Piperacillin-Tazobactam versus Cefotaxime as Empiric Treatment for Febrile Urinary Tract Infection in Hospitalized Children.

BACKGROUND: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs. MATERIALS AND METHODS: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed. RESULTS: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months. CONCLUSION: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial.

Enhancement of Efficiency of a TiO2-BiFeO3 Dye-Synthesized Solar Cell through Magnetization.

Enhancement in the efficiency of a TiO2 dye-sensitized solar cell (DSSC) has been demonstrated by introducing ferromagnetic perovskite BiFeO3 and controlling the magnetic field, which induces two-dimensional material-like properties in the bulk of the TiO2-BiFeO3 DSSC (a 3-dimensional material). The effect of the concentration of BiFeO3 as well as the magnetization direction on the performance of the TiO2-BiFeO3 DSSC has been investigated. After magnetization, it was confirmed that the current density, efficiency, and open circuit voltage of the TiO2-BiFeO3 DSSC were increased. The observed phenomena have been explained in terms of the Hall effect which is responsible for the reduction of the degree of freedom of the electron movement resulting in the two-dimensional material-like properties in the bulk of the TiO2-BiFeO3 DSSC.

Effects of vinpocetine on atopic dermatitis after administration via three different routes in HR-1 hairless mice.

This study aimed to examine the effects of vinpocetine on atopic dermatitis (AD) by administering it via oral, intraperitoneal, and topical routes to HR-1 hairless mice. AD was induced in the mice for five weeks with ovalbumin, and vinpocetine was administered twice daily through each route of administration for two weeks after the induction of AD. Vinpocetine (20, 10, and 2 mg/kg) was administered by oral, intraperitoneal, and topical routes, respectively. The administration of vinpocetine suppressed the increase in serum immunoglobulin (Ig) E and IgG1 levels and the production of interleukin (IL)-4 and IL-13-cytokines linked to T helper 2 cells in skin tissue. In addition, the invasion of inflammatory cells, including eosinophils, into the skin tissue was reduced, and changes in skin structure were also suppressed. These results show the potential for the use of vinpocetine in patients with AD and even for targeted treatment against PDE. In most of the experiments, symptom relief in the groups receiving oral and topical vinpocetine was slightly superior to that in the group receiving vinpocetine intraperitoneally. In particular, topical application of vinpocetine was found to be the most effective route when considering the dose of vinpocetine used in each route.

Vinpocetine alleviates lung inflammation via macrophage inflammatory protein-1ß inhibition in an ovalbumin-induced allergic asthma model.

Asthma is a well-known bronchial disease that causes bronchial inflammation, narrowing of the bronchial tubes, and bronchial mucus secretion, leading to bronchial blockade. In this study, we investigated the association between phosphodiesterase (PDE), specifically PDE1, and asthma using 3-isobutyl-1-methylxanthine (IBMX; a non-specific PDE inhibitor) and vinpocetine (Vinp; a PDE1 inhibitor). Balb/c mice were randomized to five treatment groups: control, ovalbumin (OVA), OVA + IBMX, OVA + Vinp, and OVA + dexamethasone (Dex). All mice were sensitized and challenged with OVA, except for the control group. IBMX, Vinp, or Dex was intraperitoneally administered 1 h before the challenge. Vinp treatment significantly inhibited the increase in airway hyper-responsiveness (P<0.001) and reduced the number of inflammatory cells, particularly eosinophils, in the lungs (P<0.01). It also ameliorated the damage to the bronchi and alveoli and decreased the OVA-specific IgE levels in serum, an indicator of allergic inflammation increased by OVA (P<0.05). Furthermore, the increase in interleukin-13, a known Th2 cytokine, was significantly decreased by Vinp (P<0.05), and Vinp regulated the release and mRNA expression of macrophage inflammatory protein-1ß (MIP-1ß) increased by OVA (P<0.05). Taken together, these results suggest that PDE1 is associated with allergic lung inflammation induced by OVA. Thus, PDE1 inhibitors can be a promising therapeutic target for the treatment of asthma.

Pinus thunbergii Parl. Extracts Reduce Acute Inflammation by Targeting Oxidative Stress.

Pinus thunbergii Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and H2O2-induced lipid peroxidation capacity of PTP were assessed in vitro in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). PTP inhibited NO production by 53.5% (P < 0.05) and iNOS expression by 71.5% (P < 0.01) at 100 µg/mL. PTP at 100 µg/mL also inhibited ROS generation by 58.2% (P < 0.01) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% (P < 0.01) and PGE2 expression by 98.6% (P < 0.01). The anti-inflammatory effects of PTP were confirmed in vivo using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% (P < 0.05) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997-2016: a Nationwide Retrospective Cohort Study.

BACKGROUND: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. METHODS: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. RESULTS: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. CONCLUSION: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Physical exercise during exposure to 40-Hz light flicker improves cognitive functions in the 3xTg mouse model of Alzheimer's disease.

BACKGROUND: Exercise promotes brain health and improves cognitive functioning in the elderly, while 40-Hz light flickering through the visual cortex reduces amyloid beta (Aß) by stabilizing gamma oscillation. We examined whether exercise was associated with hippocampus-mediated improvement in cognitive functioning in the 3xTg-Alzheimer's disease (3xTg-AD) murine model following exposure to 40-Hz light flickering and exercise. METHODS: We subjected 12-month-old 3xTg-AD mice to exercise and 40-Hz light flickering for 3 months to investigate spatial learning, memory, long-term memory, Aß levels, tau levels, mitochondrial functioning including Ca2+ retention and H2O2 emission, apoptosis, and neurogenesis in the hippocampus. RESULTS: Treatments had a positive effect; however, the combination of exercise and 40-Hz light flickering exposure was most effective in reducing Aß and tau levels. Reducing Aß and tau levels by combination of exercise and 40-Hz light flickering improves Ca2+ homeostasis and reactive oxygen species such as H2O2 in mitochondria and apoptosis including bax, bcl-2, cytochrome c, and cleaved caspase-3 and cell death, cell differentiation, and neurogenesis in the 3xTg-AD model of the hippocampus, resulting in improving cognitive impairment such as spatial learning, memory and long term memory. CONCLUSION: Our results show that exercising in a 40-Hz light flickering environment may improve cognitive functioning by reducing Aß and tau levels, thereby enhancing mitochondrial function and neuroplasticity.

Is the Diagnostic Trial with Proton Pump Inhibitors Reasonable for School Age Children with Gastroesophageal Reflux Symptoms?

PURPOSE: On the basis of evidence, we aimed to reevaluate the necessity of the empirical proton pump inhibitor (PPI) trial for children with suspected gastroesophageal reflux disease (GERD). METHODS: We analyzed the frequency of GERD in 85 school-age children with gastroesophageal reflux (GER) symptoms, who received 24-hour esophageal pH monitoring and/or upper endoscopy. According to the reflux index (RI), the children were classified into normal (RI <5%), intermediate (5%≤ RI <10%), or abnormal (RI ≥10%) groups. RESULTS: Fifty six were female and 29 were male. Their mean age was 12.6±0.5 (±standard deviation) years (range: 6.8-18.6). The RI analysis showed that the normal group included 76 patients (89.4%), the intermediate group included 6 patients (7.1%), and the abnormal group included 3 patients (3.5%). The DeMeester score was 5.93±4.65, 14.68±7.86 and 40.37±12.96 for the normal, intermediate and abnormal group, respectively (p=0.001). The longest reflux time was 5.56±6.00 minutes, 9.53±7.84 minutes, and 19.46±8.35 minutes in the normal, intermediate, and abnormal group, respectively (p=0.031). Endoscopic findings showed reflux esophagitis in 7 patients. On the basis of the Los Angeles Classification of Esophagitis, 5 of these patients were included in group A, 1 patient, in group B and 1 patient, in group C. CONCLUSION: The incidence of GERD was very low in school-age children with GER symptoms. Therefore, injudicious diagnostic PPI trials would be postponed until the actual prevalence of GERD is verified in future prospective studies.

Comparative study on long-term stability in mandibular sagittal split ramus osteotomy: hydroxyapatite/poly-l-lactide mesh versus titanium miniplate.

BACKGROUND: Resorbable devices have recently been adopted in the field of orthognathic surgery with controversies about their postoperative skeletal stability. Hence, we determined the long-term skeletal stability of unsintered hydroxyapatite/poly-l-lactic acid (HA/PLLA) mesh for osteofixation of mandibular sagittal split ramus osteotomy (SSRO), and compared it with that of titanium miniplate. METHODS: Patients were divided into resorbable mesh and titanium miniplate fixation groups. A comparative study of the change in the mandibular position was performed with preoperative, 1-day, 6-month, and 2-year postoperative lateral cephalograms. RESULTS: At postoperative 6 months-compared with postoperative 1 day, point B (supra-mentale) was significantly displaced anteriorly in the titanium-fixation group. Moreover, at postoperative 2 years-compared with postoperative 6 months, point B was significantly displaced inferiorly in the titanium-fixation. However, the HA/PLLA mesh-fixation group did not show any significant change with respect to point B postoperatively. CONCLUSIONS: The HA/PLLA mesh-fixation group demonstrated superior long-term skeletal stability with respect to the position of mandible, when compared with the titanium-fixation group.

Meckel's Diverticulum Diagnosed in a Child with Suspected Small Bowel Crohn's Disease.

We report a rare case of Meckel's diverticulum in a boy who initially presented with chronic iron deficiency anemia (IDA) without any history of gastrointestinal (GI) bleeding at 8 years-old. Isolated small bowel Crohn's disease was suspected based on findings of small bowel ulcers on capsule endoscopy. At four years from initial presentation, he developed massive GI bleeding. Abdominal computed tomographic angiography and small bowel series revealed findings suggestive of Meckel's diverticulum. Meckel's diverticulum should be suspected in children with unexplained chronic IDA even in the absence of prominent GI bleeding and negative findings on repetitive Meckel's scans. Moreover, Meckel's diverticulum should be included in the differential diagnosis of isolated small bowel Crohn's disease when the disease is limited to a short segment of the distal small bowel, as ulcers and inflammation may result as a consequence of acid secreted from adjacent heterotopic gastric mucosa constituting the Meckel's diverticulum.

Associations among the Degree of Nonalcoholic Fatty Liver Disease, Metabolic Syndrome, Degree of Obesity in Children, and Parental Obesity.

PURPOSE: To analyze the associations among the degrees of nonalcoholic fatty liver disease (NAFLD) by ultrasonography and metabolic syndrome, degrees of obesity in children, and degrees of parental obesity. METHODS: A total of 198 children with obesity who visited a pediatric obesity clinic were prospectively enrolled in this study. The severity of NAFLD based on ultrasonography was classified into no, mild, moderate, or severe NAFLD group. The degree of obesity based on the percentage over standard weight for height per sex was classified into mild, moderate, or severe. RESULTS: Of 132 patients evaluated for the degree of NAFLD and metabolic syndrome, the p-value of correlation between the two factors was 0.009. Therefore, metabolic syndrome might significantly affect the degree of NAFLD. Of 158 patients evaluated for the degree of NAFLD and the degree of obesity, the p-value of correlation between the two factors was 0.122. Of 154 patients evaluated for the degree of obesity and father's obesity, the p-value was 0.076. Of 159 patients evaluated for the degree of obesity and mother's obesity, the p-value was 0.000, indicating that mother's obesity could significantly affect the degree of obesity in children. Of 142 patients evaluated for the degree of obesity and metabolic syndrome, the p-value was 0.288. CONCLUSION: Metabolic syndrome might significantly affect the degree of nonalcoholic fatty liver in children. In addition, mother's obesity might be a significant factor that affects the degree of obesity in children.

Sonographic Growth Charts for Kidney Length in Normal Korean Children: a Prospective Observational Study.

Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 × height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 × height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders.

The effect of physical activity on serum IL-6 and vaspin levels in late elementary school children.

PURPOSE: This study investigates the effects of physical activity on serum IL-6 and vaspin in late elementary school children. METHODS: Those who (n = 220) completed the 7-day physical activity monitoring underwent a second round of measurements including body fat, serum glucose and insulin, and serum IL-6 and vaspin. One way ANOVAs followed by LSD post hoc tests were used to test for significant differences in dependent variables across incremental physical activity levels at p=0.05. Multivariate stepwise linear regression analyses were used to determine significant predictors for serum IL-6 and vaspin levels at p=0.05. RESULTS: The results showed significant inverse linear trends for body fat parameters across incremental physical activity levels (from low to high); the lower the body fat, the higher the physical activity levels. On the other hand, there were no significant linear trends for insulin resistance markers or dietary intake across incremental physical activity levels. Multiple stepwise linear regression analyses were used to determine significant predictors for individual variations in serum IL-6 and vaspin in the study population. We found that body mass index (p=0.002) and low- and moderate-intensity physical activities (p=0.002 and p=0.0045, respectively) were significant determinants of serum IL-6. In addition, low- and moderate-intensity physical activities (p=0.01 & p=0.022, respectively) were significant determinants of serum vaspin levels in this study population. CONCLUSION: In summary, the findings of the current study suggest that promotion of physical activity along with a healthy diet should be key components of lifestyle interventions to improve serum cytokine profiles associated with insulin resistance syndrome in late elementary school children.

Single Cavernous Hemangioma of the Small Bowel Diagnosed by Using Capsule Endoscopy in a Child with Chronic Iron-Deficiency Anemia.

Cavernous hemangiomas of the gastrointestinal tract are extremely rare. In particular, the diagnosis of small bowel hemangiomas is very difficult in children. A 13-year-old boy presented at the outpatient clinic with dizziness and fatigue. The patient was previously diagnosed with iron-deficiency anemia at 3 years of age and had been treated with iron supplements continuously and pure red cell transfusion intermittently. Laboratory tests indicated that the patient currently had iron-deficiency anemia. There was no evidence of gross bleeding, such as hematemesis or bloody stool. Laboratory findings indicated no bleeding tendency. Gastroduodenoscopy and colonoscopy results were negative. To obtain a definitive diagnosis, the patient underwent capsule endoscopy. A purplish stalked mass was found in the jejunum, and the mass was excised successfully. We report of a 13-year-old boy who presented with severe and recurrent iron-deficiency anemia caused by a cavernous hemangioma in the small bowel without symptoms of gastrointestinal bleeding.

Long-term outcome of patients with p22 (phox) -deficient chronic granulomatous disease on Jeju Island, Korea.

PURPOSE: This study investigated the long-term clinical outcomes of patients with p22 (phox) -deficient chronic granulomatous disease (CGD) on Jeju Island and retrospectively evaluated the effects of interferon-gamma (IFN-γ) prophylaxis. METHODS: The medical records of 15 patients with CGD were retrospectively reviewed. The efficacy of IFN-γ prophylaxis was evaluated by comparing the frequency of severe infections before and after starting continuous prophylaxis with IFN-γ. RESULTS: At the time of the analysis, 14 patients were alive, with a median age of 14.3 years. The diagnosis of CGD was made at a median age of 2.4 years, and the median age at onset of severe infection was 0.3 years. Thirteen of the 15 patients had their first severe infection within the first year of life. The overall incidence of severe infection was 1.36 infections per patient-year; pneumonia, suppurative lymphadenitis, and skin and subcutaneous abscesses were the most common infections. Aspergillus species were the most frequently isolated microorganisms, present in 15.8% of isolates. IFN-γ did not significantly change the rate of severe infection. The survival rate for patients after 2 years of age was 93%; there was a prolonged survival plateau beyond the age of 2. CONCLUSION: Compared with cases of X-linked CGD reported in other studies, patients with CGD on Jeju Island did not show obviously different clinical manifestations, but they had a significantly higher survival rate. Further studies with a substantially longer period of observation, and with more patients under intensive surveillance are necessary to elucidate the prophylactic efficiency of IFN-γ.

Antidepressant effects of exercise are produced via suppression of hypocretin/orexin and melanin-concentrating hormone in the basolateral amygdala.

Physical exercise is considered beneficial in the treatment of depression, but the underlying mechanism is not clearly understood. In the present study, we investigated the mechanism regulating antidepressant effects of exercise by focusing on the role of the amygdala using a well-defined animal model of depression. C57BL/6 mice treated with repeated restraint showed depression-like behaviors, which was counteracted by post-stress treatment with physical exercise. The two neuropeptides hypocretin/orexin (Hcrt/Orx) and melanin-concentrating hormone (MCH) were transcriptionally upregulated in the BLA after repeated stress, and their enhanced expression was downregulated by treatment with exercise, mirroring stress-induced depression-like behaviors and their reversal by exercise. Stereotaxic injection of either Hcrt/Orx peptide or MCH peptide within the BLA commonly increased phospho-CaMKIIα level and produced depression-like behaviors, mimicking the neural states in the BLA of mice subjected to repeated stress. In contrast, siRNA-mediated suppression of Hcrt/Orx or MCH in the BLA blocked stress-induced depression-like behaviors. Furthermore, siRNA-mediated inhibition of CaMKIIα in the BLA also counteracted stress-induced depression-like behaviors. Local injection of Hcrt/Orx peptide or MCH peptide within the BLA in exercise-treated animals blocked antidepressant-like effects of exercise. Together these results suggest that exercise produces antidepressant effects via suppression of Hcrt/Orx and MCH neural systems in the BLA.

High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

INTRODUCTION: Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. CASE PRESENTATION: A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. CONCLUSIONS: High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.

Relationship of PGC-1α gene polymorphism with insulin resistance syndrome in Korean children.

This study aimed to investigate the associations between peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene Gly482Ser polymorphism (rs8192678) and parameters of insulin resistance in a sample of Korean children. A total of 286 children aged 10 to 12 years old were recruited from local elementary schools. Measured variables included body fat, blood pressures, blood lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and accelerometer-based physical activity (PA). Significant differences in percentage body fat (P = .016), insulin (P = .013), and HOMA-IR (P = .007) were found according to Gly482Ser genotype, with no significant genotype differences in the other measured variables. The genotype-specific differences in insulin (P = .136) and HOMA-IR (P = .067) were significantly attenuated when adjusted for age, sex, Tanner stage, body fat, and PA. The findings of the study suggest that the genetic effects of the PGC-1α genotypes on parameters of insulin resistance might be modulated by lifestyle factors, including PA and body fatness.