Purpose : Empirical antimicrobial treatment is indicated before bacteriological results are available for young children with febrile UTI to minimize renal scarring. To ensure appropriate therapy, knowledge of the prevalence of causative organisms and their susceptibility patterns to antimicrobials is mandatory. We performed a retrospective analysis investigating the local prevalence and resistance patterns of uropathogens, primarily E. coli, isolated from community-acquired UTIs. Methods : A total of 103 positive urine cultures from children with febrile UTI collected at Bundang CHA General Hospital from February 2004 to February 2005 were analyzed. Inclusion criteria were fever higher than $37.5^{\circ}C$, significant bacteriuria with single strain growth of at least 10s colony forming units/mL urine, and leukocyturia >5/HPF. Results : E. coli(89.3%) was the leading uropathogen followed by Enterococcus spp.(3.9%) Klebsiella spp.(2.9%), Citrobctcter spp.(1.9%) and Enterobacter spp.(1.9%). E. coli strains revealed a low proportion of antimicrobial susceptibility to ampicillin(AMP; 27.2%) ampicillinsulbactam(AMS; 34.8%) and trimethoprim-sulfamethoxazole(SXT; 65.2%). Susceptibility patterns to cephalosporins were as follows; cefazolin(1st generation; 91.3%), cefoxitin(2nd; 100%), ceftriaxone(3rd; 97.8%) and cefepime(4th; 97.8%). Three E. coli isolates produced ex tended - spectrum beta-lactamase(ESBL). Conclusion : Empirical treatment with AMP, AMS and SXT, which are commonly used in pediatric clinics, is not recommended for childhood UTI due to high incidence of resistance. The high level of susceptibility to cephalosporins makes these drugs reasonable alternatives. However the emergence of ESBL-producers, even though they are quite few, may have an impact on cephalosporin treatment in the future. (J Korean Soc Pediatr Nephrol 2006;10:18-26)
Purpose : Lipoprotein(a) is a genetically determined risk factor for atherosclerotic vascular disease and is elevated in patients with renal disease. Especially the patients with nephrotic syndrome exhibit excessively high Lp(a) plasma concentrations. Also the patients with end-stage renal disease have elevated Lp(a) levels. But the mechanism underlying this elevation is unclear. Thus, in this study, by measuring the level of serum Lp(a) in common renal diseases in children, we hoped to see whether there would be a change in Lp(a) in renal diseases other than nephrotic syndrome. Then, we figured out its implications, and looked for the factors that affect the Lp(a) concentrations. Methods : A total of 75 patients(34 patients with hematuria of unknown etiology, 10 with hematuria and hypercalciuria, 8 with IgA nephropathy, 8 with poststreptococcal glomerulone phritis, 3 with $Henoch-Sch\"{o}nlein$ nephritis, 7 with urinary tract infection, and 5 with or- thostatic proteinuria) were studied. The control group included 20 patients without renal and liver disease. Serum Lp(a), total protein, and albumin levels, 24-hour urine protein and calcium excretions, creatinine clearance and the number of RBCs and WBCs in the urinary sediment were evaluated. Data analysis was peformed using the Student t-test and a P-value less than 0.05 was considered to be statistically significant. Results : LP(a) was not correlated with 24-hour urine calcium and creatinine. Lp(a) level had a positive correlation with proteinuria and negative correlation with serum albumin and serum protein. Among the common renal diseases in children, Lp(a) was elevated only in orthostatic proteinuria (P<0.05). Conclusion : Lp(a) is correlated with proteinuria, serum protein, and serum albumin, but not with any kind of specific renal disease. Afterward, Lp(a) needs to be assessed in patients with orthostatic proteinuria and its possible role as a prognostic factor could be confirmed.
Journal of agricultural medicine and community health
/
v.47
no.3
/
pp.181-188
/
2022
Objectives: The prevalence of diabetes mellitus was approximately 16% in populations of over age 30 years, and deaths from diabetes mellitus became the sixth most prevalent cause of death by disease. To assess the relationship between HbA1c and heavy metal level in blood and urine, targeted residents were evaluated in a vast steel industrial complex. Methods: We selected 414 subjects for analysis after applying the following exclusion criterion: 18 persons with diabetes mellitus. They took part in a questionnaire survey and underwent blood and urinary assessments. HbA1c and lead (Pb) level were measured in blood and, cadmium (Cd), inorganic arsenic (iAs) and mercury (Hg) were evaluated in urine. Two subgroups were divided by HbA1c 6.5%. Each subgroup was divided by 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th and 90th percentile levels of biological exposure index of the heavy metals for logistic regression. Results: Odd ratios have a tendency to increase as they go from the 90th to the 10th percentile of cadmium. However, lead, arsenic and mercury did not have significant relationships with HbA1c. In correction of age, region, gender and smoking history, a higher distribution in the subgroup with cadmium above 0.8318 ㎍/g creatinine (30th percentile) was demonstrated in the subgroup with HbA1c levels above the 6.5%, with an odds ratio of 5.26 (95% C.I. ; 1.44~19.17). Conclusion: This study found a significant correlation between urinary levels of cadmium and HbA1c in correction of several factors. It is meaningful that this outcome may be used as a basis for a study to establish the acceptable limit of urinary cadmium in Korea.
Kim, Yoo-Mi;Lim, Han Hyuk;Gang, Mi Hyeon;Lee, Yong Wook;Kim, Sook Za;Kim, Gu-Hwan;Yoo, Han-Wook;Ko, Jung-Min;Chang, Meayoung
Journal of Genetic Medicine
/
v.16
no.2
/
pp.85-89
/
2019
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.
Kim, Yun-Ho;Park, Han-Kyul;Choi, Na-Rae;Kim, Seong-Won;Kim, Gyoo-Cheon;Hwang, Dae-Seok;Kim, Yong-Deok;Shin, Sang-Hun;Kim, Uk-Kyu
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.43
no.1
/
pp.16-22
/
2017
Objectives: Bisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ. Materials and Methods: Ninety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level. Results: BRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and 'responder group' and 'non-responder group,' but there was no significant difference with the 'worsened group.' In addition, the age of the patients was a relative factor with BRONJ stage. Conclusion: With older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment.
Geochemical characteristics, water quality, $NO_3{^-}$ contamination and the origin of $NO_3{^-}$ were analyzed for the groundwater located at Ogcheon, Korea. The water qualities were weakly acidic to weakly alkalic and redox potentials indicated reduction condition. Compared to granitic rocks, metamorphic sedimentary rocks with intercalations of limestones and dolomites tended to be more effectively dissolved, resulting in higher pH and higher concentrations of dissolved ingredients. Contamination of heavy metals was not revealed. Geochemical reactions of carbonate rocks and influxes of artificial contamination ingredients seemed to simultaneously determine the geochemical characteristics and water qualities in the study area. From the results of ${\delta}^{15}N$ isotope analysis, the origin of $NO_3{^-}$ was estimated to be influenced dominantly by agricultural activities and human feces and urine.
Bang, Jun Suck;Nam, Sang Jung;Lee, Kyung Hwa;Bae, Eun Joo;Park, Won-Il;Lee, Hyun Sook;Son, Bae Young;Choi, Hwan Suck;Lee, Hong Jin
Clinical and Experimental Pediatrics
/
v.49
no.3
/
pp.273-277
/
2006
Purpose : The prevalence of Reye syndrome has decreased since late 1980's. But we report that recently there were concentrative attacks of Reye syndrome after acute enteritis during the neonatal period. Methods : Clinical symptoms and laboratory results(quantitative organic acid analysis, routine chemistry, arterial blood gas analysis, serum ammonia) of seven patients admitted at the Samsung Medical Center, Sanggye Paik Hospital, Wonju Christian Hospital and Chuncheon Sacred Heart Hospital, referred from Jan. 2005 to Apr. 2005, were analysed retrospectively. The major clinical symptoms were derived from the patients' clinical records sended with urine samples and quantification of organic acids were done with gas chromatography and mass spectrometry. Results : The mean age of seven cases is 18 days and the major preceding symptoms were gastrointestinal symptoms(vomiting, diarrhea, refusal to feeding). The major clinical symptoms were clouded conciousness, repiratory difficulty, vomiting, seizures, and diarrhea. One patient died; that patient's serum ammonia was twenty times higher than normal. Conclusion : The seven patients were neonates. Reye syndrome has been known to be closely related with upper respiratory infections as a preceding disease and to internal use of aspirin, but in our study, the major preceding disease of the seven cases was gastrointestinal infection and none of these used aspirin.
Kim, Kyung-Ran;Kim, Jinsup;Huh, Rim;Park, Hyung-Doo;Cho, Sung Yoon;Jin, Dong-Kyu
Journal of The Korean Society of Inherited Metabolic disease
/
v.16
no.1
/
pp.47-51
/
2016
Propionic acidemia (PA) is an autosomal recessively inherited disorder of the organic acid metabolism. It is caused by a deficiency of propionyl-CoA carboxylase (PCC). PCC is a heteropolymeric enzyme composed of ${\alpha}$- and ${\beta}$-subunits. The clinical symptoms of PA are heterogeneous and present vomiting, dehydration, hypotonia, and lethargy, and it can result in death. The typical presentations of neonatal onset PA are life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of neonatal onset PA with mild clinical presentations. She was born to a healthy mother without complications. No significant illness was observed until nine days after birth. She started exhibiting poor oral feeding, vomiting, lethargy, and hypotonia at ten days old. Her laboratory results showed mild hyperammonemia and acidosis. The initial diagnosis was neonatal sepsis and she was treated with antibiotics. However, her clinical symptoms didn't improve. So we considered a metabolic disease. She was given nothing by mouth and intravenous hydration and nutrition support was performed. Propionylglycine and 3-hydroxypropionic acid were showed high concentrations in urine by gas chromatograph mass spectrometry (GC-MS). C3 level of acylcarnitine analysis elevated 10.4 uM/L (range, 0.200-5.00) in plasma. We took gene analysis for PA to be based on the symptoms and laboratory results. We detected PCCB gene mutation and diagnosed PA. She survived without severe neurologic defects and complications and was hospitalized only three times with upper respiratory tract infections for 7 years. We report a case of a ten days old neonate with PA presenting without severe metabolic acidosis and hyperammonemia who was effectively treated with early aggressive care and conventional methods.
Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.
Five dogs with renal failure were referred to the Veterinary Medical Teaching Hospital at Kangwon National University. These dogs had the common history of consumption of Pedigree dry dog food produced in Thailand plant for over 1 month. The dogs showed anorexia, emaciation, vomiting, and polydipsia/polyuria. And in one severely affected dog, bloody diarrhea and hypothermia were seen. The remarkable clinicopathological signs were high value of BUN and creatinine. In some dogs, GGT, phosphorus and lipase were increased. However, no significant changes of complete blood count were found. In urinalysis, hematuria, low specific gravity urine, proteinuria, and calcium oxalate-like crystals were observed. Two severely affected dogs were died. The remained dogs were recovered gradually after change of dog food and supportive therapy. Pathological findings were seen typically in kidneys. Renal atrophy, congestion of the glomerular capillary, and diffuse degeneration, necrosis, dystrophic calcification and regeneration in the tubular epithelium were seen. Yellowish brown fluorolucent laminated materials or particles were quite often found in the lumina of the necrotizing renal tubules of cortex and medulla. Proliferation of fibrous tissue in the interstitium was also seen. By the mycotoxin analysis of the Pedigree dry dog food, ochratoxin A (OTA) and citrinin were detected as much as the concentration of 372.8 ppb and 8.3 ppb, respectively. The final diagnosis of renal failure caused by OTA and citrinin toxicosis was made on the basis of history takings, clinical signs, clinicopathological and pathological findings, and analysis of mycotoxins.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.