Follow-up study of the regional quota system of Japanese medical schools and prefecture scholarship programmes: a study protocol

Introduction: Given the shortage of physicians, particularly in rural areas, the Japanese government has rapidly expanded the number of medical school students by adding chiikiwaku (regional quotas) since 2008. Quota entrants now account for 17% of all medical school entrants. Quota entrants are usually local high school graduates who receive a scholarship from the prefecture government. In exchange, they temporarily practise in that prefecture, including its rural areas, after graduation. Many prefectures also have scholarship programmes for non-quota students in exchange for postgraduate in-prefecture practice. The objective of this cohort study, conducted by the Japanese Council for Community-based Medical Education, is to evaluate the outcomes of the quota admission system and prefecture scholarship programmes nationwide. Methods and analysis: There are 3 groups of study participants: quota without scholarship, quota with scholarship and non-quota with scholarship. Under the support of government ministries and the Association of Japan Medical Colleges, and participation of all prefectures and medical schools, passing rate of the National Physician License Examination, scholarship buy-out rate, geographic distribution and specialties distribution of each group are analysed. Participants who voluntarily participated are followed by linking their baseline information to data in the government’s biennial Physician Census. Results to date have shown that, despite medical schools’ concerns about academic quality, the passing rate of the National Physician License Examination in each group was higher than that of all medical school graduates. Ethics and dissemination: The Ethics Committee for Epidemiological Research of Hiroshima University and the Research Ethics Committee of Nagasaki University Graduate School of Biomedical Sciences permitted this study. No individually identifiable results will be presented in conferences or published in journals. The aggregated results will be reported to concerned government ministries, associations, prefectures and medical schools as data for future policy planning.This study is funded by the Ministry of Education, Culture, Sports, Science and Technology KAKENHI Grant-in-Aid for Scientific Research (C), grant number (25460803)

Cultivable Anaerobic Microbiota of Infected Root Canals

Objective. Periapical periodontitis is an infectious and inflammatory disease of the periapical tissues caused by oral bacteria invading the root canal. In the present study, profiling of the microbiota in infected root canals was performed using anaerobic culture and molecular biological techniques for bacterial identification. Methods. Informed consent was obtained from all subjects (age ranges, 34–71 years). Nine infected root canals with periapical lesions from 7 subjects were included. Samples from infected root canals were collected, followed by anaerobic culture on CDC blood agar plates. After 7 days, colony forming units (CFU) were counted and isolated bacteria were identified by 16S rRNA gene sequencing. Results. The mean bacterial count (CFU) in root canals was (0.5 ± 1.1) × 106 (range 8.0 × 101–3.1 × 106), and anaerobic bacteria were predominant (89.8%). The predominant isolates were Olsenella (25.4%), Mogibacterium (17.7%), Pseudoramibacter (17.7%), Propionibacterium (11.9%) and Parvimonas (5.9%). Conclusion. The combination of anaerobic culture and molecular biological techniques makes it possible to analyze rapidly the microbiota in infected root canals. The overwhelming majority of the isolates from infected root canals were found to be anaerobic bacteria, suggesting that the environment in root canals is anaerobic and therefore support the growth of anaerobes

Rapid Quantification of Bacteria in Infected Root Canals Using Fluorescence Reagents and a Membrane Filter: A Pilot Study on Its Clinical Application to the Evaluation of the Outcomes of Endodontic Treatment

Objective. The bacterial examination has been performed during the course of the root canal treatment. In the present pilot study, the new developed method, using fluorescence reagents and a membrane filter, was applied to the detection and quantification of bacteria in infected root canals, in order to evaluate the outcomes of the treatment. Methods. Six infected root canals with periapical lesions from 5 subjects were included. Informed consent was obtained from all subjects (age ranges, 23–79 years). Samples from infected root canals were collected at the beginning of the treatment (termed #25 First), the end of the first day of treatment (termed #55 First), and the next appointment day (termed #55 Second). Then, the bacterial count (CFU) was measured using fluorescence reagents (4′,6′-diamidino-2-phenylindole and propidium iodide) and the polycarbonate membrane filter by Bioplorer. Results. The mean ± SD of CFU in the sample of “#25 First” was (1.0 ± 1.4) × 105. As the root canal treatment progressed, the CFU decreased as 7.9 × 103 (#55 First) and 4.3 × 102 (#55 Second). Conclusion. In the present pilot study, rapid detection and quantification of bacteria in infected root canals were found to be successfully performed using fluorescence reagents and a membrane filter (Bioplorer analysis)

Immunohistochemistry or Molecular Analysis : Which Method Is Better for Subtyping Craniopharyngioma?

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (β-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining and one PCP showed membranous β-catenin expression and negative for BRAF V600E immunostaining. Among the 26 nuclear β-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features between, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear β-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice

Three Dimensional Motion Analysis of Hand Tremors During Endoscopic Ear Surgery

[Background] Endoscopic surgery is developing in various clinical specialties. During ear endoscopic surgery, a surgeon has to hold an endoscope with one hand and operate the surgical instruments with another hand. Therefore, the stability of the surgeon’s hand affects the field of surgical view and quality of the surgery considerably. There are few techniques which are used during surgery to stabilize the endoscope. However, no study has evaluated the efficacy of such techniques in detail. This study examined the three dimensional movement of an endoscope to compare and evaluate the effect of various stabilization techniques to reduce the hand tremor while using the endoscope. [Methods] A non-randomized controlled trial involving 15 medical students was conducted in Tottori University, Japan. Subjects held an endoscope with their non-dominant hand and manipulated it using three different stabilization techniques i.e. with resting the elbow on the table, resting the endoscope on the ear canal, both with the elbow on the table and endoscope on the ear canal. For the control, subjects were made to use the endoscope without any stabilization technique. The endoscopic movement was measured with and without using the stabilization techniques. [Results] The results obtained in this study indicated that manipulating the endoscope with resting the elbow on the table restrains both vertical (Y-axis) and optical axis (Z-axis) direction of tremor, and manipulating the endoscope by resting it on the ear canal restrains both vertical (Y-axis) and horizontal axis (X-axis) direction while the combined use of both the techniques reduces the endoscope movement in all the three X, Y and Z axes. [Conclusion] In conclusion, concomitant use of both techniques appears to be clinically beneficial in endoscopic ear surgery

The cDNA sequence and expression of the AAA-family peroxin genes pex-1 and pex-6 from the nematode Caenorhabditis elegans

We cloned cDNAs encoding two peroxins, PEX-1 and PEX-6, of the nematode Caenorhabditis elegans. Peroxins are proteins that play essential roles in peroxisome biogenesis and are encoded by pex genes. Among the peroxins, PEX-1 and PEX-6 constitute the subfamily 2 of AAA (ATPases associated with diverse cellular activities) proteins. Each cDNA agreed well with the respective mRNA in size (3.4 kb for pex-1 and 2.3 kb for pex-6) and did not carry any spliced leader sequence. The pex-1 cDNA was composed of 24 exons, which were encoded by a genomic region containing three open reading frames (ORFs), c11h1.4, c11h1.5, and c11h1.6; the predicted ORF c11h1.5 was encompassed in the 15th intron. Although many exon-intron borders in pex-1 were inconsistent with those predicted for c11h1.4 and c11h1.6, those in pex-6 coincided with those for the ORF f39g3.7. The pex-1 and pex-6 genes encoded proteins with 996 and 720 amino acid residues, respectively. Both pex-1 mRNA and pex-6 mRNA were detectable mainly in intestinal cells throughout the life cycle of C. elegans.The erratam is attached for this article

The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses

Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed “The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research” based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap‐frozen samples should be stored in liquid nitrogen (about −180°C) until use. When intending to use genomic DNA extracted from formalin‐fixed paraffin‐embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine

Amebiasis in HIV-1-Infected Japanese Men: Clinical Features and Response to Therapy

Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves