A Revision of the Phylogeny of Helicotylenchus Steiner, 1945 (Tylenchida: Hoplolaimidae) as Inferred from Ribosomal and Mitochondrial DNA.

Identification of Helicotylenchus species is very challenging due to phenotypic plasticity and existence of cryptic species complexes. Recently, the use of rDNA barcodes has proven to be useful for identification of Helicotylenchus. Molecular markers are a quick diagnostic tool and are crucial for discriminating related species and resolving cryptic species complexes within this speciose genus. However, DNA barcoding is not an error-free approach. The public databases appear to be marred by incorrect sequences, arising from sequencing errors, mislabeling, and misidentifications. Herein, we provide a comprehensive analysis of the newly obtained, and published DNA sequences of Helicotylenchus, revealing the potential faults in the available DNA barcodes. A total of 97 sequences (25 nearly full-length 18S-rRNA, 12 partial 28S-rRNA, 16 partial internal transcribed spacer [ITS]-rRNA, and 44 partial cytochrome c oxidase subunit I [COI] gene sequences) were newly obtained in the present study. Phylogenetic relationships between species are given as inferred from the analyses of 103 sequences of 18S-rRNA, 469 sequences of 28S-rRNA, 183 sequences of ITS-rRNA, and 63 sequences of COI. Remarks on suggested corrections of published accessions in GenBank database are given. Additionally, COI gene sequences of H. dihystera, H. asiaticus and the contentious H. microlobus are provided herein for the first time. Similar to rDNA gene analyses, the COI sequences support the genetic distinctness and validity of H. microlobus. DNA barcodes from type material are needed for resolving the taxonomic status of the unresolved taxonomic groups within the genus.

Uric acid regulates α-synuclein transmission in Parkinsonian models.

Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson's disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model. In a cellular model, UA treatment decreased internalized cytosolic α-syn levels and neuron-to-neuron transmission of α-syn in donor-acceptor cell models by modulating dynamin-mediated and clathrin-mediated endocytosis. Moreover, UA elevation in α-syn-inoculated mice inhibited propagation of extracellular α-syn which decreased expression of phosphorylated α-syn in the dopaminergic neurons of the substantia nigra leading to their increased survival. UA treatment did not lead to change in markers related with autophagolysosomal and microglial activity under the same experimental conditions. These findings suggest UA may control the pathological conditions of PD via additive mechanisms which modulate the propagation of α-syn.

What Is the Optimal Digoxin Level? Challenging Case of Fetal Atrial Flutter Treatment in a Monochorionic Diamniotic Twin.

Background: Atrial flutter is an infrequent yet potentially fatal arrhythmia. Digoxin is the preferred first-line treatment for fetal atrial flutter due to its efficacy and favorable safety profile. The optimal digoxin serum target level for neonatal atrial flutter management remains uncertain, with the standard target level ranging from 1.0 to 2.0 ng/mL due to potential toxicity concerns above this threshold. Case Presentation: We present a case of atrial flutter in a fetus within a monochorionic diamniotic (MCDA) twin pregnancy that was successfully managed using a higher-than-standard target level of digoxin. A 34-year-old nulliparous woman was referred to our institution at 31 + 3 weeks of gestation due to fetal distress in an MCDA twin pregnancy. Fetal echocardiography revealed a ventricular rate of 214 bpm in twin A, while twin B exhibited no abnormal findings. Conclusions: Our case highlights a distinct correlation between the serum digoxin level and its impact on atrial flutter. A higher target serum level of digoxin may be necessary to achieve sinus conversion due to the unique maternal and fetal circulatory characteristics in MCDA pregnancies.

Renoprotective Effect of Chrysanthemum coronarium L. Extract on Adenine-Induced Chronic Kidney Disease in Mice.

Chronic kidney disease (CKD) gradually leads to loss of renal function and is associated with inflammation and fibrosis. Chrysanthemum coronarium L., a leafy vegetable, possesses various beneficial properties, including anti-oxidative, anti-inflammatory, and antiproliferative effects. In this study, we investigated the renoprotective effect of Chrysanthemum coronarium L. extract (CC) on adenine (AD)-induced CKD in mice. CKD was induced by feeding mice with an AD diet (0.25% w/w) for 4 weeks. Changes in renal function, histopathology, inflammation, and renal interstitial fibrosis were analyzed. The adenine-fed mice were characterized by increased blood urea nitrogen, serum creatinine, and histological changes, including inflammation and fibrosis; however, these changes were significantly restored by treatment with CC. Additionally, CC inhibited the expression of the inflammatory markers, monocyte chemoattractant protein-1, interleukins-6 and -1ß, intercellular adhesion molecule-1, and cyclooxygenase 2. Moreover, CC suppressed the expression of the fibrotic markers, type IV collagen, and fibronectin. Furthermore, CC attenuated the expression of profibrotic genes (tumor growth factor-ß and α-smooth muscle actin) in AD-induced renal injury mice. Thus, our results suggest that CC has the potential to attenuate AD-induced renal injury and might offer a new option as a renoprotective agent or functional food supplement to manage CKD.

Mobile educational tool based on augmented reality technology for tooth carving: results of a prospective cohort study.

BACKGROUND: Augmented reality (AR) technology has been shown to be effective in displaying information and presenting three-dimensional objects. Although AR applications are commonly used by learners via mobile devices, plastic models or two-dimensional images are still commonly used in tooth carving practice. Learners practicing tooth carving face a challenge due to the three-dimensional features of teeth as there is a lack of tools available that provide sequential guidance. In this study, we developed an AR-based tooth carving practice tool (AR-TCPT) and compared it to a plastic model to evaluate its potential as a practice tool as well as its user experience. METHODS: To model tooth carving, we created a three-dimensional object from sequential steps that included the maxillary canines and maxillary first premolars (16 steps), mandibular first premolars (13 steps), and mandibular first molars (14 steps). Image markers, created using Photoshop software, were assigned to each tooth. An AR-based mobile application was developed using the Unity engine. For tooth carving, 52 participants were randomly assigned to a control group (n = 26; using a plastic tooth model) or an experimental group (n = 26; using the AR-TCPT). User experience was evaluated using a 22-item questionnaire. Data were comparatively analyzed using the nonparametric Mann-Whitney U test via the SPSS program. RESULTS: The AR-TCPT detects image markers with the mobile device camera and displays three-dimensional objects for tooth fragmentation. Users can manipulate the device to view each step or examine the shape of a tooth. The results of the user experience survey revealed that the AR-TCPT experimental group scored significantly higher in tooth carving experience compared with the control group that used the plastic model. CONCLUSION: Compared with the conventional plastic model, the AR-TCPT provided a better user experience for tooth carving. The tool is highly accessible as it is designed to be used on mobile devices by users. Further studies are required to determine the educational impact of the AR-TCTP on quantitative scoring of carved teeth as well as individual user's carving abilities.

Morphological and Molecular Characterization of Diplogasteroides sp., a Cryptic Population of the Haslacheri Group (Diplogastridae), and Parasitorhabditis terebranus (Rhabditidae) from Korea.

Diplogasteroides sp., a cryptic population of D. haslacheri, and Parasitorhabditis terebranus were reported from the frass of Monochamus alternatus galleries in dead Pinus thunbergii for the first time in Korea. Females and males are morphologically characterized and their linked DNA barcodes (18S-rRNA, 28S-rRNA, ITS-rRNA and COI) supplied. Females and males of the two species from Korea conform to the original species descriptions from Europe and the USA, with variations in a few details in morphometrics. Specifically, Diplogasteroides sp. is morphologically very similar to D. haslacheri. However, it cannot be designated as D. haslacheri due to the existence of cryptic species complex within the haslacheri group (D. haslacheri, D. asiaticus, D. nix, D. andrassyi, and D. carinthiacus), a condition requiring hybridization studies to test species identity within the group. Based on analysis of COI sequences, differences among these cryptic species are evident. Thus, in addition to hybridization tests, the COI might be a powerful DNA barcoding marker for the precise identification of these cryptic species within the genus. Additionally, this is the first molecular characterization of P. terebranus, and the species is herein recorded for the first time outside its type locality.

Comparative Bioactivity of Emamectin Benzoate Formulations against the Pine Wood Nematode, Bursaphelenchus xylophilus.

The pine wood nematode (PWN), Bursaphelenchus xylophilus is a well-known devastating pathogen of economic importance in the Republic of Korea and other countries. In the Republic of Korea, trunk injection of nematicides is the preferred method of control. In this study, the efficacy of 16 locally produced formulations of emamectin benzoate against the PWN are compared through determining their sublethal toxicities and reproduction inhibition potentials. Nematodes were treated with varying concentrations of the tested chemicals in multi-well culture plates, and rates of paralysis and mortality were determined after 24 h. Reproduction inhibition potential was tested by inoculating pre-treated nematodes onto Botrytis cinerea, and in pine twig cuttings. Despite the uniformity in the concentration of the active ingredient, efficacy was contrastingly different among formulations. The formulations evidently conformed to three distinct groups based on similarities in sublethal activity (group 1: LC95 of 0.00768-0.01443 mg/ml; group 2: LC95 of 0.03202-0.07236 mg/ml, and group 3: LC95 of as high as 0.30643-0.40811 mg/ml). Nematode paralysis generally occurred at the application dose of 0.0134-0.1075 µg/ml, and there were significant differences in nematode paralysis rates among the products. Nematode reproduction was only evident at lower doses both on B. cinerea and pine twigs, albeit the variations among formulations. Group 1 formulations significantly reduced nematode reproduction even at a lower dose of 0.001075 µg/ml. The variations in efficacy might be attributed to differences in inert ingredients. Therefore, there is need to analyze the potential antagonistic effects of the large number of additives used in formulations.

Priming mesenchymal stem cells with α-synuclein enhances neuroprotective properties through induction of autophagy in Parkinsonian models.

BACKGROUND: Mesenchymal stem cells (MSCs) may be one of candidates for disease-modifying therapy in Parkinsonian diseases. As knowledge regarding the therapeutic properties of MSCs accumulates, some obstacles still remain to be overcome, especially, successful clinical translation requires the development of culture systems that mimic the natural MSC niche, while allowing clinical-scale cell expansion without compromising quality and function of the cells. In recent years, priming approaches using bioactive peptide or complement components have been investigated to enhance the therapeutic potential of MSCs. METHODS: We investigated an innovative priming strategy by conditioning the MSCs with α-synuclein (α-syn). To induce priming, MSCs were treated with different concentrations of α-syn and various time course. We evaluated whether α-syn enhances stemness properties of MSCs and priming MSCs with α-syn would modulate autophagy-related gene expression profiles. RESULTS: Treatment of naïve MSCs with α-syn upregulated transcriptional factors responsible for regulation of stemness, which was associated with the elevated expression of genes involved in glycolysis and cell re-programming. Primed MSCs with α-syn enhanced the expression of autophagy-regulating miRNA, and exosomes derived from primed MSCs were packed with autophagy-associated miRNA. In α-syn-overexpressing neuronal cells, primed MSCs with α-syn enhanced neuronal viability relative to naïve MSCs, through the induction of autophagy and lysosome activity. Animal study using an α-syn-overexpressing mice showed that the pro-survival effect of MSCs on dopaminergic neurons was more prominent in primed MSC-treated mice compared with that in naïve MSC-treated mice. CONCLUSIONS: The present data suggest that MSC priming with α-syn exerts neuroprotective effects through augmented stemness and possibly the enhancement of autophagy-mediated α-syn modulation in Parkinsonian models.

Uric Acid Enhances Neurogenesis in a Parkinsonian Model by Remodeling Mitochondria.

Background: Adult neurogenesis is the process of generating new neurons to enter neural circuits and differentiate into functional neurons. However, it is significantly reduced in Parkinson's disease (PD). Uric acid (UA), a natural antioxidant, has neuroprotective properties in patients with PD. This study aimed to investigate whether UA would enhance neurogenesis in PD. Methods: We evaluated whether elevating serum UA levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model would restore neurogenesis in the subventricular zone (SVZ). For a cellular model, we primary cultured neural precursor cells (NPCs) from post-natal day 1 rat and evaluated whether UA treatment promoted cell proliferation against 1-methyl-4-phenylpyridinium (MPP+). Results: Uric acid enhanced neurogenesis in both in vivo and in vitro parkinsonian model. UA-elevating therapy significantly increased the number of bromodeoxyuridine (BrdU)-positive cells in the SVZ of PD animals as compared to PD mice with normal UA levels. In a cellular model, UA treatment increased the expression of Ki-67. In the process of modulating neurogenesis, UA elevation up-regulated the expression of mitochondrial fusion markers. Conclusion: In MPTP-induced parkinsonian model, UA probably enhanced neurogenesis via regulating mitochondrial dynamics, promoting fusion machinery, and inhibiting fission process.

Implantable cardioverter defibrillator as a treatment for massive left ventricular fibroma-induced ventricular arrhythmia in a child.

Pediatric cardiac tumors are rare. Among these, cardiac fibroma is the second most common. Its clinical manifestations depend on size and location of the tumor and include arrhythmia or obstruction to blood flow. Symptomatic cardiac fibroma is generally treated with surgical resection or cardiac transplantation. We present the case of a 12-year-old boy with a lethal ventricular arrhythmia induced by a remnant tumor that was previously partially resected. An implantable cardioverter defibrillator was inserted as the arrhythmia was resistant to medical treatment. He was discharged in stable condition with an implantable cardioverter defibrillator generator and followed up in the outpatient clinic.

The "Intermediate" CD14 + CD16 + monocyte subpopulation plays a role in IVIG responsiveness of children with Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. Intravenous immunoglobulin (IVIG)-resistance are related to greater risk for permanent cardiac complications. We aimed to determine the correlation between monocytes and the phenotype of KD in relation to IVIG responsiveness in children. MATERIALS AND METHODS: The study cohort included 62 patients who were diagnosed with KD, 20 non febrile healthy controls (NFC), and 15 other febrile controls (OFC). In all enrolled patients, blood was taken at least 4 times and laboratory tests were performed. In addition, subtypes of monocytes were characterized via flow cytometry. RESULTS: The numbers of intermediate monocytes were significantly lower in IVIG-resistant group compared to IVIG-responsive group before IVIG infusion (p < 0.0001). After infusion, intermediate monocytes decreased in the responsive group, while a trend of increase was observed in the resistant group. Only intermediate monocytes were significant in logistic regression with adjusted OR of 0.001 and p value of 0.03. CONCLUSIONS: CD14 + CD16 + intermediate monocyte may play an important role in IVIG responsiveness among KD children. Low starting levels of intermediate monocytes, followed by a dramatic increase post-IVIG infusion during acute phase of KD are associated with IVIG-resistance. Functional studies on intermediate monocyte may help to reveal the pathophysiology.

PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo.

Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis. PF-3845 significantly suppressed osteoclast differentiation and decreased the induction of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific markers. Actin ring formation and osteoclastic bone resorption were also reduced by PF-3845, and the anti-osteoclastogenic and anti-resorptive activities were mediated by the suppression of phosphorylation of rapidly accelerated fibrosarcoma (RAF), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase, (ERK) and nuclear factor κB (NF-κB) inhibitor (IκBα). Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases.

The progression of an acceptable pulmonary stenosis immediately after total correction of tetralogy of Fallot.

BACKGROUND: A certain degree of pulmonary stenosis after total correction of tetralogy of Fallot has been considered acceptable. But the long-term outcomes are not well understood. We observed the natural course of immediate pulmonary stenosis and investigated related factors for progression. METHODS: Fifty-two patients with acceptable pulmonary stenosis immediately after operation were enrolled. Acceptable pulmonary stenosis was defined as peak pressure gradient between 15 and 45 mmHg by Doppler echocardiography. Latent class linear mixed model was used to differentiate patients with progressed pulmonary stenosis, and the factors related to progression were analysed. RESULTS: Pulmonary stenosis progressed in 14 patients (27%). Between the progression group and no progression group, there were no significant differences in operative age, sex, and the use of the transannular patch technique. However, immediate gradient was higher in the progression group (32.1 mmHg versus 25.7 mmHg, p = 0.009), and the cut-off value was 26.8 mmHg (sensitivity = 65.3%, specificity = 65.8%). Main stenosis at the sub-valve was observed more frequently in the progression group (85.7% versus 52.6%, p = 0.027). Despite no difference in the preoperative pulmonary valve z value, the last follow-up pulmonary valve z value was significantly lower in the progression group (-1.15 versus 0.35, p = 0.002). CONCLUSIONS: Pulmonary stenosis immediately after tetralogy of Fallot total correction might progress in patients with immediate pulmonary stenosis higher than ≥26.8 mmHg and the main site was sub-valve area.

Repair of tricuspid valve with pulmonary valve replacement in repaired tetralogy of fallot.

Objectives: We aimed to investigate the outcome of tricuspid valve repair (TVR) performed concomitantly with pulmonary valve replacement in repaired tetralogy of Fallot (TOF) patients. Design: This retrospective study included all patients who underwent pulmonary vale replacement from 2000 to 2016 after TOF correction. TVR patient data were compared to those of patients who underwent pulmonary vale replacement alone. Results: Thirty-eight patients were enrolled. The degree of tricuspid regurgitation was significantly decreased after operation in the TVR group. Tricuspid valve annulus and annuloectasia before operation did not vary between groups (21.1 ± 6.3 and 41.4% in no TVR vs. 21.3 ± 4.8 and 52.6% in TVR). However pre-operative right ventricular volumes were larger in the TVR group. Normal tricuspid valve coaptation (body to body) was observed less frequently in the TVR group than in the other group (52.6% vs. 93.1%, p < .001). Pre-operative tricuspid regurgitation had a linear correlation with right ventricular volume, but not with tricuspid annulus size. Conclusion: Tricuspid annulus diameter decreased significantly regardless of TVR. Abnormal coaptations were observed more in patients group and the degree of pre-operative tricuspid regurgitation was linearly correlated with right ventricular volume rather than tricuspid annulus size.

Alteration in Uterine Protease-Activated Receptor 2 Expression in Preterm Birth Induced Experimentally in Brp-39 Null Mutant Mice.

Breast regression protein 39 (Brp-39) is a mouse homolog of human Chitinase 3-like 1, which belongs to the 18-glycosyl-hydrolase family and plays a role in inflammatory reaction and tissue remodeling. The aim of this study is to investigate the role of Brp-39 in a mouse model of preterm birth. Pregnant wild-type (WT) or Brp-39(-/-) mice were injected intraperitoneally with lipopolysaccharide (LPS) at embryonic day 15. Pregnancy outcomes were evaluated for 24 hours after LPS injection. Quantitative real-time polymerase chain reaction and immunoblotting were performed to analyze messenger RNA (mRNA) and protein expressions of cytokines and contraction-associated proteins in uterine and/or placental tissue after LPS injection. LPS injection led to preterm birth in both WT and Brp-39(-/-) mice, but the proportion of pubs delivered was reduced in Brp-39(-/-) mice, along with a longer interval from the LPS injection to delivery, compared to WT mice. Inflammatory cell infiltration and mRNA expression of cytokines and Ptgs2 in the uteri and the placentas were not significantly different between WT and Brp-39(-/-) mice. Par-2 mRNA expression in the WT uteri was increased before delivery after LPS injection and decreased after delivery, while there was no significant change in Par-2 expression in the Brp-39(-/-) uteri. Protein expressions of Par-2 and Ptgs2 were lower in the Brp-39(-/-) uteri than in the WT uteri before and after delivery. Attenuated preterm birth in Brp-39(-/-) mice indicates the significance of Brp-39 during murine preterm birth. Altered expression of Par-2 in Brp-39(-/-) uteri suggests its potential role in attenuated preterm birth of Brp-39(-/-) mice.

Outcomes of transcatheter closure of ductus arteriosus in infants less than 6 months of age: a single-center experience.

PURPOSE: Transcatheter device closure of patent ductus arteriosus (PDA) is challenging in early infancy. We evaluated PDA closure in infants less than 6 months old. METHODS: We performed a retrospective review of infants less than 6 months of age who underwent attempted transcatheter device closure in our institution since 2004. To compare clinical outcomes between age groups, infants aged 6-12 months in the same study period were reviewed. RESULTS: A total of 22 patients underwent transcatheter PDA closure during the study period. Patient mean age was 3.3±1.5 months, and weight was 5.7±1.3 kg. The duct diameter at the narrowest point was 3.0±0.8 mm as measured by angiography. The most common duct type was C in the Krichenko classification. Procedural success was achieved in 19 patients (86.3%). Major complications occurred in 5 patients (22.7%), including device embolization (n=1), acquired aortic coarctation (n=2), access-related vascular injury requiring surgery (n=1), and acute deterioration requiring intubation during the procedure (n=1). Two patients had minor complications (9.1%). Twenty-four infants aged 6-12 months received transcatheter device closure. The procedural success rate was 100%, and there were no major complications. The major complication rate was significantly higher in the group less than 6 months of age (P=0.045). There was a trend toward increased major complication and procedural failure rates in the younger age group (P<0.01). CONCLUSION: A relatively higher incidence of major complications was observed in infants less than 6 months of age. The decision regarding treatment modality should be individualized.

Study of muscle contraction induced by electrical pulse stimulation and nitric oxide in C2C12 myotube cells.

PURPOSE: This study aimed to examine the independent effect of electrical pulse stimulation(EPS) and nitric oxide(NO) on muscle contraction and their synergistic or combined effect on contraction phenomenon using C2C12 mouse skeletal muscle cells. METHODS: Some differentiated C2C12 myotube cells were untreated (control). Other cells did not receive EPS and did receive 0.5, 1.0, or 2.0 mM of the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP; -E/S0.5, -E/S1.0, and -E/S2.0, respectively). For the EPS treatments (0.3 V/mm, 1.0 Hz, and 4.0 ms), differentiated C2C12 myotube cells received only EPS or both EPS and the SNAPtreatments at the same concentrations (+E/-S, +E/S0.5, +E/S1.0, and +E/S2.0, respectively). All samples were then cultured for 4 days. RESULTS: Differentiated C2C12 cellswere stimulated by the EPS, NO, and EPS+NO treatments. The cell length of the +E/S2.0 Group after the 4-day culture (84.2±13.2㎛) was the shortest of all the groups. The expressions of AMPK, JNK, Akt, eNOS, GLUT4, and PGC1α proteins were noticeably dominant. The results indicated synergistic effect on muscle contraction of simultaneously applied EPS and SNAP. CONCLUSION: Motor skills were significantly improved when exercise was accompanied by the intake of NO precursor and/or NO, compared to that upon their independent application or treatment.

Etiology and clinical characteristics of fever of unknown origin in children: a 15-year experience in a single center.

PURPOSE: Fever is one of the most common symptoms in children. In previous studies, infectious disease was the most common cause of pediatric fever of unknown origin (FUO). The aim of this study is to investigate the etiology, clinical characteristics and prognosis of pediatric FUO in 21 century with more diagnostics available and to analyze the factors for certain disease categories. METHODS: Among the children under 18 years old who were hospitalized at Samsung Medical Center from January 2000 to December 2014, the patients who met the criteria including fever of ≥38.0℃ for longer than ≥14 days and failure to reach a diagnosis after one week of investigations were included. RESULTS: Total 100 patients were identified. Confirmed diagnosis was achieved in 57 patients (57%). Among them, infectious diseases (n=19, 19%) were most common, followed by connective tissue diseases (n=15, 15%), necrotizing lymphadenitis (n=8, 8%), and malignancies (n=7, 7%). Children with fever duration over 28 days had a trend for higher frequency of connective tissue diseases (28.3%) except undiagnosed etiology. The symptoms such as arthritis, lymph node enlargement and only fever without other symptoms were significantly related with connective tissue diseases, necrotizing lymphadenitis and undiagnosed respectively (P<0.001). Ninety-two patients have become afebrile at discharge and 1 patient died (1%). CONCLUSION: Almost half of our patients were left without diagnosis. Although it has been known that infectious disease was most common cause of pediatric FUO in the past, undiagnosed portion of FUO have now increased due to development of diagnostic techniques for infectious diseases.

Differential immunophenotype of macrophages in acute and chronic chorioamnionitis.

AIM: The aim of this study was to investigate the involvement and immunophenotype of macrophages in acute chorioamnionitis (ACA) and chronic chorioamnionitis (CCA), marking amniotic fluid infection and anti-fetal rejection, respectively. METHODS: Chorioamniotic membranes from (1) gestational age-matched cases without chorioamnionitis, (2) cases with ACA, and (3) cases with CCA were studied after immunohistochemical staining using antibodies against CD14, CD68, CD163, and DC-SIGN. RESULTS: Macrophages increased prominently in the chorionic trophoblastic layer of both ACA and CCA cases in contrast to non-inflammatory cases. Macrophages in the decidua and the chorioamniotic membranes of ACA cases expressed CD14. Macrophages in the chorionic trophoblastic layer of CCA cases were characterized by CD68 positivity. DC-SIGN-positive cells were increased in the chorioamniotic mesodermal layer of CCA cases. CONCLUSIONS: Macrophages participate in the inflammatory response in ACA and CCA. The differential immunophenotypes of macrophages in the decidua and chorioamniotic membranes of ACA and CCA cases suggest their disease-specific and region-specific roles at the feto-maternal interface.