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Shin-Woo Ha,1,2,* Kihwan Hwang,3,* Jun Jin,3 Ae-Sin Cho,1 Tae Yoon Kim,1,2 Sung Il Hwang,1 Hak Jong Lee,1–2,4–5 Chae-Yong Kim3,61Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 2Research Institute, IMGT Co., Ltd, Seongnam, 13605, South Korea; 3Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam-si, South Korea; 4Department of Nanoconvergence, Seoul National University Graduate School of Convergence Science and Technology, Seoul, South Korea; 5Research Strategy and Management Division and Medical Device R&D Center, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 6Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea*These authors contributed equally to this workBackground: Crossing the blood–brain barrier (BBB) is crucial for drug delivery to the brain and for treatment of brain tumors, such as glioblastoma, the most common of all primary malignant brain tumors. Microbubble (MB) is oscillated and destroyed by controlling ultrasound (US) parameters. This oscillation and destruction of MB can open the BBB transiently, and a drug can be delivered to the brain.Materials and methods: For testing the efficiency of delivery to the brain, we synthesized a US-sensitizing nanoparticle (NP) complex via chemically binding MBs and NPs for the BBB opening, including near-infrared dye-incorporated albumin nanoparticles (NIR-Alb NPs) for fluorescence detection.Results: The human-derived, biocompatible NIR-Alb NPs did not show significant cytotoxicity to 500 μg/mL for 3 days in four human glioma cell lines. In an in vivo animal study, some US parameters were investigated to determine optimal conditions. The optimized US conditions were applied in a U87MG orthotopic mouse model. We found that the fluorescence intensity in the brain was 1.5 times higher than in the control group.Conclusion: Our US-sensitizing NP complex and US technique could become one of the critical technologies for drug delivery to the brain.Keywords: blood–brain barrier, ultrasound, nanoparticle, microbubble, complex, drug delivery

Transient tachypnea of the newborn (TTN) is a clinical syndrome associated with respiratory distress usually seen shortly after delivery in infants. This study aims to determine the risk factors predicting treatment outcomes in infants with TTN.Data from 236 infants diagnosed with TTN during the study period were evaluated retrospectively. Logistic regression analyses were performed to select significant risk factor for prognosis (prolonged oxygen therapy, application of mechanical ventilator, and prolonged hospital stay) of TTN among components of clinical variables.Of the 236 TTN infants, 111 (47.0%) infants were delivered via cesarean section (CS) without labor, 29 (12.3%) infants were delivered via CS with labor, and 96 (40.7%) were delivered via vaginal birth. Lower Apgar score at 1 min (OR: 3.03; 95%CI: 1.25-7.36) and lower umbilical artery pH (OR: 4.00; 95%CI 1.55-10.49) were associated with a significantly increased risk for mechanical ventilator care. Also, late-preterm delivery (OR: 4.70; 95%CI: 2.11-10.49) was independently associated with risk of prolonged duration of hospital stay.Late-preterm delivery, lower initial umbilical artery pH (7.25), and lower Apgar score at 1 min were independently associated with poor prognostic treatment outcomes in infants with TTN.

Purpose:The aim of this study is to explore the effect of the Toll-like receptor 9 (TLR9) expressed in plasmacytoid dendritic cells (pDCs) that respond to antigen to Th2 immune deviation in allergic patients. Methods:Subjects consisted of 19 allergic patients and 17 healthy volunteers. Skin prick tests and nasal provocation tests were performed for the two groups. Peripheral blood mononuclear cells (PBMCs) were collected from subjects and analyzed for the Lineage Cocktail (CD3, CD14, CD16, CD19, CD20, CD56) (-), HLA-DR (+), and CD123 (+) using flow cytometry. In addition, we analyzed TLR9 mRNA by reverse transcriptase-polymerase chain reaction. The level of interferon (IFN) of the PBMCs following stimulation with the TLR9 ligand CpG-ODN 2216 was also evaluated. Results:Analyses of CD123 (+) revealed a nearly similar distribution for the classical pDC markers in the allergic group (0.1%0.04%) and in the controls (0.25%0.23%). The mRNA levels of TLR9 on PBMCs were not different between the allergic group and the controls (1.290.41 vs. 1.250.23, respectively). Additionally, the level of IFN in PBMCs exposed to stimuli of the TLR9 ligand CpG-ODN 2216 was not significantly different between the two groups (911829 vs. 1,095 888 pg/mL, respectively). Conclusion:We found no evidence that TLR9-dependent immune responses in human pDCs are associated with allergic status.