Assembly of Six Types of Heteroleptic Pd2L4 Cages under Kinetic Control.

Heteroleptic assemblies composed of several kinds of building blocks have been seen in nature. It is still unclear how natural systems design and create such complicated assemblies selectively. Past efforts on multicomponent self-assembly of artificial metal-organic cages have mainly focused on finding a suitable combination of building blocks to lead to a single multicomponent self-assembly as the thermodynamically most stable product. Here, we present another approach to selectively produce multicomponent Pd(II)-based self-assemblies under kinetic control based on the selective ligand exchanges of weak Pd-L coordination bonds retaining the original orientation of the metal centers in a kinetically stabilized cyclic structure and on local reversibility given in certain areas of the energy landscape in the presence of the assist molecule that facilitates error correction of coordination bonds. The kinetic approach enabled us to build all six types of Pd2L4 cages and heteroleptic tetranuclear cages composed of three kinds of ditopic ligands. Although the cage complexes thus obtained are metastable, they are stable for 1 month or more at room temperature.

Changing clinical and molecular characteristics of hepatitis E virus infection in Mie Prefecture, Japan: Disappearance of indigenous subtype 3e strains.

AIM: To evaluate the clinical and molecular characteristics of hepatitis E virus (HEV) infection in Mie Prefecture, Japan, from 2004 through 2018. METHODS: The clinical information of hepatitis E cases was collected from 21 medical institutions in Mie Prefecture. The nucleotide sequences of infecting HEV strains were determined for cases with available serum samples. The origins or transmission routes were inferred from phylogenetic analyses of the nucleotide sequences. RESULTS: Fifty-three patients were diagnosed with HEV infection. The number of cases increased each year through 2012 and then decreased. Analyses of the clinical characteristics of the cases indicated that even mild cases were detected in the latter 10 years of the study. Nucleotide sequence analyses were undertaken on 38 of the 53 cases. The HEV subtype 3e (HEV-3e) strains identified for 13 cases were closely related to a swine HEV-3e strain that was isolated from the liver of a pig bred in Mie Prefecture. The number of cases infected with the indigenous Mie HEV-3e strains increased until 2012 but have not been reported since 2014. In the latter half of the study, cases involving various HEV strains of different genotypes and subtypes emerged. CONCLUSIONS: The disappearance of indigenous Mie HEV-3e strains appeared to be the primary cause for the decrease in hepatitis E cases in Mie Prefecture. The disappearance might have been associated with improved hygienic conditions on pig farms or the closure of contaminated farms. The results suggest that indigenous HEV strains can be eradicated by appropriate management.

[Case of lymphomatoid gastropathy detected during follow-up after chemoradiotherapy for esophageal cancer].

A man in his 70s underwent chemoradiotherapy for squamous cell carcinoma of the esophagus in 2009. A follow-up gastroendoscopy performed 3 years later revealed a reddish depressed lesion in the greater curvature of the middle stomach body. On the basis of histological and immunohistochemical findings and clinical features, including endoscopic findings, a diagnosis of lymphomatoid gastropathy was made. Follow-up studies revealed a decrease in the size of the lesion and the development of chronic gastritis. Although lymphomatoid gastropathy is rare, recognition of this disease is important because misdiagnosis as lymphoma may lead to unnecessary radical therapeutic procedures.

Knockdown of legumain inhibits cleavage of annexin A2 in the mouse kidney.

Legumain (EC 3.4.22.34) is an asparaginyl endopeptidase. Strong legumain activity was observed in the mouse kidney, and legumain was highly expressed in tumors. We previously reported that bovine kidney annexin A2 was co-purified with legumain and that legumain cleaved the N-terminal region of annexin A2 at an Asn residue in vitro. In this study, to determine whether annexin A2 is cleaved by legumain in vivo, siRNA-lipoplex targeting mouse legumain was injected into mouse tail veins. Mouse kidneys were then isolated and the effect of knockdown of legumain expression on annexin A2 cleavage was examined. The results showed that both legumain mRNA and protein expression levels were decreased in the siRNA-treated mouse kidneys and that legumain activity toward a synthetic substrate, Z-Ala-Ala-Asn-MCA, was decreased by about 40% in the kidney but not in the liver or spleen. Furthermore, cleavage of annexin A2 at the N-terminal region was decreased in the mouse kidney that had been treated with the legumain siRNA-lipoplex. These results suggest that legumain siRNA was delivered to the kidney by using LipoTrust and that the reduced legumain expression inhibited legumain-induced degradation of annexin A2 in vivo.

Transcriptional regulation of the legumain gene by p53 in HCT116 cells.

Legumain (EC 3.4.22.34) is an asparaginyl endopeptidase. Strong legumain activity was observed in the mouse kidney, and legumain was found to be highly expressed in tumors. We previously reported that bovine kidney annexin A2 was co-purified with legumain and that legumain cleaved the N-terminal region of annexin A2 at an Asn residue in vitro and in vivo. In this study, we found a p53-binding site in intron 1 of the human legumain gene using computational analysis. To determine whether transcription of the legumain gene is regulated by p53, HCT116 cells were transfected with p53 siRNA and the effect of knockdown of p53 expression on legumain expression was examined. The results showed that expression levels of both legumain mRNA and protein were decreased in the siRNA-treated cells. Furthermore, enzyme activity of legumain was also increased by doxorubicin and its activity was reduced by knockdown of p53 in HCT116 cells. These results suggest that legumain expression and its enzyme activity are regulated by p53.

Rurality and participation in mass preventive health services: a nationwide descriptive study.

People's engagement in community activities is reportedly stronger in rural areas than in urban areas. However, it is unknown whether this affects the health-seeking behaviour of residents in rural communities. We examined whether the rurality-related index of a community was associated with the participation rate of residents in community-based preventive health services. Based on the national census data on all the 1816 municipalities in Japan in 2007, the correlation was evaluated between the participation rate in cancer screening (stomach cancer, colorectal cancer) or influenza vaccination programmes among those older than 65, and each of the municipality-level variables. The correlations were examined by simple correlation and multiple regression analyses. The correlations were also evaluated between voting rate (a parameter of people's engagement in community activities) and each municipality-level variable with multiple regression analysis. Simple correlation analysis showed that the population density was negatively correlated with the participation rate of all (stomach cancer, colorectal cancer, and influenza) preventive programmes (r = -0.367, -0.171 and -0.188, respectively; each p < 0.001). The significant correlations were maintained even after adjustment for other socioeconomic factors in multiple regression analysis in stomach cancer screening and influenza vaccination (beta = -0.279 and -0.133, respectively: each p < 0.05). Population density was negatively correlated with voting rate (beta = -0.488: p < 0.001). Residents in rural communities were more likely to participate in community-based mass preventive services and were more actively engaged in political activities than their urban counterparts. These results suggest that rural residents have a stronger sense of community, and this could potentially facilitate residents' engagement in mass preventive services.

Do rural and remote areas really have limited accessibility to health care? Geographic analysis of dialysis patients in Hiroshima, Japan.

INTRODUCTION: For an equitable distribution of health resources, resource-allocation policies focus on rural and also remote areas, assuming that these areas are underserved. However, definitions of 'rural' and 'remote' vary, and are not necessarily synonymous with 'underserved'. This Japanese study evaluated the association between the rurality/remoteness of the community in which a patient lives and his/her geographic accessibility to dialysis facilities. METHODS: Based on 1867 communities (census blocks) in Hiroshima Prefecture, Japan, predictive powers of five community-level rural/remote parameters (population size, population density, elderly rate, agriculture rate, and distance to the nearest city) were evaluated to identify communities where dialysis patients had a longer commute time to dialysis facilities. The proportion of low-access communities was examined when those communities were merged to form larger geographic units (four-level stepwise merger). One-way driving times of dialysis patients were used as the access parameter of a community and were calculated using geographic information systems based on the addresses of all the 7374 patients certified by municipalities as having renal disability, and on the addresses and capacities of all 98 dialysis facilities in Hiroshima. RESULTS: The average driving time was negatively correlated with population and population density, and positively correlated with elderly rate, agriculture rate, and distance to nearest city. When low-access was defined as >20, >30 & >40 min driving time, all rural/remote parameters showed better sensitivities (range 63.5-94.9%) than specificities (55.2-77.9%) to identify low-access communities, and positive predictive values were less than 50% for most parameters. When low-access was defined as >30 min driving time, the proportion of low-access communities substantially decreased when the geographic unit was expanded. In the administrative 'rural' area, the largest geographic unit, the percentage of low-access communities was 30%. CONCLUSIONS: In any definition of 'rural/remote', and in any definition of 'low-access', the rural/remote areas contain a substantial proportion of high-access communities. In addition, a substantial proportion of low-access communities was excluded from rural/remote areas. The accuracy of the term 'low-access' deteriorated when the geographic unit of analysis was expanded. In order to identify underserved areas precisely, it is necessary to set the geographic unit of analysis as small as possible and measure the geographic accessibility itself, rather than designate some areas as 'rural' or 'remote', based on conventional geographic/demographic/distance parameters.

Domain 5 of high molecular weight kininogen inhibits collagen-mediated cancer cell adhesion and invasion in association with α-actinin-4.

High molecular weight kininogen (HK) is a plasma glycoprotein with multiple functions, including the regulation of coagulation. We previously demonstrated that domain 5 (D5(H)), a functional domain of HK, and its derived peptides played an important role in the vitronectin-mediated suppression of cancer cell adhesion and invasion. However, the underlying mechanisms of the D5(H)-mediated suppressive effects remain to be elucidated. Here, we showed that D5(H) and its derivatives inhibited the collagen-mediated cell adhesion and invasion of human osteosarcoma MG63 cells. Using purified D5(H) fused to glutathione-S-transferase (GST) and D5(H)-derived peptides for column chromatography, an actin-binding protein, α-actinin-4, was identified as a binding protein of D5(H) with high-affinity for P-5m, a core octapeptide of D5(H). Immunofluorescence microscopy demonstrated that D5(H) co-localized with α-actinin-4 inside MG63 cells. In addition, exogenous GST-D5(H) added to the culture media was transported into MG63 cells, although GST alone as a control was not. As α-actinin-4 regulates actin polymerization necessary for cell adhesion and is related to the integrin-dependent attachment of cells to the extracellular matrix, our results suggest that D5(H) may modulate cell adhesion and invasion together with actinin-4.

Purification, molecular cloning and functional characterization of swine phosphatidylethanolamine-binding protein 4 from seminal plasma.

Phosphatidylethanolamine-binding proteins (PEBPs) are found in various species and have multiple functions. In this study, we purified the swine homolog of human PEBP4 (sPEBP4) from swine seminal plasma, cloned the sPEBP4 cDNA and functionally characterized this protein. The molecular mass of the purified protein was calculated to be 25 kDa by SDS-polyacrylamide gel electrophoresis under reducing conditions. The full-length cDNA of sPEBP4 contains 815 bp with an open reading frame of 669 bp that encodes a protein 222 residues in length. sPEBP4 contains a putative phosphatidylethanolamine-binding domain between residues 79 and 195; however, this domain did not show lipid binding activity. The overall amino acid sequence identity of PEBP4s from swine, human, mouse, bovine and canine ranges between 56.1% and 82.4%. Immunohistochemical staining and western blotting analysis showed that sPEBP4 is secreted from epithelial cells in the epididymis to the seminal plasma. To explore the role of sPEBP4 in the seminal plasma, we tested the effect of sPEBP4 on swine sperm motility. Sperms suspended in phosphate-buffered saline began to swim after the addition of purified sPEBP4, but not when swine serum albumin was added, indicating that sPEBP4 promotes sperm motility.

The impact of rural hospital closures on equity of commuting time for haemodialysis patients: simulation analysis using the capacity-distance model.

BACKGROUND: Frequent and long-term commuting is a requirement for dialysis patients. Accessibility thus affects their quality of lives. In this paper, a new model for accessibility measurement is proposed in which both geographic distance and facility capacity are taken into account. Simulation of closure of rural facilities and that of capacity transfer between urban and rural facilities are conducted to evaluate the impacts of these phenomena on equity of accessibility among dialysis patients. METHODS: Post code information as of August 2011 of all the 7,374 patients certified by municipalities of Hiroshima prefecture as having first or third grade renal disability were collected. Information on post code and the maximum number of outpatients (capacity) of all the 98 dialysis facilities were also collected. Using geographic information systems, patient commuting times were calculated in two models: one that takes into account road distance (distance model), and the other that takes into account both the road distance and facility capacity (capacity-distance model). Simulations of closures of rural and urban facilities were then conducted. RESULTS: The median commuting time among rural patients was more than twice as long as that among urban patients (15 versus 7 minutes, p<0.001). In the capacity-distance model 36.1% of patients commuted to the facilities which were different from the facilities in the distance model, creating a substantial gap of commuting time between the two models. In the simulation, when five rural public facilitiess were closed, Gini coefficient of commuting times among the patients increased by 16%, indicating a substantial worsening of equity, and the number of patients with commuting times longer than 90 minutes increased by 72 times. In contrast, closure of four urban public facilities with similar capacities did not affect these values. CONCLUSIONS: Closures of dialysis facilities in rural areas have a substantially larger impact on equity of commuting times among dialysis patients than closures of urban facilities. The accessibility simulations using the capacity-distance model will provide an analytic framework upon which rational resource distribution policies might be planned.

Characteristics of physicians, their migration patterns and distance: a longitudinal study in Hiroshima, Japan.

INTRODUCTION: Although some characteristics of physicians are known to be associated with their recruitment in rural and remote areas, the factors that predict mobility of physicians, and in particular, their mobility to rural and distant areas are largely unknown. METHODS: Flows of all physicians (n=4268) among municipalities in Hiroshima Prefecture, Japan, between 2002 and 2008 were analysed. Physician data were obtained from the National Physician Census. Municipality-level population data derived from the National Basic Resident Register were merged with the physician data. Information on the road distances of two municipalities measured with a geographic information system (GIS) was added to the physician cohort. RESULTS: During the period of study, 24.8% of physicians crossed municipal borders, and among them, 66.6% moved distances of less than 60 min travel time. The number of migrated physicians decreased as the distance increased, which held true for both migration to urban and rural areas. In the univariate analysis, female, younger, and hospital physicians were more mobile to rural areas than were male, older, and clinic physicians. Male and younger (&#8804;40 years) physicians moved a longer distance than female and older physicians. Multivariate analysis revealed that age was a negative predictor (odds ratio [OR] per 10 years 0.62, 95% confidence interval [CI] 0.55-0.70]), and affiliation with a hospital was a positive predictor of migration to rural areas (OR 6.19 [95% CI 4.21-9.10]). Male sex (OR 1.67 [95% CI 1.11-2.50]) and hospital affiliation (OR 5.61 [95% CI 3.33-9.45]) were positive predictors, and age (OR per 10 years 0.39 [95% CI 0.33-0.46]) was a negative predictor of migrating a long distance. CONCLUSION: In order to attract physicians to rural and remote areas, health workforce policies need to set a target population of physicians who are highly mobile to such places. Combining known predictors of rural practice, such as physicians with rural background and primary care physicians, and the mobility predictors shown in this study (ie young, hospital and male physicians) would make the target more appropriate and policies more effective.

Factor H in porcine seminal plasma protects sperm against complement attack in genital tracts.

We found that factor H (FH) exists in porcine seminal plasma. Purified FH strongly inhibited serum alternative pathway complement activation against lipopolysaccharide. The molecular weight, pI, and heparin-binding activity of the purified protein were different from those of purified FH from porcine serum. The complement regulatory activity of seminal plasma FH was approximately 2-fold stronger than that of serum FH. Treatment of purified serum FH with sialidase and N-glycosidase F gave almost the same results as those of seminal plasma FH. The deletion of sialic acid from the carbohydrate chains of both FHs contributed to heparin-binding and complement regulatory activities. Results of reverse transcriptase-PCR, Western blot analysis, and immunohistochemistry showed that seminal plasma FH is mainly secreted from epithelial cells of the seminal vesicle in male genital tracts. FH was also detected in the outer acrosomal region of ejaculated sperm by immunofluorescence staining, and found that the purified FH from the sperm membrane has the same complement regulatory activity as that of seminal plasma FH. The ejaculated sperm possessing FH in the outer acrosomal region considerably evaded complement attack. We also found that there is strong complement activity in fluids from female genital tract ducts. These findings indicate that FH bound to the outer acrosomal region and soluble FH play important roles in protecting sperm against complement attack in male and female genital tracts.

Retention of physicians in rural Japan: concerted efforts of the government, prefectures, municipalities and medical schools.

CONTEXT: In post-war Japan, a number of factors lead to a general shortage of physicians by the 1950s, which became acute in rural areas and has continued until recent times. ISSUE: Teamwork among national, prefectural, municipal governments and public medical schools has addressed this shortage of physicians. The national government doubled the number of medical schools in the 1960s and 1970s; each of the country's 47 prefectures, whether rural or not, has at least one medical school. In rural areas where private hospitals are not profitable, municipal governments have funded public hospitals and physician recruitment from their own budgets. A cooperative project among Japan's 47 prefectural governments and the national government established Jichi Medical University (JMU), which conducts a bound medical education program followed by obligatory rural service. As a result, the number of 'non-physician communities' (muichiku) nationwide has decreased by 73%; however, the gap between physician concentrations in urban and rural areas has not changed. Therefore, the government has recently implemented a JMU-like contractual program as a form of 'rural quota' at other medical schools in all 47 prefectures. If all the replicated programs work as successfully as JMU, the impact on the geographic distribution of physicians will be substantial. LESSONS LEARNED: The Japanese public-sector-led rural physician securing system could also be effective in countries where rural healthcare provision is the responsibility of the public sector and close cooperation among levels of government is possible.

Frequency scale for symptoms of gastroesophageal reflux disease predicts the need for addition of prokinetics to proton pump inhibitor therapy.

BACKGROUND AND AIM: Proton pump inhibitor (PPI) monotherapy cannot cure all cases of gastroesophageal reflux disease (GERD), and combination therapy with prokinetics and PPI achieves symptomatic improvement for some GERD patients. Few studies have been performed to predict the need for prokinetics. METHODS: Subjects were 163 patients (64 male, mean age 53.1 +/- 16.6 years) with GERD symptoms. They were evaluated using the frequency scale for the symptoms of GERD (FSSG), a GERD-specific questionnaire developed in Japan(1) and endoscopy. They were administered with rabeprazole 10 mg daily. At 12 and 24 weeks of treatment, subjects were offered a choice of four treatment regimens according to their degree of satisfaction (1, no need for further treatment; 2, opt for continued PPI treatment; 3, step-down to H2RA; 4, dissatisfied with present treatment, so opt for combination treatment with prokinetics, mosapride 5 mg tid). RESULTS: The choice of treatment after 12 weeks of treatment placed 79.1% of subjects in the satisfied group (1, 21; 2, 98; 3, 10). After 24 weeks, 98.2% of subjects were in the satisfied group. Pretreatment FSSG scores were significantly higher in the dissatisfied group (4, 17.4 +/- 1.4) than in the satisfied group (1, 12.3 +/- 1.3; 2, 12.8 +/- 0.8; 3, 10.2 +/- 1.8) (P < 0.05). CONCLUSIONS: The satisfaction rate with these treatment regimens was 98.2% at 24 weeks, suggesting that combination therapy with prokinetics was effective for patients dissatisfied with PPI monotherapy. The FSSG is a useful predictor of the necessity for combination therapy.

Genomic overview of mRNA 5'-leader trans-splicing in the ascidian Ciona intestinalis.

Although spliced leader (SL) trans-splicing in the chordates was discovered in the tunicate Ciona intestinalis there has been no genomic overview analysis of the extent of trans-splicing or the make-up of the trans-spliced and non-trans-spliced gene populations of this model organism. Here we report such an analysis for Ciona based on the oligo-capping full-length cDNA approach. We randomly sampled 2078 5'-full-length ESTs representing 668 genes, or 4.2% of the entire genome. Our results indicate that Ciona contains a single major SL, which is efficiently trans-spliced to mRNAs transcribed from a specific set of genes representing approximately 50% of the total number of expressed genes, and that individual trans-spliced mRNA species are, on average, 2-3-fold less abundant than non-trans-spliced mRNA species. Our results also identify a relationship between trans-splicing status and gene functional classification; ribosomal protein genes fall predominantly into the non-trans-spliced category. In addition, our data provide the first evidence for the occurrence of polycistronic transcription in Ciona. An interesting feature of the Ciona polycistronic transcription units is that the great majority entirely lack intercistronic sequences.

Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells.

Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells.

Porcine germinal angiotensin I-converting enzyme: isolation, characterization and molecular cloning.

Germinal angiotensin I-converting enzyme (gACE) was purified to homogeneity from porcine seminal plasma. The molecular weight of the purified enzyme was calculated to be 182,000 on non-denaturing PAGE and 94,000 and 93,000 on SDS-PAGE in the absence and presence of beta-ME, respectively. These findings suggest that the enzyme is composed of two identical subunits in seminal plasma. The K(m), V(max), K(cat) and K(cat)/K(m) values of gACE at optimal pH (pH 7.2) were 680 microM, 1.0 micromol/mg/min, 33.1 s(-1) and 4.87 x 10(4) s(-1) M(-1) for Z-Val-Lys-Met-MCA, respectively. gACE was potently inhibited by EDTA, 1,10-phenanthroline, captopril and lisinopril, and it promptly released the dipeptides His-Leu and Phe-Arg from angiotensin I and bradykinin. Met- and Leu-enkephalins, neuromedine B and beta-neo-endorphin were also good natural substrates for gACE. We determined the structure of gACE cDNA from the porcine testis, and deduced the amino acid sequence of gACE. The cDNA is composed of 2508 bp of nucleotides in length and encodes 745 amino acids in the coding region. The overall homology of amino acid sequences between porcine, human, sheep and rat gACEs is 72.6 to 84.7%. Zinc-binding motif, chloride-binding site and positions of cysteine residues were well conserved.

The Vanguard of Community-based Integrated Care in Japan: The Effect of a Rural Town on National Policy.

INTRODUCTION: Japan has the largest percentage of elderly people in the world. In 2012 the government implemented a community-based integrated care system which provides seamless community healthcare resources for elderly people with chronic diseases and disabilities. METHODS: This paper describes the challenges of establishing a community-based integrated care system in 1974 in Mitsugi, a rural town of Japan. This system has influenced the government and become the model for the nationwide system. RESULTS: In the 1970s, Mitsugi's aging population was growing faster than Japan's, but elder care was fragmented among a variety of service sections. A community-based integrated care system evolved because of the small but aging population size and the initiative of some local leaders of medical care and politics. After the system took effect, the proportion of bedridden people and medical care costs for the elderly dropped in Mitsugi while it continued to rise everywhere else in Japan. Mitsugi's community-based integrated care system is now shaping national policy. CONCLUSION: Mitsugi is in the vanguard of Japan's community-based integrated care system. The case showed the community-based integrated care system can diffuse from rural to urban areas.

Results of physician licence examination and scholarship contract compliance by the graduates of regional quotas in Japanese medical schools: a nationwide cross-sectional survey.

OBJECTIVES: Responding to the serious shortage of physicians in rural areas, the Japanese government has aggressively increased the number of entrants to medical schools since 2008, mostly as a chiikiwaku, entrants filling a regional quota. The quota has spread to most medical schools, and these entrants occupied 16% of all medical school seats in 2016. Most of these entrants were admitted to medical school with a scholarship with the understanding that after graduation they will practise in designated areas of their home prefectures for several years. The quota and scholarship programmes will be revised by the government starting in 2018. This study evaluates the intermediate outcomes of these programmes. DESIGN: Cross-sectional survey to all prefectural governments and medical schools every year from 2014 to 2017 to obtain data on medical graduates. SETTINGS: Nationwide. PARTICIPANTS: All quota and non-quota graduates with prefecture scholarship in each prefecture, and all the quota graduates without scholarship in each medical school. PRIMARY OUTCOME MEASURES: Passing rate of the National License Examination for Physicians and the percentage of graduates who have not bought out the scholarship contract after graduation. RESULTS: Most prefectures and medical schools in Japan participated in this study (97.8%-100%). Quota graduates with scholarship were significantly more likely to pass the National License Examination for Physicians than the other medical graduates in Japan at all the years (97.9%, 96.7%, 97.4% and 94.7% vs 93.9%, 94.5%, 94.3% and 91.8%, respectively). The percentage of quota graduates with scholarship who remained in the scholarship contract 3 years after graduation was 92.2% and 89.9% for non-quota graduates with scholarship. CONCLUSIONS: Quota entrants showed better academic performance than their peers. Most of the quota graduates remained in the contractual workforce. The imminent revision of the national policy regarding quota and scholarship programmes needs to be based on this evidence.