IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth.

BACKGROUND: The elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator of the RAS-ERK pathway, how it drives cancer growth remains unclear. OBJECTIVE: We define the function of IQGAP3 in gastric cancer (GC) development and progression. DESIGN: We studied the phenotypic changes caused by IQGAP3 knockdown in three molecularly diverse GC cell lines by RNA-sequencing. In vivo tumorigenesis and lung metastasis assays corroborated IQGAP3 as a mediator of oncogenic signalling. Spatial analysis was performed to evaluate the intratumoral transcriptional and functional differences between control tumours and IQGAP3 knockdown tumours. RESULTS: Transcriptomic profiling showed that IQGAP3 inhibition attenuates signal transduction networks, such as KRAS signalling, via phosphorylation blockade. IQGAP3 knockdown was associated with significant inhibition of MEK/ERK signalling-associated growth factors, including TGFß1, concomitant with gene signatures predictive of impaired tumour microenvironment formation and reduced metastatic potential. Xenografts involving IQGAP3 knockdown cells showed attenuated tumorigenesis and lung metastasis in immunodeficient mice. Accordingly, immunofluorescence staining revealed significant reductions of TGFß/SMAD signalling and αSMA-positive stromal cells; digital spatial analysis indicated that IQGAP3 is indispensable for the formation of two phenotypically diverse cell subpopulations, which played crucial but distinct roles in promoting oncogenic functions. CONCLUSION: IQGAP3 knockdown suppressed the RAS-TGFß signalling crosstalk, leading to a significant reduction of the tumour microenvironment. In particular, IQGAP3 maintains functional heterogeneity of cancer cells to enhance malignant growth. IQGAP3 is thus a highly relevant therapy target in GC.

Deep Learning Model Using Stool Pictures for Predicting Endoscopic Mucosal Inflammation in Patients With Ulcerative Colitis.

INTRODUCTION: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation. METHODS: This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photographs of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2,161 stool pictures from 306 patients and tested on 1,047 stool images from 126 patients. The UC endoscopic index of severity was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal). RESULTS: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong P = 0.458]). When rectal-sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P = 0.002). DISCUSSION: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photographs are a useful monitoring tool for typical UC.

Efficacy of Tegoprazan-Containing Sequential Eradication Treatment Compared to Esomeprazole-Containing Sequential Eradication of Helicobacter pylori in South Korea, a Region With High Antimicrobial Resistance: A Prospective, Randomized, Single Tertiary Center Study.

BACKGROUND: Treatment with potassium-competitive acid blockers has shown acceptable efficacy in Helicobacter pylori eradication. In regions like Korea, where the clarithromycin resistance rate is high, alternative combinations like non-bismuth quadruple therapies have shown favorable results. This study compared the outcomes of sequential eradication therapy with new potassium-competitive acid blocker tegoprazan and conventional esomeprazole-containing sequential therapy. MATERIALS AND METHODS: Patients with Helicobacter pylori (H. pylori) infection were consecutively recruited. Patients were allocated to either an esomeprazole-containing sequential or a tegoprazan-containing sequential therapy group. Sequential therapy comprised esomeprazole (40 mg) or tegoprazan (50 mg) plus amoxicillin (1000 mg) twice daily for the initial 5 days, followed by esomeprazole (40 mg) or tegoprazan (50 mg) with clarithromycin (500 mg) and metronidazole (500 mg) twice daily for the remaining 5 days. Eradication rate, compliance, and adverse events were recorded. RESULTS: A total of 406 patients with H. pylori infection were enrolled in the trial and analyzed per protocol. Eradication rate by intention-to-treat and per-protocol was 83.8% (95% confidence interval [CI]: 78.7-88.9) for esomeprazole-containing sequential therapy, and 87.1% (95% CI: 82.5-91.8) for tegoprazan-containing sequential therapy, with no statistical significance (p = 0.399). Additionally, there was no statistically significant difference in treatment compliance between the two groups. Nausea was more prevalent (23.3%, 27/202) with sequential tegoprazans than with esomeprazole-containing sequential therapy (14.2%, 29/204; p = 0.022). CONCLUSION: Tegoprazan-containing 10-day sequential eradication treatment demonstrated similar eradication efficacy compared to esomeprazole-containing treatment, even in regions with high antimicrobial resistance, such as Korea. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06382493.

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples.

PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

Association between long-term PM2.5 exposure and risk of Kawasaki disease in children: A nationwide longitudinal cohort study.

BACKGROUND: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM2.5) with the risk of KD. METHODS: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders. RESULTS: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM2.5 exposed to the entire cohort was 28.2 µg/m³ (Standard Deviation 2.9). For each 5 µg/m³ increase in annual PM2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39). CONCLUSIONS: In this nationwide, population-based, cohort study, long-term childhood exposure to PM2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM2.5 and KD, but further studies are needed to confirm our findings.

Genotype-phenotype correlations in children with Gitelman syndrome.

BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.

Prevalence and trends of multiple antimicrobial resistance of Helicobacter pylori in one tertiary hospital for 20 years in Korea.

BACKGROUND: Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period. MATERIALS AND METHODS: Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. RESULTS: From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase. CONCLUSIONS: The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).

Glycogen Synthase Kinase 3ß Is a Key Regulator in the Inhibitory Effects of Accumbal Cocaine- and Amphetamine-Regulated Transcript Peptide 55-102 on Amphetamine-Induced Locomotor Activity.

Microinjection of cocaine- and amphetamine-regulated transcript (CART) peptide 55-102 into the nucleus accumbens (NAcc) core significantly attenuates psychostimulant-induced locomotor activity. However, the molecular mechanism remains poorly understood. We examined the phosphorylation levels of Akt, glycogen synthase kinase 3ß (GSK3ß), and glutamate receptor 1 (GluA1) in NAcc core tissues obtained 60 min after microinjection of CART peptide 55-102 into this site, followed by systemic injection of amphetamine (AMPH). Phosphorylation levels of Akt at Thr308 and GSK3ß at Ser9 were decreased, while those of GluA1 at Ser845 were increased, by AMPH treatment. These effects returned to basal levels following treatment with CART peptide 55-102. Furthermore, the negative regulatory effects of the CART peptide on AMPH-induced changes in phosphorylation levels and locomotor activity were all abolished by pretreatment with the S9 peptide, an artificially synthesized indirect GSK3ß activator. These results suggest that the CART peptide 55-102 in the NAcc core plays a negative regulatory role in AMPH-induced locomotor activity by normalizing the changes in phosphorylation levels of Akt-GSK3ß, and subsequently GluA1 modified by AMPH at this site. The present findings are the first to reveal GSK3ß as a key regulator of the inhibitory role of the CART peptide in psychomotor stimulant-induced locomotor activity.

Favorable outcomes of rescue second- or third-line culture-based Helicobacter pylori eradication treatment in areas of high antimicrobial resistance.

BACKGROUND: Failure of second or third-line eradication treatment against Helicobacter pylori (H. pylori) is principally caused by antimicrobial resistance and reduced treatment adherence. AIMS: To evaluate the efficacy and safety of culture-based rescue eradication treatments in patients who have previously experienced failed eradication treatment. METHODS: Patients who had persistent H. pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14-day administration of clarithromycin-containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes. RESULTS: A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n = 11), MEA (n = 15), quadruple (n = 53), or RLA triple (n = 5) therapy group. The eradication rates in the intention-to-treat and per-protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%). CONCLUSIONS: As a rescue therapy, culture-based susceptibility-guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance.

Lower albumin level and longer disease duration are risk factors of acute kidney injury in hospitalized children with nephrotic syndrome.

BACKGROUND: Children with nephrotic syndrome (NS) are at an increased risk of acute kidney injury (AKI) and the incidence of AKI in this population is reportedly increasing. This study aimed to investigate the incidence, clinical profiles, and risk factors of AKI in hospitalized children with NS through a nationwide study. METHODS: This retrospective multicenter study included 14 pediatric nephrology centers in Korea. From 2013 to 2017, a total of 814 patients with idiopathic NS were cared for at participating centers. Among them, 363 patients were hospitalized for NS and investigated in this study. RESULTS: A total of 363 children with NS were hospitalized 574 times. AKI occurred in 93 admissions (16.2%) of 89 patients: 30 (32.3%) stage 1; 24 (25.8%) stage 2; and 39 (41.9%) stage 3. Multivariate logistic regression analysis showed that longer disease duration, lower albumin level, and methylprednisolone pulse treatment were significantly associated with AKI development in hospitalized children with NS. AKI was associated with a longer hospital stay than non-AKI (median 10 vs. 7 days, P = 0.001). Among 93 admissions, 85 (91.4%) episodes recovered from AKI without complication, whereas 6 (6.5%) progressed to advanced chronic kidney disease (CKD). CONCLUSIONS: AKI is not uncommon in hospitalized children with NS, and its incidence in this nationwide study was 16.2%. Risk factors for AKI in hospitalized children with NS include longer disease duration, lower albumin level, and methylprednisolone pulse therapy. Pediatric NS patients with these characteristics should be under more strict scrutiny for the occurrence of AKI. Graphical abstract.

Annual eradication rate of bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: A 15-year prospective study at a tertiary hospital in Korea.

BACKGROUND: Bismuth-containing quadruple therapy is widely used as second-line treatment for Helicobacter pylori infection. This prospective study investigated the changes in the annual H. pylori eradication rates of quadruple therapy. METHODS: This study included an intention-to-treat (ITT) population of 452 subjects who failed first-line eradication therapy for H. pylori between 2003 and 2018. All subjects received a 14-day course of bismuth-containing quadruple therapy consisting of esomeprazole (40 mg twice daily), metronidazole (500 mg thrice daily), bismuth subcitrate (120 mg four times daily), and tetracycline (500 mg four times daily). Per-protocol (PP) analysis of data was performed in subjects who followed up with strict treatment adherence. Eradication was confirmed based on the results of the 13 C-urea breath test, rapid urease test (CLOtest® ), and histopathologic evaluation. Compliance and adverse effects were also investigated. A minimal inhibitory concentration test was performed on tissue samples obtained from 103 subjects. RESULTS: The overall eradication rates following ITT and PP analyses were 78.8% (356/452) and 89.5% (314/351), respectively. The annual eradication success rate did not show significant changes (P = .062 [ITT], P = .857 [PP]) over the 15-year study period. Adverse events were reported in 57.3% of the ITT population. The rates of resistance to metronidazole and tetracycline were 44.7% and 18.4%, respectively. CONCLUSIONS: Despite high antibiotic resistance rates, no significant reduction in annual eradication rates was observed during the study period.

Primary and secondary antibiotic resistance of Helicobacter pylori in Korea from 2003 to 2018.

BACKGROUND: Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea. METHODS: The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method. RESULTS: An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively). CONCLUSIONS: The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.

Risk factors of rescue bismuth quadruple therapy failure for Helicobacter pylori eradication.

BACKGROUND AND AIM: Failure of bismuth quadruple therapy for Helicobacter pylori eradication is frequently observed. To increase the eradication rate, comprehensive analyses need to be performed regarding risk factors of bismuth quadruple therapy failure based on complete standard culture and antimicrobial susceptibility testing results. METHODS: Patients with history of failed first therapy who had H. pylori colonies isolated from culture and successful minimum inhibitory concentration (MIC) test were enrolled. Esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapies for 7 or 14 days were given. Eradication rate, treatment compliance, adverse events, and risk factors for the failure of bismuth quadruple therapy were analyzed. RESULTS: A total 54 patients were enrolled. Overall eradication rate in the present study was 88.8%. The eradication rate for cases with metronidazole resistance such as MIC 8-16 µg/mL or 16-32 µg/mL was 92.8% (13/14). For cases with high level metronidazole resistance (MIC > 32 µg/mL), the eradication rate was only 60% (6/10). Multivariate analysis regarding compliance, treatment duration, age > 60, three kinds of metronidazole MICs, tetracycline MIC > 4 µg/mL, adverse events and any other parameters, "metronidazole resistance, high level (MIC > 32 µg/mL)" was the only independent risk factor for eradication failure (P = 0.007). CONCLUSION: For cases with metronidazole resistance at MIC > 32 µg/mL, rescue therapy other than bismuth-containing quadruple therapy is needed.

Favorable outcomes of prepackaged low-residue diet on bowel preparation for colonoscopy: Endoscopist-blinded randomized controlled trial.

BACKGROUND AND AIM: 2 L polyethylene glycol plus an ascorbic acid (PEGA) is known to be as effective. However, 2 L polyethylene glycol-based regimens are often still difficult for patients to tolerate. Therefore, we conducted this study to evaluate the potential of 1 L PEGA with prepackaged low-residue diet (PLD) as an alternative to 2 L PEGA before colonoscopy. METHODS: The subjects were randomly assigned to either of the two groups. The 2 L PEGA group received 2 L PEGA split regimen. The 1 L PEGA with PLD group received PLD on the day preceding colonoscopy and 1 L PEGA. All endoscopic procedures were performed by one physician who did not know patients allocation. Bowel preparation status were graded using Boston Bowel Preparation Score (BBPS). A questionnaire regarding tolerability and safety was administered. This trial is registered at ClinicalTrials.gov (NCT03329339). RESULTS: A total of 173 patients completed the study (86 in the 2 L PEGA group and 87 in the 1 L PEGA with PLD group). Bowel preparation was adequate in 88.4% (76/86) of patients in the 2 L PEGA group and 93.1% of patients in the 1 L PEGA with PLD group (81/87, P = 0.28). The patients in the 1 L PEGA with PLD group had higher whole Boston Bowel Preparation Scale score (P = 0.02) and expressed more satisfaction and willingness to repeat the procedure (P < 0.01). There was no significant difference with respect to compliance or safety. CONCLUSION: 1 L PEGA with PLD showed equivalent efficacy, greater satisfaction, and more willingness to repeat compared with 2 L PEGA for bowel preparation.

The Protective Effect of Exclusive Breastfeeding on Overweight/Obesity in Children with High Birth Weight.

BACKGROUND: A positive association between birth weight (BW) and body mass index (BMI) has been shown among children in many populations. The aim of this study was to investigate BMI trajectory according to BW status and the protective effect of breastfeeding on the prevalence of overweight/obesity in children 6 years of age. METHODS: A retrospective cohort study was conducted between January 1, 2008 and December 31, 2016 utilizing data from the National Health Information Database of Korea. The 38,049 subjects were followed until the end of 2016, providing that subjects were completely eligible for all health check-ups from birth to 6 years of age. At each check-up period, multiple logistic regressions were used to investigate the association between BW status (low birth weight [LBW], normal birth weight [NBW], high birth weight [HBW]) and growth development. RESULTS: HBW infants were highly likely to be overweight/obese compared to NBW infants (odds ratio [OR], 1.70-2.35) and LBW infants were highly likely to be underweight (OR, 1.69-2.20) through 6 years of age. The risk of overweight/obesity decreased significantly if HBW infants were breast-fed for 6 months (OR, 0.54-0.76). CONCLUSION: HBW status is associated with overweight/obesity during early childhood. Exclusive breastfeeding is a significant protective factor against overweight/obesity in children with HBW.

Effects of Prenatal Growth Status on Subsequent Childhood Renal Function Related to High Blood Pressure.

BACKGROUND: Hypertension is one of the major causes of chronic diseases. The effect on high blood pressure (BP) with fetal growth restriction is now well-established. Recent studies suggest that a reduced number of nephrons programmed during the intrauterine period contribute to a subsequently elevated BP, due to a permanent nephron deficit. However, few studies have examined this in children. We investigated the effects of low birth weight (LBW) and preterm birth on the renal function markers related to a high BP in childhood. METHODS: We used data from 304 children aged 7-12 years who participated in the 2014 Ewha Birth and Growth Cohort survey in Korea. We assessed the serum uric acid, cystatin C, blood urea nitrogen (BUN), creatinine levels, and the estimated glomerular filtration rate (eGFR) in childhood. Anthropometric characteristics, BP in childhood, birth weight and gestational age were collected. RESULTS: The serum uric acid was significantly higher in LBW children (4.0 mg/dL) than in normal birth weight children (3.7 mg/dL). The cystatin C levels were highest among children who were very preterm (0.89 mg/dL) compared with those who were not (preterm, 0.84 mg/dL; normal, 0.81 mg/dL), although the result was only borderline significant (P for trend = 0.06). Decreased birth weight was found to be significantly associated with an increased serum BUN level in childhood. In the analysis of the effects of renal function on BP, subjects with an eGFR lower than the median value had a significantly higher diastolic BP in childhood (difference = 2.4 mmHg; P < 0.05). CONCLUSION: These findings suggest that LBW and preterm birth are risk factors for increased serum levels of renal function markers in childhood. Reduced eGFR levels were significantly associated with elevated diastolic BP in childhood. It is necessary to identify vulnerable individuals during their life and intervene appropriately to reduce the risk of an increased BP in the future.

Long-term renal outcome in children with OCRL mutations: retrospective analysis of a large international cohort.

Background: Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies. Methods: Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point. Results: Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD. Conclusions: CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.

D-dimer as a marker of acute pyelonephritis in infants younger than 24 months with urinary tract infection.

BACKGROUND: D-dimer, as well as other biomarkers related to coagulation, is significantly increased during severe bacterial infection and sepsis. The aim of this study was to evaluate the usefulness of serum D-dimer as a biological marker in diagnosing acute pyelonephritis (APN) and in predicting vesicoureteric reflux (VUR) in infants with urinary tract infection (UTI). METHODS: We retrospectively analyzed the data of 177 young infants (<2 years) with febrile UTI between 2005 and 2014, grouped as APN and lower UTI groups. Conventional inflammatory markers (white blood cell count (WBC), erythrocyte sedimentation rates (ESR), C-reactive protein (CRP)), and D-dimer were measured. RESULTS: The WBC counts (P = 0.002), ESR (P < 0.0001), CRP (P < 0.0001), D-dimer levels (P = 0.006) and the presence of VUR (P < 0.0001) were significantly higher in the APN group than in the lower UTI group. Multiple logistic regression analyses showed that D-dimer (odds ratio [OR]:1.003, 95% CI: 1.001-1.006, P = 0.002) was an independent predictive factor for VUR in young children with UTI. The area under the curve (AUC) value from the receiver operating characteristic (ROC) curve of D-dimer (0.621, P = 0.046, 95% CI: 0.499-0.743) for prediction of VUR was higher than other inflammatory markers, but was inferior to CRP in predicting APN. CONCLUSIONS: Our results demonstrate that D-dimer can be used as an inflammatory marker in infants with febrile UTI in addition to other inflammatory markers.

Locomotor sensitization is expressed by ghrelin and D1 dopamine receptor agonist in the nucleus accumbens core in amphetamine pre-exposed rat.

Ghrelin modulates mesolimbic dopaminergic pathways in the brain in addition to its role in feeding. We investigated what roles ghrelin in the nucleus accumbens (NAcc) core may play in mediating locomotor activating effects of amphetamine (AMPH). First, when rats were administered with AMPH (1 mg/kg, i.p.) following a bilateral microinjection of ghrelin (0.1 or 0.5 µg/side) into the NAcc core, their locomotor activity was significantly enhanced, while these effects were blocked by co-microinjection of ghrelin receptor antagonist (0.5 µg/side) into this site. Second, we pre-exposed rats to saline or amphetamine (1 mg/kg, i.p.) every 2 to 3 days for a total of four times. After 2 weeks of drug-free withdrawal period, we examined the effect of saline, ghrelin (0.5 µg/side), D1 dopamine receptor agonist, SKF81297 (0.5 µg/side) or ghrelin (0.5 µg/side) + SKF81297 (0.5 µg/side) directly microinjected into the NAcc core on locomotor activity. When we measured rats' locomotor activity for 1 hour immediately following microinjections, only ghrelin + SKF81297 produces sensitized locomotor activity, while all others have no effects. These results suggest that ghrelin may have a distinct role in the NAcc core to provoke the sensitized locomotor activity induced by psychomotor stimulants, and further, it may produce these effects by interaction with D1 dopamine receptors.

Effects of elastic band exercises on physical ability and muscular topography of elderlyfemales.

[Purpose] This study examined the effects of band exercise types on the physical ability and muscular topography for elderly females. [Subjects and Methods] Twenty-six females older than 65 years were divided into the dynamic band exercise (DBE; n=13) group and the Static band exercise (SBE; n=13) group. Each participant performed 12 weeks of elastic band exercises. Physical abilities were measured by leg extension power, sitting trunk flexion, closed eyes foot balance, and time to get up. Changes in muscle topography were evaluated with Moire measurement equipment for the chest, abdomen, and lumbar region. All results were compared before and after 12 weeks of exercise. [Results] Changes in physical ability were significantly increased in both groups. The scores for the muscular topography of the chest, abdomen, lumbar region, and all body parts was significantly improved in both groups for closed eyes foot balance. There were more improvements in the DBE group. [Conclusion] Two types of static and dynamic elastic band exercises effectively changed the physical fitness and muscle topography of elderly females. Therefore, to increase the effects of exercise, dynamic band exercises are considered useful. Because band exercises are simple, they can be used to maintain the health of elderly people.