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Effects of NG-monomethyl-L-arginine and L-arginine on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion after cerebral hypoxia-ischemia in newborn piglets (급성 저산소성 허혈성 뇌손상이 유발된 신생자돈에서 재산소-재관류기 동안 NG-monomethyl-L-arginine과 L-arginine이 뇌의 혈역학 및 에너지 대사에 미치는 영향)

  • Ko, Sun Young;Kang, Saem;Chang, Yun Sil;Park, Eun Ae;Park, Won Soon
    • Clinical and Experimental Pediatrics
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    • v.49 no.3
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    • pp.317-325
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    • 2006
  • Purpose : This study was carried out to elucidate the effects of nitric oxide synthase(NOS) inhibitor, NG-monomethyl-L-arginine(L-NMMA) and nitric oxide precursor, L-arginine(L-Arg) on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion(RR) after hypoxia-ischemia(HI) in newborn piglets. Methods : Twenty-eight newborn piglets were divided into 4 groups; Sham normal control(NC), experimental control(EC), L-NMMA(HI & RR with L-NMMA), and L-Arg(HI & RR with L-Arg) groups. HI was induced by occlusion of bilateral common carotid arteries and simultaneously breathing with 8 percent oxygen for 30 mins, and followed RR by release of carotid occlusion and normoxic ventilation for one hour. All groups were monitored with cerebral hemodynamics and cytochrome $aa_3$ (Cyt $aa_3$) using near infrared spectroscopy(NIRS). $Na^+$, $K^+$-ATPase activity, lipid peroxidation products, and tissue high energy phosphate levels were determined biochemically in the cerebral cortex. Results : In experimental groups, mean arterial blood pressure, $PaO_2$, and pH decreased, and base excess and blood lactate level increased after HI compared to NC group(P<0.05). These variables subsequently returned to baseline after RR except pH. There were no differences among the experimental groups. In NIRS, oxidized hemoglobin($HbO_2$) decreased and hemoglobin(Hb) increased during HI(P<0.05) but returned to base line immediately after RR; 40 min after RR, the $HbO_2$ had decreased significantly compared to NC group(P<0.05). Changes of Cyt $aa_3$ decreased significantly compared to NC after HI and recovered at the end of the experiment. Significantly reduced cerebral cortical cell membrane $Na^+$, $K^+$-ATPase activity and increased lipid peroxidation products(P<0.05) were not improved with L-NMMA or L-Arg. Conclusion : These findings suggest that NO is not involved in the mechanism of HI and RR brain damage during the early acute phase of RR.

A Phase I/II Trial of $DCVac/IR^{(R)}$ Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases (기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험)

  • Choi, Young-Min;Lee, Hyung-Sik;Kwon, Hyuk-Chan;Han, Sang-Young;Choi, Jong-Cheol;Chung, Ju-Seop;Kim, Chang-Won;Kim, Dong-Won;Kang, Chi-Duk
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.104-112
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    • 2008
  • Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

The Etiologies and Initial Antimicrobial Therapy Outcomes in One Tertiary Hospital ICU-admitted Patient with Severe Community-acquired Pneumonia (국내 한 3차 병원 중환자실에 입원한 중증지역획득폐렴 환자의 원인 미생물과 경험적 항균제 치료 성적의 고찰)

  • Lee, Jae Seung;Chung, Joo Won;Koh, Yunsuck;Lim, Chae-Man;Jung, Young Joo;Oh, Youn Mok;Shim, Tae Sun;Lee, Sang Do;Kim, Woo Sung;Kim, Dong-Soon;Kim, Won Dong;Hong, Sang-Bum
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.5
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    • pp.522-529
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    • 2005
  • Background : Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. Method : retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. Results : One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: ${\beta}$-lactam plus macrolide; ${\beta}$-lactam plus fluoroquinolone; anti-Pseudomonal ${\beta}$-lactam plus fluoroquinolone; Aminoglycoside combination regimen; ${\beta}$-lactam plus clindamycin; and ${\beta}$-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. Conclusion : S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.

Global Charity Operations of Cleft Lip and Palate by Korean Cleft Lip and Palate Association ; Charity Operations in Kenya, east Africa (대한구순구개열학회의 글로벌 자선 수술 활동 : 케냐에서의 자선 수술 활동)

  • Choung, Pill-Hoon;Park, Joo-Young;Park, Joo-Young;Ahn, Kang-Min;Baek, Jin-Woo;Cho, Il-Hwan;Choi, Cheol-Min;Choi, Seon-Hyu;Chung, Il-Hyuk;Gao, En-Feng;Hong, Jong-Rak;Hyun, Seung-Don;Jang, Hyon-Seok;Jun, Sang-Ho;Jung, Sung-Uk;Kang, Na-Ra;Kang, Young-Ho;Kim, Byung-Ryul;Kim, Dong-Hyun;Kim, Eun-Seok;Kim, Ho-Sung;Kim, In-Soo;Kim, Ji-Hyuck;Kim, Jong-Ryoul;Kim, Joong-Min;Kim, Myung-Jin;Kim, Soung-Min;Ko, Bong-Hwa;Koh, Sung-Hee;Lee, Bu-Kyu;Lee, Eui-Seok;Lee, Jong-Ho;Lee, Ui-Lyong;Lee, Won;Lee, Won-Deok;Min, Byong-Il;Nam, Il-Woo;Paeng, Jun-Young;Park, Jong-Chul;Park, Jung-Seok;Park, Sung-Hee;Park, Young-Wook;Pyo, Sung-Woon;Rim, Chae-Hong;Rim, Jae-Suk;Seo, Byoung-Moo;Suh, Je-Duck;Yoon, Jeong-Ho;Yoon, Jung-Ju;Yun, Hyung-Jin
    • Korean Journal of Cleft Lip And Palate
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    • v.9 no.2
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    • pp.85-92
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    • 2006
  • Korean Cleft Lip and Palate Association (KCLPA) was founded in 1996. The first overseas charity operation was in Karachi, Pakistan, 2002 and our association has visited fourteen times in six countries for the free cleft surgery: Pakistan, Egypt, Kenya, Morocco, Jordan and Vietnam. The cumulated number of operated patients reaches to 280. Before our association, many Korean oral and maxillofacial surgeons have performed charity operations individually since 1964. It was started from Vietnam but the activity is now carried on in Africa, middle-east Asia, south-east Asia, China, and Korea as an official team. LG electronics, a Korean company helped to propagate our team's activity to middle-east Asia to Africa. This paper is a report concerning about the results of our association's charity activities especially in Kenya, east Africa. We provided free cleft surgery for 30 patients in 2004 and 27 patients in 2005, in Nairobi. As the blood test for HIV of the cleft patients was not allowed before and during surgery, our surgeons and nurses were cautious about every movement during the surgeries. Thus the operation time for each patient was longer than any other time. The attitude of the local hospital and the doctors seemed to be accustomed to this situation. They helped us in case of needle injuries. Safety of medical staff and patients is more important than the number of the patients operated in charity operation. This belief should be approached being parallel and multidisciplinary as an international cooperation, focusing on international funding for medical support and continuous education for local doctors who are willing to devote to their people.

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The Role of Protein Kinase C in Acute Lung Injury Induced by Endotoxin (내독소에 의한 급성폐손상에서 Protein Kinase C의 역할)

  • Kim, Yong-Hoon;Moon, Seung-Hyug;Kee, Sin-Young;Ju, Jae-Hak;Park, Tae-Eung;Im, Keon-Il;Cheong, Seung-Whan;Kim, Hyeon-Tae;Park, Choon-Sik;Jin, Byung-Won
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.349-359
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    • 1997
  • Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.

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The Landscape Configuration and Semantic Landscape of Hamheo-pavilion in Gokseong (곡성 함허정(涵虛亭)의 경관짜임과 의미경관)

  • Lee, Hyun-Woo;Sim, Woo-Kyung;Rho, Jae-Hyun;Shin, Sang-Sup
    • Journal of the Korean Institute of Traditional Landscape Architecture
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    • v.33 no.1
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    • pp.52-64
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    • 2015
  • This research traced the characteristics of the semantic landscape, construction intent, landscape composition, and geomantic conditions of the area subject to the research based on the research methods of 'field investigation, document studies, and interviews,' centering around the entire area of Gokseong Hamheo-pavilion (Jeonnam Tangible Cultural Assets No. 160). The result of the research, specifically revealing the forms and methods by which the reciprocal view of nature and landscape composition appearing in the landscape of the entire area of Hamheo-pavilion, as part of the analysis and interpretation over the view-based construction characteristics and position of the entire area of Gokseong Hamheo-pavilion, can be summarized as follows. First, Hamheo-pavilion is a pavilion built as a resting area and as a venue for educational activities in 1543 in the nearby areas after Gwang-hyeon Sim founded Gunjichon-jeongsa for educational activities and dwelling purposes at Gunchon at the 30th year of King Jungjong. Gunchon, where Hamheo-pavilion and Gunjichon-jeongsa is located, exhibits the typical form having water in the front, facing Sunja-river(present Seomjin-river), and a mountain in the back side. Dongak-mountain, which is a guardian mountain, is in a snail-type form where cows leisurely ruminate and lie on the riverside, and the Hamheo-pavilion area is said to be an area bordering on one's way of enjoying peace and richness as it is a place with plentiful grass bushes available for cows to ruminate and lie down while sheppards may leisurely play their flutes at the riverside. The back hill of Hamheo-pavilion is a blood vessel that enters the water into the underwater palace of the turtle, and the building sitting on the turtle's back is Hamheo-pavilion, and the Guam-jodae(龜巖釣臺) and lava on the southern side below the cliff can be interpreted to be the underwater fairly land wanted by the turtle.6) Second, Hamheo-pavilion is the scenery viewpoint of Sungang-Cheongpung (3rd Scenery) and Seolsan-Nakjo(雪山落照, 9th Scenery) among the eight sceneries of Gokseong, while also the scenery viewpoint of Hamheo-Sunja(2nd Scenery) and Cheonma-Gwiam(天馬歸岩, 3rd Scenery) among the eight sceneries of Ipmyeon. On the other hand, the pavilion is reproduced through the aesthetics of bends through sensible penetration and transcendental landscape viewed based on the Confucian-topos and ethics as the four bends among the five bends of Sunja-river arranged in the 'Santaegeuk(山太極) and Sutaeguek(水太極, formation of the yin-yang symbol by the mountain and water)' form, which is alike the connection of yin and yang. In particular, when based on the description over Mujinjeong (3rd Bend), Hoyeonjeong(4th Bend), andHapgangjeong(2nd Bend) among the five bends of Sunja-river in the records of Bibyeonsainbangan-jido(duringthe 18th century) and Okgwahyeonji(1788), the scenery of the five bends of Sunja-river allow to glimpse into its reputation as an attraction-type connected scenery in the latter period of the Joseon era, instead of only being perceived of its place identity embracing the fairyland world by crossing in and out of the world of this world and nirvana. Third, Hamheo-pavilion, which exhibits exquisite aesthetics of vacancy, is where the 'forest landscape composed of old big trees such as oak trees, oriental oak trees, and pine trees,' 'rock landscape such as Guam-jodae, lava, and layered rocks' and 'cultural landscape of Gunchon village' is spread close by. In the middle, it has a mountain scenery composed of Sunja-river, Masan-peak, and Gori-peak, and it is a place where the scenery by Gori-peak, Masan-peak, Mudeung-mountain, and Seol-mountain is spread and open in $180^{\circ}$ from the east to west. Mangseo-jae, the sarangchae (men's room)of Gunjichon-jeongsa, means a 'house observing Seoseok-mountain,' which has realized the diverse view-oriented intent, such as by allowing to look up Seol-mountain or Mudeung-mountain, which are back mountains behind the front mountain, through landscape configuration. Fourth, the private home, place for educational activities, pavilion, memorial room, and graveyard of Gunji-village, where the existence and ideal is connected, is a semantic connected scenery relating to the life cycle of the gentry linking 'formation - abundance - transcendence - regression.' In particular, based on the fact that the descriptions over reciprocal views of nature regarding an easy and comfortable life and appreciations for a picturesque scene of the areas nearby Sunja-river composes most of the poetic phrases relating to Hamheo-pavilion, it can be known that Hamheo-pavilion is expressed as the key to the idea of 'understanding how to be satisfied while maintaining one's positon with a comfortable mind' and 'returning to nature,' while also being expressed of its pedantic character as a place for reclusion for training one's mind and training others through metaphysical semantic scenery.

Pre-operative Concurrent Chemoradiotherapy for Stage IlIA (N2) Non-Small Cell Lung Cancer (N2 병기 비소세포 폐암의 수술 전 동시화학방사선요법)

  • Lee, Kyu-Chan;Ahn, Yong-Chan;Park, Keunchil;Kim, Kwhan-Mien;Kim, Jhin-Gook;Shim, Young-Mog;Lim, Do-Hoon;Kim, Moon-Kyung;Shin, Kyung-Hwan;Kim, Dae-Yong;Huh, Seung-Jae;Rhee, Chong-Heon;Lee, Kyung-Soo
    • Radiation Oncology Journal
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    • v.17 no.2
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    • pp.100-107
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    • 1999
  • Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.

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