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.

Background: Among the various diaphragm-sparing alternatives to interscalene block, costoclavicular block (CCB) demonstrated a low hemidiaphragmatic paresis (HDP) occurrence but an inconsistent analgesic effect in arthroscopic shoulder surgery. We hypothesized that a larger volume of local anesthetic for CCB could provide sufficient analgesia by achieving sufficient supraclavicular spreading. Methods: Sixty patients scheduled for arthroscopic rotator cuff repair were randomly assigned to receive CCB using one of two volumes of local anesthetic (CCB20, 0.75% ropivacaine 20 ml; CCB40, 0.375% ropivacaine 40 ml). The primary outcome was the rate of complete analgesia (0 on the numeric rating scale of pain) at 1 h postoperatively. The secondary outcomes included a sonographic assessment of local anesthetic spread, diaphragmatic function, pulmonary function, postoperative opioid use, and other pain-related experiences within 24 h postoperatively. Results: The rates of complete analgesia were not significantly different (23.3% [7/30] and 33.3% [10/30] in the CCB20 and CCB40 groups, respectively; risk difference 10%, 95% CI [–13, 32], P = 0.567). There were no significant differences in other pain-related outcomes. Among the clinical factors considered, the only factor significantly associated with postoperative pain was the sonographic observation of supraclavicular spreading. There were no significant differences in the incidence of HDP and the change in pulmonary function between the two groups. Conclusions Using 40 ml of local anesthetic does not guarantee supraclavicular spread during CCB. Moreover, it does not result in a higher rate of complete analgesia compared to using 20 ml of local anesthetic in arthroscopic shoulder surgery.

Purpose: Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors. Materials and Methods: We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel. Results: Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability–high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively. Conclusion ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.

Endometriosis is defined by the presence of extrauterine endometrial tissue and presents with symptoms of dysmenorrhea, chronic pelvic pain, and impaired fertility. This condition often follows a chronic progressive course with favorable recurrence, even after surgical or medical treatment. The etiology or exact pathophysiology of endometriosis remains to be clarified, although it is thought to be a complex and multifactorial disease. Prior epidemiological or population-based studies have reported several risk factors related to endometriosis, such as environmental, menstrual, habitual, and lifestyle factors. Moreover, anthropometry has been found to be significantly associated with the diagnosis of endometriosis, as a lower body mass index is associated with an elevated risk of endometriosis. Here, we review studies that have examined the association between body size and the risk of endometriosis and discuss the clinical and biological significance of the relationship between adiposity and endometriosis.

Non-Hodgkin lymphoma comprises 2.1% of the total number of cancers in South Korea. Among those, diffuse large B cell lymphoma (DLBCL) comprises the largest percentage. Nutrition interventions have been highlighted because nutritional status in non-Hodgkin's lymphoma patients has a significant impact on treatment and prognosis, but relevant studies are inadequate. Therefore, the aim of this study was to share the case of a nutrition intervention for a patient with primary gastrointestinal non-Hodgkin lymphoma underlying chronic kidney disease who was comorbid with tumor lysis syndrome, which was a complication of a specific chemotherapy. The subject is a 76-year-old patient who was diagnosed with DLBCL. He had abdominal pain, constipation, and anorexia. After chemotherapy, he experienced the tumor lysis syndrome. The patient's condition was continuously monitored, and various nutrition interventions, such as nutrition counseling and education, provision of therapeutic diet, oral nutritional supplement, change of meal plans, and parenteral nutrition support were attempted. As a result of the nutrition intervention, oral intake was increased from 27% of the energy requirement to 70% and from 23% of the protein requirement to 77%. Despite the various nutrition interventions during the hospitalization, there were no improvements in weight and nutrition-related biochemical parameters or malnutrition. However, it was meaningful in that the patient was managed to prevent worsening and the planned third chemotherapy could be performed. These results can be used as the basis for establishing guidelines for nutritional interventions customized to patients under the same conditions.

Non-Hodgkin lymphoma comprises 2.1% of the total number of cancers in South Korea. Among those, diffuse large B cell lymphoma (DLBCL) comprises the largest percentage. Nutrition interventions have been highlighted because nutritional status in non-Hodgkin's lymphoma patients has a significant impact on treatment and prognosis, but relevant studies are inadequate. Therefore, the aim of this study was to share the case of a nutrition intervention for a patient with primary gastrointestinal non-Hodgkin lymphoma underlying chronic kidney disease who was comorbid with tumor lysis syndrome, which was a complication of a specific chemotherapy. The subject is a 76-year-old patient who was diagnosed with DLBCL. He had abdominal pain, constipation, and anorexia. After chemotherapy, he experienced the tumor lysis syndrome. The patient's condition was continuously monitored, and various nutrition interventions, such as nutrition counseling and education, provision of therapeutic diet, oral nutritional supplement, change of meal plans, and parenteral nutrition support were attempted. As a result of the nutrition intervention, oral intake was increased from 27% of the energy requirement to 70% and from 23% of the protein requirement to 77%. Despite the various nutrition interventions during the hospitalization, there were no improvements in weight and nutrition-related biochemical parameters or malnutrition. However, it was meaningful in that the patient was managed to prevent worsening and the planned third chemotherapy could be performed. These results can be used as the basis for establishing guidelines for nutritional interventions customized to patients under the same conditions.

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.
Amino Acids ; Binding Sites ; Calcium ; Cytosol ; Glutamic Acid ; Myocytes, Smooth Muscle ; Permeability ; Polyamines ; Receptors, Muscarinic ; Spermine ; Transient Receptor Potential Channels

The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or GTPγS. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.
Calcium ; Carbachol ; Humans ; Hydrogen-Ion Concentration ; Ion Channels ; Kidney ; Mass Screening ; Mutagenesis, Site-Directed ; Mutant Proteins ; Protein Kinase C ; Receptors, Muscarinic

Gα(q)-coupled receptor stimulation was implied in the activation process of transient receptor potential canonical (TRPC)1/4 and TRPC1/5 heterotetrameric channels. The inactivation occurs due to phosphatidylinositol 4,5-biphosphate (PI(4,5)P₂) depletion. When PI(4,5)P₂ depletion was induced by muscarinic stimulation or inositol polyphosphate 5-phosphatase (Inp54p), however, the inactivation by muscarinic stimulation was greater compared to that by Inp54p. The aim of this study was to investigate the complete inactivation mechanism of the heteromeric channels upon Gα(q)-phospholipase C β (Gα(q)-PLCβ) activation. We evaluated the activity of heteromeric channels with electrophysiological recording in HEK293 cells expressing TRPC channels. TRPC1/4 and TRPC1/5 heteromers undergo further inhibition in PLCβ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by Ca²⁺ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic Ca²⁺ due to Ca²⁺ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following PI(4,5)P₂ depletion.
Calcium ; Cytoplasm ; Endoplasmic Reticulum ; GTP-Binding Proteins ; HEK293 Cells ; Inositol ; Phosphatidylinositol 4,5-Diphosphate ; Phospholipases ; Phosphotransferases ; Protein Kinase C ; Transient Receptor Potential Channels ; Type C Phospholipases

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.
Child ; Classification ; Endoscopy ; Esophageal pH Monitoring ; Esophagitis ; Esophagitis, Peptic ; Female ; Gastroesophageal Reflux ; Humans ; Incidence ; Male ; Prevalence ; Prospective Studies ; Proton Pump Inhibitors ; Proton Pumps ; Protons