The Oikawa-Nagao (ON) mouse is a polygenic animal model of type 2 diabetes and obesity developed by selective breeding of mice with inferior glucose tolerance [diabetes-prone (ON mouse DP^®; ON-DP) strain] and superior glucose tolerance [diabetes-resistant (ON mouse DR^®; ON-DR) strain]. Hybrid mice of three different inbred strains (C57BL/6, AKR, and AKR) were fed a high-fat diet and then selectively bred for higher and lower post-challenge blood glucose levels in oral glucose tolerance tests over 20 generations. Compared to ON-DR mice, ON-DP mice were found to be predisposed to develop obesity and diabetes after being fed a high-fat diet. Our recent studies suggest that the emergence of these phenotypes is associated with novel pathophysiology of type 2 diabetes and obesity, such as low insulin secretion capacity associated with high CD36 expression in pancreatic β-cells and hypoleptinemia preceding obesity due to low leptin secretion capacity in adipocytes. In addition, it has been suggested that ON-DP mice fed an atherogenic diet are a suitable model to reproduce atherosclerotic lesion formation due to fluctuations in blood glucose levels. This may facilitate the elucidation of mechanisms underlying diabetic macrovascular complications. This review will present the development strategy of the ON mouse strain, representative metabolic phenotypes and their underlying mechanisms. Furthermore, their relevance to the pathophysiology of type 2 diabetes and obesity in humans will be discussed.

Informed consent (IC) is closely related to shared decision making (SDM), and SDM can lead to IC. IC is fundamental to medical ethics as described in the Geneva, Helsinki, and Lisbon declarations and is essential for clinical practice, as it provides legal protection for healthcare professionals. IC should be achieved through SDM based on both narrative-based medicine and evidence-based medicine. SDM should also involve healthcare professionals other than physicians (e.g., nurses, pharmacists, social workers). Communication skills for IC are important and are encapsulated in the SPIKES protocol. IC for breast cancer treatment requires explanation of the roles of local and systemic therapy. A documented "do not attempt resuscitation" order should be obtained for end-of-life IC.

MicroRNA (miRNA) is a small RNA molecule that does not code for proteins, and organ- and disease-specific miRNAs are being investigated as diagnostic tools and therapeutic targets, particularly for cardiovascular disease and cancer. Much remains unknown about how anesthetics, other drugs, and perioperative management affect miRNAs, but miRNA-targeted drugs might eventually be used perioperatively. This review examines changes in miRNA expression related to anesthesia management. Sevoflurane results in gene expression patterns that differ by organ. The author investigated changes in miRNA expression induced by anesthetics in the brain, lungs, and liver and found that changes in miRNA expression differ by drug and organ. Since miRNA does not have a one-to-one correspondence with its target mRNA and exhibits complex effects within and between cells, as well as remotely, drug- and organ-specific changes in mRNA expression caused by anesthetics likely involve complex alterations. Cardiovascular disease and cancer are related to perioperative management via miRNAs. Inhalational anesthetics may exacerbate or suppress cellular activity, depending on the type of cancer, and the mechanisms of action differ depending on the inhalational anesthetic. These findings suggest that propofol is more likely to contribute to suppression of cancer cells through intercellular communication. The role of miRNA in perioperative management remains unclear. In the future, it is expected that changes in miRNA expression will be considered when selecting and administering anesthetic drugs perioperatively.

Background: The purpose of this study was to determine whether cases of placenta previa and low-lying placenta previa in patients with retroverted uterus are significantly associated with endometriosis. Methods: Participants were patients who underwent cesarean section at our hospital with a diagnosis of placenta previa or low-lying placenta previa within a 7-year period from January 2015 to December 2022. Of these, patients with multiple pregnancies and those without a complete uterine image in the medical record at less than 12 weeks' gestation were excluded. Included patients were divided into two groups according to the presence or absence of endometriosis. The presence of endometriosis was determined based on intraoperative findings. A retrospective case-control study was conducted by examining the presence or absence of retroverted uterus during early pregnancy and the presence or absence of posterior placenta. Results: A total of 110 patients were included, 32 in the group with endometriosis and 78 in the group without endometriosis. There were 15 (46.9%) cases of retroverted uterus in the group with endometriosis and 17 (21.8%) in the group without endometriosis, indicating significantly more cases in the group with endometriosis (P=0.01). There were 15 (46.9%) cases of retroverted uterus with posterior placenta in the group with endometriosis and 16 cases (20.5%) in the group without endometriosis, indicating significantly more cases in the group with endometriosis (P=0.009). Conclusion: Placenta previa and low-lying placenta previa in cases of retroverted uterus are significantly associated with endometriosis.

Background: Osteoporosis-related fragility fractures such as proximal femoral and vertebral fractures are associated with decreased activities of daily living and a shorter life span. Many persons with osteoporosis do not receive testing or treatment. Introducing fracture liaison services (FLSs) to hospitals is an effective approach for reducing this treatment gap. Understanding interest in osteoporosis among nurses and physicians, their knowledge of osteoporosis, and their thoughts on team medicine for treatment of osteoporosis might be helpful when implementing FLSs. Methods: An FLS had not been introduced at our hospital. We conducted a questionnaire survey of nurses and physicians at our hospital regarding their interest in osteoporosis, their knowledge of osteoporosis, and their thoughts on team medicine for osteoporosis. Results: About half of the nurses and physicians were interested in osteoporosis. About 70% of nurses and physicians believed that team medicine was necessary for treating osteoporosis, and 50-60% believed that it should be introduced in the hospital. Only 5% of nurses and 18% of physicians had knowledge of FLSs. Conclusion: Staff perceptions of team care for osteoporosis were generally supportive in our hospital. However, the introduction of an FLS to the hospital required educational activities for staff. The results of this survey will be helpful to other hospitals introducing FLSs.

Background: Diagnosis of bone metastases would be hastened if they could be detected on plain radiographs obtained at the first visit to an orthopedic surgeon. However, lesions are often undetectable on plain radiography. Bone metastasis is diagnosed at the first visit in only a few patients, and diagnosis is delayed in many cases. We investigated the diagnostic performance of plain radiography that used a new image processing method, Dynamic Visualization II (DV), to diagnose bone metastases. Methods: We enrolled 29 patients with symptomatic pelvic bone metastases who visited our hospital between April 2018 and March 2021. The evaluation images were created by processing the original plain radiography data with the default settings for DV (Presets 1-4). Processing with Preset 1 resulted in an image converted to conventional film parameters, whereas Presets 2-4 utilized different DV processing methods. The readers were six orthopedic trainees, and the reading time was 30 seconds per image. The rate of correct answers for images processed with Preset 1 was compared to the rates for those processed with the other presets. Additionally, the rate of correct answers was analyzed in relation to clinical variables. Results: The correct answer rate was significantly higher for Preset 3 (43.7%) and Preset 4 (42.5%) than for Preset 1 (28.7%). Correct answer rates for Presets 3 and 4 were significantly higher for elderly patients, male patients, patients with innominate bone lesions, patients with osteolytic bone metastases, and patients with a normal body weight. Conclusions: Image processing by DV improved diagnosis of bone metastases by plain radiography. DV might hasten diagnosis of bone metastases and help prevent associated complications.

Background: Although advances in neoadjuvant chemotherapy (NAC) are improving the rate of pathological complete response (pCR) and outcomes for triple-negative breast cancer (TNBC) patients, the prognosis remains poor. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression was recently reported to be associated with chemotherapy resistance and poor prognosis in TNBC. Methods: We evaluated IMP3 expression in 40 female TNBC patients to assess its association with NAC sensitivity and outcome. Results: Among the cohort, 11 patients (27.5%) had IMP3-positive TNBC, which was associated with a higher Ki-67 labeling index (p = 0.119), indicating greater malignancy. However, IMP3 positivity showed no significant correlation with NAC resistance or differences in disease-free survival (DFS) as compared with IMP3-negative patients. Conclusions: Patients receiving effective immunotherapy or high-dose chemotherapy achieved pCR regardless of IMP3 status, which suggests that the NAC regimen is more important than IMP3 status for pCR. Even in IMP3-positive TNBC, NAC may improve prognosis by achieving pCR. Thus, while IMP3 might predict poor prognosis, it may not serve as a definitive marker in the context of NAC. Because IMP3 is involved in cancer stem cell (CSC) function, further research is necessary to understand its complex role in CSCs and TNBC.

Background: Both ultraviolet B (UVB) phototherapy with 308-nm excimer light and excimer laser devices are widely used to treat vitiligo. While the devices share the 308-nm wavelength, they have distinct characteristics. Notably, the excimer laser exhibits laser properties (monochromatic coherent light) and unique device specifications (a high frequency of 400 Hz and a remarkably high irradiance of 83 million mW/cm²). This study compared excimer light and laser irradiation, focusing on the depth of penetration into hair follicles and the effects on activation of melanocyte lineage cells, including melanocyte stem cells (McSCs) and melanoblasts. Methods: We irradiated the dorsal skin of mice with both devices at 1,000 mJ/cm². Samples taken at 15 min and 3, 24, and 72 h after irradiation were used for immunostaining analysis. We evaluated penetration depth by using the staining pattern of cyclobutane pyrimidine dimers (CPDs), induction of apoptosis by using a terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate nick end-labeling (TUNEL) assay, and activation of melanocyte lineage cells by using fluorescent double immunostaining for TRP2 and β-catenin. Results: The excimer laser induced significantly more CPDs in the deeper regions of hair follicles while causing significantly faster removal of CPDs and less apoptosis in the epidermis. Moreover, the percentage of TRP2-positive cells with nuclear β-catenin in the follicles was significantly higher with the excimer laser. Conclusions: As compared with excimer light, the excimer laser penetrated more deeply into hair follicles, resulted in fewer epidermal side effects, and activated significantly more melanocyte-lineage cells.

Background: We evaluated the effects of drug therapy on T lymphocyte subsets and their associations with recurrent chronic bronchitis (CB) attacks. Methods: A total of 162 CB patients treated from April 2020 to April 2021 were selected. All patients underwent anti-infective, cough-relieving, and phlegm-eliminating treatment, as detailed in Clinical Pathway for Chronic Bronchitis. They were divided into a recurrent attack group (n=95) and a non-recurrent attack group (n=67). Changes in T lymphocyte subsets at different time points of treatment and their associations with the number of attacks were analyzed. Associated factors were analyzed in a multivariate logistic regression model, and their predictive value was validated using a nomogram prediction model and receiver operating characteristic (ROC) curves. Results: The number of attacks at 1 year after treatment was positively correlated with CD8⁺ and negatively correlated with CD3⁺, CD4⁺, and CD4⁺/CD8⁺. A history of smoking, CD3⁺, CD4⁺, CD8⁺, and CD4⁺/CD8⁺ were independent risk factors for recurrent attacks. The nomogram prediction model showed that the total risk value corresponding to smoking history, low CD3⁺, CD4⁺, and CD4⁺/CD8⁺, and elevated CD8⁺ was 0.86, and the concordance index and area under the ROC curve of the model was 0.896 (95% CI: 0.782-0.997, P<0.05) and 0.816 (95% CI: 0.803-0.847, P<0.001), respectively. There was an association between T lymphocyte subsets and recurrent attacks before and after treatment of CB. Conclusions: Low CD3⁺, CD4⁺/CD8⁺ and CD4⁺, elevated CD8⁺, and smoking history were risk factors for recurrent attack.

Background: We retrospectively examined image quality (IQ) of thin-slice virtual monochromatic imaging (VMI) of half-iodine-load, abdominopelvic, contrast-enhanced CT (CECT) by dual-energy CT (DECT) with deep learning image reconstruction (DLIR). Methods: In 28 oncology patients with moderate-to-severe renal impairment undergoing half-iodine-load (300 mgI/kg) CECT by DECT during the nephrographic phase, we reconstructed VMI at 40-70 keV with a slice thickness of 0.625 mm using filtered back-projection (FBP), hybrid iterative reconstruction (HIR), and DLIR; measured contrast-noise ratio (CNR) of the liver, spleen, aorta, portal vein, and prostate/uterus; and determined the optimal keV to achieve the maximal CNR. At the optimal keV, two independent radiologists compared each organ's CNR and subjective IQ scores among FBP, HIR, and DLIR to subjectively grade image noise, contrast, sharpness, delineation of small structures, and overall IQ. Results: CNR of each organ increased continuously from 70 to 40 keV using FBP, HIR, and DLIR. At 40 keV, CNR of the prostate/uterus was significantly higher with DLIR than with FBP; however, CNR was similar between FBP and HIR and between HIR and DLIR. The CNR of all other organs increased significantly from FBP to HIR to DLIR (P < 0.05). All IQ scores significantly improved from FBP to HIR to DLIR (P < 0.05) and were acceptable in all patients with DLIR only. Conclusions: The combination of 40 keV and DLIR offers the maximal CNR and a subjectively acceptable IQ for thin-slice VMI of half-iodine-load CECT.

Background: In the field of orthopedics, few studies have examined pain associated with soft tissue tumors. To accurately and promptly diagnose soft tissue tumors and provide appropriate treatment, it is necessary to have a comprehensive understanding of the relationship between soft tissue tumors and pain. Methods: We analyzed data from patients with mass lesions in the extremities or trunk diagnosed by biopsy or surgery in our department and patients with ganglion cysts diagnosed by puncture between October 1, 2005, and September 30, 2011. Using medical records, we retrospectively investigated the clinical data. Results: Data from 473 patients with 482 lesions were analyzed. Pain was observed in 204 of the 482 lesions (42.3%). So-called painful tumors accounted for approximately half of the painful lesions (45.0%). Logistic regression indicated that pain was significantly associated with so-called painful tumors (odds ratio [OR]: 5.64; P < 0.001), inflammatory nodules (OR: 3.42; P = 0.007), and sites with strong physical stimulation (OR: 2.45; 95% confidence interval [CI]: 1.58-3.81; P < 0.001) but not with long diameter (OR: 0.90; P = 0.001) or malignancy (OR: 1.78; P = 0.144). Conclusion: Our findings suggest that so-called painful tumors account for approximately half of soft tissue mass lesions requiring surgery, biopsy, or puncture in orthopedics. It is thus important to have a clear understanding of such tumors. Inflammatory nodules are also important in the differential diagnosis of painful soft tissue lesions. Lesions at sites exposed to strong physical stimulation can cause pain.

Background: Psoriasis is accompanied by systemic inflammation that includes the liver. The fibrosis-4 (FIB-4) index was developed to predict significant liver fibrosis. The present study evaluated the effects of biologics, including TNF inhibitors, on the FIB-4 index in psoriasis patients. Methods: All adult patients with psoriasis who were prescribed biologics (TNF inhibitors, IL-17 inhibitors, or IL-23 inhibitors) at Nippon Medical School from June 2014 to January 2024 for the first time (biologic-naïve patients) were included in this study. The FIB-4 index was calculated before and after 6 months of treatment with biologics. Results: A total of 105 patients were enrolled. The FIB-4 index was higher after 6 months of treatment with TNF inhibitors (P=0.0018) and IL-17 inhibitors (P=0.045) but did not change with IL-23 inhibitors. Aspartate aminotransferase and alanine aminotransferase levels did not change after treatment with TNF inhibitors, IL-17 inhibitors, or IL-23 inhibitors. Platelet count decreased after treatment with TNF inhibitors (P=0.0011) and IL-23 inhibitors (P=0.039) but did not change with IL-17 inhibitors. Conclusions: Downregulation of platelets seems to be a major contributing factor for the increase in FIB-4 index in patients treated with TNF inhibitors. Although the FIB-4 index is a simple marker to screen for liver fibrosis, changes in this index should be interpreted with caution, and imaging findings such as transient elastography should also be used to evaluate the status of liver fibrosis.

Background: Rapid treatment of patients with emergency large vessel occlusion (ELVO) improves outcomes. With Vitrea software, the cerebral infarct size and penumbra can be quantified, and 4D images can be constructed quickly. We investigated the performance of Vitrea in ELVO patients. Methods: To evaluate indications for mechanical thrombectomy, we performed plain brain CT, then MRI (group 1, n=30). In May 2022 we acquired perfusion CT scans with Vitrea after plain CT on the same equipment (group 2, n=27) and then compared time from onset to the end of mechanical thrombectomy. At 1 month post-treatment we recorded the neurological outcome by using the modified Rankin scale (mRS). We also compared the infarction areas identified with Vitrea and MRI the day after treatment using DWI-ASPECTS in 25 of 27 patients in group 2. We excluded 2 patients with basilar artery occlusion because this type of occlusion is not included in DWI-ASPECTS. Results: There were no significant intergroup differences in patient characteristics, time from admission or puncture to re-canalization, and outcome 1 month after treatment. Vitrea overestimated the infarct area in 1 of 25 patients (4.0%). Times from admission to transit for examination, to the examination end, and time from admission to puncture, were significantly shorter in group 2. Conclusions: In ascertaining indications for thrombectomy in patients with acute cerebral stroke, perfusion CT with Vitrea shortened time to treatment. However, further investigation is needed to confirm the accuracy of Vitrea in determining the infarct area.

Simple radiography is the most frequently and widely available technology to examine bone pathologies. Computed tomography (CT) can evaluate pathologies more accurately in multiple planes and three dimensions; however, radiation exposure is much higher than with simple radiography. In addition, diagnostic ability is decreased for both technologies when metal devices are present. Tomosynthesis is a radiographic technology used to evaluate tissues quasi-three-dimensionally with less radiation exposure. Tomosynthesis technology was recently upgraded to reduce the effects of metal artifacts. This case report compares examination time, medical expense, image resolution, and radiation exposure for upgraded tomosynthesis, simple radiography, CT, and standard tomosynthesis in three patients with metal devices in the affected knees. Examination times were similar for the imaging technologies. Diagnostic performance was better for upgraded tomosynthesis than for simple radiography and standard tomosynthesis, and similar to that for CT. Moreover, radiation exposure and expense were higher for tomosynthesis than for simple radiography but lower than for CT. These findings suggest that upgraded tomosynthesis is the best method for evaluating bone pathology when metal devices are present and radiation exposure must be limited.

Sellar reconstruction is important for preventing cerebrospinal fluid (CSF) leakage after transsphenoidal pituitary surgery. This report describes how, despite standard sellar reconstruction, CSF exudation resulted from dural thinning at the anterior skull base, outside the intrasellar area manipulated during pituitary tumor resection. A 76-year-old man underwent endoscopic transsphenoidal surgery for a pituitary tumor extending toward the anterior skull base. After opening the sellar floor, intractable bleeding from the anterior intercavernous sinus occurred during bone removal at the anterior skull base. Pseudocapsule-based extracapsular resection was completed after stopping the bleeding. On the 10th postoperative day, the patient developed CSF rhinorrhea complicated by marked pneumocephalus, and emergency endoscopic repair of the CSF leak was performed. CSF leakage originated from the thinned dura at the anterior skull base located outside the intrasellar area manipulated during tumor resection. The thinned dural area at the anterior skull base coincided with the site of intractable bleeding of the anterior intercavernous sinus during bone removal in tumor resection. The thinned anterior skull base dura was covered with fascia, overlaid with fat, and closed with the nasoseptal flap. Endoscopic CSF leak repair was successful. Severe damage to the anterior intercavernous sinus can cause extensive exposure of the single-layered inner meningeal dura, where thinning might result in CSF exudation. Therefore, use of autologous tissues to cover and reinforce the severely damaged area of the anterior intercavernous sinus might help prevent postoperative CSF exudation.

A 56-year-old right-handed man was referred to our hospital for evaluation of sudden-onset transient quadrantanopia, which was followed by throbbing headache consistent with migraine with aura (MA). Magnetic resonance imaging (MRI) of the right parieto-occipital cortex on admission showed a hyperintense region on diffusion-weighted imaging, which disappeared 7 days later. A small cortical infarct in the parieto-occipital cortex can cause MA-like headache, and the present infarct lesion was only detectable on MRI during the acute phase. Performing MRI for patients with suspected acute MA might help identify the cause of MA-like headache and ensure appropriate management of patients.