electron microscopy (STEM) is limited by scanning system of an electron probe, leading to only a few frames per second (fps) at most in the current ...microscopes. This situation enforces us to stay atomic-resolution STEM imaging and spectroscopy in the state of static observations. To push the boundary of atomic-resolution STEM imaging into dynamic observations, an unprecedentedly faster scanning system combined with fast electron detection systems should be prerequisite. Here we develop a new scanning probe system with the acquisition time of 83 nanoseconds per pixel and the fly-back time of 35 microseconds, leading to 25 fps STEM imaging with the image size of 512 × 512 pixels that is faster than a human perception speed. Using such high-speed probe scanning system, we have demonstrated the observations of shape-transformation of Pt nanoparticle and Pt single atomic motions on TiO2 (110) surface at atomic-resolution with the temporal resolution of 40 milliseconds. The present probe scanning system opens the door to use atomic-resolution STEM imaging for in-situ observation of materials dynamics under the temperatures of cooling or heating, the atmosphere of liquid or gas, electric-basing or mechanical test.
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) ...and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks. BCAA supplementation significantly improved hepatic steatosis, inflammation, fibrosis, and tumors in Ath+HF mice at 68 weeks. GeneChip analysis demonstrated the significant resolution of pro-fibrotic gene expression by BCAA supplementation. The anti-fibrotic effect of BCAA was confirmed further using platelet-derived growth factor C transgenic mice, which develop hepatic fibrosis and tumors. In vitro, BCAA restored the transforming growth factor (TGF)-β1-stimulated expression of pro-fibrotic genes in hepatic stellate cells (HSC). In hepatocytes, BCAA restored TGF-β1-induced apoptosis, lipogenesis, and Wnt/β-Catenin signaling, and inhibited the transformation of WB-F344 rat liver epithelial stem-like cells. BCAA repressed the promoter activity of TGFβ1R1 by inhibiting the expression of the transcription factor NFY and histone acetyltransferase p300. Interestingly, the inhibitory effect of BCAA on TGF-β1 signaling was mTORC1 activity-dependent, suggesting the presence of negative feedback regulation from mTORC1 to TGF-β1 signaling. Thus, BCAA induce an anti-fibrotic effect in HSC, prevent apoptosis in hepatocytes, and decrease the incidence of HCC; therefore, BCAA supplementation would be beneficial for patients with advanced liver fibrosis with a high risk of HCC.
Rho family guanosine triphosphatases (GTPases) regulate cellular signaling and cytoskeletal dynamics, playing a pivotal role in cell adhesion, migration, and cell cycle progression. The Rac subfamily ...of Rho GTPases consists of three highly homologous proteins, Rac 1-3. The proper function of Rac1 and Rac3, and their correct interaction with guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs) are crucial for neural development. Pathogenic variants affecting these delicate biological processes are implicated in different medical conditions in humans, primarily neurodevelopmental disorders (NDDs). In addition to a direct deleterious effect produced by genetic variants in the RAC genes, a dysregulated GTPase activity resulting from an abnormal function of GEFs and GAPs has been involved in the pathogenesis of distinctive emerging conditions. In this study, we reviewed the current pertinent literature on Rac-related disorders with a primary neurological involvement, providing an overview of the current knowledge on the pathophysiological mechanisms involved in the neuro-RACopathies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aim. Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the ...efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. Methods. A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Results. Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. Conclusions. ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
WAC is an adaptor protein involved in gene transcription, protein ubiquitination, and autophagy. Accumulating evidence indicates that
WAC
gene abnormalities are responsible for neurodevelopmental ...disorders. In this study, we prepared anti-WAC antibody, and performed biochemical and morphological characterization focusing on mouse brain development. Western blotting analyses revealed that WAC is expressed in a developmental stage-dependent manner. In immunohistochemical analyses, while WAC was visualized mainly in the perinuclear region of cortical neurons at embryonic day 14, nuclear expression was detected in some cells. WAC then came to be enriched in the nucleus of cortical neurons after birth. When hippocampal sections were stained, nuclear localization of WAC was observed in Cornu ammonis 1 – 3 and dentate gyrus. In cerebellum, WAC was detected in the nucleus of Purkinje cells and granule cells, and possibly interneurons in the molecular layer. In primary cultured hippocampal neurons, WAC was distributed mainly in the nucleus throughout the developing process while it was also localized at perinuclear region at 3 and 7 days in vitro. Notably, WAC was visualized in Tau-1-positive axons and MAP2-positive dendrites in a time-dependent manner. Taken together, results obtained here suggest that WAC plays a crucial role during brain development.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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