Neuropsychiatric disorders such as multiple sclerosis, Alzheimer's disease, and autism spectrum disorder exhibit significant sex differences in prevalence, progression, and response to treatment. Emerging evidence suggests that oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs) play pivotal roles in these pathologies via mechanisms involving neuroinflammation, energy metabolism, and hormonal modulation, resulting in distinct functional outcomes. Specifically, female OPCs display higher proliferative and migratory capacities, whereas male OPCs are more prone to differentiation and myelination, thus contributing to robust myelin integrity. Dysregulation of these cells disrupts myelination and exacerbates disease progression. Addressing sex-specific gene expression in OPCs and OLs is therefore considered crucial for the development of targeted therapeutic strategies. This review highlights the significance of sex differences in the proliferation and differentiation of OPCs, as well as gene expression changes in OPCs and OLs, and emphasizes their contribution to the pathophysiology of neuropsychiatric disorders. Improved understanding of these differences is vital for advancing personalized sex-specific treatments and improving the clinical outcomes of neuropsychiatric disorders.

Cancers originating from the same tissue vary significantly in genetic mutations and patient drug response. Furthermore, tumor tissue is composed of diverse cancer cell clones. This phenomenon, known as "cancer cell heterogeneity," occurs among tumors (between patients) and within individual tumors and is an important mechanism driving resistance to cancer therapy. Therefore, an understanding of cancer cell heterogeneity is essential for the development and delivery of more effective personalized treatments. The cancer cell lines typically used in cancer research cannot accurately replicate this heterogeneity. However, patient-derived tumor organoids (PDTOs), three-dimensional cultures of tumor cells, can precisely replicate the histological, molecular, and cellular heterogeneity of the original tumor. PDTOs generated from human cancers are now widely used as innovative tools in cancer research, including in studies of the mechanisms of cancer development and progression and in screening of anti-cancer drug. This review summarizes recent advances in human tumor research that uses PDTOs.

The principles of hyperbaric oxygen therapy (HBOT) have been known since ancient times. Empirical knowledge regarding relief of decompression sickness (DCS) symptoms in divers re-entering a pressurized environment was reported as early as 4,500 BC. DCS was recognized as a disease after deep diving became possible because of diving helmets. DCS also occurs in high-pressure dry workspaces (caissons) developed to construct bridges and tunnels. After the discovery of oxygen in the 18th century, its administration was found to be beneficial in treating conditions that developed after rapid decompression, and HBOT is now established as a part of recompression therapy. This review describes the indications for HBOT in Japan and its effectiveness, as indicated by the author's experience with HBOT in the Department of Emergency Room and General Medicine at Nippon Medical School.

Background: Several studies have reported that persons with Parkinson's disease (PD) exhibit a preference for sweet foods. However, because many people favor such foods, this study investigated whether the preference for sweet foods was stronger among patients with PD than among those without PD. Methods: We analyzed 150 patients treated in the neurology department of Nippon Medical School Hospital between July 2021 and November 2021. Forty-nine (33%) had PD and 101 patients (control group) did not. Participants were asked to rate three sweet foods, three salty foods, and three bitter foods (total, nine foods) on a questionnaire where a score of 3 indicated "like", 2 indicated "neutral", and 1 indicated "dislike". The score for each taste preference was defined as the sum of the scores for the three foods representing each taste. Differences in baseline characteristics and taste preference scores between patients with and without PD were then statistically analyzed. Results: The PD group was significantly older than the control group. The PD group obtained a significantly higher sweetness score than the control group (8 [6-9] vs. 7 [3-9], p<0.01). There was no difference in scores for either saltiness (7 [3-9] vs. 7 [3-9], p=0.49) or bitterness (7 [4-9] vs. 7 [3-9], p=0.25). The sweetness score was not significantly correlated with L-dopa dose, L-dopa equivalent dose, or PD disease duration. Conclusion: Patients with PD were more likely than those without PD to prefer sweet foods. These results are important new information on the taste preferences of persons with Parkinson's disease.

Background: Acoustic trauma is a common cause of acute sensorineural hearing loss associated with tinnitus; however, the underlying molecular mechanisms remain unclear. Extracellular signal-regulated kinase 2 (ERK2), a member of the mitogen-activated protein kinase family, is crucial in cellular signaling, especially in the nervous system, where it helps regulate neuroprotection, neurogenesis, and neuronal plasticity. ERK2 is activated in the cochlea by acoustic stimuli and plays a protective role in cochlear hair cells (HCs), which are the primary sensory receptors for hearing. However, the significance of ERK2 expression in HCs associated with development and etiology of tinnitus is largely unexplored. Methods: To investigate the role of ERK2 in tinnitus development, the gap detection test (GAP) was used to evaluate HC-specific ERK2-conditional knockout mice (HC-E2CKO) exposed to moderate acoustic stimuli. Results: Both control and HC-E2CKO mice showed normal prepulse inhibition levels (<0.6) before and after auditory damage, indicating normal functioning of sensorimotor gating pathways, excluding gross sensorimotor deficits. This confirmed that the animals were eligible for the GAP. HC-E2CKO mice showed a transient increase in the GAP ratio, indicating tinnitus development, 1 week after noise exposure, although the hearing threshold was not significantly elevated. The GAP ratio returned to normal after 2 weeks. In contrast, control mice did not exhibit elevation in hearing threshold and the GAP ratio remained normal. Conclusion: Our findings suggest that ERK2 in the inner ear plays a role in tinnitus onset or perception after acoustic stress, potentially through inhibitory mechanisms.

Background: The standard of care in Japan for preterm very low-birth-weight (VLBW) infants has long been at the highest level internationally, owing to advances in technology and the perinatal medical system throughout the country. Methods: To identify issues for further improvement of outcomes for preterm VLBW infants in our neonatal intensive care unit (NICU), perinatal care practice was reviewed by analyzing data from medical records on pregnancy complications and management and infant mortality and morbidity. Results: Data from 250 preterm VLBW infants, excluding those with severe congenital anomalies, were analyzed. There were 49 cases (19.6%) of cumulative morbidity, including infants who died before discharge and those who had major complications such as bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, and retinopathy of prematurity. The prevalence remained constant throughout the study period. Infants born via medically indicated preterm birth had a higher cumulative morbidity rate than those born via spontaneous preterm birth. Small-for-gestational-age status was the only factor significantly associated with cumulative morbidity in multivariate analysis. Of all the infants, 69 (47.3%) completed a course of antenatal corticosteroids (ACS). Conclusions: The quality of neonatal intensive care for preterm VLBW infants in our NICU was consistent with outcomes for top-ranked NICUs in Japan. Critical issues in improving outcomes for these infants include determining the optimal timing of delivery by comprehensively assessing fetal well-being and promoting ACS.

Background: We investigated the association between the number of patients presenting to an emergency room (ER) with vertigo/dizziness (V/D) and seasonal variations, monthly trends, and weather factors. Methods: We retrospectively investigated age, sex, cause of V/D, emergency triage level (Japan Triage and Acuity Scale), month, and seasonality among patients with V/D transported to the ER of Nippon Medical School between October 2014 and September 2017. We examined weather data, including monthly average precipitation and humidity, with respect to the number of patients with V/D. Results: Among 706 patients with V/D, 481 presented with vertigo and 225 with dizziness. The mean age was 59±18 years and 66% were female. Regarding triage level, emergent (level 2) and urgent (level 3) cases accounted for 86% of cases and were more frequent in June-September (p=0.012). Regarding seasonality, 158 (22%), 195 (28%), 183 (26%), and 170 (24%) patients presented in spring, summer, autumn, and winter, respectively (p=0.744). The monthly number of V/D emergency transports tended to be higher between June and October and was significantly associated with average temperature (r=0.648, p=0.023), precipitation (r=0.655, p=0.021), humidity (r=0.676, p=0.016), and vapor pressure (r=0.648, p=0.023). Conclusions: Although no apparent seasonality was observed in the monthly number of V/D-related emergency transports, the emergency triage level increased from the rainy season to early autumn. The monthly number of V/D cases transported by emergency services was significantly associated with average temperature, precipitation, humidity, and vapor pressure. These findings could inform public health policy and increase emergency preparedness.

Background: In emergency interventional radiology (IR), patient motion and poor breath-holding often result in misregistration during digital subtraction angiography (DSA). As a countermeasure, digital angiography (DA) without subtraction processing is used for observation; however, evaluation is limited to areas overlapping with low X-ray transmissivity structures, such as bone. Dynamic trace (DT) is capable of real-time background compression processing of peripheral blood vessels in DA images and ensures visibility of blood vessels in such areas, without being affected by body motion. We evaluated the image quality and visualization of peripheral vascularity of DA and DT images obtained from DSA of the trunk and examined the usefulness of DT. Methods: Data from 13 patients who underwent emergency IR involving trunk DSA between October 2022 and June 2023 were analyzed. DA and DT images were created from these angiographic images, and two independent IR specialists used a 4-point scale to visually evaluate the contrast, sharpness, and peripheral vascular visibility of the proximal and distal portions of 42 arteries. The image quality scores for DA and DT images were compared using the Wilcoxon signed-rank test, and inter-rater agreement was evaluated using weighting coefficients. Results: As compared with the DA images, the DT images were significantly better at all endpoints (P < 0.001). Inter-rater agreement was moderate for all assessment items. Conclusions: DT images are not affected by body motion and display better image quality and visualization of peripheral vascularity than DA images, making them useful for emergency IR of the trunk.

Schizophrenia develops during adolescence. Maternal infections during the fetal period increase the incidence of schizophrenia in children, which suggests that the pathogenesis involves neuroinflammation. Here, we report a case of new-onset schizophrenia in a 16-year-old boy after COVID-19. After developing COVID-19, he entered a catatonic state 4 days later and was hospitalized. Benzodiazepines alleviated his catatonia, but hallucinations and delusions persisted. Encephalitis and epilepsy were excluded by magnetic resonance imaging (MRI), encephalography, and cerebrospinal fluid examination. Psychosis persisted after the virus titer declined and the inflammatory response subsided. Moreover, the patient exhibited delusions of control-a Schneider's first-rank symptom. Schizophrenia was diagnosed, and olanzapine improved his symptoms. He had a brief history of insomnia before COVID-19 but his symptoms did not satisfy the ultra-high-risk criteria. However, COVID-19 may have facilitated development of schizophrenia through neuroinflammation and volume reduction in the gray matter of the right medial temporal lobe. This case demonstrates that infectious diseases in adolescents should be carefully managed, to prevent schizophrenia.

Painless thyroiditis, which is rare in children, exhibits the characteristic sequence of hyperthyroidism, including aggressive and disruptive behaviors. Unlike subacute thyroiditis or Graves' disease, painless thyroiditis is challenging to diagnose because of its mild symptoms and minimal or absent physical findings. Moreover, aggressive and disruptive behaviors in children with psychiatric disorders may be misconstrued as exacerbation of underlying symptoms. The present patient was a 16-year-old male with adjustment disorder who presented to a pediatric psychiatric clinic for assessment of irritability. After 4 months, he developed aggressive and disruptive behaviors that prompted initiation of risperidone but without improvement. After 1 month, he reported palpitations and dyspnea. His neck was supple and non-tender without thyroid enlargement. Thyroid studies revealed elevated free T4 and T3 levels and suppressed thyroid-stimulating hormone level, suggesting hyperthyroidism. A radioactive iodine uptake test revealed a barely visible thyroid gland, consistent with thyroiditis. Painless thyroiditis, without thyroid tenderness, was diagnosed. We describe a case of painless thyroiditis in an adolescent patient with aggressive and disruptive behaviors that were initially attributed to worsening of an underlying adjustment disorder. Even when minimal or no signs of hyperthyroidism are present, painless thyroiditis should be considered in the differential diagnosis of children with aggressive and disruptive behaviors. Awareness of potential anchoring bias is also recommended to prevent its delayed diagnosis of such behaviors.

Mixed connective tissue disease (MCTD) is characterized by mixed features of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis and is rare in children. Here, we report a case of MCTD in a 10-year-old girl who presented at our hospital with arthralgia, Raynaud's phenomenon, and fatigue. Blood tests were positive for anti-U1-ribonucleoprotein (RNP) antibodies and for rheumatoid factors (RFs) IgG-RF and anti-galactose-deficient IgG. Levels of myogenic enzymes and hypergammaglobulinemia were elevated. Macrophages were prominent in bone marrow, with scattered phagocytic macrophages. MCTD was diagnosed based on the patient's symptoms and laboratory findings. Methylprednisolone pulse therapy combined with oral tacrolimus was administered, which led to resolution of symptoms. Three months after pulse therapy, arthralgia worsened and methotrexate was administered. Arthralgia improved but did not resolve. Magnetic resonance imaging performed to investigate the hip pain revealed a mature ovarian teratoma, which was surgically removed. Because the pain persisted and interfered with her daily life, she was treated with tocilizumab for joint pain relief, which decreased the pain level. Tocilizumab is a candidate for additional treatment of juvenile idiopathic arthritis-like arthritis associated with childhood-onset MCTD.