Intravenous fluid prescription practices among pediatric residents in Korea

PurposeRecent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children. The present paper investigated the pattern of current practice in intravenous fluid prescription among Korean pediatric residents, to underscore the need for updated education.MethodsA survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question proposed a unique scenario in which the respondents had to prescribe either a hypotonic or an isotonic fluid for the patient.ResultsNinety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively). Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7%) selected the isotonic fluids for hydration therapy.ConclusionIn the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required

Synergistic interaction between APOE and family history of Alzheimers disease on cerebral amyloid deposition and glucose metabolism

Background Recently, the field of gene-gene or gene-environment interaction research appears to have gained growing interest, although it is seldom investigated in Alzheimers disease (AD). Hence, the current study aims to investigate interaction effects of the key genetic and environmental risks—the apolipoprotein ε4 allele (APOE4) and family history of late-onset AD (FH)—on AD-related brain changes in cognitively normal (CN) middle-aged and older adults. Methods [11C] Pittsburg compound-B (PiB) positron emission tomography (PET) imaging as well as [18F] fluoro-2-deoxyglucose (FDG) PET that were simultaneously taken with T1-weighted magnetic resonance imaging (MRI) were obtained from 268 CNs from the Korean Brain Aging Study for Early Diagnosis and Prediction of AD (KBASE). Composite standardized uptake value ratios were obtained from PiB-PET and FDG-PET images in the AD signature regions of interests (ROIs) and analyzed. Voxel-wise analyses were also performed to examine detailed regional changes not captured by the ROI analyses. Results A significant synergistic interaction effect was found between the APOE4 and FH on amyloid-beta (Aβ) deposition in the AD signature ROIs as well as other regions. Synergistic interaction effects on cerebral glucose metabolism were observed in the regions not captured by the AD signature ROIs, particularly in the medial temporal regions. Conclusions Strong synergistic effects of APOE4 and FH on Aβ deposition and cerebral glucose metabolism in CN adults indicate possible gene-to-gene or gene-to-environment interactions that are crucial for pathogenesis of AD involving Aβ. Other unspecified risk factors—genes and/or environmental—that are captured by the positive FH status might either coexpress or interact with APOE4 to alter AD-related brain changes in CN. Healthy people with both FH and APOE4 need more attention for AD prevention.This study was supported by a grant from the Ministry of Science and ICT, Republic of Korea (grant no. NRF-2014M3C7A1046042). The funding source had no role in the study design, data collection, data analysis, data interpretation, writing of the manuscript, or decision to submit it for publication

Potential Role of Hedgehog Pathway in Liver Response to Radiation

<div><p>Radiation-induced fibrosis constitutes a major problem that is commonly observed in the patients undergoing radiotherapy; therefore, understanding its pathophysiological mechanism is important. The Hedgehog (Hh) pathway induces the proliferation of progenitors and myofibroblastic hepatic stellate cells (MF-HSCs) and promotes the epithelial-to-mesenchymal transition (EMT), thereby regulating the repair response in the damaged liver. We examined the response of normal liver to radiation injury. Male mice were sacrificed at 6 weeks and 10 weeks after exposure to a single dose of 6 Gy and the livers were collected for biochemical analysis. Irradiated (IR) and control mice were compared for progenitors, fibrosis, Hh pathway, and EMT at 6 and 10 weeks post irradiation. Fatty hepatocytes were observed and the expressions of Hh ligand, Indian Hh. were greater in the livers at 6 weeks, whereas expression of another Hh ligand, Sonic Hh, increased at 10 weeks post irradiation. Both Smoothened, Hh receptor, and Gli2, Hh-target gene, were up-regulated at 6 and 10 weeks after irradiation. Accumulation of progenitors (CD44, Pan-cytokeratin, and Sox9) was significant in IR livers at 6 and 10 weeks. RNA analysis showed enhanced expression of the EMT–stimulating factor, tgf-β, in the IR livers at 6 weeks and the upregulation of mesenchymal markers (α-SMA, collagen, N-cadherin, and s100a4), but down-regulation of EMT inhibitors, in IR mouse livers at 6 and 10 weeks. Increased fibrosis was observed in IR mouse livers at 10 weeks. Treatment of mice with Hh inhibitor, GDC-0449, suppressed Hh activity and block the proliferation of hepatic progenitor and expression of EMT-stimulating genes in irradiated mice. Therefore, those results demonstrated that the Hh pathway increased in response to liver injury by radiation and promoted a compensatory proliferation of MF-HSCs and progenitors, thereby regulating liver remodeling.</p></div

Ihh expression in the injured livers of mice by radiation.

<p>IHC for Ihh in the liver at 6 and 10 weeks post radiation. Brown color indicated Ihh-positive cells. Magnified representative image from IR livers at 6 weeks (x63) is shown in right panel (arrow and arrowhead indicate the oval cell and HSC-looking cells, respectively). The number of Ihh-postive cells were counted and graphed (*p<0.005 vs own control group).</p

Enhanced activation of the Hh signaling pathway in the liver post irradiation.

<p>(A) QRT-PCR analysis of liver mRNA from radiation-treated mice for ihh, shh, smo, and gli2 ((n ≥3 mice/group) Mean±SD results are graphed. (B) and (C). Western blot analysis of Ihh, Shh, Smo, and Gli2 (GAPDH was used as an internal control). Data shown represent one of three experiments with similar results (B: Immuoblot/C: Band density) (n ≥3 mice/group). Data represent the mean ± SD of three independent experiments (*p<0.05 vs own control group).</p

Sequences of primers used for QRT-PCR.

<p>Sequences of primers used for QRT-PCR.</p

Accumulation of liver progenitors in the radiation-damaged livers.

<p>(A) Accumulation of CD44, Pan-Ck, and Sox9-positive progenitor cells in mouse livers from representative radiation-treated mice (X40). (B) The number of CD44, Pan-Ck, and Sox-9-postive cells were counted and graphed (*p<0.05 vs own control group).</p

Increased fibrosis and EMT in the irradiated liver.

<p>(A) QRT-PCR analysis of liver mRNA from radiation-treated mice for tfg- β, α -sma, collagen a1, n-cadherin, s100a4, and bmp7(n ≥3 mice/group). Mean±SD results are graphed. (B) & (C). Western blot analysis of TGF-β (25 kDa: processed form) (inducer of fibrosis) and α-SMA (fibrogenic marker) expression (GAPDH was used as an internal control) (n≥3 mice/group). Data shown represent one of three experiments with similar results (B: Immunoblot/C: Band density of TGF-β and α-SMA). Data represent the mean ± SD of three independent experiments. (D) Sirius red staining in liver sections from representative control and irradiated mice (X40) (*p<0.05, vs own control group).</p