BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

The importance of promoting self-medication is increasing, and the active participation of pharmacies is required to support this. We developed a training program based on the Attention, Relevance, Confidence, and Satisfaction (ARCS) model, which is a motivational design process to train pharmacists who support the proper use of OTC drugs, and for insurance pharmacists who usually perform dispensing work. In the six months of training, we conducted six sessions for insurance pharmacists on the subject of colds and constipation. In addition to conducting lectures and exercises on OTC drugs, we provided pharmacists with an opportunity to practice the training content during their daily work, and discuss solutions to the problems that they encountered. Of the eight participants who attended all workshops and were part of the final evaluation, seven provided OTC drugs after considering whether it was necessary to provide them. A total of six advised patients who came to the pharmacy to have their prescription medications dispensed that there were OTC medications that they should be careful about taking. These results suggest the usefulness of this training program based on the ARCS motivational design model.

Abstract: We report a case of intractable pain in a patient with amyotrophic lateral sclerosis (ALS) that was successfully managed by administering a fentanyl transdermal patch. Case: A 75-year-old man was diagnosed with ALS in 2013 after he became aware of difficulty in walking and systemic pain since 2010. In 2019, he underwent gastrostomy and tracheostomy, and intractable generalized pain necessitated the administration of morphine hydrochloride six times a day; however, it could not provide adequate pain relief. Later, morphine was replaced with a fentanyl patch under a very strict safe-monitored setting and the pain became bearable. Discussion: Although high-level evidence is lacking, pain experts have reported the effectiveness of morphine for intractable pain in patients with ALS. Frequent short-acting morphine dosing is often burdensome due to the complexity of its administration and it also causes end-of-dose pain. A fentanyl patch may possibly improve these drawbacks.

Lenvatinib hasapplicationsin thyroid and hepatocellular carcinomas. When lenvatinib wasapproved for hepatocellular carcinoma in Japan, the manufacturer noted an increase of 5% in the incidence of side effects than those observed in thyroid cancer, based on the clinical-trial data. The monitoring of side effectsisimportant during chemotherapy. It isdifficult to confirm all the side effects within a single practice, and it is important to consider the incidence and severity of side effects before prescribing a particular treatment regimen. An antineoplastic agent is often used for different diseases, and it may be difficult to confirm a specific side effect. Because clinical conditions vary among different diseases, it is likely that the onset of side effects also differs. We investigated the difference between the onset of side effects in thyroid and hepatocellular carcinomas using the Japanese Adverse Drug Event Report database. The main side effects reported for thyroid cancer included bleeding, hypertension, cardiac disorders, myelosuppression,acute cholecystitis, delayed wound healing, infection, gastrointestinal perforation, fistula formation, and pneumothorax. In addition,patients with hepatocellular carcinoma experienced liver damage and hepatic encephalopathy. A significant strong correlation was observed between the drug dose and number of reports of the varied side effects. We compared the side effects in patients with thyroid cancer to those with hepatocellular carcinoma; although the same drug was used, there was varied expression of the side effects. Thisneedsto be taken into account when determining which drugsare to be used for the treatment of a particular cancer type.

Objective: The importance of occupational exposure control in cancer therapy is widely recognized, and measurement of anti-cancer drug exposure during preparation, as well as comprehensive measures, including administrative control, patients’ excrements, and environmental pollution, among others, are becoming important. The Osaka Women’s and Children’s Hospital introduced the closed system drug transfer device (CSTD) for administering anticancer drugs, and conducted consistent exposure measures from preparation to disposal. We simultaneously conducted an awareness survey on anti-cancer drug exposure measures for health care workers,observed the changes in their awareness and behavior, and examined the issues that constantly challenge anti-cancer drug exposure measures.Method: We surveyed doctors, nurses, and pharmacists who handle anticancer drugs belonging to the Osaka Women’s and Children’s Hospital from March 2018 to October 2018. The questionnaire was anonymous and was collected within one week after distribution. In the questionnaire survey, we obtained permission to present the contents on paper and orally.Results: The questionnaire response rate was approximately 70%. Following the training and introduction sessions, the participants had an improved understanding of Hazardous Drugs and CSTD. The introduction of the workshops on anti-cancer drug exposure measures and CSTD encouraged the nurses to reflect on the exposure measures and revisit the manuals on in-hospital treatment with anti-cancer drugs; however, there was little or no change in the behavior of the pharmacists.Discussion: Since nurses work primarily in the field of patient care, their awareness of anti-cancer drugs has gradually declined, and it was observed that procedures for exposure control were not being followed. In order to ensure that anti-cancer drug exposure measures are properly observed, pharmacists need to take initiatives and conduct in-hospital workshops once every six months. It is also necessary to educate the medical staff about electronic devices in order to ensure their easy participation in workshops and encourage e-learning.

BACKGROUND: The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population. METHODS: We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA). RESULTS: We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA). CONCLUSIONS We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.
Adult ; Aged ; Aged, 80 and over ; Atherosclerosis ; epidemiology ; etiology ; Biomarkers ; Carotid Intima-Media Thickness ; statistics & numerical data ; Cross-Sectional Studies ; Female ; Humans ; Japan ; epidemiology ; Male ; Middle Aged ; Oxidation-Reduction ; Risk Factors ; Serum Albumin ; metabolism ; Serum Albumin, Human ; metabolism

OBJECTIVE: It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. METHODS: Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. RESULTS: Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. CONCLUSION: Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan.
Agranulocytosis ; Clozapine* ; Constipation ; Delivery of Health Care* ; Hand ; Humans ; Japan* ; Patient Satisfaction ; Psychiatry ; Schizophrenia* ; Sialorrhea ; Sleep Stages

Purpose: This study aimed at identifying difficulties among post thoracic esophagectomy cancer patients during outpatient follow-up. Methods: Patients who had radical esophagectomy at a cancer center hospital in Japan were prospectively observed and were interviewed by a certified nurse assigned at esophageal surgical outpatient division. Their responses were documented in medical records and were analyzed by content analysis method. This study was approved by the study hospital's research ethics committee. Results: The data from 66 patients were obtained. Content analysis yielded 221 extracts, 25 categories, and 65 codes of difficulties, including: concerns or signs/symptoms associated with dietary intake, physical activity, and anxiety. Implications: The majority of post-thoracoabdominal esophagectomy patients experienced multiple dysfunctions and symptoms after discharge. The results underscore the significance of nurses' role in assessing and instructing patients to address these issues.

Background: Patients having thoracic esophagectomy, a standardized treatment for esophageal cancer patients in Japan, are known to have various postsurgical signs and symptoms for a period of time. The current status of nursing interventions at outpatients need to be clarified. Purpose: This study aimed at identifying the nurses' interventions for cancer patients at the outpatient setting who previously had thoracic radical esophagectomy. Methods: Patients who had esophagectomy at a cancer center hospital in Japan were prospectively observed and interviewed by outpatient nurses between January 2009 and December 2010. Their documented responses in medical record were prospectively investigated and were qualitatively analyzed via content analysis method. This study was approved by the study hospital's research ethics committee. Results and discussion: The data analysis of nursing interventions for 66 patients yielded 372 extracts, 12 categories, and 74 codes. Nurses were assessing patients' signs and symptoms affected by postsurgical changes, and were utilizing patients' active self-monitoring skills. The results also showed the significance of facilitating postsurgical recovery in relation to nutritional intake and physical activity in patients' daily life. Implications: Based upon the study results, the development of a systematic program is underway, which facilitates esophageal cancer patients' postsurgical recovery.

With aging of inpatients, the prevention of falls in old people is an important task nurses have to take upon themselves. In our hospital, we have been tackling the task in earnest by utilizing a fall prevention assessment score sheet. Our efforts have resulted in changes in the attitude of nurses as shown by a survey. (1) By working on the nursing plan with use of the fall prevention assessment score sheet, nurses have become alert to risk factors for falling. (2) They have realized that assistance suited to the needs of each patient is vital and that collaboration between patients, their families and hospital staff contributes to the prevention of falls greatly. (3) The use of an intervention manual has made it easy for nurses to cope with falls and consequent injury. (4) To share information of every factor for falling among the nursing staff has added greatly to the prevention of the recurrence of the fall.
Prevention ; Fall, NOS ; Surveys ; Attitude ; Knowledge acquisition using a method of assessment