Sleep disordered breathing, represented by sleep apnea syndrome, not only significantly reduces the quality of daily life but is also known to contribute to the development of various cardiovascular diseases. Since 2000, sleep apnea syndrome has become widely recognized by the general public. However, the number of suspected patients who seek medical consultation remains low, and even fewer receive a proper diagnosis and treatment. One reason for this is the lack of information that apnea is linked to cardiovascular disease, even among individuals experiencing typical sleep apnea syndrome symptoms such as daytime sleepiness and general fatigue. Additionally, healthcare providers may not be effectively guiding patients while providing sleep hygiene education. Furthermore, the limited number of medical facilities and technicians capable of conducting overnight polysomnography tests for diagnosing sleep disordered breathing is another factor preventing more patients from benefiting from treatment. This article explores the relationship between sleep disordered breathing and the onset of cardiovascular diseases, as well as the latest treatment approaches.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a significant global health concern, affecting approximately 30% of the population. In Japan, its prevalence is also rising rapidly and is expected to reach 50% by 2040. This situation can be described as a “MASLD pandemic”, emphasizing the urgent need for effective therapeutic interventions. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that play essential roles in lipid metabolism, inflammation regulation, and fibrosis modulation. Among them, PPARα is a key regulator of lipid homeostasis, primarily expressed in the liver and other metabolically active tissues. Its activation promotes fatty acid oxidation and improves lipid profiles, making it a crucial target for metabolic disorders. In Japan, a novel selective PPARα modulator (SPPARMα) was developed as a lipid-lowering agent for treating dyslipidemia. Over time, increasing clinical evidence has suggested that SPPARMα has beneficial effects on MASLD patients’ liver function. This review aims to summarize the therapeutic potential of SPPARMα in MASLD by examining the functional mechanisms of PPARα, preclinical studies in animal models, and accumulating clinical evidence from MASLD patients. Furthermore, we provide an overview of ongoing clinical trials investigating SPPARMα for MASLD treatment.

Background Despite evidence regarding the effectiveness of screening and brief interventions for excessive alcohol consumption, these interventions are not widely used. Although several studies have suggested that face-to-face interventions in the workplace may be effective, developing an implementable intervention strategy for alcohol users, including light drinkers, is warranted. This study aimed to develop a study protocol to evaluate the effect of providing an educational leaflet at the workplace on reducing hazardous or harmful alcohol use.

Methods A randomized controlled trial involving employees (aged ≥ 20 years) of a local administrative office in Japan who were screened using the Alcohol Use Disorder Identification Test (AUDIT) is ongoing. Participants were randomized into “Educational leaflet” and “Control (no intervention)” groups. The primary outcome was the difference in negative status on the AUDIT (proportion of participants scoring < 8 points on the AUDIT) between the intervention and control groups in the following year. For the secondary outcomes, laboratory marker data at annual health checkups were collected and assessed.

Results A total of 400 participants were randomized into educational leaflet (n = 200) and control (n = 200) groups. The basic characteristics of all participants included sex (men 79.3%; women 20.8%), mean (standard deviation) of age 48.5 (9.7 years), 40.0% of AUDIT ≥ 8 points, 46.8% of drinking alcohol ≥ 4 times a week, and 33.8% of heavy episodic drinking. No significant differences were observed between the intervention and control groups in terms of the baseline variables.

Conclusions This study protocol developed the first trial in Japan to investigate the impact of providing an educational leaflet after screening for hazardous and harmful alcohol use in a workplace setting. The findings of this study can provide the first evidence that an implementable alcohol intervention strategy targeting alcohol users, including light drinkers in the workplace, is effective in reducing hazardous or harmful alcohol use.

Background Metronomic photodynamic therapy (mPDT) is a novel cancer treatment strategy that uses low-dose light delivery and photosensitizers. 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX) was previously used to treat human colorectal and esophageal cancer cells. However, no study has evaluated the efficacy of 5-ALA-mPDT using light of different wavelengths. Therefore, we evaluated cytotoxicity induced by 5-ALA-PDT and the antitumor effect of 5-ALA-mPDT.

Methods In an in vitro experiment, we evaluated the cytotoxicity induced by 5-ALA-PDT using several fluence rates of light-emitting diode (LED) at wavelengths of 532 and 620 nm. In an in vivo experiment, we evaluated the antitumor effect of 5-ALA-mPDT using a newly developed implantable device emitting 532 or 620 nm. Moreover, we used in silico simulations to compare the differences in the distribution of the accumulated singlet oxygen concentrations between 532 and 620 nm.

Results In the in vitro experiment, the percentages of late apoptotic/Dead and Dead cells in the 542-nm groups irradiated at light intensities of 1 mW/cm² were significantly higher than those of cells in the 620-nm group. In contrast, in the in vivo experiment, the antitumor effect of mPDT using an implantable organic light-emitting diode (OLED) at 620 nm was significantly higher than that of mPDT using OLED at 542 nm.

Conclusion Considering the results of our in silico study, the antitumor effect of 5-ALA-mPDT may be dependent on the distribution range of the accumulated singlet oxygen concentration rather than the accumulated singlet oxygen concentration.

Background Epilepsy patients often exhibit symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). This study aimed to compare the clinical characteristics of epilepsy in patients comorbid with ADHD/ASD and those diagnosed with ADHD/ASD after epilepsy onset.

Methods We retrospectively reviewed patients under 18 years of age with epilepsy who visited Tottori University Hospital’s Child Neurology Department during 2013–2022. Eligible patients had at least 2 years of follow-up after epilepsy onset and were taking antiseizure medication (ASM). We excluded those with epileptic encephalopathy, abnormal perinatal history, imaging abnormalities, or intellectual disabilities. We compared clinical characteristics between epilepsy patients with and without ADHD/ASD.

Results Data were collected from 28 patients with ADHD/ASD and 87 without. Patients with ADHD/ASD had an earlier seizure onset (6.6 ± 3.9 vs. 8.7 ± 4.1 years, P = 0.018) and were more likely to receive ASM polytherapy (39% vs. 16%, P = 0.010). Seizure outcomes did not differ between the two groups. Of the 28 patients with ADHD/ASD, 11 were diagnosed after epilepsy onset, and these patients were more likely to require multiple ASMs than those without ADHD/ASD (45% vs. 16%, P = 0.035).

Conclusion Patients comorbid with ADHD/ASD tend to have earlier seizure onset and require more ASM, while those diagnosed with ADHD/ASD after epilepsy onset also often need polytherapy. These findings suggest that severe early epilepsy can lead to developmental disorders, though long-term seizure outcomes are not necessarily poor in these patients.

Background Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) and is a risk factor for liver cancer. This study investigated the anti-fibrotic effect of the Wnt/β-catenin signalling inhibitor HC-1 in human hepatic stellate cells and a mouse liver fibrosis model.

Methods The effects of HC-1 on Wnt/β-catenin and transforming growth factor (TGF)-β/Smad signalings were examined by a reporter assay. The effects of HC-1 on the mRNA expression of fibrogenesis- and fibrolysis-related genes were analysed after 24 and 48 h of exposure of HC-1. In the animal study, 30 male C57/BL6 mice treated with CCl₄ for 4 weeks were divided into three groups, namely vehicle, 8.7 mg/kg HC-1 and 17.4 mg/kg HC-1, respectively. Mice in the vehicle group underwent continued treatment with CCl₄, whereas those in the HC-1 groups were treated with both CCl₄ and HC-1 for another 4 weeks. The livers of mice were examined by histological and biochemical analyses.

Results HC-1 decreased Wnt/β-catenin and TGF-β/Smad signallings. HC-1 potently reduced the mRNA expression of α-smooth muscle actin, collagen 1A1, TGF-β and lysyl oxidase. Conversely, HC-1 increased matrix metalloproteinase-1 expression in a concentration-dependent manner. In the animal model, HC-1 treatment significantly suppressed liver fibrosis in association with the inhibition of activated hepatic stellate cells. Although the Mmp-13, the murine functional homologue of MMP-1, was not increased, collagenase activity was increased in 8.7 mg/kg HC-1 group.

Conclusion HC-1 exerts potent anti-fibrotic effects on liver fibrosis.

Background The number of hikikomori individuals has been increasing not only in Japan but also worldwide while few studies have looked into the societal elements that could lead to further isolation of hikikomori individuals. This study examines the psychological factors in local residents related to social exclusion of hikikomori individuals.

Methods 365 participants living in Tottori, Japan were analyzed. The questionnaire includes key questions such as social exclusion of hikikomori individuals, daily lifestyle, personal opinions and attitudes towards hikikomori individuals.

Results Those who are unwilling to interact with people who have different sense of values were 3.6 times likely to exclude hikikomori individuals than those who did not. Those who believe that hikikomori is a family issue so that others should not intervene were 2.2 times likely to exclude them than those who did not. Conversely, those who think that people can make a fresh start in the society even after making mistakes were 0.5 times likely to exclude hikikomori than those who did not. Those who feel that they have something in common with hikikomori individuals were 0.4 times likely to exclude them than those who did not. Those who think that they can enjoy activities such as hobbies together with hikikomori individuals were 0.3 times likely to exclude them than those who did not.

Conclusion The analysis indicates that the tendency to reject relationships with people who have different sense of values and the opinion that hikikomori is a family issue are the risk factors for social exclusion of hikikomori individuals. Contrarily, the opinion that even if we make a mistake or fail, we can make a fresh start, awareness of the similarities between oneself and hikikomori individuals, and willingness to share enjoyable activities with them are shown to be the protective factors which could reduce social exclusion of hikikomori.

The number of reports of robotic surgery for rectal cancer with combined resection of other organs is increasing gradually, with most procedures performed using the da Vinci Surgical System. The hinotori Surgical Robot System, developed in Japan, was approved for gastrointestinal surgery and gynecology in 2022. Here, we report the first case of en-bloc rectal resection with hysterectomy using the hinotori Surgical Robot System. A 77-year-old woman was referred to our institution with a diagnosis of rectal cancer (cT4bN1bM1a), with uterine invasion and a resectable liver metastasis. We performed rectal resection with total hysterectomy and bilateral salpingo-oophorectomy using the hinotori Surgical Robot System. Two surgical teams, a gastroenterological team and a gynecological team, performed en-bloc resection of the rectum and uterus. Because of in-depth consultation between the teams, the operation was performed safely with no unplanned additional ports, robotic arm interference or arm collision with the assistant surgeon. Including the preceding stoma closure, the operative time was 473 minutes, and blood loss was 60 mL. The patient experienced no complications ≥ Clavien–Dindo classification grade III. Robot-assisted extended surgery for locally advanced rectal cancer using the hinotori Surgical Robot System can be performed safely, which may lead to an expanded treatment option in the future.

Coronavirus disease 2019 (COVID-19) is a significant risk factor for autonomic dysfunction, with approximately 20% of COVID-19-infected children suffering from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). The autonomic nervous system regulates functions like blood pressure and heart rate, and the disruption of the system can lead to issues such as postural orthostatic tachycardia syndrome (POTS) and orthostatic dysregulation (OD). Individuals with autonomic dysfunction may have a heightened risk of sudden death during diving activities. We report the case of a patient who drowned after diving in a bathtub following COVID-19 infection. The patient exhibited findings consistent with POTS during the head-up tilt test (HUTT), suggesting the influence of autonomic dysregulation. A healthy 9-year-old boy had a mild COVID-19 infection. He recovered but experienced difficulty getting out of bed. Nevertheless, his daily activities remained largely unaffected. On the 11th day post-infection, he lost consciousness while diving in a bathtub and was quickly rescued by his father. Initial assessments revealed mild aspiration pneumonia and OD. On day 20, a HUTT revealed tachycardia, confirming POTS. Bathing alone was prohibited, and a reevaluation three months later indicated subjective symptom improvement, with no evidence of POTS during HUTT. This case highlights the potential association between mild autonomic dysfunction post-COVID-19 and increased drowning risk during cardiovascular-intensive activities like diving. Even when subjective symptoms are minimal, using tests such as HUTT to assess potential underlying autonomic dysfunction can help prevent secondary accidents.

Papillary renal neoplasm with reverse polarity (PRNRP) is a distinct subtype of papillary renal tumors first described in 2019. Here, we present the imaging and histopathological findings of two cases of PRNRP. Case 1 involved a 71-year-old man with an incidental right renal mass. A 30 mm tumor in the right kidney exhibited iso- to slight hyperattenuation on non-contrast computed tomography (CT). Dynamic contrast-enhanced (DCE)-CT revealed a tumor with solid and cystic components. The solid portion showed mild enhancement, followed by gradual enhancement. Regarding magnetic resonance imaging (MRI), the cystic component revealed mild hyperintensity on T2-weighted imaging (WI) and hyperintensity on T1WI. The small, lobulated solid component showed hyperintensity on T2WI and no apparent hyperintensity on diffusion-weighted imaging, with high ADC values. Case 2 involved a 74-year-old woman with a gradually enlarging left renal mass. A 20 mm tumor in the left kidney showed heterogeneous mild hyperattenuation on non-contrast CT. On DCE-CT, a small solid component exhibited mild enhancement, followed by gradual enhancement. Retrospectively, the mass showed an 8 mm homogeneous nodule on CT images obtained 7 years earlier. Although the tumor appears heterogeneous on CT, a small PRNRP may exhibit homogeneous attenuation. Additionally, the solid portion can show T2 hyperintensity related to stromal edema. Recognition of these imaging variations is important for the correct diagnosis of PRNRP.

Herein, we report the case of a 60-year-old female patient diagnosed with acute promyelocytic leukemia (APL) following pericoronitis. The patient was referred to our department for the extraction of a wisdom tooth. On initial examination, tissue swelling and necrosis were observed in the gingiva around the right mandibular wisdom tooth. After 1 week of no improvement, purpura were observed on the patient’s forearms and lower legs, signifying the presence of a blood disorder. Following the detection of pancytopenia, the patient was referred to the Department of Hematology and Oncology. Bone marrow aspiration confirmed the diagnosis of APL. Chemotherapy with all-trans retinoic acid was started immediately, and the patient is currently in complete molecular remission. The mandibular wisdom tooth was extracted after complete molecular remission and the patient is doing well.