JMA Journal

Establishment of Integrated Biobank for Precision Medicine and Personalized Healthcare: The Tohoku Medical Megabank Project

2019-08-06T08:30:01+09:00

The Tohoku Medical Megabank (TMM) project was established to provide creative reconstruction of the Tohoku area that suffered from a huge earthquake and ensuing tsunami (the Great East Japan Earthquake, GEJE). TMM aims to establish two large-scale genome cohorts and an integrated biobank managing biospecimen and related information. It supports community medicine by establishing next-generation medical systems through a combination of the prospective genome cohort studies with a total of 150,000 participants and genomic medicine. The strategies for genome analyses in TMM are to develop an elaborate genome reference panel by means of high-fidelity Japanese whole-genome sequence, to design custom single nucleotide polymorphism (SNP) arrays based on the reference panel, and to obtain genotype data for all the TMM cohort participants subsequently. Disease-associated genomic information and omics data, including metabolomics and microbiome analysis, provide an essential platform for precision medicine and personalized healthcare (PHC). Ethical, legal, and social issues (ELSI) and education are important for implementing genomic medicine. The major considerations of ELSI regarding each participant of the cohort studies are the respect for the autonomy and the protection of privacies. Moreover, developing and provide human resources not only for the TMM project but also for the social implementation of precision medicine and PHC is required. We started a pilot study of the return of genomic results for familial hypercholesterolemia (FH) as a target disease. TMM aims to establish solid platforms that support precision medicine and PHC based on the genomic and omics information and environmental and lifestyle factors of the individuals, which is one of the most advanced medical care beyond the evidenced-based medicine in the near future.

Hepatocyte-like Cells Derived from Human Pluripotent Stem Cells Can Be Enriched by a Combination of Mitochondrial Content and Activated Leukocyte Cell Adhesion Molecule

2019-08-06T08:30:01+09:00

: Non-genetic purification methods for pluripotent stem cell-derived hepatocyte-like cells are useful for liver regenerative therapy and pharmaceutical applications.　: Fluorescent activated cell sorting (FACS) was used to separate cells by combining two parameters: cellular mitochondrial content evaluated by the mitochondrial membrane potential-dependent fluorescent probe (TMRM) and immunocytochemical detection of activated leukocyte cell adhesion molecule (ALCAM). This method was applied to murine fetal, human embryonic stem cell (ESC)-derived, and human induced pluripotent stem cell (iPSC)-derived cell-mixtures. Separately sorted cell fractions were evaluated by quantitative PCR, immunohistochemistry, and cytochemistry for HNF4a, AFP, and albumin mRNA and/or protein expression.　: Hepatocyte-like cells were segregated into the high TMRM signal and ALCAM-positive population. The purity of hepatocyte-like cells derived from human iPSCs was 97 ± 0.38% (n = 5).　: This hepatocyte-like cell purification method may be applicable to the quality control of cells for liver regenerative cell therapy and pharmaceutical development.

Characteristics of Locomotive Syndrome in Japanese Patients with Chronic Pain and Results of a Path Analysis Confirming the Relevance of a Vicious Cycle Involving Locomotive Syndrome, Musculoskeletal Pain, and Its Psychological Factors

2019-08-06T08:30:01+09:00

The current aging population has a major impact on public health. Locomotive syndrome (LS) is a condition that carries a high risk for developing systemic musculoskeletal disability.　 Participants were patients with chronic pain (n = 415) who were examined at the Japanese multidisciplinary pain centers of the research consortium. They completed the 25-question geriatric locomotive function scale (GLFS-25; LS screening tool), an 11-point numerical rating scale (NRS) of pain intensity and its psychological distresses, health-related quality of life (HRQOL) questionnaire, and a survey of exercise habits. A multifaceted analysis of the relevance of the pain, psychological distresses, and LS were conducted using SPSS and AMOS software.　: 337 patients (81.2%) were found to have LS. The final model of a multifaceted analysis demonstrated good fitness for the “vicious cycle” model among the results of LS, pain intensity, impairment of self-efficacy, and depression; these parameters independently impaired HRQOL. Anxiety related to falling (GLFS-25) and exercise habits affected the model.　: These findings indicate LS, LS-related pain, and psychological distress create a vicious cycle, resulting in the impairment of HRQOL. Treatment strategies for LS should inclusively focus on musculoskeletal disorders, pain, and pain-related psychological factors.

Refined Auditory Brainstem Response Measurement Identified Potential Models of Congenital Deafness in Laboratory Mouse Strains

2019-07-08T08:30:01+09:00

To detect congenital hearing loss in mice, an objective measure is needed other than mouse behavioral observation. This study aimed to refine the methodology of auditory brainstem response measurement and identify potential congenital hearing loss models in laboratory mouse strains.　 Mice were anesthetized and fitted with head electrodes. Each mouse underwent four ABR measurements according to four testing conditions: A - no chamber; conventional tone; B - chamber; conventional tone; C - no chamber; short tone; D - chamber; short tone. Potential congenital hearing loss models were identified using 10 mice from each strain (C57BL, BALB/c, CH3, ICR, and ddY) through sound-attenuated ABR measurements with short-tone bursts. Potential congenital hearing loss models exhibited hearing thresholds ≥30 dB in both ears. Data were analyzed for normal distribution and variance homogeneity using the D’Agostino-Pearson/Kolmogorov-Smirnov and F value tests, respectively. One-way analysis of variance (ANOVA), with the Tukey-Kramer test, was used to conduct parametric analysis, and the Kruskal-Wallis/Friedman test, with a Dunn’s test for post hoc analysis, was used to perform non-parametric analysis.　 The simultaneous use of a sound-attenuating chamber and short-tone bursts provided clearly defined wave patterns, even at lower sound intensities. Inbred strains, especially C57BL/6 sub-strains, constitute suitable congenital hearing loss models.　 Our study shows that environmental factors should be addressed in animal studies of hearing function. Potential congenital hearing loss models may be found amongst commercially available inbred strains.

Cardiac Sympathetic Hyperactivity of Lung Cancer-Associated Harlequin Syndrome

2019-07-08T08:30:01+09:00

Strengthening the Healthcare System in Low- and Middle-income Countries by Integrating Emergency Care Capacities

2019-06-28T08:30:01+09:00

Primary healthcare (PHC) principles provide a framework for strengthening the healthcare system to tackle increasing and diversifying health needs in low- and middle-income countries (LMICs). Currently, PHC systems in LMICs require expanded care capabilities in order to deal with noncommunicable diseases and injuries, including emergency conditions. In this article, we discuss the possibility of applying PHC principles to emergency care in LMICs and integrating emergency care into PHC; such principles include providing first points of contact with healthcare through nonprofessional providers close to communities in order to improve accessibility, providing high-quality (i.e., comprehensive, coordinated, and continuous) primary care, and addressing primary causes of ill-health through community empowerment. These principles are applicable to emergency care, which has the same attributes: it also requires increasing first points of contact through layperson first aid and the ambulance system, and it also provides comprehensive care for diverse diseases and injuries, with various facilities and personnel involved in its coordinated and continuous delivery; collective community actions also develop and strengthen the emergency care system, particularly through components outside the health sector (e.g., transport, communication, and mutual aid). Integrating emergency care into PHC could enhance the general health system and is more efficient than having separate systems.

Quality Improvement Based on Quality Indicators Editorial on the Article “Development and Pilot-testing of Quality Indicators for Primary Care in Japan”

2019-06-28T08:30:01+09:00

Importance of Neuropathological Diagnosis of Dementia Patients in Family Practice

2019-06-06T08:30:01+09:00

: Creutzfeldt–Jakob disease (CJD) is an important dementia disorder. However, clinical diagnosis can be difficult and delayed for many primary physicians caring for dementia patients. The aim of the present study was to describe clinical and neuropathological results of an individual with CJD who was seen by a community hospital. Our report may inform many primary physicians on understanding the significance of CJD.　: Clinical information was obtained from medical records. Neuropathological and biochemical analyses were performed using autopsied brain.　: A 58-year-old Japanese man who had worked as a carpenter developed memory and executive function impairments. He was initially diagnosed as having Alzheimer’s disease based on clinical and neuroradiological analyses. Myoclonus was observed in the later stage of clinical course. Hyperintense lesions on diffusion-weighted images were observed in the cerebral cortex in later stage. Analysis of cerebrospinal fluid showed increased levels of total tau and phospho-tau protein. However, 14-3-3 protein and amyloid β (1–42) were normal. Genetic analysis of the 　 gene showed methionine homozygosity at codon 129 and glutamate homozygosity at codon 219. The results of neuropathological analysis were consistent with sporadic CJD (MM2 cortical type with some type 1 pattern of 3F4 immunoreactivity). Western blot analysis of the frontal and cerebellar cortex revealed a type 2 and type 1 pattern of proteinase K (PK)-resistant prion protein, respectively. No Alzheimer’s pathology was present.　: Our experience may help primary physicians to assess dementia patients. Since atypical forms of prion disease are now well-established, we need to consider prion disease in dementia patients. Clinical examination alone is not enough for dementia workup; thus, we must understand the importance of neuropathological study and encourage autopsy to reach a definite diagnosis of dementia.

Multifaceted Evaluation of Ultra-high-field 9.4-T Magnetic Resonance Imaging after Inorganic Tattoos: An Animal Study

2019-06-06T08:30:01+09:00

: Tattooing techniques for reconstruction and rectification of the sequelae of cancer treatments, surgery, and scarring have received attention in the medical field. There is concern that tattooed skin is at risk of being burned by magnetic resonance imaging (MRI) examination. However, a detailed evaluation of the impact of MRI imaging on medically tattooed skin has not yet been performed. This study aimed to clarify the changes in common inorganic tattoo pigments during MRI examinations in an animal model.　: Tattooed hairless mice with eight typical pigments for tattoos were evaluated for changes in temperature, color tone, and histology of the tattoos during a 9.4-T MRI.　: None of specimens had signs of burns, such as redness or blisters. In terms of temperature changes, the black iron oxide and carbon black specimens had a maximum temperature increase of 0.4 degrees. In the Munsell color system, no specific color changes were observed before or after the MRI. Color changes, evaluated as the ΔE　 in the L　a　b　 color space, were all below 3.0 and were thus regarded as being indistinguishable and within the color unevenness of the tattoo. Histologic analysis of the specimens showed no significant changes before and after the MRIs.　: The observed temperature changes, color tone changes, and histological changes in the tattooed areas in this animal model were not of a magnitude considered likely to adversely affect the human body.

Do Preys Prey on Their Predators? Confusion over Predatory “Hage-taka” Journals

2019-06-06T08:30:01+09:00

For the last several years, predatory journals have been a topic of discussion in top scientific journals, such as 　. Predatory journals are problematic because they create public mistrust of scientific publication as a whole by the mass production of non-credible publications with the sole aim of profit. Recently, articles in a Japanese newspaper and online articles exposed domestic institutions for the number of publications in predatory journals, saying that they “abused predatory journals to increase the number of their publications and falsely inflate their academic achievements.” We do not subscribe to this point of view because publications in predatory journals do not count as scholarly achievements, and we believe it is an information literacy problem. We feel strongly that it is both important and beneficial for the readers of 　　 to be aware of and understand this issue.

The Heart Failure “Pandemic” in Japan: Reconstruction of Health Care System in the Highly Aged Society

2019-05-16T08:30:01+09:00

An increase in the number of patients with heart failure is an international health-related problem. In advanced countries, the number of such patients has rapidly increased since the beginning of the 21　 century, raising an important issue regarding medical practice and public health. In 2010, the concept of “heart failure pandemic” was proposed, and it has been recognized as a global social/economic issue. In particular, the number of elderly patients with heart failure has increased with the rapid aging of society and a decrease in the number of children in Japan. A rapid increase in the number of heart failure patients increases stress and social disease-related/medical economic burdens on individuals and their families. The prognosis of patients with chronic heart failure is unfavorable, and the quality of life markedly reduces. To improve the prognosis of elderly patients with heart failure and reduce the readmission rate, the innovation of a medical-care-providing system for heart failure is required. In addition to the provision of medical practice based on a potent heart failure disease control program, manifold strategies, such as lifestyle improvements, self-care practice, cardiac rehabilitation, and environmental intervention, are essential. It is necessary to innovate hospital-based medical practice to a regional-care-system-based medical care system. In addition, to efficiently promote future heart failure strategies, an investigational study with disease registration must be conducted. Recently a new basic act on countermeasures to cardiovascular diseases has been established which may help the reform for this purpose.

Development and Pilot Testing of Quality Indicators for Primary Care in Japan

2019-05-16T08:30:01+09:00

: To the best of our knowledge, no quality indicators (QIs) for primary care provided by local clinics have yet been developed in Japan. We aimed to develop valid and applicable QIs to evaluate primary care in Japan.　: Two focus group interviews were held to identify conceptual categories. Existing indicators for these categories were identified, and initial sets of potential QIs were developed. Using a modified Delphi appropriateness method, a multidisciplinary expert panel then developed and selected the QIs. Feasibility and applicability of these QIs were then confirmed in pilot testing at six local clinics in Hokkaido, Japan. To determine patient acceptance of these quality improvement activities, the survey asked two questions, “Do you think it is preferable that the patients of this clinic be periodically surveyed?” and “Do you think it is preferable that this clinic periodically undergo an external quality review by an independent body?”　: Seven categories emerged from the focus group discussions as key components of primary care in Japan. Thirty-nine QIs under five categories (Comprehensive care/Standardized care, Access, Communication, Co-ordination, and Understanding of patient background) were finally selected and named the QIs for Primary Care Practice in Japan. In pilot testing at six primary care clinics in 2015, 65.4% of patients answered favorably to the idea that clinics should conduct regular patient surveys, and 71.8% answered favorably to the idea that clinics should undergo periodic external quality review by an independent body.　: We developed QIs to assess primary care services provided by clinics in Japan, for the first time. Although further refinement is required, establishment of these QIs is the first step in quality improvement for primary care practices in Japan.

Cerebral Microbleeds Detected Using 3.0T Magnetic Resonance Imaging in 2,003 Patients with Ischemic or Hemorrhagic Stroke

2019-05-16T08:30:01+09:00

: Compared with 1.5T magnetic resonance imaging (MRI), using 3.0T MRI makes it easier to detect cerebral microbleeds (CMBs). We used 3.0T MRI to investigate the backgrounds, risk factors, and number and location of CMBs in patients with ischemic or hemorrhagic stroke.　: We extracted data on clinical characteristics, risk factors, and number and location of CMBs in 2,003 patients treated between January 2010 and December 2014 within one week of stroke occurrence. We then carried out multivariate analysis of the data.　: CMBs were present in 1,025 patients. The numbers of CMBs in ischemic stroke and hemorrhagic stroke patients were 9,410 and 6,419, respectively. Patients with CMBs showed significantly higher rates of cognitive impairment (p < 0.001, odds ratio [OR] = 1.514), hypertension (p < 0.001, OR = 3.145), previous history of stroke (p < 0.001, OR = 1.782), and presence of hemorrhagic stroke (p < 0.001, OR = 2.066). The use of antithrombotic medication before the stroke did not affect the incidence of CMBs. In ischemic stroke patients, patients with small vessel occlusion had a significantly greater rate of previous history of hemorrhagic stroke (p = 0.046) and number of patients with CMBs (p < 0.001) than those with cardioembolism.　: CMBs were well observed in patients with small vessel disease, and hypertension was an important factor in ischemic and hemorrhagic stroke. Antithrombotic medication is not associated with the development of CMBs if adequate antihypertensive therapy is provided.

A Case Report of an Intrathoracic Mass Lesion Caused by 　 that Required Exclusion of a Malignant Tumor Diagnosis

2019-05-16T08:30:01+09:00

A 57-year-old man with untreated diabetes mellitus was admitted to our hospital due to an intrathoracic mass lesion infiltrating the vertebral body and mediastinum. The mass was suspected to be invasive lung cancer; however, percutaneous needle biopsy revealed that the mass was inflammatory granulation tissue caused by an 　 infection. To the best of our knowledge, this is the first report of an intrathoracic mass lesion caused by an 　 infection. When an intrathoracic mass lesion is suspected, clinicians should consider possible infections that cause granulation tissue, such as 　. This is particularly important in immunocompromized hosts such as patients with diabetes.

Vascular Complication after Collagenase Injection and Manipulation for Dupuytren’s Contracture: A Case Report

2019-05-16T08:30:01+09:00

A case of a vascular complication after collagenase injection and manipulation for Dupuytren’s contracture in a 57-year-old Japanese man is described. The patient presented with a 10-year history of worsening primary Dupuytren’s contracture. The metacarpophalangeal joint of his left little finger had a flexion contracture of 40° and was treated by collagenase injection. When the patient returned to our hospital for manipulation 24 hours later, however, his left little finger was almost completely improved because he hit his finger on the car’s gear lever. Then, 9 months after collagenase injection, in the first winter, he complained of a painful and pale left little finger occurring a few times a day, lasting for about 10 minutes. Now, two years after collagenase injection, the episodes of Raynaud’s phenomenon remain. Although Raynaud’s phenomenon after collagenase injection and manipulation for Dupuytren’s contracture is considered rare, it is a complication to be noted.

JMA Journal

Establishment of Integrated Biobank for Precision Medicine and Personalized Healthcare: The Tohoku Medical Megabank Project

Hepatocyte-like Cells Derived from Human Pluripotent Stem Cells Can Be Enriched by a Combination of Mitochondrial Content and Activated Leukocyte Cell Adhesion Molecule

Characteristics of Locomotive Syndrome in Japanese Patients with Chronic Pain and Results of a Path Analysis Confirming the Relevance of a Vicious Cycle Involving Locomotive Syndrome, Musculoskeletal Pain, and Its Psychological Factors

Refined Auditory Brainstem Response Measurement Identified Potential Models of Congenital Deafness in Laboratory Mouse Strains

Cardiac Sympathetic Hyperactivity of Lung Cancer-Associated Harlequin Syndrome

Strengthening the Healthcare System in Low- and Middle-income Countries by Integrating Emergency Care Capacities

Quality Improvement Based on Quality Indicators Editorial on the Article “Development and Pilot-testing of Quality Indicators for Primary Care in Japan”

Importance of Neuropathological Diagnosis of Dementia Patients in Family Practice

Multifaceted Evaluation of Ultra-high-field 9.4-T Magnetic Resonance Imaging after Inorganic Tattoos: An Animal Study

Do Preys Prey on Their Predators? Confusion over Predatory “Hage-taka” Journals

The Heart Failure “Pandemic” in Japan: Reconstruction of Health Care System in the Highly Aged Society

Development and Pilot Testing of Quality Indicators for Primary Care in Japan

Cerebral Microbleeds Detected Using 3.0T Magnetic Resonance Imaging in 2,003 Patients with Ischemic or Hemorrhagic Stroke

A Case Report of an Intrathoracic Mass Lesion Caused by that Required Exclusion of a Malignant Tumor Diagnosis

Vascular Complication after Collagenase Injection and Manipulation for Dupuytren’s Contracture: A Case Report

A Case Report of an Intrathoracic Mass Lesion Caused by 　 that Required Exclusion of a Malignant Tumor Diagnosis