Search

Introduction Transverse testicular ectopia is a rare anomaly in which both testes descend toward the same side of the hemiscrotum. Case presentation A 35‐year‐old man presented with right inguinal enlargement. Computed tomography showed a normal testis in the right hemiscrotum and a 58 mm heterogeneous mass in the right inguinal area. No testis was observed in the left hemiscrotum. The vascular structures extended from the right inguinal mass to the left renal vein. Consequently, the left testicular tumor was diagnosed as transverse testicular ectopia, and a left orchiectomy was performed. The histological diagnosis was seminoma stage pT2. Furthermore, left para‐aortic lymph node metastasis developed 10 months postoperatively. A complete response was obtained after systemic chemotherapy. Conclusion Awareness of seminomas in transverse testicular ectopia could facilitate appropriate diagnosis and treatment. Furthermore, the location of the lymph node metastasis indicated that the ectopic testis could have originated from the left side.

Abstract We report a case of severe Aicardi–Goutières syndrome caused by a novel homozygous RNASEH2B intronic variant, NC_000013.10(NM_024570.4):c.65-13G > A p.Glu22Valfs*5. The patient was born with pseudo-TORCH symptoms, including intracranial calcification, cataracts, and hepatosplenomegaly. Furthermore, the patient exhibited profound intellectual impairment and died at 14 months due to aspiration pneumonia accompanied by interstitial lung abnormalities. The severity of the patient’s symptoms underscores the critical role of the C-terminal region of RNase H2B.

Abstract Background Prostate ductal adenocarcinoma, a rare histology observed in 0.4–0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. Case presentation A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. Conclusion This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.

A cavity-based X-ray free-electron laser (CBXFEL) is a possible future direction in the development of fully coherent X-ray sources. CBXFELs consist of a low-emittance electron source, a magnet system with several undulators and chicanes, and an X-ray cavity. The X-ray cavity stores and circulates X-ray pulses for repeated FEL interactions with electron pulses until the FEL reaches saturation. CBXFEL cavities require low-loss wavefront-preserving optical components: near-100%-reflectivity X-ray diamond Bragg-reflecting crystals, outcoupling devices such as thin diamond membranes or X-ray gratings, and aberration-free focusing elements. In the framework of the collaborative CBXFEL research and development project of Argonne National Laboratory, SLAC National Accelerator Laboratory and SPring-8, we report here the design, manufacturing and characterization of X-ray optical components for the CBXFEL cavity, which include high-reflectivity diamond crystal mirrors, a diamond drumhead crystal with thin membranes, beryllium refractive lenses and channel-cut Si monochromators. All the designed optical components have been fully characterized at the Advanced Photon Source to demonstrate their suitability for the CBXFEL cavity application.

Abstract We report on the feasibility of Fourier transform holography in the hard X-ray regime using a Free Electron Laser source. Our study shows successful single and multi-pulse holographic reconstructions of the nanostructures. We observe beam-induced heating of the sample exposed to the intense X-ray pulses leading to reduced visibility of the holographic reconstructions. Furthermore, we extended our study exploring the feasibility of recording holographic reconstructions with hard X-ray split-and-delay optics. Our study paves the way towards studying dynamics at sub-nanosecond timescales and atomic lengthscales.

Abstract A intermediate multidomain state and large crystallographic tilting of 1.78° for the (hh0)pc planes of a (001)pc-oriented single-domain Mn-doped BiFeO3 (BFMO) thin film were found when an electric field was applied along the [110]pc direction. The anomalous crystallographic tilting was caused by ferroelastic domain switching of the 109° domain switching. In addition, ferroelastic domain switching occurred via an intermediate multidomain state. To investigate these switching dynamics under an electric field, we used in situ fluorescent X-ray induced Kossel line pattern measurements with synchrotron radiation. In addition, in situ inverse X-ray fluorescence holography (XFH) experiments revealed that atomic displacement occurred under an applied electric field. We attributed the atomic displacement to crystallographic tilting induced by a converse piezoelectric effect. Our findings provide important insights for the design of piezoelectric and ferroelectric materials and devices.

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60.

Abstract Mitochondrial diseases are mainly caused by dysfunction of mitochondrial respiratory chain complexes and have a variety of genetic variants or phenotypes. There are only a few approved treatments, and fundamental therapies are yet to be developed. Leigh syndrome (LS) is the most severe type of progressive encephalopathy. We previously reported that apomorphine, an anti- “off” agent for Parkinson’s disease, has cell-protective activity in patient-derived skin fibroblasts in addition to strong dopamine agonist effect. We obtained 26 apomorphine analogs, synthesized 20 apomorphine derivatives, and determined their anti-cell death effect, dopamine agonist activity, and effects on the mitochondrial function. We found three novel apomorphine derivatives with an active hydroxy group at position 11 of the aporphine framework, with a high anti-cell death effect without emetic dopamine agonist activity. These synthetic aporphine alkaloids are potent therapeutics for mitochondrial diseases without emetic side effects and have the potential to overcome the low bioavailability of apomorphine. Moreover, they have high anti-ferroptotic activity and therefore have potential as a therapeutic agent for diseases related to ferroptosis.

Introduction Low‐grade fibromyxoid sarcoma is an uncommon deep‐seated soft‐tissue sarcoma that occurs rarely in young adults and children. Although surgical resection provides a long‐term prognosis, late local recurrence and metastasis may occur. Case presentation A 44‐year‐old woman with no prior medical history presented with breathing and abdominal discomfort. Contrast‐enhanced computed tomography scan revealed a retroperitoneal tumor protruding into the thoracic cavity and pleural effusion on the left side. Tumor biopsy revealed sarcoma. We performed complete resection of the tumor along with part of the diaphragm and replaced the diaphragm with a prosthetic patch. Histopathologic findings indicated low‐grade fibromyxoid sarcoma. The patient experienced no postoperative complications and received no adjuvant therapy. Furthermore, she survived 4 years after surgery without recurrence. Conclusion Complete surgical resection is effective for low‐grade fibromyxoid sarcoma; therefore, it is important to plan appropriately for complete resection when biopsy reveals malignant findings.

Introduction Inflammatory myofibroblastic tumors are difficult to diagnose because of the lack of specific indicators. We describe a diagnostically challenging case of an inflammatory myofibroblastic tumor primary to the peritoneum. Case presentation The patient was a 25‐year‐old male who presented at our hospital with lower abdominal pain. Computed tomography revealed a mass lesion 80 mm in diameter just above the bladder. This was suspected to be a bleeding tumor of the urachus. Since malignancy could not be ruled out, surgery was planned. This revealed a fragile tumor arising from the peritoneum. Following its removal, the tumor was diagnosed by histopathological analysis as an inflammatory myofibroblastic tumor. Conclusion We describe a case of inflammatory myofibroblastic tumor primary to the peritoneum diagnosed by histopathology. Inflammatory myofibroblastic tumor should be considered in the differential diagnosis of abdominal wall and anterior bladder tumors.

Abstract Ancillary service provision and peak shaving (PS) play essential roles in the current day‐to‐day power system operation, which is challenged by the increasing renewable generation penetration. Providing these critical services using classical approaches such as peak load generators has been limited due to high operational costs and environmental impacts. The use of battery energy storage systems (BESS) is another popular method that is limited by high initial investment costs and high degradation rates. In this work, a novel approach to utilize industrial loads and BESS to provide multiple power system services in different stages is proposed. Industrial loads such as aluminium crushers are known for their intensive electricity consumption. Nevertheless, when applied in frequency regulation (FR), they perform poorly due to their discrete nature in operation. This drawback and the aforementioned BESS shortcomings are addressed by combining on‐site BESS with plant machinery to provide FR services and recover BESS related costs. Later, depending on the optimal capacity distribution, BESS usage is extended into the energy arbitrage market to provide PS services. This approach resulted in higher earnings for participating customers and network operators, as well as in less CO2 emissions, and minimal BESS degradations. An Australian case study of the South West Interconnected System, along with Worsley Alumina refinery data of Western Australia has been used to showcase the model performances.

Abstract Background For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. Methods We retrospectively reviewed 65 patients with advanced NIDCM (LVEF

Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin like GTPase (OPA1) gene. OPA1 encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant-negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of the dOPA1 gene in Drosophila can imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the human OPA1 (hOPA1) gene, indicating that hOPA1 is functionally interchangeable with dOPA1 in the fly system. However, mutations previously identified did not ameliorate the dOPA1 deficiency phenotype. By expressing both WT and DOA plus mutant hOPA1 forms in the optic nerve of dOPA1 mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant-negative mutations in hOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initial hOPA1 mutation treatment strategies.

Anastomosis of the prosthetic graft to the double-barreled aorta with intimal flap fenestration is a useful technique in surgery for chronic aortic dissection. Conversely, anastomosis to the false lumen's outer wall is prone to complications such as pseudoaneurysms, but little is known about the technique of reinforcing the double-barreled aorta. In this report, we describe a surgical case of chronic aortic dissection in which an H-shaped prosthetic graft was sutured to both aortic lumens, including the intimal flap, to prevent complications at the anastomosis site.

Diet therapy is one of the most important treatments for people with type 2 diabetes (T2D). However, dietary restrictions due to diet therapy may reduce quality of life (QOL). This cross-sectional study aimed to investigate the association between diabetes diet-related QOL and dietary fiber intake in 238 people with T2D. The Diabetes Diet-related Quality of Life–Revised version (DDRQOL-9-R) and the brief-type self-administered diet history questionnaire were used to evaluate diabetes diet-related QOL and nutritional intake, respectively. Higher scores of each DDRQOL-9-R subscale means greater satisfaction with diet, perceived merits of diet therapy, and lower burden of diet therapy, which indicates good QOL. The median scores for perceived merits of diet therapy, satisfaction with diet, and burden of diet therapy were 58.3 [41.7–75.0], 75.0 [66.7–91.7], and 66.7 [50.0–75.0] points, respectively. HbA1c levels in people with high perceived merits of diet therapy (7.3 [6.7–7.8] vs. 7.5 [7.1–8.2] %, p = 0.007) and people with high satisfaction with diet (7.3 [6.8–7.8] vs. 7.5 [7.1–8.4] %, p = 0.010) were lower than those without. Dietary fiber intake was higher in people with high perceived merits of diet therapy (11.6 [8.8–16.7] vs. 10.0 [7.9–13.8] g/day, p = 0.010), high satisfaction with diet (11.4 [8.8–16.1] vs. 9.7 [7.8–13.2] g/day, p = 0.007), and low burden of diet therapy (11.8 [8.7–16.5] vs. 9.7 [7.8–12.6] g/day, p = 0.004) than in those without. Dietary fiber intake was related to perceived merits of diet therapy (Odds ratio [OR]1.07 [95%CI: 1.00–1.15], p = 0.049), burden of diet therapy (OR 0.90 [95%CI: 0.82–0.98], p = 0.022), and satisfaction with diet (OR 1.18 [95%CI: 1.09–1.27], p < 0.001) after adjusting for covariates. Dietary fiber intake is associated with diabetes diet-related QOL in people with T2D.

Abstract In this study, we investigated the composition of free amino acids and lactate (Lac) in polychaetes in river estuaries and inner bays using chromatographic techniques. Both l-amino acids and d-amino acids (d-asparagine, d-alanine (d-Ala), d-serine, d-aspartic acid, and d-proline (d-Pro)) were detected, indicating that polychaetes contain some d-amino acids. Some polychaete species exhibited notable amino acid levels, such as glycine in Capitellidae sp. and Thelepus sp., d-Pro in Glycera sp., and β-Ala in Scoletoma nipponica and Scoletoma sp.. High d-Lac levels were detected in Tylorrhynchus osawai and Hediste diadroma, (691 and 797 μmol/100 g-wet, respectively), with the d-form exceeding 98%. T. osawai was dominant in the upper tidal-sensitive zone, wherein other organisms were less abundant because of low salinity (3–8 PSU). Seasonal differences in the concentrations of components in T. osawai were observed, particularly a significant increase in d-Lac in the reproductive period. Notably, the d-Lac concentrations of T. osawai were higher upstream than downstream. Thus, d-Lac might be involved in strategies underlying adaptations to low salinity and reproductive activity. These results suggest that both the d-form of Lac and amino acids may play certain physiological roles in the life of polychaetes.

Abstract Purpose The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer.

Abstract Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.

Abstract Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.

Abstract Background Bivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan. Methods We adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 − odds ratio) × 100%. Results A total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14–20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults. Conclusions Bivalent vaccines are effective against COVID-19 infections among older adults without a history of infection.

One of the threats to industrial unmanned aerial vehicles (UAVs), which require a high level of safety, is the degradation of control wireless communication performance due to electromagnetic interference. Self-jamming caused by unintentional electromagnetic (EM) noises from the multiple electronic devices installed in a UAV, such as the power supply and camera, is a fundamental issue independent of the surrounding environment. UAVs are susceptible to self-jamming since electronic devices as noise sources are densely mounted inside their chassis. Therefore, evaluating the self-jamming problem and taking countermeasures to achieve high safety in wireless communication performance are important. In this paper, we focus on mobile communications used for UAV operation and evaluate the impact of EM noise generated by a commercial industrial UAV on the receiver sensitivity of an onboard mobile communication device. It was found that EM noise generated by the UAV degrades the sensitivity in the three communication bands, 800 MHz, 1800 MHz, and 2100 MHz, used over the air. In particular, receiver sensitivity was degraded by up to 29 dB in the 800 MHz band. These results indicate that the self-jamming problem is not negligible for the safe operation of industrial UAVs. In addition, countermeasures for self-jamming were taken at the mechanical design level to suppress EM noise to a level that does not degrade mobile communication performance. This paper clarified that countermeasures for self-jamming are an important element for safe UAV operation.

AbstractMeningoencephalocele (MEC) is a rare clinical entity caused by herniation of the dura mater and brain tissue through bony defects in the skull base. We herein report a case of bilateral MECs found after recurrent bacterial meningitis. The patient subsequently underwent simultaneous bilateral resection of the MECs and repair of the lateral skull base using a combined mastoid-middle cranial fossa approach. The bone and dura were reconstructed using free bone grafts and a temporalis fascia flap. Three years after surgery, temporal bone computed tomography showed that the reconstructed tegmen was preserved bilaterally, and there was no recurrence of meningitis or MECs. The appropriate surgical approach should be chosen based on the localization and size of the herniated tissue, and the presence of active infection or other coexisting pathology. Simultaneous bilateral resection using the combined mastoid-middle cranial fossa approach is a promising option for the treatment of bilateral multiple MECs.

Yuta Okazawa,1 Hayato Kizaki,1 Nobuyuki Suzuki,2 Wakako Osaka,3 Satoko Hori1,2 1Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, 105-8512, Japan; 2Patient Salon Association, Tokyo, Japan; 3Keio University Faculty of Nursing and Medical Care, Tokyo, 160-8582, JapanCorrespondence: Satoko Hori, Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan, Tel +81-3-5400-2650, Fax +81-3-5400-2799, Email hori-st@pha.keio.ac.jpPurpose: This study aims to investigate the impact of a Science Café (SC) dealing with medical topics on participants’ patient activation (PA), a concept that refers to patients’ involvement in managing their own health, working with their healthcare providers, and maintaining their health.Material and Methods: Semi-structured interviews were conducted with patients who had participated in a medical SC (n = 10) to identify the medical SC-associated factors that influenced PA. Through a questionnaire of medical SC participants (n = 23), the impact on PA and correlations with relevant psychological measures were quantitatively assessed.Results: The interviews revealed three factors: “Experience & acceptance of chronic conditions”, “Features of medical SC” and “Changes as a result of participation.” The questionnaire results showed a positive correlation between PA and resilience and a negative correlation with decision regret.Conclusions: Participation in a medical SC by people with illnesses can improve PA by improving knowledge and skills for self-management and increasing self-awareness of illness in a supportive environment. The study highlights the potential benefits of using medical SC as a strategy for healthcare providers to improve PA and health outcomes.Keywords: self-management, psychological measures, patient community, supportive environment

The patient was a 52-year-old woman. She had a history of left breast cancer at age 32 years, with no recurrences. She was examined for a feeling of oral dryness and nocturia, and central diabetes insipidus was diagnosed. A mass was seen in the posterior pituitary on magnetic resonance imaging, and multiple pulmonary nodules were seen on computed tomography. Breast cancer metastases were diagnosed in both tissues. Since this patient had no cancer other than the breast cancer treated 20 years earlier, it was difficult to reach a diagnosis of pituitary metastasis with pituitary gland imaging alone. In estrogen receptor-positive breast cancer, there may be recurrences after a long period of time. It may be that recommending a full body examination could be useful in the differential diagnosis of metastasis even in patients who have had a long disease-free period, if they had undergone surgery for breast cancer.

ABSTRACT: Objectives: Japan's universal health insurance covers a wide range of dental treatments, and the co-payment rates differ by age. We investigated whether the inequality in gingival bleeding and dental visits was smaller amongst those with lower co-payment rates. Methods: This cross-sectional study used data from the 2019 Japan Gerontological Evaluation Study. The participants were functionally independent adults aged 65 years or older. The dependent variables were current gingival bleeding as a symptom of periodontal diseases and dental nonattendance for treatment in the past year. The independent variables were ridit scores of equivalent income and educational status. For covariates, we used age, sex, and the number of remaining teeth. To evaluate the inequalities, we used the slope index of inequality (SII) and the relative index of inequality (RII). We also conducted stratified analyses by co-payment rates (30%, 20%, and 10%) to clarify the difference in inequalities by co-payment rate. Results: A total of 15,389 participants were included in the analysis; their mean age was 71.8 (SD = 4.1) and 51.8% were women. There were significant absolute and relative inequalities in gingival bleeding and dental visits by equivalent income and education. With regards to educational status, inequalities were lower with a decrease in the co-payment rate. In particular, relative inequality by education in gingival bleeding was the largest amongst the 30% co-payment group (RII, 1.918; 95% confidence interval [CI], 1.386 to 2.656). For gingival bleeding, the absolute and relative inequality by equivalent income were not significant amongst the 10% co-payment group (SII, −0.003; 95% CI, −0.003 to 0.028; RII, 1.006; 95% CI = 0.676 to 1.498). Conclusions: A low co-payment rate was associated with smaller inequalities in gingival bleeding and dental visits by equivalent income and educational status.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric α-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with α-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of α-actinin and enhanced the α-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to α-actinin via its globular ends. The interaction between α-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with α-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

The role of ferroptosis in steatohepatitis development is largely unknown. We investigated (1) whether hepatocyte ferroptosis occurs in a gene-modified steatohepatitis model without modifying dietary components, (2) whether ferroptosis occurs at an early stage of steatohepatitis, and (3) whether apomorphine, recently reported as a ferroptosis inhibitor, can ameliorate steatohepatitis. Hepatocyte-specific PTEN KO mice were used. Huh 7 and primary cultured hepatocytes isolated from the mice were used in this study. The number of dead cells increased in 10-week-old PTEN KO mice. This cell death was suppressed by the administration of ferroptosis inhibitor ferrostatin-1 for 2 weeks. Apomorphine also ameliorated the severity of steatohepatitis. Treatment with ferroptosis inhibitors, including apomorphine, decreases the level of lipid peroxidase. Apomorphine suppressed cell death induced by RSL-3 (a ferroptosis inducer), which was not suppressed by apoptosis or necroptosis inhibitors. Apomorphine showed a radical trapping capacity with much more potent activity than ferrostatin-1 and Trolox, a soluble form of vitamin E. In addition, apomorphine activated nrf2 and its downstream genes, including HO-1 and xCT. In conclusion, ferroptosis occurs in steatohepatitis from an early stage in PTEN KO mice. In addition, apomorphine ameliorates the severity of steatohepatitis by inhibiting ferroptosis.

Eating out of home (EOH), with its diverse food options, can benefit those with difficulty preparing their meals, especially older adults. Oral health status may be a determinant of EOH, as food accessibility is influenced by oral health, but this association remains unclear. This cross-sectional study used merged data from two national statistical surveys conducted in 2019. Participants were individuals aged ≥ 65 years who responded to both surveys. The frequency of EOH (

Background: Acinetobacter species are environmental microorganisms that inhabit the skin and can become opportunistic pathogens in immunocompromised hosts. This study investigated the pathogenicity of proteins released extracellularly by Acinetobacter radioresistens (A. radioresistens), isolated from the small intestine of two patients with severe Kawasaki disease, in a mouse model. Methods: The sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of culture supernatants derived from Acinetobacter species showed large variations in protein compositions among species and strains. The biological effects of soluble proteins secreted by A. radioresistens were evaluated in mice by intraperitoneal injection of culture supernatants. Results: The administration of culture supernatant derived from A. radioresistens caused weight loss, electrolyte imbalance, and decreased aldosterone levels. The sustained infiltration of the inflammatory mononuclear cells was observed in the liver of mice 6 weeks after the last administration. Conclusions: A. radioresistens expressed virulence through its extracellular proteins, leading to acute adrenal gland insufficiency and chronic inflammation of the livers.

Abstract This review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease‐modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.

IntroductionSARS-CoV-2 infection increases the risk of worse outcomes in cancer patients, including those with breast cancer. Our previous study reported that the SARS-CoV-2 membrane protein (M-protein) promotes the malignant transformation of triple-negative breast cancer cells (triple-negative BCC).MethodsIn the present study, the effects of M-protein on the ability of extracellular vesicles (EV) derived from triple-negative BCC to regulate the functions of tissue stem cells facilitating the tumor microenvironment were examined.ResultsOur results showed that EV derived from M-protein-induced triple-negative BCC (MpEV) significantly induced the paracrine effects of adipose tissue-derived mesenchymal stem cells (ATMSC) on non-aggressive BCC, promoting the migration, stemness phenotypes, and in vivo metastasis of BCC, which is related to PGE2/IL1 signaling pathways, in comparison to EV derived from normal triple-negative BCC (nEV). In addition to ATMSC, the effects of MpEV on endothelial progenitor cells (EPC), another type of tissue stem cells, were examined. Our data suggested that EPC uptaking MpEV acquired a tumor endothelial cell-like phenotype, with increasing angiogenesis and the ability to support the aggressiveness and metastasis of non-aggressive BCC.DiscussionTaken together, our findings suggest the role of SARS-CoV-2 M-protein in altering the cellular communication between cancer cells and other non-cancer cells inside the tumor microenvironment via EV. Specifically, M-proteins induced the ability of EV derived from triple-negative BCC to promote the functions of non-cancer cells, such as tissue stem cells, in tumorigenesis.

Summary: The heritability of major depressive disorder (MDD) is reportedly 30–50%. However, the genetic basis of its heritability remains unknown. Within SITH-1, a risk factor for MDD in human herpesvirus 6B (HHV-6B), we discovered a gene polymorphism with a large odds ratio for an association with MDD. It was a sequence whose number of repeats was inversely correlated with SITH-1 expression. This number was significantly lower in MDD patients. Rates for 17 or fewer repeats of the sequence were 67.9% for MDD and 28.6% for normal controls, with an odds ratio of 5.28. For patients with 17 or less repeats, the rate for presence of another MDD patient in their families was 47.4%, whereas there were no MDD patients in the families of patients with more than 17 repeats. Since HHV-6B is transmitted primarily mother to child and within families and persists for life, this gene polymorphism could potentially influence heritability of MDD.

Purpose: The aim of this study was to examine the effects of foveal thickness (FT) fluctuation (FTF) on 2-year visual and morphological outcomes of eyes with central retinal vein occlusion (CRVO) undergoing anti-VEGF treatment for recurrent macular edema (ME) based on a pro re nata regimen. Design: Retrospective, observational case series. Participants: We analyzed 141 treatment-naive patients (141 eyes) with CRVO-ME at a multicenter retinal practice. Methods: We assessed FT using OCT at each study visit. Patients were divided into groups 0, 1, 2, and 3 according to increasing FTF. Main Outcome Measures: We evaluated the logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA), the length of the foveal ellipsoid zone (EZ) band defect measured using OCT, and the association of FTF with VA and EZ band defect length. Results: The mean baseline logMAR BCVA and FT were 0.65 ± 0.52 (Snellen equivalent range: 20/20–20/2000) and 661.1 ± 257.4 μm, respectively. The mean number of anti-VEGF injections administered was 5.6 ± 3.6. At the final examination, the mean logMAR BCVA and FT values were significantly improved relative to the baseline values (both P

Summary: Neurons establish specific synapses based on the adhesive properties of cell-surface proteins while also retaining the ability to form synapses in a relatively non-selective manner. However, comprehensive understanding of the underlying mechanism reconciling these opposing characteristics remains incomplete. Here, we have identified Side-IV/Beat-IIb, members of the Drosophila immunoglobulin superfamily, as a combination of cell-surface recognition molecules inducing synapse formation. The Side-IV/Beat-IIb combination transduces bifurcated signaling with Side-IV’s co-receptor, Kirre, and a synaptic scaffold protein, Dsyd-1. Genetic experiments and subcellular protein localization analyses showed the Side-IV/Beat-IIb/Kirre/Dsyd-1 complex to have two essential functions. First, it narrows neuronal binding specificity through Side-IV/Beat-IIb extracellular interactions. Second, it recruits synapse formation factors, Kirre and Dsyd-1, to restrict synaptic loci and inhibit miswiring. This dual function explains how the combinations of cell-surface molecules enable the ranking of preferred interactions among neuronal pairs to achieve synaptic specificity in complex circuits in vivo.

Summary: Background: Developing strategies to prevent breast cancer-related arm lymphoedema (BCRAL) is a critical unmet need because there are no effective interventions to eradicate it once it reaches a chronic state. Certain strategies such as prospective surveillance programs and prophylactic lymphatic reconstruction have been reported to be effective in clinical trials. However, a large variation exists in practice based on clinician preference, organizational standards, and local resources. Methods: A two-round international Delphi consensus process was performed from February 27, 2023 to May 25, 2023 to compile opinions of 55 experts involved in the care and research of breast cancer and lymphoedema on such interventions. Findings: Axillary lymph node dissection, use of post-operative radiotherapy, relative within-arm volume increase one month after surgery, greater number of lymph nodes dissected, and high body mass index were recommended as the most important risk factors to guide selection of patients for interventions to prevent BCRAL. The panel recommended that prospective surveillance programs should be implemented to screen for and reduce risks of BCRAL where feasible and resources allow. Prophylactic compression sleeves, axillary reverse mapping and prophylactic lymphatic reconstruction should be offered for patients who are at risk for developing BCRAL as options where expertise is available and resources allow. Recommendations on axillary management in clinical T1–2, node negative breast cancer patients with 1–2 positive sentinel lymph nodes were also provided by the expert panel. Routine axillary lymph node dissection should not be offered in these patients who receive breast conservation therapy. Axillary radiation instead of axillary lymph node dissection should be considered in the same group of patients undergoing mastectomy. Interpretation: An individualised approach based on patients' preferences, risk factors for BCRAL, availability of treatment options and expertise of the healthcare team is paramount to ensure patients at risk receive preventive interventions for BCRAL, regardless of where they are receiving care. Funding: This study was not supported by any funding. RJC received investigator grant support from the Australian National Health and Medical Research Council (APP1194051).

BackgroundSecondary healthcare data use has been increasing in the dental research field. The validity of the number of remaining teeth assessed from Japanese dental claims data has been reported in several studies, but has not been tested in the general population in Japan.ObjectivesTo evaluate the validity of the number of remaining teeth assessed from Japanese dental claims data and assess its predictability against subsequent health deterioration.MethodsWe used the claims data of residents of a municipality that implemented oral health screening programs. Using the number of teeth in the screening records as the reference standard, we assessed the validity of the claims-based number of teeth by calculating the mean differences. In addition, we assessed the association between the claims-based number of teeth and pneumococcal disease (PD) or Alzheimer's disease (AD) in adults aged ≥65 years using Cox proportional hazards analyses.ResultsOf the 10,154 participants, the mean number of teeth assessed from the claims data was 20.9, that in the screening records was 20.5, and their mean difference was 0.5. During the 3-year follow-up, PD or AD onset was observed in 10.4% (3,212/30,838) and 5.3% (1,589/30,207) of participants, respectively. Compared with participants with ≥20 teeth, those with 1-9 teeth had a 1.29 (95% confidence interval [CI]: 1.17-1.43) or 1.19 (95% CI: 1.04-1.36) times higher risk of developing PD or AD, respectively.ConclusionHigh validity of the claims-based number of teeth was observed. In addition, the claims-based number of teeth was associated with the risk of PD and AD.

Abstract In π-conjugated polymers, the amorphous region absent from π–π stacking order typically limits polymer functions compared to the crystalline region with high π–π stacking order. Here, we show that a benzodithiophene–thiazolothiazole copolymer containing tripropylsilyl groups (PSTz2) has a greater coplanar backbone structure when the π–π stacking order is absent, such as in solution and in a film blended with a nonfullerene acceptor, than when it is present in a neat film. The excitons and charge carriers generated in PSTz2 are more highly delocalized in the blend film than in the neat film, presumably through the backbone. The unconventional structural feature of PSTz2 shows higher photovoltaic performance in nonfullerene-based cells compared to its alkyl-functionalized counterpart. Our results show that it is possible to develop π-conjugated polymers that perform well in amorphous blends due to the ordered backbone structure.

The BL09XU beamline of SPring-8 has been reorganized into a beamline dedicated for hard X-ray photoelectron spectroscopy (HAXPES) to provide advanced capabilities with upgraded optical instruments. The beamline has two HAXPES analyzers to cover a wide range of applications. Two sets of double channel-cut crystal monochromators with the Si(220) and (311) reflections were installed to perform resonant HAXPES analyses with a total energy resolution of less than 300 meV over a wide energy range (4.9–12 keV) while achieving a fixed-exit condition. A double-crystal X-ray phase retarder using diamond crystals controls the polarization state with a high degree of polarization over 0.9 in the wide energy range 5.9–9.5 keV. Each HAXPES analyzer is equipped with a focusing mirror to provide a high-flux microbeam. The design and performance of the upgraded instruments are presented.

COVID-19 remains a global health threat. Compliance with nonpharmaceutical interventions is essential because of limited effectiveness of COVID-19 vaccines, emergence of highly contagious variants, and declining COVID-19 antibody titers over time. We evaluated compliance with 14 nonpharmaceutical intervention–related COVID-19 preventive behaviors, including mask wearing, ventilation, and surface sanitation, in a longitudinal study in Japan using 4 waves of Internet survey data obtained during 2020–2022. Compliance with most preventive behaviors increased or remained stable during the 2-year period, except for surface sanitation and going out behaviors; compliance with ventilation behavior substantially decreased in winter. Compliance patterns identified from latent class analysis showed that the number of persons in the low compliance class decreased, whereas those in the personal hygiene class increased. Our findings reflect the relaxation of mobility restriction policy in Japan, where the COVID-19 pandemic continues. Policymakers should consider behavioral changes caused by new policies to improve COVID-19 prevention strategies.

In spite of emphasis on patient-centered care and promotion of their quality, shortcomings have been seen in psychiatric care due to lack of compassion. To improve the quality of psychiatric caring in nursing, it is important to develop and implement in-service education based on Locsin’s Technological Competency as Caring in Nursing (TCCN) theory. Objectives to determine psychiatric nurse managers' perception and practice status as a preliminary survey to serve as a resource for in-service psychiatric nursing education. This survey was conducted in August 2022 using the Technological Competency as Caring in Nursing Instrument-Revised for Practice (TCCNI-Repract) scale at "A" psychiatric hospital. Descriptive statistics and Wilcoxon's signed-rank tests were used. Eleven head nurses and assistant head nurses participated in this study. Mean values for the perception dimension of each item of the TCCNI-RePract were high, whereas mean values for practice dimension were low. The results indicated that perception dimension was significantly higher than practice dimension in 21 of 26 items of the TCCNI-RePract. Nurse managers demonstrated a high level of perception of the TCCN theory; however, many practical items scored low. Nurse managers suggested developing a current educational program to inform practice based on the TCCN theory.

Abstract Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy (FCS) to quantify changes in the local environment by measuring the fluorescence lifetime and the diffusion of the monomeric enhanced green fluorescent protein (eGFP), respectively. Real-time monitoring of eGFP fluorescence lifetime showed that a faster response to environmental changes due to MMC is observed than when measuring the acceptor/donor emission ratio using the MMC-sensitive Förster resonance energy transfer sensor (GimRET). This suggests that eGFP molecular electronic states and/or collision frequency are affected by changes in the immediate surroundings due to MMC without requiring conformational changes as is the case for the GimRET sensor. Furthermore, eGFP diffusion assessed by FCS indicated higher intracellular viscosity due to increased MMC during hyperosmotic stress. Our findings reveal that changes in eGFP fluorescence lifetime and diffusion are early indicators of elevated intracellular MMC. Our approach can therefore be used to reveal in live cells short-lived transient states through which MMC builds over time, which could not be observed when measuring changes in other physical properties that occur at slower time scales.

Abstract High sensitivity of the Kβ fluorescence spectrum to electronic state is widely used to investigate spin and oxidation state of first-row transition-metal compounds. However, the complex electronic structure results in overlapping spectral features, and the interpretation may be hampered by ambiguity in resolving the spectrum into components representing different electronic states. Here, we tackle this difficulty with a nonlinear resonant inelastic X-ray scattering (RIXS) scheme, where we leverage sequential two-photon absorption to realize an inverse process of the Kβ emission, and measure the successive Kα emission. The nonlinear RIXS reveals two-dimensional (2D) Kβ-Kα fluorescence spectrum of copper metal, leading to better understanding of the spectral feature. We isolate 3d-related satellite peaks in the 2D spectrum, and find good agreement with our multiplet ligand field calculation. Our work not only advances the fluorescence spectroscopy, but opens the door to extend RIXS into the nonlinear regime.

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE–RAGE-induced oxidative stress and inflammation in the testes of DM mice.

In recent years, diseases such as age-related macular degeneration and retinal pigment degeneration caused by excessive exposure to short-wavelength visible light have become significant concerns. With the aim of quantitatively evaluating the toxicity of short-wavelength light, proliferating cell nuclear antigen (PCNA) accumulation at the irradiation site was investigated using live cell imaging techniques to irradiate individual living cells with short-wavelength laser light. By examining the dependency of PCNA accumulation on the irradiation site within the cells and their cell cycle, it was observed that PCNA accumulation occurred only when the cell nucleus of cells in the S phase of the cell cycle was irradiated. We investigated the accumulation of PCNA at the laser irradiation site using laser light at wavelengths of 405 nm and 375 nm, with intensities ranging from 0.5 μW to 9.0 μW. The results confirmed an increase in PCNA accumulation with increasing intensity, and a higher accumulation was observed with laser light irradiation at a wavelength of 375 nm compared to 405 nm. By comparing the PCNA accumulation and 24 h cell viability, we demonstrated the feasibility of quantitatively assessing laser light toxicity through the measurement of PCNA accumulation.

Abstract The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract.

Abstract Aims Risk‐scoring systems for colorectal liver metastasis (CRLM) after hepatectomy allow prognoses to be predicted preoperatively. We investigated the clinical outcomes of neoadjuvant chemotherapy for resectable CRLM according to patient risk status, aiming to determine the subgroup of patients who could benefit from neoadjuvant chemotherapy. Methods In this multi‐institutional retrospective analysis, the preoperative risk score was calculated from six previously reported factors: synchronous metastases, primary lymph node positivity, tumor number, largest tumor diameter, extrahepatic metastasis, and the preoperative carbohydrate antigen 19–9 level. Patients were divided into three groups according to their risk scores: low risk (score = 0), intermediate risk (score 1–10), and high risk (score ≥11). Overall and recurrence‐free survival curves were calculated using the Kaplan–Meier method. After propensity‐score matching in the intermediate‐risk group, we compared clinicopathological features and outcomes. Results There were 318 cases, from 20 institutions. The preoperative risk score could be calculated in 277 cases. There were 34, 192, and 51 patients in the low‐, intermediate‐, and high‐risk groups, respectively. Intermediate‐risk group patients who received neoadjuvant chemotherapy had significantly better recurrence‐free survival than that of patients without neoadjuvant chemotherapy (P = .0453). After propensity‐score matching in the intermediate‐risk group, the recurrence‐free survival rate was better in patients who received neoadjuvant chemotherapy (P = .0261). But the overall survival rate was not improved after the matching. Conclusion Neoadjuvant chemotherapy for resectable CRLM might prolong the recurrence‐free survival period for intermediate‐risk patients with preoperative risk scores in the range of 1–10, but the overall survival was not improved by neoadjuvant chemotherapy.

Abstract The chemical order and disorder of solids have a decisive influence on the material properties. There are numerous materials exhibiting chemical order/disorder of atoms with similar X-ray atomic scattering factors and similar neutron scattering lengths. It is difficult to investigate such order/disorder hidden in the data obtained from conventional diffraction methods. Herein, we quantitatively determined the Mo/Nb order in the high ion conductor Ba7Nb4MoO20 by a technique combining resonant X-ray diffraction, solid-state nuclear magnetic resonance (NMR) and first-principle calculations. NMR provided direct evidence that Mo atoms occupy only the M2 site near the intrinsically oxygen-deficient ion-conducting layer. Resonant X-ray diffraction determined the occupancy factors of Mo atoms at the M2 and other sites to be 0.50 and 0.00, respectively. These findings provide a basis for the development of ion conductors. This combined technique would open a new avenue for in-depth investigation of the hidden chemical order/disorder in materials.

ABSTRACT: Objectives: The association between toothbrushing and coronavirus disease 2019 (COVID-19) infections is unknown. The aim of this study was to test the hypothesis that the change in time and frequency of toothbrushing is associated with having COVID-19 symptoms. Methods: In this 8-month retrospective cohort study, we used the data from the Japan COVID-19 and Society Internet Survey (JACSIS; N = 22,366), which was conducted between August and September 2020. The logistic regression analyses were used to calculate the odds ratios (ORs) of having the 3 main COVID-19 symptoms (high fever, cough, and taste and smell disorder). Confounders were age, sex, educational attainment, equivalised income level, self-rated health, health literacy, and living area. Results: The mean age of the participants was 49 years (SD = ±17.3), and 49.2% were male. Overall 2704 (12.1%) participants changed (increased or decreased) the time and frequency of toothbrushing, whilst 19,662 (87.9%) did not change. Only 60 participants (0.3%) had the 3 main COVID-19 symptoms. All logistic regression models showed that those who had a change in time and frequency of toothbrushing had higher odds of having the 3 main COVID-19 symptoms compared to those who had unchanged time and frequency of toothbrushing. The ORs ranged from 6.00 (95% confidence interval [CI], 3.60–9.99) in the crude model to 4.08 (95% CI, 2.38–6.98) in the fully adjusted model. Conclusions: The change in time and frequency of toothbrushing from before to after the COVID-19 pandemic was associated with having the 3 main COVID-19 symptoms.

Abstract The domain of psychiatric drug development is currently witnessing a notable transformation, with a paramount emphasis on targeting nonmonoamine receptors and exploring inventive mechanisms of action. This paper presents an overview of the ongoing advancements in antipsychotic and antidepressant drug development. Historically, antipsychotics predominantly targeted dopamine receptors, but there is now an escalating interest in drugs that act on alternative receptors, exemplified by the TAAR1 receptor. One noteworthy candidate is Ulotaront (SEP‐363856), an agent acting as a TAAR1 agonist with 5‐HT1A agonist activity, demonstrating promising outcomes in the treatment of schizophrenia, devoid of extrapyramidal symptoms or metabolic side‐effects. Similarly, MIN‐101 (Roluperidone) and KarXT are currently in development, with its focus on addressing the symptoms in schizophrenia. In the domain of antidepressants, novel therapeutic approaches have surfaced, such as Auvelity, a Food and Drug Administration (FDA)‐approved NMDA receptor antagonist synergistically combined with Bupropion to enhance its effects. Another notable candidate is Zuranolone, operating as a GABA A receptor‐positive allosteric modulator, showcasing efficacy in treating major depressive disorder (MDD) and postpartum depression. Additionally, TAK‐653 (NBI‐1065845) and MJI821 (Onfasprodil) have emerged as potential antidepressants targeting AMPA receptors and NMDA receptor 2B (NR2B) negative allosteric modulation, respectively. This paper underscores the transformative potential of these novel drug candidates in psychiatric treatment and their ability to address cases that were previously treatment‐resistant. By focusing on nonmonoamine receptors and introducing innovative mechanisms, these drugs offer a promising prospect of improved outcomes for individuals suffering from schizophrenia and MDD. Thus, sustained attention and dedication to the development of such drugs are essential to augmenting the therapeutic options available for psychiatric patients.