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Early gonadotropin-releasing hormone antagonist protocol in women with polycystic ovary syndrome: A preliminary randomized trial

  • Shin, Jae Jun;Park, Kyung Eui;Choi, Young Min;Kim, Hye-Ok;Choi, Dong-Hee;Lee, Woo Sik;Cho, Jung-Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.45 no.3
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    • pp.135-142
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    • 2018
  • Objective: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods: Randomized patients in all three groups (early antagonist, n = 14; conventional antagonist, n = 11; long agonist, n = 11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. Results: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p= 0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p= 0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p= 0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p= 0.324). Conclusion: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.

Modalities in managing postherpetic neuralgia

  • Shrestha, Meera;Chen, Aijun
    • The Korean Journal of Pain
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    • v.31 no.4
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    • pp.235-243
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    • 2018
  • Postherpetic neuralgia (PHN) is the most troublesome side effect of Herpes Zoster (HZ), which mainly affects the elderly and immunocompromised populations. Despite the current advancement of treatments, PHN persists in many individuals influencing their daily activities and reducing their quality of life. Anticonvulsants, antidepressants, topical therapies including lidocaine and capsaicin, and opioids, are the most widely used therapies for the treatment of PHN. These medications come with their adverse effects, so they should be used carefully with the elderly or with patients with significant comorbidities. Other measures like botulinum toxin, nerve blocks, spinal cord stimulation, and radiofrequency have also contributed significantly to the management of PHN. However, the efficacy, safety, and tolerability of these invasive methods need to be carefully monitored when administering them. Early diagnosis and early initiation of treatment can reduce the burden associated with PHN. The zoster vaccine has effectively reduced the incidence of HZ and PHN. In this article, we discuss the treatment options available for the management of PHN, mainly focusing on the efficacy and safety of different therapeutic modalities.

The Early Induction of Suppressor of Cytokine Signaling 1 and the Downregulation of Toll-like Receptors 7 and 9 Induce Tolerance in Costimulated Macrophages

  • Lee, Hyo-Ji;Kim, Keun-Cheol;Han, Jeong A;Choi, Sun Shim;Jung, Yu-Jin
    • Molecules and Cells
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    • v.38 no.1
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    • pp.26-32
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    • 2015
  • Toll-like receptors (TLR) 7 and 9 transduce a cellular signal through the MyD88-dependent pathway and induce the production of inflammatory mediators against microbial nucleotide components. The repeated stimulation of TLR4 leads to endotoxin tolerance, but the molecular mechanisms of tolerance induced through the costimulation of individual TLR has not yet been established, although endosomal TLRs share signaling pathways with TLR4. In the present study, mouse macrophages were simultaneously stimulated with the TLR7 agonist, gardiquimod (GDQ), and the TLR9 agonist, CpG ODN 1826, to examine the mechanism and effector functions of macrophage tolerance. Compared with individual stimulation, the costimulation of both TLRs reduced the secretion of TNF-α and IL-6 through the delayed activation of the NF-κB pathway; notably, IL-10 remained unchanged in costimulated macrophages. This tolerance reflected the early induction of suppressor of cytokine signaling-1 (SOCS-1), according to the detection of elevated TNF-α secretion and restored NF-κB signaling in response to the siRNA-mediated abrogation of SOCS-1 signaling. In addition, the restimulation of each TLRs using the same ligand significantly reduced the expression of both TLRs in endosomes. These findings revealed that the costimulation of TLR7 and TLR9 induced macrophage tolerance via SOCS-1, and the restimulation of each receptor or both TLR7 and TLR9 downregulated TLR expression through a negative feedback mechanisms that protects the host from excessive inflammatory responses. Moreover, the insufficient and impaired immune response in chronic viral infection might also reflect the repeated and simultaneous stimulation of those endosomal TLRs.

Early Linguistic Developments of Simultaneous Bilateral Cochlear Implantees (양이 동시 인공와우 사용자의 조기 언어발달)

  • Suh, Michelle J.;Lee, Hyun-Jin;Choi, Hyun Seung
    • Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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    • v.61 no.12
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    • pp.650-657
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    • 2018
  • Background and Objectives The present study aimed to compare receptive and expressive language development in children who have undergone simultaneous bilateral cochlear implantation (SCI) and those who have undergone bimodal stimulation (unilateral CI+ hearing aid). Subjects and Method In a retrospective analysis of clinical data, 15 pediatric patients who have received SCI and nine patients who have received bimodal stimulation (BM group) were enrolled. CI was performed for all patients at 24 months of age. Category of Auditory Performance (CAP) scores, Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) scores, and developmental quotients (DQ) for expressive and receptive language were compared between the groups at 12 month of follow-up. The Percentage of Consonants Correct (PCC) of children evaluated at 4 years old was also compared. Results At 12 months of follow-up, significantly greater improvements in CAP scores (Δ4.25±0.5) were noted in the SCI group compared to the BM group (Δ3.56±0.88, p=0.041). Significantly greater improvements in IT-MAIS scores were also noted in the SCI group (Δ36.17±4.09) than in the BM group (Δ30.17±2.91, p=0.004). The DQ of receptive language was higher in the SCI group than in the BM group (87.6±15.4 vs. 75.5±12.0, p=0.023) at 12 months of follow-up. Moreover, early SCI was associated with better receptive language skills. PCC index of children at 4 years old was higher in the SCI group than in the BM group (88.5±13.2 vs. 62±15.8, p=0.014). Earlier SCI was associated with even greater improvements. Conclusion Bilateral SCI is associated with significant improvements in language development when compared with bimodal stimulation. Earlier SCI was associated with better outcomes.

Clinical Application of AR System in Early Rehabilitation Program After Stroke: 2 Case Study

  • An, Chang Man;Kim, Dae Hyun
    • The Journal of Korean Physical Therapy
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    • v.31 no.3
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    • pp.141-146
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    • 2019
  • Purpose: To investigate the effect of an augmented reality (AR) system on muscle strength and function level of the paretic lower limb and the balance ability in the early rehabilitation program of acute stroke patients. Methods: The participants (30 or fewer days after stroke) were randomly assigned to receive intervention with an early rehabilitation program using an AR system (n=1) or an early rehabilitation program consisting of functional electrical stimulation and tilt table use (n=1). Patients in both subjects received interventions 4-5 times a week for 3 weeks. Results: In the paretic limb muscle strength, AR subject was increased from 15 to 39.6 Nm and Control subject was increased from 5 to 30.2 Nm. The paretic limb function of AR subject motor function was increased from 8 to 28 score and Control subject motor function was increased from 6 to 14 score. But sensory function was very little difference between the two subjects (AR subject: from 4 to 10 score, Control subject: from 3 to 10 score). In the balance ability, AR subject had more difference after intervention than control subject (AR subject: 33 score, Control subject: 22 score). Conclusion: The early rehabilitation program using the AR system showed a slightly higher improvement in the motor function of the paretic lower limb and balance ability measurement than the general early rehabilitation program. The AR system, which can provide more active, task-oriented, and motivational environment, may provide a meaningful environment for the initial rehabilitation process after stroke.

Interleukin-8 and MCP(Monocyte Chemoattractant Protein)-1 expression by the Human Dental Pulps in cultures stimulated with Substance P (사람치수에서 Interleukin-8과 Monocyte chernoattractant protein-1의 분비에 대한 Substance P의 효과에 관한 연구)

  • Shin, Han-Ju;Park, Sang-Hyuk;Choi, Gi-Woon
    • Restorative Dentistry and Endodontics
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    • v.30 no.3
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    • pp.193-203
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    • 2005
  • The induction of the IL-8 and MCP-1 by the stimulation of Substance P and TNF-α (IL-8 agonist) and the specificity for SP using Spantide (SP antagonist) in the dental pulp tissues was measured quantitatively. In addition, the secretion of the IL-8 in the human dental pulp tissue 36 hrs after the stimulation of SP was observed after the stimulation of SP qualitatively. According to this study the results were as follows: 1. There was the significant IL-8 induction at 36 h after SP (104M) stimulation of the pulp tissue comparing with the unstimulated dental pulp tissues (p < 0.05) . IL-8 irnmunostaining was weakly detected along the periphery of the pulp tissue after Mock stimulation and IL-8 immunostaining was detected around the fibroblast in the pulp tissue 36h After SP (104M) stimulation, 2. The secretion of MCP-1 from the dental pulp tissues comparing with Mock stimulation was induced at 36 hrs after TNF-α (40 ng/ml) stimulation, but no induction with SP(104M) TNF-α (40 ng/ml) did not induce the IL-8 secretion from the pulp tissue, weak IL-8 imrnunostaining was detected along the periphery of the pulp tissue 3. Spantide (105M) inhibited IL-8 induction from the pulp tissues 36 h after SP (104M) stimulation These results suggest that SP significantly induces IL-8 recruiting neutrophils in localized human dental pulp tissue MCP-1 appears to be less involved in the early establishment of pulpal inflammation in response to irritation such as mechanical insult of dentin. SP may have positive relation with the inflammation of the human dental pulp tissues.

The Effects of Presented Media Types on Spatial Cognition Task Performance in Preschool Children

  • Kim, Bokyung;Pack, Yun Hyun;Yi, Soon Hyung
    • Child Studies in Asia-Pacific Contexts
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    • v.7 no.1
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    • pp.27-38
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    • 2017
  • As the use of digital media is becoming more universal and is being used in early-childhood education, understanding the effects of digital media on development is required. The purpose of this study was to examine whether child performance on a spatial cognition task depends on the type of media used to present the task and if the effect of media type is different depending on child's age and sex. To do this, a spatial cognition task set (consisting of direction, rotation, symmetry, conjugation, and part/whole tasks) was prepared, and these tasks were presented to 60 3-, 4-, and 5-year-old children using paper- and tablet-based measures. Our results showed that the correct answer rate of task performance differed significantly when completing the task on a tablet than when completing the task on paper. Generally, response times when completing the tasks on a tablet was significantly shorter than when completing the tasks on paper. Although there was no interaction between the type of media and age, and partial interaction was found between the type of media and sex. This result implies an influence of digital stimulation on child performance on the spatial cognitive task. This study provides a basic understanding for follow-up studies to examine the consequences of exposure to digital stimulation.

A Ser/Thr Specific Protein Kinase Activates the Mouse Rantes Gene after Lipolpolysaccharide STimulation

  • Kim, Youn-Uck;Kim, Youn-Hwoan;An, Duek -Jun;Kwon, Hyuk-Chu
    • Journal of Microbiology
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    • v.39 no.4
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    • pp.314-320
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    • 2001
  • Macrophages stimulated by lipopolysaccharide(LPS) from gram negative bacteria undergo activation of a group of immediate early genes including Rantes. The mouse Rantes gene promoter region contains an LPS rsponsive element(LPE) We detected 3 specific bands termed B1, B2 and 3 formed by the interaction of the LPE and proteins found in LPS-stimulated RAW 367.7 cells. An additional band B4 was determined to be an Ap-1 binding protein. The B1 band appears within 1 hour of LPS nuclear extracts from LPS-stimulation, and this protein kinase enhances B1 and formation. The B1 band can be converted to band B2/B3 by adding specific heparin column fraction purified Ser/Thr specific protein phosphatases PP-1 and PP-2A can stimulate the same conversion to about the same extent. Thus, the formation of the LRE sequence binding complex appears to be regulated by Ser/Thr protein kinase and one or more Ser/Thr specific phosphatases. At least four proteins are involved in the trgulation of the LRE-dependent Rants experssion: two binding factors that bind directly to the target sequences. and two factors that control their binding. The future purification and characterization of these binding pro-teins will reveal in detail the mechanism of Rantes gene activation after LPS stimulation.

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MAP Kinase Activation is Required for the MMP-9 Induction by TNF-Stimulation

  • Kim, Kyung-Chan;Lee, Chu-Hee
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1257-1262
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    • 2005
  • MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-α stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-α stimulation. To investigate the signaling pathway underlined in TNF-α induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-α treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-α. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-α induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-α. Taken together, we found that TNF-α stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.