REM sleep behavior disorder (RBD) is a REM sleep-related parasomnia characterized by action of dream content, which is often an aggressive or terrible nightmare. Because of the self-defense movements and behaviors in dreams, sleep-talking (e.g., yelling and screaming) and violent movements of the arms and legs may injure the patient or bed partner. Idiopathic or isolated RBD that develops after middle age may progress to neurodegenerative diseases, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy, in half of the patients after 10 years. The development of a method that can accurately diagnose RBD by polysomnography may help to identify patients at high short-term risk of developing α-synucleinopathies. Such patients may be enrolled in trials of disease-modifying therapy. Several techniques for the early diagnosis of α-synucleinopathies are under development for clinical use and await application in clinical trials of candidate therapies.

Phosphatidylethanolamine (PE) and cholesterol are major lipid components of mammalian cell membranes. The rate limiting enzymes for the synthesis of PE and cholesterol are CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), respectively. The transcription and activity of these enzymes in NIH3T3 cells are suppressed by fetal bovine serum (FBS) and hydroxylated cholesterol (oxysterols) in similar dose-dependent manners. These results suggested that the intrinsic oxysterol concentration in cells is important for maintaining membrane lipid components, leading us to investigate the regulation of oxysterol-producing enzyme activity in cells. Using NIH3T3 cells, we found that of all oxysterol-producing enzymes, only the 24S-hydroxycholesterol producing enzyme cytochrome P450 46A1 (Cyp46A1) is expressed. Transcription of Cyp46A1 is suppressed by FBS, and we identified insulin-like growth factor II (IGF-II) in FBS as the factor suppressing Cyp46A1 transcription. The oxysterol level in NIH3T3 cells is also suppressed by IGF-II. These results suggested that the classical hormone IGF-II regulates the oxysterol content in cells and transduces cellular signals.

α-Taxilin is a member of the taxilin family, a binding partner of the syntaxin family involved in intracellular vesicle traffic. The taxilin family members share a long coiled-coil structure, which is homologous to that of Uso1, a yeast homologue of p115. It has been revealed that a parallel homodimerization of p115, an elongated polypeptide, is required for tethering of the transport vesicles to the acceptor membrane. In this study we examined whether α-taxilin has similar biochemical properties to p115. Gel filtration and sedimentation analyses suggest that α-taxilin is an elongated polypeptide containing a long coiled-coil structure. A pull-down assay revealed that His₆-α-taxilin binds to GST-α-taxilin, and not to GST in dose-dependent and saturable manners. α-Taxilin formed a parallel homodimer through at least two independent regions. Together, α-taxilin may be involved in tethering of the transport vesicles to the acceptor membranes in a similar way to p115.

PURPOSE: To evaluate the characteristics and formation mechanism of condensation on the posterior surface of various types of intraocular lenses (IOLs) during vitreous surgery.

METHODS: A model eye was immersed in a constant-temperature bath, and the temperature and humidity inside the vitreous cavity were maintained at 35˚C and 97%, respectively, to cause condensation (moisture formation) on the IOL. The condensation was video recorded under a microscope, and the size of the condensation droplets and the number per unit area (500 μm²) were determined. The contact angle of the water droplets on each IOL was evaluated by using the sessile-drop method.

RESULTS: The condensation droplet diameter for the polymethyl methacrylate (PMMA), acrylic, and silicone IOLs was 115 ± 32 μm, 74 ± 23 μm, and 50 ± 13 μm, respectively. The number of droplets per unit area was 18.4 ± 1.8, 48.2 ± 16.8, and 86.8 ± 6.7, respectively. Statistical analysis showed significantly smaller sizes but a greater number of droplets per unit area for the silicone IOL. The contact angle for the PMMA, acrylic, and silicone IOLs was 76.4˚, 85.7˚, and 112.8˚, respectively. Thus, for silicone, the contact angle was lowest and the water droplets were spherical.

CONCLUSIONS: Condensation occurs regardless of the IOL material. Compared to other IOLs, the silicone IOL had smaller-sized but a larger number of spherical condensation droplets. This can cause a large amount of refraction of intraocular light, thus leading to decreased visibility.

In patients with Parkinson's disease (PD), fatigue and sleep disturbances are important non-motor symptoms. In this study, we aimed to evaluate the relationship between fatigue and sleep disturbances in patients with Parkinson's disease (PD). A total of 93 outpatients with PD (age, 69.7 ± 8.9 years) and 93 healthy controls (age, 69.6 ± 10.2 years) were included in this study. The participants completed the Parkinson Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's disease sleep scale (PDSS) -2 and Beck Depression Inventory (BDI) -II. For PD patients, the PD Questionnaire (PDQ-39) was used to evaluate quality of life. Fatigue was defined as a PFS score of 3.3 or greater. Fatigue was observed in 7.5% of healthy controls and 44.0% of PD patients (p < 0.001). In the healthy control group, subjects with fatigue were older than those without fatigue, but there was no difference in the PDSS-2, ESS or BDI-II scores. PD patients with fatigue had significantly higher scores of the ESS, BDI-II, PDQ-39 and PDSS-2 and greater motor symptoms compared with those without fatigue. Fatigue was associated with the PDSS-2 sub-item 2 (Difficulty falling asleep), item 10 (Pain in arms or legs), item 13 (Tremor on waking), item 14 (Tired and sleepy after waking in the morning) and item 15 (Snoring or difficulties in breathing). Logistic regression analysis showed that the PDSS-2 subitem 14 (Tired and sleepy after waking in the morning) and the PDQ-39 summary index were significant determinants for fatigue. In conclusion, we showed the significant relationship between fatigue and various aspects of PD-related nocturnal problems. Our findings emphasize the importance of fatigue assessment in patients with PD.

Although thyroid disorders induced by immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have attracted much attention, little research has been done on thyroid dysfunction in conventional cancer treatment containing anthracyclines and taxanes. We retrospectively studied thyroid function in 61 patients who underwent conventional chemotherapy for breast cancer. Of the 61 patients, 17 (28%) developed thyroid dysfunction, including sub-clinical and overt hypothyroidism following chemotherapy, and 9 (15%) developed overt clinical hypothyroidism. Eight of the nine patients needed thyroid hormone replacement therapy with levothyroxine (L-T4). Taxane-based regimens tended to reduce free T4 levels and increase TSH levels more markedly compared to non-taxane-based regimens. Since the present study showed, for the first time, that conventional chemotherapy, as well as ICIs and TKIs, may induce hypothyroidism, it may be appropriate to evaluate thyroid function during chemotherapy. When patients show the clinical features of hypothyroidism, thyroid hormone replacement therapy merits consideration.

Background: A new role of a regional core hospital for educating medical personnel through a regional therapy association has been previously reported in the COVID-19 crisis. In the present study, physical (PT), occupational (OT), and speech language hearing therapist (ST) and physiatrists, who have been providing COVID-19 rehabilitation in a regional core hospital, were instructed how to control infection via a webinar. The purpose of this report was to investigate the effects of webinars on therapists working in local facilities. Methods: The webinar was sponsored by the Wakayama Physical Therapy Association. A PT, OT, ST, and physiatrist from Wakayama Medical University Kihoku Hospital, who had been providing rehabilitation for mildly and/or moderately infected COVID-19 patients. All participants answered the 18-item online questionnaire after the webinar to assess the educational effects. Results: There were 41 participants in this region and 30 participants from 19 facilities responded the questionnaire (valid responses ratio was 73%) and 30% of the respondents had experienced COVID-19 rehabilitation. Most responders (83%) felt that difficulty level of the contents was appropriate and 80% of the respondents replied that rehabilitation was necessary for the patients. 70% of the respondents replied that got confidence after this webinar, even 7 of the 13 respondents (43%), who attended the webinar about infection control of COVID-19 for the first time, were involved. Conclusion: A webinar from therapists and physiatrists in a regional core hospital, who had experiences to provide COVID-19 rehabilitation, were satisfactory and effective for the education of regional therapists.

In January 2010, the Tochigi Prefecture launched the Doctor Helicopter Services at Dokkyo Medical University Hospital. More than ten years have passed since the implementation of the service, and the total number of requests has exceeded 9,000 while the number of dispatches without any significant accidents has reached 8,000. We now report on the performance of Tochigi prefecture's "Doctor Helicopter." Based on the total number of helicopter operations compiled by the hospital, we surveyed the number of requests, dispatches, and un-dispatched cases; the number of requests from each fire department; the status of cooperation with neighboring prefectures; the medical institutions to which the helicopter is transported; and the classification by injury and disease. The number of requests and dispatches has increased each year of the operation. Un-dispatched cases owing to duplicate requests also increased along with the number of requests. Many of the requests were from the fire department in medical control areas. The number of cases in which Tochigi's Doctor Helicopter was dispatched to neighboring prefectures was much higher than the number of cases received by the neighboring prefectures from Tochigi. Endogenous diseases were more frequently encountered than exogenous diseases during the study period, with cerebrovascular disease accounting for the most significant proportion. Moreover, more than 50% of the patients were transported to the base hospital. Tochigi Prefecture Helicopter Emergency Medical Services are now indispensable for emergency medical care in the prefecture.

Polysomnography (PSG) is necessary for the diagnosis of REM sleep behavior disorder (RBD) according to the diagnostic criteria of the International Classification of Sleep Disorders, 2^nd edition. We administered the REM sleep behavior disorder screening questionnaire-Japanese version (RBDSQ-J) to patients admitted to the hospital for PSG due to suspected sleep disorders and evaluated the background factors in patients with suspected RBD. We analyzed data from 261 out of 269 consecutive patients who were administered the RBDSQ-J and underwent PSG. Probable RBD was defined as a total RBDSQ-J score of ≥ 5. Sixty-six of the 261 patients (25.3%) had a total RBDSQ-J score of ≥ 5. Among the 66 patients, 10 (15.2%) had idiopathic or isolated RBD, 1 (1.5%) had secondary RBD with multiple system atrophy, and 55 (83.3%) did not have RBD. Among patients aged 50 years or older, all patients (n = 11) had RBD, whereas among those aged less than 50 years, none had RBD. The background factor in patients with false positive results was mainly obstructive sleep apnea syndrome (OSAS), whereas among young patients, the factors other than OSAS included narcolepsy, migraine, psychological disorders (such as PTSD, depression, or schizophrenia), and complications of central neurological disorders (such as sequelae of brainstem infarction or limbic encephalitis). RBDSQ-J is useful to screen for idiopathic/isolated RBD-associated synucleinopathies among middle-aged and elderly people aged ≥ 50 years, but among young patients and those with positive result of RBDSQ-J, various background factors may be present and the results should be interpreted with caution.

Among the components of renin-angiotensin-aldosterone system, aldosterone facilitates the progression of cardiovascular organ injuries not only by promoting renal tubular Na reabsorption but also by causing oxidative stress, inflammation and cardiovascular tissue hypertrophy and fibrosis. Therefore, mineral corticoid receptor blockers (MRB) supposedly exhibit protective effects against cardiovascular organ injuries in hypertensive patients. In this study, the therapeutic effects of MRB in the combination antihypertensive treatment were examined in hypertensive patients.

Fifty mg eplerenone (EPL) was added to 24 hypertensive patients under antihypertensive drug therapy who had not achieved the target blood pressure. The combination was continued for 3 to 4 months and the effects on blood pressure (BP) and laboratory data including renal function and cardiovascular endocrine system were evaluated.

After 3-4 months, office BP was lowered from 148/91 to 135/86 mmHg (p<0.001/p=0.002) as well as the home BP (morning 150/86 to 134/81, p = 0.001/p = 0.033; evening 139/80 to 127/74, p = 0.005/p = 0.030). Serum K (4.2 to 4.3 mEq/L, p = 0.014) and creatinine (0.82 to 0.87 mg/dL, P<0.001) increased slightly but significantly. Serum uric acid also increased significantly from 5.8 to 6.4 mg/dL (p = 0.015). However, the indices of glucose metabolism and serum lipids were not affected. In addition to the natural increases in plasma renin and aldosterone, plasma B-type natriuretic peptide (BNP: 23 to 17 pg/mL, p = 0.028) and urinary albumin excretion (111 to 70 mg/gCr, p = 0.009) were significantly decreased.

In the combination antihypertensive drug therapy, MRB is expected to reduce cardiac and renal injuries and the influences on glucose and lipid metabolisms seem negligible, however, care should be taken for the development of hyperuricemia and renal dysfunction in addition to hyperkalemia.

The optimal timing of acute myocardial infarction-associated ventricular septal rupture surgery is controversial. Therefore, we examined the appropriateness of our ventricular septal rupture surgical strategy for early surgery in absence of organ failure and delayed surgery after organ failure recovery. We retrospectively included 22 patients who underwent surgery for ventricular septal rupture between January 2012 and February 2021. After diagnosis, patients without organ failure underwent early surgery; those with organ failure underwent delayed surgery after organ failure recovery. In the early- (n = 17) and delayed-surgery (n = 5) groups, the mean ± standard deviation time from diagnosis to surgery was 0.3 ± 0.7 (0-2) and 5.2 ± 2.3 (3-8) days, respectively. The early-surgery group was treated with preoperative mechanical circulatory support using an intra-aortic balloon pump. The delayed-surgery group was treated with an Impella (n = 1), intra-aortic balloon pump combined with venous artery extracorporeal membrane oxygenation (n = 1), and Impella combined with venous artery extracorporeal membrane oxygenation (ECpella) (n = 3). The hospital and mid-term (52.1 ± 42.9 months) mortality rates were 9.1% (early-surgery group, 11.8%; delayed-surgery group, 0%) and 18.2% (early-surgery group, 23.5%; delayed-surgery group, 0%), respectively. Further, 70.6% and 82.4% patients without organ failure had cardiogenic shock and an anterior rupture location, respectively. In the early-surgery group, combined treatment with an intra-aortic balloon pump and medical therapy yielded hemodynamic stability until surgery. However, in patients with organ failure requiring long-term management, ECpella therapy was preferable, depending on the rupture size. Our treatment strategy was reasonable. Further research is warranted to determine the optimal support duration, especially for patients requiring long-term management.

A 65-year-old man visited our hospital with the complaint of rapid exacerbation of dysphagia. He had no otolaryngological or digestive system disorders. He was initially suspected to have acute bulbar palsy, a subtype of Guillain-Barré syndrome, and managed accordingly; however, the patient did not respond to treatment. Subsequently, he developed multiple cranial neuropathies and sensory neuronopathy. Additional tests revealed that he had positive anti-Hu antibodies. No obvious mass lesions were noted, but 3 months later, the patient developed enlarged isolated lymph node near the para-aortic lymph nodes. Excision of the focal lymph node revealed small cell carcinoma, without evidence of small cell carcinoma in the lungs. Therefore, the primary lesion was unknown. The patient was diagnosed with paraneoplastic neurological syndrome. In such cases, tumor search often needs to be repeated because neurological symptoms may precede the tumor onset.

A 13-year-old girl presented with fever for the past ten days without any other symptoms. Laboratory findings revealed leukopenia, low platelet count, and high lactate dehydrogenase and ferritin levels. Abdominal ultrasonography revealed mild splenomegaly and lymphadenopathy in proximity to the head of the pancreas. The patient's condition suggested macrophage activation syndrome associated with systemic juvenile idiopathic arthritis. However, her serum interleukin-18 level was 1743 pg/mL; therefore, urgent systemic corticosteroid treatment was deemed unnecessary as macrophage activation syndrome associated with systemic juvenile idiopathic arthritis was ruled out. The patient was afebrile the following day and showed improved laboratory and ultrasonographic findings without treatment. Clinical Kikuchi-Fujimoto disease was diagnosed based on transient lymphadenopathy, laboratory findings, and a self-limited clinical course. Although this patient met the early diagnostic criteria of macrophage activation syndrome with suspected systemic juvenile idiopathic arthritis, serum interleukin-18 is useful for ruling it out. Pediatricians should keep in mind that Kikuchi-Fujimoto disease may cause abdominal lymphadenopathy.

Clostridioides difficile infection (CDI) is an intestinal infection caused by intestinal dysbiosis due to exposure to antibiotics. We describe the case of a 2-year-old girl who developed CDI after antibiotic treatment for acute appendicitis. She presented to our hospital with fever, abdominal pain, and frequent diarrhea. She was diagnosed with acute appendicitis following abdominal contrast-enhanced computed tomography and was treated with cefmetazole for 5 days. Eight days after discontinuation of cefmetazole treatment, she experienced abdominal pain, associated with the passage of loose stools. Abdominal ultrasonography revealed no swelling of the appendix. Both the Clostridium difficile antigen and toxin tests were positive. She was diagnosed with CDI due to her recent antibiotic treatment for acute appendicitis. Intravenous metronidazole (30 mg/kg/day) and probiotics were administered for 10 days. Her abdominal pain improved gradually and did not recur after discontinuation of metronidazole. The increasing global prevalence of CDI in low-risk populations and children necessitates its consideration in both pediatric patients, and even children without preceding underlying disease. There have been no reports on the development of CDI in patients receiving antibiotic treatment for appendicitis. If gastrointestinal symptoms relapse after an antibiotics treatment for acute appendicitis, CDI should be considered while investigating for possible relapse of appendicitis.