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This experiment was conducted to investigate the effect of stimbiotic (STB) in broilers with necrotic enteritis (NE). A total of 180 one-day-old Arbor Acres (initial body weight of 34.81 ± 1.04 g) were used in this experiment for 32 days. All broilers were randomly allocated into six treatments, and each experimental group had 10 replicate cages with three broilers per cage. The experiment was conducted in a 2 × 3 factorial design consisting of two levels of challenge (challenge and non-challenge) and three levels of STB (0, 0.05, and 0.1%). The NE challenge significantly decreased (P

Cannabis has been cultivated for thousands of years for a variety of purposes, including fiber, seeds, oil, and medicinal compounds. The cannabis industry is growing rapidly because several countries have recently legalized the use of cannabis. In these countries, the industry related to cannabinoid ingredients such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) is steadily increasing every year. High concentrations of cannabinoids are mainly produced in unfertilized female flowers. Maintaining plants with high cannabinoid content is essential for producing uniform substances in large quantities. This study established an in vitro micropropagation protocol that can maintain the mother plant characteristics of Cannabis sativa ‘Cheungsam’. As a result of this experiment, the shoot tips and nodes of Cannabis sativa ‘Cheungsam’ at various concentrations (0, 0.25, 0.5, 1.0 mg/L) of 2iP, BA, and mT plant growth regulators (PGRs), and all concentrations of 2iP showed better results compared to two other hormones. However, the cut surfaces turned black, and excessive hyperhydricity occurred. Based on these symptoms, activated charcoal was added to the medium with the assumption that necrosis and hyperhydricity occur due to the accumulation of reactive oxygen species (ROS). When treated with 0.5 g/L charcoal, hyperhydricity was not overcome, and there was no difference compared to the control. As a new alternative, we divided the experiments into MS (Murashige and Skoog) and DKW (Driver and Kuniyuki Walnut) medium, which were commercially available. As a result, the rate of hyperhydricity was reduced, the cut surface did not turn black, and the growth conditions were also improved. Subsequently, ½ MS medium and ½ DKW medium were treated with various concentrations of IBA alone and with combinations of IBA and NAA for rooting. As a result, ½ DKW with IBA 0.5 mg/L showed the highest rooting rate and the best root condition for Cheungsam. After 4 weeks, when considering rooted plants with a height above 5 cm that were acclimatized, the acclimatization rate reached 100%. In conclusion, the Cannabis sativa ‘Cheungsam’ plants used in this study produced healthy shoots on DKW medium containing 1.0 mg/L 2iP and 0.5 mg/L of IBA in ½ DKW medium showed the best rooting rate.

This study investigated the effects of lairage conditions on the welfare and meat quality of pigs during lairage periods. A total of 3070 finishing pigs were assigned to one of six groups arranged in two trials in a 2 × 3 factorial design according to the illuminance (under 40 lux (LX), over 40 lux (HX)) and stocking density (low density (LD), higher than 0.83 m2/100 kg; normal density (ND), 0.50–0.83 m2/100 kg; high density (HD), lower than 0.50 m2/100 kg) with high temperature (HT), higher than 24 °C; low temperature (LT), lower than 10 °C. Pigs stocked with HD showed lower aggression behavior and overlap behavior than those stocked with LD at LT. Pigs stocked with HD showed higher standing, sitting, and aggression behavior than those stocked with LD at HT. Pigs stocked with HD showed higher pH than those stocked with LD at LT. At HT, pigs stocked with LD showed higher pH, WHC, DL, and CL than those stocked with HD. At LT, pigs stocked with LD showed higher cortisol levels than those stocked with HD. However, pigs stocked with LD showed lower cortisol levels than those stocked with HD at HT. Based on the obtained results, stocking of too-high (lower than 0.50 m2/100 kg) density at HT and stocking of too-low (higher than 0.83 m2/100 kg) density at LT are generally not good for meat quality and animal welfare.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene for which no therapies are available. HTT mutation causes protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of the basal ganglia. Transcriptional perturbations in synaptic genes and neuroinflammation are key processes that precede MSN dysfunction and motor symptom onset. Understanding the interplay between these processes is crucial to develop effective therapeutic strategies to treat HD. We investigated the role of protein kinase CK2α’, a kinase upregulated in MSNs in HD and previously associated with Parkinson’s disease (PD), in the regulation of neuroinflammation and synaptic function in HD. We used the heterozygous knock-in zQ175 HD mouse model and compared that to zQ175 mice lacking one allele of CK2α’ (zQ175:CK2α’(±)). CK2α’ haploinsufficiency in zQ175 mice resulted in decreased levels of pro-inflammatory cytokines, HTT aggregation, astrogliosis and transcriptional alterations of synaptic genes related to glutamatergic signaling. zQ175:CK2α’(±) mice also presented increased frequency of striatal miniature excitatory postsynaptic currents (mEPSCs), an indicator of synaptic activity, and improved motor coordination compared to zQ175 mice. Neuropathological and phenotypic changes mediated by CK2α’ were connected to alpha-synuclein (α-syn) dysregulation and correlated with differences in α-syn serine 129 phosphorylation (pS129-α-syn), a post-translational modification involved in α-synucleinopathy and shown to be regulated by CK2 in PD. pS129-α-syn was increased in the nuclei of MSNs in zQ175 mice and in the striatum of patients with HD, and it decreased in zQ175:CK2α’(±) mice. Collectively, our data established a novel connection between CK2α’, neuroinflammation and synaptic gene dysregulation with synucleinopathy in HD and suggested common molecular mechanisms of neurodegeneration between HD and PD. Our results also support CK2α’ inhibition as a potential therapeutic strategy to modulate neuronal function and neuroprotection in HD.

Abstract Despite the many comorbidities and high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors are based on small sample populations. We aimed to compare the performance of artificial intelligence (AI) analysis with that of conventional analysis to identify risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants. This nationwide cohort study included 8369 very low birth weight (VLBW) infants. The participants were divided into an sPDA group and an asymptomatic PDA or spontaneously close PDA (nPDA) group. The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression was used as a standard analytic tool, and five AI algorithms were used to identify the factors associated with sPDA. Combining a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance of the PDA prediction tasks, and the ensemble methods showed the best performances.

Background We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. Methods Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. Results G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. Conclusion Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

Abstract Background The aim of this study was to determine the feasibility and outcomes of early surgical ligation in preterm neonates with hemodynamically significant patent ductus arteriosus (HSPDA) and to investigate predictors for surgical treatment after unsuccessful medical management. Methods Medical records from the neonatal intensive care unit of Hanyang University Seoul Hospital from January 2010 to December 2018 were retrospectively reviewed. 233 preterm neonates weighing less than 1500g with HSPDA were enrolled in our study. Of these preterm neonates, 134 underwent surgical ligation and were subdivided into the early ligation group (n = 49; within 10 days of age) and the late ligation group (n = 85; after 10 days of age). Results The mean gestational age and birth weight were significantly lower in the patent ductus arteriosus (PDA) ligation group than in the Non-ligation group (p 2.0 mm (p 4 weeks (p = 0.007), necrotizing enterocolitis stage (NEC) ≥ III (p = 0.022), and intraventricular hemorrhage (IVH) grade ≥ III (p = 0.035). Conclusions Early surgical ligation minimizes the adverse effects of HSPDA in predicted preterm neonates who subsequently require surgical treatment for PDA. This result suggests that in preterm neonates weighing less than 1500g with HSPDA that is unresponsive to medical treatment, delayed ductal closure should be avoided to reduce severe NEC, severe IVH, culture-proven sepsis, and facilitate earlier endotracheal extubation.

BackgroundRecent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.MethodsRats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.ResultsG-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.ConclusionOur results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.

Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule (MT) network. Among various factors that regulate MT dynamics and stability, post-translational modifications (PTMs) of MTs play a critical role in conferring specificity of regulatory protein binding to MTs. Thus, it is important to understand the regulation of PTMs during brain development as multiple developmental processes are dependent on MTs. In this study, we identified that carboxypeptidase E (CPE) changes tubulin polyglutamylation, a major PTM in the brain, and we examine the impact of CPE-mediated changes to polyglutamylation on cortical neuron migration and dendrite morphology. We show, for the first time, that overexpression of CPE increases the level of polyglutamylated α-tubulin while knockdown decreases the level of polyglutamylation. We also demonstrate that CPE-mediated changes to polyglutamylation are dependent on the CPE zinc-binding motif and that this motif is necessary for CPE action on p150 Glued localization. However, overexpression of a CPE mutant that does not increase MT glutamylation mimics the effects of overexpression of wild type CPE on dendrite branching. Furthermore, although overexpression of wild type CPE does not alter cortical neuron migration, overexpression of the mutant may act in a dominant-negative manner as it decreases the number of neurons that reach the cortical plate (CP), as we previously reported for CPE knockdown. Overall, our data suggest that CPE changes MT glutamylation and redistribution of p150 Glued and that this function of CPE is independent of its role in shaping dendrite development but plays a partial role in regulating cortical neuron migration.

Background: The relationship between the size of bullae and pneumothorax recurrence is controversial. The aim of this study was to retrospectively evaluate the role of blebs or bullae in predicting ipsilateral recurrence in young patients experiencing their first episode of primary spontaneous pneumothorax (PSP) who underwent conservative treatment. Methods: A total of 299 cases of first-episode PSP were analyzed. The status of blebs or bullae was reviewed on high-resolution computed tomography (HRCT). The dystrophic severity score (DSS; range, 0 to 6 points) was calculated based on HRCT. Results: The 5-year recurrence rate was 38.2%. In univariate analysis, age (＜20 years), body mass index (＜20 kg/m2), a unilateral lesion, and intermediate risk (DSS 4 and 5) were associated with recurrence. Sex; smoking history; and the presence, number, and maximal size of blebs or bullae were not related to recurrence. In Cox regression, age and intermediate risk were independent risk factors for recurrence. High risk (DDS 6) was not an independent risk factor. Conclusion: The presence, number, and size of blebs or bullae did not affect ipsilateral recurrence. DSS failed to show a positive correlation between severity and recurrence. The decision to perform surgery in patients experiencing their first episode of PSP should not be determined by the severity of blebs and bullae.

Protopine is a substance used for hemostasis with an anti-inflammatory action and is one of the substances that are actively undergoing experiments to confirm their utility as anticancer agents. This study examined the molecular changes in the cellular signaling pathways associated with inflammatory responses in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The inhibition of PMA-induced phosphorylation of I-κB in HepG2, the effect of protopine on the MAPK signals, the inhibition of COX-2 activity, and the inhibition of MMP-9 as a medium of inflammatory response were evaluated by Western blot and qPCR. The effect of protopine on the survival rates in HepG2 cells was evaluated and found to be stable to a processing concentration of up to 40μM. Subsequent Western blot analyses showed that protopine blocks the transfer of the MAPKs cell signals induced by PMA and the transfer of the subunit of the nuclear factor-kappa B (NF-κB) to the nucleolus. Protopine inhibited the kappa alpha (I-κBα) phosphorylation in the cytosol and blocked PMA-induced inflammation via COX-2 activity inhibition. The expression of MMP-9 at the gene and protein levels, which is associated with cell migration and metastasis, was reduced by protopine.

Primary pulmonary meningioma is a rare disease, and chordoid meningioma is an uncommon variant of meningioma in the central nervous system (CNS) with a high recurrence rate. We report a case of primary pulmonary chordoid meningioma that presented as a solitary pulmonary nodule (SPN). The SPN was resected by thoracoscopic wedge resection and was revealed to have characteristics of chordoid meningioma. After confirming the absence of a meningioma in the CNS by brain imaging, the nodule was diagnosed as a primary pulmonary chordoid meningioma. The patient remained disease-free after 26 months postoperatively. To our knowledge, this is the third case of primary pulmonary chordoid meningioma to be reported.

Background. We previously reported that the granulocyte colony stimulating factor (G-CSF) ameliorated hepatic steatosis with the enhancement of β-oxidation-related gene expression. However, the mechanisms underlying this process remain unclear. This study aimed to determine whether the improvement of hepatic steatosis by G-CSF was associated with autophagy in a rat model of diabetes. Methods. Eight rats were fed a standard diet, and 16 rats were fed high-fat diet (HFD) for 5 weeks. All HFD-fed rats were then injected with streptozotocin (STZ). One week later, HFD rats injected with STZ were randomly treated with either G-CSF (200 μg/kg/day; diabetes mellitus (DM)/G-CSF) or saline (DM/saline) for 5 consecutive days. Four weeks later, serum biochemical and histology analyses were conducted. The expression of autophagy-associated proteins was determined by Western blotting. The mRNA expression of β-oxidation-related genes was determined by quantitative real-time polymerase chain reaction. HepG2 cells were cultured under high glucose (HG) conditions with G-CSF treatment, followed by Oil Red O staining for quantification of lipids. Results. Histological analysis showed lower lipid accumulation in the DM/G-CSF group than in the DM/saline-treated rats. Protein levels of LC3 and beclin-1 were higher, and those of p62 were lower in the DM/G-CSF rats than in the DM/saline-treated rats. The mRNA expression of β-oxidation-related genes was higher in DM/G-CSF rats than in the DM/saline-treated rats. Quantification of lipid levels in HepG2 cells cultured with HG and G-CSF treatment revealed no significant differences. Conclusions. Our data suggested that G-CSF potentially improves hepatic steatosis and autophagy in the liver of diabetic rats.

Background and aims. Previously, we reported that granulocyte-colony stimulating factor (G-CSF) improves hepatic steatosis in experimental animals. It may also have preventive effects on the development of hepatic steatosis. Therefore, we investigated the preventive effects of G-CSF by using a high-fat diet (HFD) rat model. Materials and methods. Twelve rats were fed HFD and 6 rats were fed control diet from 10 weeks of age. Once little steatosis was confirmed in the liver (after 10 weeks of feeding the HFD; at 20 weeks of age), HFD rats were randomly divided into two groups and treated with either G-CSF (100 Mg kg-1 day-1 for 5 consecutive days every other week; HFD/G-CSF rats) or saline (HFD/saline rats) for 10 weeks at 20 weeks of age. All rats were sacrificed at 30 weeks of age. Histology was examined by hematoxylin and eosin (H-E) and Oil Red O staining, and the expression levels of genes of associated with lipogenesis and β-oxidation enzymes were determined by qRT-PCR.Results. Histological examinations revealed that HFD/G-CSF rats had significantly lower lipid accumulation in their hepatocytes than did HFD/saline rats (p < 0.05). HFD/G-CSF rats also showed lower expression levels of genes associated with lipogenesis and higher expression levels of genes associated with β-oxidation than HFD/saline rats (p < 0.05). Conclusion. In conclusion, we found that G-CSF prevented development of hepatic steatosis in an HFD rat model. The preventive effect may be associated with the regulation of gene expression involved in hepatic lipogenesis and β-oxidation.

We present a case of left ventricular pseudoaneurysm, which is a very rare and fatal complication of cardiac procedures such as mitral valve replacement. A 55-year-old woman presented to the Department of Thoracic and Cardiovascular Surgery at Hanyang University Seoul Hospital with chest pain. Ten years prior, the patient had undergone double valve replacement due to aortic regurgitation and mitral steno-insufficiency. Surgical repair was successfully performed using a prosthetic pericardial patch via a left lateral thoracotomy.

Primary sternal osteomyelitis is a rare disease. Common infectious organisms causing primary sternal osteomyelitis include Staphylococcus aureus and Pseudomonas aeruginosa. Actinomyces species are common saprophytes of the oral cavity, but there have been few reports in the literature of primary sternal osteomyelitis caused by Actinomyces species. We describe a case of primary sternal osteomyelitis caused by Actinomyces israelii without pulmonary involvement.

Bone marrow-mesenchymal stem cell (BM-MSC) therapy improves the recovery of cardiac function after myocardial infarction (MI); however, the underlying molecular mechanisms are not completely understood. Recent studies have shown that microRNAs (miRNAs) modulate the pathophysiology of cardiovascular diseases. Here, we investigated the mechanisms underlying the effects of BM-MSC-derived paracrine factors and cardiac miRNAs on myocardial regeneration after MI. In our study, MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery. BM-MSCs transplanted in infarcted rats significantly downregulated the expression of miRNA-23a and miRNA-92a and inhibited apoptosis in the myocardium. An in vitro experiment showed that supernatant from BM-MSCs cultured under hypoxia contained higher levels of vascular endothelial growth factor (VEGF) than that from BM-MSCs under normoxia. In addition, inhibition of miRNA-23a and miRNA-92a reduced cardiac apoptosis. Moreover, the VEGF-containing BM-MSC supernatant inhibited miRNA-23a and miRNA-92a expression and reduced apoptotic signaling in cardiomyocytes under hypoxia. These effects were inhibited when the supernatant was treated with neutralizing antibodies against VEGF. Our results indicate that the paracrine factor, VEGF, derived from transplanted BM-MSCs, regulated the expression of miRNAs such as miRNA-23a and miRNA-92a and exerted anti-apoptotic effects in cardiomyocytes after MI.

Human amniotic epithelial cells (h-AECs) have been shown to differentiate into cardiomyocyte-like cells in vivo that can regenerate myocardial tissue and improve cardiac function in a rat model of myocardial infarction (MI). In this study, we investigated the paracrine factors released from h-AECs under hypoxic conditions to elucidate the possible mechanisms underlying this previously reported phenomenon of h-AEC-mediated cardiac repair. We used hypoxic cell culture conditions to simulate myocardial infarction in vitro. In comparison to normal conditions, we found that h-AECs secreted higher levels of several cytokines, including angiogenin (ANG), epidermal growth factor (EGF), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. To determine whether transplanted h-AECs express these proangiogenic cytokines in vivo, we ligated the coronary artery of rats to cause MI and injected either h-AECs or saline into the infarcted area. We found that the infarct and border zones of rat myocardium treated with h-AECs had higher expression levels of the human-origin cytokines ANG, EGF, IL-6, and MCP-1 compared to the tissues of saline-treated rats. In conclusion, h-AECs secreted proangiogenic cytokines in a rat model of MI, which may suggest that the paracrine effect by h-AECs could regenerate myocardial tissue and improve cardiac function.

Granulocyte-colony stimulating factor (G-CSF) has molecular structures and intracellular signaling pathways that are similar to those of leptin and ciliary neurotropic factor (CNTF). It also has immune-modulatory properties. Given that leptin and CNTF play important roles in energy homeostasis and that obesity is an inflammatory condition in adipose tissue, we hypothesized that G-CSF could also play a role in energy homeostasis. We treated 12 38-week-old male Otsuka-Long-Evans-Tokushima fatty rats (OLETF, diabetic) and 12 age-matched male Long-Evans-Tokushima rats (LETO, healthy) with 200 µg/day G-CSF or saline for 5 consecutive days. Body weight reduction was greater in G-CSF-treated OLETF (G-CSF/OLETF) than saline-treated OLETF (saline/OLETF) following 8 weeks of treatment (-6.9±1.6% vs. -3.1±2.2%, p

BACKGROUND: The protective effects of granulocyte colony-stimulating factor (G-CSF) have been demonstrated in a variety of renal disease models. However, the influence of G-CSF on diabetic nephropathy (DN) remains to be examined. In this study, we investigated the effect of G-CSF on DN and its possible mechanisms in a rat model. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats with early DN were administered G-CSF or saline intraperitoneally. Urine albumin creatinine ratio (UACR), creatinine clearance, mesangial matrix expansion, glomerular basement membrane (GBM) thickness, and podocyte foot process width (FPW) were measured. The levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and type IV collagen genes expression in kidney tissue were also evaluated. To elucidate the mechanisms underlying G-CSF effects, we also assessed the expression of G-CSF receptor (G-CSFR) in glomeruli as well as mobilization of bone marrow (BM) cells to glomeruli using sex-mismatched BM transplantation. RESULTS: After four weeks of treatment, UACR was lower in the G-CSF treatment group than in the saline group (p

Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome. In this study, we investigated histological and biochemical changes in NAFLD and the gene expression involving de novo lipogenesis in Otsuka Long-Evans Tokushima fatty (OLETF) rats. We used OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats as animal models of NAFLD and as controls, respectively. Consistent observations were made at 4-week intervals up to 50 weeks of age, and all rats were fed ad libitum with standard food. Biochemical and histological changes were observed, and gene expression involved in de novo lipogenesis was measured using real-time polymerase chain reactions. As a results hepatic micro- and macrovesicular steatosis and hepatocyte ballooning were evident in the OLETF rats at 22–38 weeks of age but disappeared after 42 weeks; no fibrosis or collagen deposition was observed. Gene expression involved in de novo lipogenesis followed a pattern similar to that of the histological changes. In conclusion, in the absence of dietary manipulation, hepatic steatosis in OLETF rats is evident at 22–38 weeks and declines after 42 weeks. Therefore, OLETF rats at 22–38 weeks are recommended as animal models of hepatic steatosis.

Background: The selection of statistical analysis methods in research is a critical and nuanced task that requires a scientific and rational approach. Aligning the chosen method with the specifics of the research design and hypothesis is paramount, as it can significantly impact the reliability and quality of the research outcomes. Methods: This study explores a comprehensive guideline for systematically choosing appropriate statistical analysis methods, with a particular focus on the statistical hypothesis testing stage and categorization of variables. By providing a detailed examination of these aspects, this study aims to provide researchers with a solid foundation for informed methodological decision making. Moving beyond theoretical considerations, this study delves into the practical realm by examining the null and alternative hypotheses tailored to specific statistical methods of analysis. The dynamic relationship between these hypotheses and statistical methods is thoroughly explored, and a carefully crafted flowchart for selecting the statistical analysis method is proposed. Results: Based on the flowchart, we examined whether exemplary research papers appropriately used statistical methods that align with the variables chosen and hypotheses built for the research. This iterative process ensures the adaptability and relevance of this flowchart across diverse research contexts, contributing to both theoretical insights and tangible tools for methodological decision-making. Conclusions: This study emphasizes the importance of a scientific and rational approach for the selection of statistical analysis methods. By providing comprehensive guidelines, insights into the null and alternative hypotheses, and a practical flowchart, this study aims to empower researchers and enhance the overall quality and reliability of scientific studies. [ABSTRACT FROM AUTHOR]

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies. [ABSTRACT FROM AUTHOR]

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To compare long-term toxicity incidences, including secondary cancer (SC) with or without total body irradiation (TBI), in Asian patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using a nationwide database. Materials and Methods: We identified 4,554 patients receiving HSCT for leukemic disease from 2009 to 2016 using the healthcare bigdata system of Korea. Incidence rate ratios (IRRs) for SC, cataracts, hypothyroidism, chronic kidney disease (CKD), myocardial infarction, or strokes were compared, and standardized incidence ratios (SIR) of SC was also estimated. Results: TBI was conducted on 1,409 patients (30.9%). No overall survival differences based on TBI were observed. With a median follow-up duration of 58.2 months, 143 patients were diagnosed with subsequent SC (3.4%). Incidence rates per 1,000 person-year were 6.56 (95% confidence interval [CI], 4.8-8.8) and 7.23 (95% CI, 5.9-8.8) in the TBI and no-TBI groups, respectively (p = 0.594). Also, the SIR (95% CI) was not significantly increased by TBI (1.32 [0.86-1.94] vs. 1.39 [1.08-1.77] in the no-TBI group). In the young age group (0-19 years), SIRs were increased in both groups regardless of TBI (8.60 vs. 11.96). The IRRs of cataracts (1.60; 95% CI, 1.3-2.0), CKD (1.85; 95% CI, 1.3-2.6), and hypothyroidism (1.50; 95% CI, 1.1-2.1) were significantly increased after TBI. However, there were no significant differences in the occurrence of myocardial infarction and stroke according to TBI. Conclusion: Our results suggest that modern TBI may not additionally increase the risk of SC after allogeneic HSCT, although increased risks of other diseases were noted. Physicians should carefully consider individualized risks and benefits of TBI, with a particular focus by age group. [ABSTRACT FROM AUTHOR]

Purpose: To examine efficacy and safety of ReMEEX implantation in patients with female stress urinary incontinence (SUI) associated with detrusor underactivity (DU), recurrence, or intrinsic sphincter deficiency (ISD). Materials and Methods: Retrospective cohort study included 303 females who underwent ReMEEX system (March 2008 to May 2021). Patients were stratified into three groups by purpose of surgery (SUI with DU, reoperation, and SUI with ISD) and evaluated with following criteria: cure (absence of subjective complaint of leakage and objective leakage in the stress test), improvement (rare leakage subjectively, but satisfaction regardless of stress test), and failure. Primary outcome was success rate of surgery assessed through patient interviews and a stress test. Surgical outcomes and complications were evaluated. Results: Mean follow-up was 34.4 months (range, 6.0-145.0 months). At the final follow-up visit, 42.9% and 49.2% of patients were cured and improved. Twenty-one point five percent required tension readjustment (mean number, 1.2). The total complication rate was 19.5% (none for grade =4). Preoperative Qmax was significantly higher in the ISD group (p<0.001) and preoperative total International Prostate Symptom Score (IPSS) score was significantly higher in the DU group (p=0.044). Moreover, at postoperative 1 year, both total IPSS score and IPSS quality of life score were significantly higher in the DU group (both p=0.001). Conclusions: The success rate of ReMEEX system was 92.1% at mean follow-up of 34.4 months in female SUI with DU, reoperation, or ISD. It also enabled postoperative readjustment of sling tension, as needed, up to 130 months after surgery. [ABSTRACT FROM AUTHOR]

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low a/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options. [ABSTRACT FROM AUTHOR]

This study employs Ordinary Least Squares (OLS) and quantile regression analyses to examine the determinants of Environmental, Social, and Governance (ESG) grades based on financial and non-financial characteristics of Korean companies amidst the global economic recession triggered by the COVID-19 pandemic. We investigate whether different determinants exist for varying levels of ESG grades (lower, middle, and higher groups). Analyzing cross-sectional data from 660 Korean companies, we find that both financial and non-financial characteristics significantly impacted ESG grades during the pandemic. Key determinants include firm value, size, and cash liquidity in financial characteristics, while firm age and industry type are vital non-financial determinants. Furthermore, the results highlight distinctions among ESG sub-dimensions, revealing that financial attributes predominantly influence environmental grades, whereas both financial and non-financial aspects shape social and governance grades. The findings elucidate ESG grade determinants and their differential relationships with various company characteristics during the challenging COVID-19 period in Korea. [ABSTRACT FROM AUTHOR]

Purpose Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. Materials and Methods Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. Results After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. Conclusion Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection. [ABSTRACT FROM AUTHOR]

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions: Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. [ABSTRACT FROM AUTHOR]