The celiac and mesenteric arterial system including the left gastric, splenic, common hepatic, and superior mesenteric arteries shows various types of origins, courses, ramifications and anastomoses. In order to explain the various expressions of this system, we have proposed a typological model, in which celiacomesenteric arteries develop as paired or bilaterally symmetrical primordial vessels originated from the anterior aspect of the aorta, and these vessels anastomose each other with longitudinal and horizontal pathways. Here, we report 3 unusual cases characterized by arterial rings, formed by the left gastric, left accessory hepatic, proper hepatic, anterior pancreaticoduodenal, and dorsal pancreatic arteries. The dorsal pancreatic and anterior pancreaticoduodenal arteries are located to the right and left of the embryonic pancreas developing in the dorsal mesentery, respectively. Such hepatopancreatic arterial rings simultaneously containing right and left elements can only be explained using our typological model, in which the concept of paired arteries or bilateral symmetry is introduced.
en-copyright= kn-copyright= en-aut-name=KosakaMotohiro en-aut-sei=Kosaka en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HoriuchiKanji en-aut-sei=Horiuchi en-aut-mei=Kanji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaguchiTakehito en-aut-sei=Taguchi en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiTakuro en-aut-sei=Murakami en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University en-keyword=arterial variation kn-keyword=arterial variation en-keyword=celiac trunk kn-keyword=celiac trunk en-keyword=superior mesenteric artery kn-keyword=superior mesenteric artery en-keyword=typology kn-keyword=typology en-keyword=bilateral symmetry kn-keyword=bilateral symmetry END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=267 end-page=269 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anterior intercostobrachial nerve penetrating the pectoralis minor or major muscle. en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two previously unknown anomalies of the anterior intercostobrachial nerve were described. In one case, the anterior intercostobrachial nerve penetrated the pectoralis minor muscle. In the other case, it penetrated the pectoralis major muscle. In both cases, the anomalous nerve supplied the skin of the upper arm.
en-copyright= kn-copyright= en-aut-name=MurakamiShinichiro en-aut-sei=Murakami en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MurakamiTakuro en-aut-sei=Murakami en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University en-keyword=anomalies of intercostobrachial nerve kn-keyword=anomalies of intercostobrachial nerve en-keyword=lateral cutaneous branch of the second intercostal nerve kn-keyword=lateral cutaneous branch of the second intercostal nerve en-keyword=pectoralis minor muscle kn-keyword=pectoralis minor muscle en-keyword=pectoralis major muscle kn-keyword=pectoralis major muscle END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=219 end-page=222 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feasibility and limitations of acridine orange fluorescence technique using a Malaria Diagnosis Microscope in Myanmar. en-subtitle= kn-subtitle= en-abstract= kn-abstract=We studied parasite detectability in thick films by an acridine orange fluorescence technique (AO) to test its applicability and the use of a Malaria Diagnosis Microscope (MDM)-ESL in the detection of parasites, compared to the conventional Giemsa staining method. This study was conducted on 1,390 clinically suspected malaria cases of Thaton township, Myanmar. We found sensitivities of 82.8% for Plasmodium falciparum (P. falciparum) and 100% for Plasmodium vivax (P. vivax) and specificities of 97.1% for P. falciparum and 98.6% for P. vivax. AO had a higher sensitivity than Giemsa-stained films at low levels of parasitemia (< 1,000/microl). AO showed lower sensitivity and higher specificity than the Giemsa method at parasite levels of more than 1,000/microl. The results of using the AO method, achieved by both novice and experienced observers, showed no significant difference and required less practice to perform the test as well as to identify the parasite. The acridine orange fluorescence technique using a malaria diagnosis microscope MDM-ESL series is simple, rapid and cost effective. The microscope is conveniently operable using standard AC power or a 12-V DC car battery, and it is easily convertible to a conventional biological microscope. With the exception of species differentiation, which is not possible with this method, this method would be appropriate for both clinical and epidemiological studies.
en-copyright= kn-copyright= en-aut-name=HtutYe en-aut-sei=Htut en-aut-mei=Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AyeKyin Hla en-aut-sei=Aye en-aut-mei=Kyin Hla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HanKay Thwe en-aut-sei=Han en-aut-mei=Kay Thwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyawMyat Phone en-aut-sei=Kyaw en-aut-mei=Myat Phone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimonoKunio en-aut-sei=Shimono en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaShigeru en-aut-sei=Okada en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Medical Research, Lower Myanmar, Yongon, Myanmar affil-num=2 en-affil= kn-affil=Medical Research, Lower Myanmar, Yangon, Myanmar affil-num=3 en-affil= kn-affil= Medical Research, Lower Myanmar, Yangon, Myanmar affil-num=4 en-affil= kn-affil=Lower Myanmar affil-num=5 en-affil= kn-affil=Shimono Hospital affil-num=6 en-affil= kn-affil=Okayama University en-keyword=malaria diagnosis kn-keyword=malaria diagnosis en-keyword=acridine orange kn-keyword=acridine orange en-keyword=fluorescence kn-keyword=fluorescence en-keyword=plasmodium kn-keyword=plasmodium END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=237 end-page=243 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diabetic gastroparesis in association with autonomic neuropathy and microvasculopathy. en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastroparesis is a frequent and sometimes life-threatening complication of diabetes mellitus. Autonomic neuropathy seems to be one of the most important mechanisms underlying this entity, together with the other probable pathologies. The present study was performed in order to identify an alternative to gastric scintigraphy as a screening test. The gastric emptying times of 60 subjects (Group 1: 20 insulin-dependent patients, Group 2: 20 non-insulin-dependent diabetes mellitus patients, and Group 3: 20 healthy volunteers) were monitored by gastric scintigraphy. Perception thresholds for cold, heat, and vibration were tested by a quantitative sensory test, and QTc dispersions were calculated from standard electrocardiography recordings. In addition, fasting blood glucose, hemoglobin A1c and urine beta2-microglobulin and microalbumin concentrations were determined for the patient groups. Funduscopic examination was performed by an independent ophthalmologist. Gastroparesis was determined in both patient groups, regardless of fasting blood glucose and hemoglobin A1c concentrations. A strong correlation was observed between nephropathy, retinopathy, and cardiac autonomic denervation (QTc) and gastroparesis. In conclusion, retinal and renal microvasculopathy parameters and cardiac autonomic function tests may be useful for screening diabetic patients for gastroparesis.
en-copyright= kn-copyright= en-aut-name=KockarM. Cem en-aut-sei=Kockar en-aut-mei=M. Cem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KayahanI. Kaan en-aut-sei=Kayahan en-aut-mei=I. Kaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BavbekNuket en-aut-sei=Bavbek en-aut-mei=Nuket kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Fatih University, Turkey affil-num=2 en-affil= kn-affil=Guven Hospital affil-num=3 en-affil= kn-affil=Fatih University en-keyword=diabetic gastroparesis kn-keyword=diabetic gastroparesis en-keyword=microvasculopathy kn-keyword=microvasculopathy en-keyword=autonomic neuropathy kn-keyword=autonomic neuropathy END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=229 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of a method for typing the microsatellite D12S391 locus using a new primer pair and capillary electrophoresis. en-subtitle= kn-subtitle= en-abstract= kn-abstract=We describe a modified method for typing a polymorphic microsatellite D12S391 locus by PCR using a newly designed primer pair. This primer pair produces shorter D12S391 amplified fragments (104-156 bp) than the primer pair originally described by Lareu et al. (209-261 bp). The detection system for the D12S391 locus using the new primer pair and capillary electrophoresis (CE) analysis was evaluated using various forensic samples. The typing results from 70 DNA samples using the new primer pair and the original primer pair were completely identical. One hundred twenty-five amplified fragments from D12S391 alleles were sized correctly within +/- 0.25 bp of the D12S391 allelic ladder. A rare allele, 19.3, previously found only in Caucasians, was found for the first time in a Japanese subject, and it was clearly distinguished from allele 20 by the CE analysis. This detection system was sensitive and could detect D12S391 types from 16 pg of genomic DNA, and from a minor component at a ratio of 1:10 in mixed samples. This system was more useful for the analysis of degraded DNA than was the method using the original primer pair, and could detect D12S391 types from bloodstains that had been stored for 26 years. In addition, the specificity of the method was demonstrated using nonhuman DNA.
en-copyright= kn-copyright= en-aut-name=ShigetaYoshiaki en-aut-sei=Shigeta en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoYuji en-aut-sei=Yamamoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DoiYusuke en-aut-sei=Doi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyaishiSatoru en-aut-sei=Miyaishi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshizuHideo en-aut-sei=Ishizu en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=short tandem repeats kn-keyword=short tandem repeats en-keyword=D12S391 kn-keyword=D12S391 en-keyword=forensic application kn-keyword=forensic application en-keyword=capillary electrophoresis kn-keyword=capillary electrophoresis END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=223 end-page=227 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells. en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that anthracyclines, which could generate reactive oxygen species (ROS), could induce the urokinase-type plasminogen activator (uPA) gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC) cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT) and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.
en-copyright= kn-copyright= en-aut-name=ShibakuraMisako en-aut-sei=Shibakura en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NiiyaKenji en-aut-sei=Niiya en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KiguchiToru en-aut-sei=Kiguchi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakataYasunari en-aut-sei=Nakata en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=CPT kn-keyword=CPT en-keyword=SN38 kn-keyword=SN38 en-keyword=uPA kn-keyword=uPA en-keyword=RC-K8 kn-keyword=RC-K8 en-keyword=H69 kn-keyword=H69 END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=261 end-page=266 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer. en-subtitle= kn-subtitle= en-abstract= kn-abstract=A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.
en-copyright= kn-copyright= en-aut-name=TakataIchiro en-aut-sei=Takata en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UeokaHiroshi en-aut-sei=Ueoka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaHideki en-aut-sei=Katayama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoMitsuhiro en-aut-sei=Takemoto en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirakiYoshio en-aut-sei=Hiraki en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HaradaMine en-aut-sei=Harada en-aut-mei=Mine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Okayama University affil-num=8 en-affil= kn-affil=Okayama University affil-num=9 en-affil= kn-affil=Kyushu University, Fukuoka affil-num=10 en-affil= kn-affil=Okayama University en-keyword=non-small-cell lung cancer kn-keyword=non-small-cell lung cancer en-keyword=concurrent chemoradiotherapy kn-keyword=concurrent chemoradiotherapy en-keyword=low-dose cisplatin kn-keyword=low-dose cisplatin en-keyword=poor-risk factor kn-keyword=poor-risk factor END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=5 article-no= start-page=255 end-page=260 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Obesity and the risk of diabetes mellitus in middle-aged Japanese men. en-subtitle= kn-subtitle= en-abstract= kn-abstract=The morbidity of diabetes mellitus is increasing gradually in Japanese populations. It is important to clarify the risk factors of diabetes in Japanese populations in order to take adequate measures against the increasing morbidity of diabetes. In order to evaluate the link between past and concurrent obesity and diabetes in middle-aged Japanese men, we conducted a worksite-based historical cohort study in Okayama, Japan in 1999. Annual health examination data of middle-aged male workers in a worksite were collected. The relative risks of past and concurrent obesity for developing diabetes were calculated. Subjects with a past history of obesity at between 40 and 50 years of age had a significantly higher risk of developing diabetes by age 55 than did subjects in the normal weight group. These results suggest that, in order to prevent diabetes in middle-aged Japanese men, health guidance for normal weight maintenance should be provided not only for middle-aged men, but also for men under age 40.
en-copyright= kn-copyright= en-aut-name=SekiAkihiko en-aut-sei=Seki en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakigawaTomoko en-aut-sei=Takigawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoTakehiko en-aut-sei=Ito en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuokaEtsuko en-aut-sei=Fukuoka en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiKayo en-aut-sei=Takahashi en-aut-mei=Kayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiraShohei en-aut-sei=Kira en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama Health Care Center affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University en-keyword=obesity kn-keyword=obesity en-keyword=body mass index kn-keyword=body mass index en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=cohort study kn-keyword=cohort study END