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Parkinson's disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms (NMS), which affect the patient's quality of life (QOL). This study aimed to compare QOL and background in patients with PD based on the disease duration and investigate the factors affecting QOL. Patients with PD were evaluated based on age, sex, disease duration (≤5 years and > 5 years groups), Mini Mental State Examination (MMSE), Japanese version of Montreal Cognitive Assessment (MoCA-J), Levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) severity, movement disorder society-sponsored revision of the unified Parkinson's disease rating scale (MDS-UPDRS) parts I-IV, and QOL using the Parkinson's disease questionnaire (PDQ-8). Overall, 102 patients with PD (58 males; mean age = 70.0 years; mean disease duration = 7.3 years) were included in this study. QOL was significantly correlated (r > 0.30, p < 0.05) with disease duration and MDS-UPDRS parts I-IV total scores. When the PDQ-8 total score was compared with MDS-UPDRS parts I-IV total scores based on disease duration classification, it was positively correlated with the scores for parts I and II in the >5 years group. Moreover, MDS-UPDRS parts I and II total scores appeared to be the factors most significantly affecting QOL. The factors affecting QOL in patients with PD were subjective NMS and motor symptoms. Since, physician-rated motor symptoms were not associated with QOL in patients with >5 years PD, subjective symptoms should be evaluated and treated to maintain QOL., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: No clinical trials have been reported on the use of focused ultrasound (FUS) for treating cervical dystonia., Objective: We aimed to confirm the efficacy and safety of FUS pallidothalamic tractotomy for cervical dystonia., Methods: This was a prospective, open-label, non-controlled pilot study. The primary outcome was defined as a change in the score for the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) from baseline to 6 months after FUS pallidothalamic tractotomy. The secondary outcomes included a change in the neck scale for the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), mood scales including Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Apathy Evaluating Scale (AES), and adverse events. Patients were assessed for TWSTRS, BFMDRS, and adverse events at baseline, 1 week, 1 month, 3 months, and 6 months after treatment. BDI, BAI, and AES were assessed at baseline and 6 months after treatment., Results: Ten patients were enrolled in this study. The mean age of onset of dystonia was 51.6 ± 10.2 years. The TWSTRS at 6 months (29.9 ± 16.0, range: 3-55) was significantly improved by 43.4% (P < 0.001) from baseline. The BFMDRS-Neck scales at 6 months (4.2 ± 2.8) were significantly improved by 38.2% (P < 0.001) from baseline. The BDI, BAI, and AES at 6 months were improved by 23.2%, 10.9%, and 30.3%, respectively from baseline. Reduced hand dexterity in three patients and weight gain in two patients were confirmed at the last evaluation., Conclusion: This study suggests that FUS pallidothalamic tractotomy may be an effective treatment option for patients with cervical dystonia. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Aobjective: The impact of fine motor impairment among adult survivors of childhood acute lymphoblastic leukemia (ALL) on life after treatment is unknown., Methods: This study evaluated prevalence and utilized multivariate logistic regression to identify risk factors for fine motor impairment among survivors of ALL, and associations with educational attainment and social independence. Latent class analysis defined social independence (independent, moderately independent, dependent), using employment, independent living, personal care assistance, routine need assistance, driver's license status, and marital status inputs., Results: Among 875 survivors who were ≥ 25 years old (age when most adults achieve independence) and ≥ 5 years from diagnosis (mean = 28.97 years), 33.6% had fine motor impairment, with scores at or below the 10th percentile of the scores of community controls (n = 460) on fine motor components of the physical performance test and the grooved peg-board test. Survivors exposed to cranial radiation had more fine motor impairment than those without (45.8% vs 20.2%). Male sex (exposed: odds ratio [OR] = 2.55, 95% confidence interval [CI] = 1.65-3.92; unexposed: OR = 3.02, 95% CI = 1.69-5.38) and lower scores on the Wechsler abbreviated scale of intelligence (exposed: OR = 0.46, 95% CI = 0.36-0.58; unexposed: OR = 0.43, 95% CI = 0.31-0.58) were risk factors for neuropathy. A 1-point-higher total neuropathy score was associated with 8% (95% CI = 1%-17%) increased odds of fine motor impairment. Fine motor impairment was associated with less than a college education (less than high school: OR = 2.23, 95% CI = 1.20-4.14; high school diploma/general equivalency diploma: OR = 2.66, 95% CI = 1.65-4.30; vocational education: OR = 2.07, 95% CI = 1.38-3.13) and less social independence (moderately independent: OR = 1.80, 95% CI = 1.15-2.83; dependent: OR = 2.65, 95% CI = 1.25-5.64)., Conclusion: Fine motor impairment in survivors of childhood ALL may interfere with optimal educational attainment and social independence., Impact: Early identification of survivors at risk for fine motor impairment, with timely intervention, may improve long-term outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey., Design: Retrospective, national trend survey., Methods: Dermatologic case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmologic CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey., Results: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < .001) and specific year in the survey (P < .001)., Conclusions: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nitride (N 3- ) or cyanamide (CN 2 2- ) based mixed-anion compounds stand as attractive materials due to their unique properties derived from the binary or multiple anions, although their synthesis remains challenging in incorporating the N 3- or CN 2 2- anions safely. This work highlights the first demonstration of in situ single phase formation of a LaCl(CN 2 ) mixed-anion compound from a stable single source precursor, melamine modified with LaCl 3 preparable under aqueous conditions. The in situ formation of LaCl(CN 2 ) involves the chemical modification of melamine with LaCl 3 to form a complex. Upon heating of the precursor under N 2 flowing, this complex generates cyanamide species around 400 °C, which react with LaCl 3 and nonsublimated melamine to afford a binary LaCl(CN 2 )/g-C 3 N 4 composite. Further pyrolysis at 800 °C decomposes the g-C 3 N 4 counterpart, resulting in the LaCl(CN 2 ) single-phase formation. The electronic properties of the precursor-derived single phase LaCl(CN 2 ) were studied by the density functional theory calculation and UV-vis spectroscopy combined with X-ray photoelectron spectroscopy analyses and characterized by measuring 4.7, 1.8, and -2.9 eV for the band gap energy, the valence band maximum, and the conduction band minimum relative to Fermi energy, respectively. This study paves the way for exploring various cyanamide-based mixed anion compounds, advancing their potential applications in various fields.

Background: Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis (N. meningitidis) are leading causes of childhood bacterial meningitis and preventable by vaccines. The aim of this hospital-based sentinel surveillance is to describe the epidemiological characteristics of pneumococcal meningitis, including disease burden, and to provide baseline data on pneumococcal serotype distribution to support decision making for pneumococcal conjugate vaccine (PCV) introduction in Vietnam., Methods: Surveillance for probable bacterial meningitis in children 1-59 months of age is conducted in three tertiary level pediatric hospitals: one in Hanoi and two in Ho Chi Minh City. Cerebrospinal fluid (CSF) specimens were collected via lumbar puncture from children with suspected meningitis. Specimens were transferred immediately to the laboratory department of the respective hospital for cytology, biochemistry, and microbiology testing, including culture. PCR testing was conducted on CSF specimens for bacterial detection (S. pneumoniae, H. influenzae, and N. meningitidis) and pneumococcal serotyping., Results: During 2015-2018, a total of 1,803 children with probable bacterial meningitis were detected; 1,780 had CSF specimens available for testing. Of 245 laboratory-confirmed positive cases, the majority were caused by S. pneumoniae (229,93.5%). Of those with S. pneumoniae detected, over 70% were caused by serotypes included in currently available PCV products; serotypes 6 A/6B (27.1%), 14 (19.7%), and 23 F (16.2%) were the most common serotypes. Children with laboratory-confirmed pneumococcal meningitis were more likely to live in Hanoi (p < 0.0001) and children 12-23 months of age were at greater odds (OR = 1.65, 95% CI: 1.11, 2.43; p = 0.006) of having confirmed pneumococcal meningitis compared to children < 12 months of age when compared to those without laboratory-confirmed bacterial meningitis. Additionally, children with confirmed pneumococcal meningitis were more likely to exhibit signs and symptoms consistent with clinical meningitis compared to negative laboratory-confirmed meningitis cases (p < 0.0001) and had a greater odds of death (OR = 6.18, 95% CI: 2.98, 12.86; p < 0.0001)., Conclusions: Pneumococcal meningitis contributes to a large burden of bacterial meningitis in Vietnamese children. A large proportion are caused by serotypes covered by PCVs currently available. Introduction of PCV into the routine immunization program could reduce the burden of pneumococcal meningitis in Viet Nam., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Polyamines are involved in various functions related to the cellular-level responses. To assess effects of polyamines on marine organisms, rearing experiments and comprehensive gene expression analyses were conducted on Acropora digitifera and Acropora sp.1, representative reef-building corals along the west-central coast of Okinawa, Japan, to evaluate effects of putrescine. Concentrations of putrescine ≥ 1 mM dissolved tissues of juvenile polyps and increased mortality of planula larvae. RNA-Seq analysis of juvenile polyps exposed to putrescine at the stage before effects became visible revealed dynamic fluctuations in gene expression in the putrescine-treated samples, with increased expression of stress-responsive genes (e.g. NAD-dependent protein deacylase sirtuin-6) and the polyamine transporter Slc18b1-like protein. These results also suggest that putrescine affects expression of genes related to ribosomes and translation. This study provides important insights into roles of polyamines and future directions regarding physiological responses of corals., (© 2024. The Author(s).)

Following the Goldilocks principle, mitochondria size must be "just right." Mitochondria balance division and fusion to avoid becoming too big or too small. Defects in this balance produce dysfunctional mitochondria in human diseases. Mitochondrial safeguard (MitoSafe) is a defense mechanism that protects mitochondria against extreme enlarging by suppressing fusion in mammalian cells. In MitoSafe, hyperfused mitochondria elicit flickering-short pulses of mitochondrial depolarization. Flickering activates an inner membrane protease, Oma1, which in turn proteolytically inactivates a mitochondrial fusion protein, Opa1. The mechanisms underlying flickering are unknown. Using a live-imaging screen, we identified Slc25a3 (a mitochondrial carrier transporting phosphate and copper) as necessary for flickering and Opa1 cleavage. Remarkably, copper, but not phosphate, is critical for flickering. Furthermore, we found that two copper-containing mitochondrial enzymes, superoxide dismutase 1 and cytochrome c oxidase, regulate flickering. Our data identify an unforeseen mechanism linking copper, redox homeostasis, and membrane flickering in mitochondrial defense against deleterious fusion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The primary objective of this study was to elucidate the predictive role of subtle motor impairment evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III on mortality and functional outcome. The secondary objective was to evaluate the association of motor impairment with small vessel disease (SVD) severity., Methods: We derived data from a Japanese cohort of patients with evidence of SVD who were enrolled from 2015 to 2019, and followed until 2023. The present study included 586 participants who agreed for UPDRS Part III evaluation. The severity of white matter hyperintensities (WMHs) and the presence of lacunes were evaluated. Cox proportional hazard models and multiple logistic regression analysis were used to examine the association between UPDRS Part III score and all-cause death and functional outcome defined by the modified Rankin Scale (mRS) score at the last visit, respectively., Results: The median age was 71 years, and the median UPDRS Part III score was 2. The UPDRS Part III score was associated with the severity of WMH (r = 0.225, p &lt; 0.001) and the number (0, 1, ≥2) of lacunes (p &lt; 0.001). During a mean follow-up period of 4.8 years, 29 patients died. The Cox proportional hazard analysis revealed that high UPDRS Part III scores (≥5) were associated with a higher risk of all-cause death compared to low (score 0) and middle (score 1-4) scores (adjusted hazard ratio 3.04; 95% confidence interval, 1.50-7.34, p = 0.005). In multivariate logistic analysis, high UPDRS Part III scores were associated with poor functional outcome (mRS of ≥3) compared with low and middle scores after adjusting for confounding factors (adjusted odds ratio 1.86; 95% confidence interval 1.02-3.41, p = 0.043)., Conclusions: Subtle motor impairment was associated with the severity of WMH and number of lacunes and could predict mortality and poor functional outcome independently of vascular risk factors and severity of WMH and lacunes., (© 2024 S. Karger AG, Basel.)

A 62-year-old man with a history of diabetes mellitus was hospitalised with numbness of lower limbs, bullous lesions of the whole body, kidney dysfunction, presence of eosinophils, and elevated antineutrophil cytoplasmic antibodies to myeloperoxidase and anti-bullous pemphigoid 180 antibodies and was diagnosed with mononeuritis multiplex. Kidney and muscle biopsies showed vasculitis with fibrinoid necrosis, whereas skin biopsies showed only blister formation between the epidermis and dermis; a high eosinophilic infiltrate was present in all three tissues. These findings led to a diagnosis of eosinophilic granulomatosis with polyangiitis combined with allergic bullous lesions. Immunohistological examination indicated cytolytic eosinophils and extracellular traps, suggesting the presence of eosinophil extracellular trap cell death (eosinophil ETosis) in diseased tissue., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Substantial changes in energy metabolism are a hallmark of pancreatic cancer. To adapt to hypoxic and nutrient-deprived microenvironments, pancreatic cancer cells remodel their bioenergetics from oxidative phosphorylation to glycolysis. This bioenergetic shift makes mitochondria an Achilles' heel. Since mitochondrial function remains essential for pancreatic cancer cells, further depleting mitochondrial energy production is an appealing treatment target. However, identifying effective mitochondrial targets for treatment is challenging. Here, we developed an approach, mitochondria-targeted cancer analysis using survival and expression (mCAUSE), to prioritize target proteins from the entire mitochondrial proteome. Selected proteins were further tested for their impact on pancreatic cancer cell phenotypes. We discovered that targeting a dynamin-related GTPase, OPA1, which controls mitochondrial fusion and cristae, effectively suppresses pancreatic cancer activities. Remarkably, when combined with a mutation-specific KRAS inhibitor, OPA1 inhibition showed a synergistic effect. Our findings offer a therapeutic strategy against pancreatic cancer by simultaneously targeting mitochondria dynamics and KRAS signaling., Competing Interests: AJE has unlicensed patents related to keratin 14 as a prognostic marker and antibody strategy for anti-cancer therapeutics. AJE is a consultant for BioNTech. AJE’s spouse is an employee of ImmunoCore., (© 2024 The Author(s).)

Introduction: Migraine is a debilitating headache disorder with a high prevalence in Japan that imposes significant societal burden. Although the Japanese Clinical Practice Guideline for Headache Disorders 2021 recommends both acute and preventive migraine treatments, the usage of preventive treatments is still limited. Therefore, it is crucial to understand the treatment preferences of patients with migraine pertaining to both acute and preventive treatments., Methods: A mixed-methods study including a discrete choice experiment (DCE) was conducted with Japanese patients with migraine (10 for the qualitative interviews, and 400 for the DCE) who were recruited from the Rakuten Insight panel. The DCE presented hypothetical treatment options including oral acute, oral preventive, and injectable preventive medications. Six attributes (method of delivery, reduction of pain, impact of headaches on daily routines, dosage adjustability, and temporary and persistent side effects) each with three levels were included in the survey. A hierarchical Bayesian model was used to estimate relative attribute importance scores (RAI) for all attributes., Results: For the 400 participants in the DCE, the most common age bracket was 40-49 years old, and the majority were female (66.75%). RAI estimates indicated that "method of delivery" was the most important attribute for patients (RAI 51.92, SD = 10.20), followed by "reduction of pain when experiencing a headache" (RAI 17.00, SD = 7.74). Oral preventive treatments were preferred over injectable preventive treatments. The qualitative interviews showed that patients prefer oral medications to injectable treatments, and a lack of awareness regarding preventive treatments., Conclusion: This study found that the "method of delivery" was the most important driver of treatment preferences of patients with migraine in Japan, with oral acute medications being preferred. Oral preventive treatments were found to be preferred over injectable treatments. These results may indicate the need for increased education regarding preventive treatments, as well as the need for further development of these treatments., (© 2024. The Author(s).)

Background: We developed a novel method to measure the angle of subjective postural vertical (SPV) and showed that the SPV may be related to the exacerbation of the forward flexed posture., Objectives: The present study prospectively tested the effects of the subjective postural vertical on the exacerbation of the forward flexion of trunk (FFT) through long-term observation of Parkinson's disease patients., Methods: Evaluation of the posture included measuring FFT, the angle of lateral flexion of trunk, and the angle at the position that the patient subjectively perceived as the vertical position at a stationary upright position immediately after standing up at the time of initial observation, 6 months later, and 1 year later., Results: The SPV angles worsened significantly at 6 months and 1 year compared to the first measurements (9.3 ± 6.7° vs. 10.8 ± 8.2° and 10.6 ± 7.8°, P < 0.05), and the FFT angles worsened significantly at one year compared to the first measurements (11.1 ± 8.1° vs. 12.2 ± 8.8°, P = 0.004). Furthermore, using a hierarchical multiple regression model, the difference in SPV from the first visit to the first half year was considered a factor contributing to annual FFT change (P = 0.002)., Conclusions: This longitudinal study of a large number of cases suggested that changes in SPV may precede changes in FFT., Competing Interests: Declaration of Competing Interest This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. 21K11321, 22H00547, 24K14361). Outside this funding, none of the authors has conflicts of interest relevant to this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Western Pacific Region's pursuit of measles elimination has seen significant progress and setbacks. Mongolia and Cambodia were the first two middle-income countries in the Western Pacific to be verified as having eliminated measles by the Western Pacific Regional Verification Commission for Measles and Rubella Elimination, in March 2014 and 2015, respectively. However, both countries experienced large-scale or prolonged importation-related measles outbreaks shortly afterwards, leading to the re-establishment of endemic transmission. We describe the path to initial elimination in both countries and explore these outbreaks' characteristics, factors contributing to the loss of elimination status, and implications for broader elimination efforts. Data sources include case-based epidemiological and laboratory surveillance reports, historical immunization coverage, genotype data, and published reports of in-depth outbreak investigations. In Mongolia, a single prolonged and large-scale outbreak revealed a hidden immunity gap among young adults and was driven in part by nosocomial transmission, leading to significant morbidity and mortality and loss of elimination status. Cambodia suffered multiple importations from neighboring endemic countries during the global measles resurgence in 2018-2019, complicated by cross-border mobility and significant nosocomial amplification, and the country was ultimately unable to sufficiently distinguish independent chains of transmission, leading to loss of elimination status. Our findings highlight the importance of broadening population immunity assessments beyond children to include adults and specific high-risk groups. Robust routine immunization programs, supplemented by tailored SIAs, are crucial for preventing and managing outbreaks. Additionally, strong outbreak preparedness plans, rapid response strategies, and cross-border collaboration and the global effort to prevent multiple resurgences and large-scale importation-induced outbreaks are vital for maintaining elimination status. The experiences of Mongolia and Cambodia underscore the challenges of sustaining measles elimination in the face of importation risks, shared borders with endemic countries, healthcare system gaps, and population movements. Strengthening the global coordination and synchronization of measles elimination activities is imperative to protect the gains achieved and prevent future setbacks.

Purpose: Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis., Methods: We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period., Results: Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function., Conclusion: These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function., Competing Interests: Yoshinori Kinugasa and Takahiro Nishizaka were employees of Kao Corporation at the time the study was conducted. Keita Okoshi, Joji Okada, and Makoto Iijima are currently affiliated with a different section within Kao Corporation. The authors have no other conflicts of interest to declare in this work., (© 2024 Okoshi et al.)

The inhibition of kynurenine production is considered a promising target for cancer immunotherapy. In this study, an amino acid derivative, compound 1 was discovered using a cell-based assay with our screening library. Compound 1 suppressed kynurenine production without inhibiting indoleamine 2,3-dioxygenase 1 (IDO1) activity. The activity of 1 was derived from the inhibition of IDO1 by a metabolite of 1, O-benzylhydroxylamine (OBHA, 2a). A series of N-substituted 2a derivatives that exhibit potent activity in cell-based assays may represent effective prodrugs. Therefore, we synthesized and evaluated novel N,O-substituted hydroxylamine derivatives. The structure-activity relationships revealed that N,O-substituted hydroxylamine 2c inhibits kynurenine production in a cell-based assay. We conducted an in vivo experiment with 2c, although the effectiveness of O-substituted hydroxylamine derivatives in vivo has not been previously reported. The results indicate that N,O-substituted hydroxylamine derivatives are promising IDO1 inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/purpose: The dental adhesive market is constantly evolving to meet the demands of dentists and patients, but new products and upgrades should be rigorously evaluated before being used in clinical practice. This study investigated the physicomechanical properties and dentin bonding efficacy of a newly upgraded universal adhesive compared to its predecessor., Materials and Methods: Twenty-four molars were divided into four groups (n = 6/group) based on adhesive (new vs. predecessor) and application mode [self-etch (SE) vs. etch-and-rinse (ER)] for evaluating their dentin microtensile bond strength (μTBS), failure pattern, and bonding interface. Additional thirty-six molars' crowns were perpendicularly sectioned to obtain flat mid-coronal dentin discs. The opposing dentin surfaces of each disc received contrasting treatments (new/predecessor adhesive applied in SE/ER mode), resulting in six interventions. The bonded discs (n = 6/intervention) were used to assess the adhesives' survival probability employing a double-sided μTBS test. The other physicomechanical properties examined were adhesives' oxygen inhibition layer (OIL), viscosity, hardness, elastic modulus, degree of conversion (DC), and in-situ DC., Results: Both adhesive versions showed similar μTBS ( P  > 0.05), failure pattern ( P  > 0.05), and survival probability ( P  > 0.008). ER mode promoted resin tag formation and exhibited a slender adhesive layer for both adhesives. The newer adhesive version showed a thinner adhesive layer in general with narrower OIL ( P  < 0.001), less viscosity ( P  < 0.001), higher hardness ( P  < 0.05), elastic modulus ( P  < 0.05), DC ( P  < 0.001), and in-situ DC ( P  < 0.001)., Conclusion: While the newly updated adhesive had superior physicomechanical properties with more fluidity, its dentin bonding efficacy and survival probability were comparable to its predecessor., Competing Interests: The authors have no conflicts of interest relevant to this study., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Papaya ( Carica papaya L.) is a herbaceous plant belonging to the family Caricaceae in the order Brassicales. The shape of papaya fruit was linked to sex, and the fruit of female plants is round, whereas that of hermaphrodites is pyriform. Although fruit shape preferences vary by region, differences in their functionalities have not been investigated. Since unripe fruit, also called green papaya, is known for its nutritional and therapeutic benefits, we performed a metabolome analysis of unripe papaya using liquid chromatography coupled with quadrupole/time of flight mass spectrometry. We first focused on capraine derivatives, major piperidine alkaloids, and bioactive compounds with significant antiplasmodial activity. Interestingly, carpaine derivatives tended to be altered in the peel and pulp but not in the seed. Multivariate analyses indicated little difference or minor differences to the extent that they can be caused by individual differences in metabolite profiling between the two sexes. Conversely, total polyphenol content and proteolytic activity were also investigated, but there were no differences between females and hermaphrodites for total polyphenol content and proteolytic activity. In conclusion, the metabolome and major functionalities were similar between hermaphrodites and female unripe fruit. However, it would be worth considering the sex of the material fruit, especially when focusing on the functional properties of carpaine derivatives., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© 2024 Japanese Society for Plant Biotechnology.)

The etiology of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains elusive and is believed to involve multiple contributing factors. There have been cases linking CIDP to the coronavirus disease 2019 (COVID-19) mRNA vaccine. However, there are no documented instances following alternative vaccines. We report a case of a 48-year-old woman, previously vaccinated with Pfizer-BioNTech's COVID-19 vaccine (BNT162b2), who subsequently received the Moderna mRNA-1273 vaccine. Within 2 days postvaccination, she developed diplopia and numbness in the lower limbs' distal extremities. Cerebrospinal fluid analysis exhibited protein-cell dissociation, while F-wave studies showed demyelinating activity in the bilateral tibial nerves. Given the disease's progressive nature, the patient was presumed to have CIDP and commenced steroid pulse therapy and intravenous immunoglobulin therapy. The onset of CIDP may be associated with variations in mRNA sequences and vaccine constituents., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Satoshi Saito et al.)

Objectives: Factors that induce bone formation during orthodontic tooth movement (OTM) remain unclear. Gli1 was recently identified as a stem cell marker in the periodontal ligament (PDL). Therefore, we evaluated the mechanism of differentiation of Cre/LoxP-mediated Gli1/Tomato + cells into osteoblasts during OTM., Methods: After the final administration of tamoxifen to 8-week-old Gli1-Cre ERT2 /ROSA26-loxP-stop-loxP-tdTomato mice for 2 days, nickel-titanium closed coil springs were attached between the upper anterior alveolar bone and the first molar. Immunohistochemical localizations of β-catenin, Smad4, and Runx2 were observed in the PDL on 2, 5, and 10 days after OTM initiation., Results: In the untreated tooth, few Gli1/Tomato + cells were detected in the PDL. Two days after OTM initiation, the number of Gli1/Tomato + cells increased in the PDL on the tension side. On this side, 49.3 ± 7.0% of β-catenin + and 48.7 ± 5.7% of Smad4 + cells were found in the PDL, and Runx2 expression was detected in some Gli1/Tomato + cells apart from the alveolar bone. The number of positive cells in the PDL reached a maximum on day 5. In contrast, on the compression side, β-catenin and Smad4 exhibited less immunoreactivity. On day 10, Gli1/Tomato + cells were aligned on the alveolar bone on the tension side, with some expressing Runx2., Conclusions: Gli1 + cells in the PDL differentiated into osteoblasts during OTM. Wnt and bone morphogenetic proteins signaling pathways may be involved in this differentiation., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this review article., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

The evolution of archosaurs provides an important context for understanding the mechanisms behind major functional transformations in vertebrates, such as shifts from sprawling to erect limb posture and the acquisition of powered flight. While comparative anatomy and ichnology of extinct archosaurs have offered insights into musculoskeletal and gait changes associated with locomotor transitions, reconstructing the evolution of motor control requires data from extant species. However, the scarcity of electromyography (EMG) data from the forelimb, especially of crocodylians, has hindered understanding of neuromuscular evolution in archosaurs. Here, we present EMG data for nine forelimb muscles from American alligators during terrestrial locomotion. Our aim was to investigate the modulation of motor control across different limb postures and examine variations in motor control across phylogeny and locomotor modes. Among the nine muscles examined, m. pectoralis, the largest forelimb muscle and primary shoulder adductor, exhibited significantly smaller mean EMG amplitudes for steps in which the shoulder was more adducted (i.e., upright). This suggests that using a more adducted limb posture helps to reduce forelimb muscle force and work during stance. As larger alligators use a more adducted shoulder and hip posture, the sprawling to erect postural transition that occurred in the Triassic could be either the cause or consequence of the evolution of larger body size in archosaurs. Comparisons of EMG burst phases among tetrapods revealed that a bird and turtle, which have experienced major musculoskeletal transformations, displayed distinctive burst phases in comparison to those from an alligator and lizard. These results support the notion that major shifts in body plan and locomotor modes among sauropsid lineages were associated with significant changes in muscle activation patterns., (© 2024 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Early diagnosis of infectious diseases is still challenging particularly in a nonlaboratory environment or limited resources areas. Thus, sensitive, inexpensive, and easily handled diagnostic approaches are required. The lateral flow immunoassay (LFIA) is commonly used in the screening of infectious diseases despite its poor sensitivity, especially with low pathogenic loads (early stages of infection). This article introduces a novel polymeric material that might help in the enrichment and concentration of pathogens to overcome the LFIA misdiagnosis. To achieve this, we evaluated the efficiency of introducing poly( N -isopropylacrylamide) (PNIPAAm) into immunoglobulin G (IgG) as a model antibody using two different conjugation methods: grafting to (GT) and grafting from (GF). The IgG-PNIPAAm conjugates were characterized using SDS-PAGE, DLS, and temperature-responsive phase transition behavior. SDS-PAGE analysis revealed that the GF method was more efficient in introducing the polymer than the GT method, with calculated polymer introduction ratios of 61% and 34%, respectively. The GF method proved to be less susceptible to steric hindrance and more efficient in introducing high-molecular-weight polymers into proteins. These results are consistent with previous studies comparing the GT and GF methods in similar systems. This study represents an important step toward understanding how the choice of polymer incorporation method affects the properties of IgG-PNIPAAm conjugates. The synthesized polymer allowed binding and enrichment of mouse IgG that was used as a model antigen with a clear LFIA band. On the basis of our findings, this system might help in improving the sensitivity of simple diagnostics., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Mitochondrial division controls the size, distribution, and turnover of this essential organelle. A dynamin-related GTPase, Drp1, drives membrane division as a force-generating mechano-chemical enzyme. Drp1 is regulated by multiple mechanisms, including phosphorylation at two primary sites: serine 579 and serine 600. While previous studies in cell culture systems have shown that Drp1 S579 phosphorylation promotes mitochondrial division, its physiological functions remained unclear. Here, we generated phospho-mimetic Drp1 S579D and phospho-defective Drp1 S579R mice using the CRISPR-Cas system. Both mouse models exhibited normal growth, development, and breeding. We found that Drp1 is highly phosphorylated at S579 in brain neurons. Notably, the Drp1 S579D mice showed decreased anxiety-like behaviors, whereas the Drp1 S579R mice displayed increased anxiety-like behaviors. These findings suggest a critical role for Drp1 S579 phosphorylation in brain function. The Drp1 S579D and S579R mice thus offer valuable in vivo models for specific analysis of Drp1 S579 phosphorylation., Competing Interests: The authors declare no competing financial interests., (© 2024 The Author(s).)

Introduction: This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission., Methods: This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization., Results: Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment., Conclusions: This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors., Competing Interests: The authors declare that they have no competing or conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Children with acute lymphoblastic leukaemia (ALL) are at risk for obesity and cardiometabolic diseases. To gain insight into body composition changes among children with ALL, we assessed quantitative computed tomography (QCT) data for specific body compartments (subcutaneous adipose tissue [SAT], visceral adipose tissue [VAT], total adipose tissue [TAT], lean tissue [LT], LT/TAT and VAT/SAT at lumbar vertebrae L1 and L2) at diagnosis and at off-therapy for 189 children with ALL and evaluated associations between body mass index (BMI) Z-score and clinical characteristics. BMI Z-score correlated positively with SAT, VAT and TAT and negatively with LT/TAT and VAT/SAT. At off-therapy, BMI Z-score, SAT, VAT and TAT values were higher than at diagnosis, but LT, LT/TAT and VAT/SAT were lower. Patients aged ≥10 years at diagnosis had higher SAT, VAT and TAT and lower LT and LT/TAT than patients aged 2.0-9.9 years. Female patients had lower LT and LT/TAT than male patients. Black patients had less VAT than White patients. QCT analysis showed increases in adipose tissue and decreases in LT during ALL therapy when BMI Z-scores increased. Early dietary and physical therapy interventions should be considered, particularly for patients at risk for obesity., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

The combination regimen of atezolizumab plus bevacizumab (Atezo/Bev) is currently used as first-line treatment in patients with unresectable hepatocellular carcinoma. Herein, we report a rare case of curative hepatic resection performed as conversion surgery in a patient with intermediate-stage hepatocellular carcinoma following preoperative Atezo/Bev therapy. After five treatment cycles of Atezo/Bev therapy, followed by four cycles of atezolizumab monotherapy, the tumor marker levels decreased to baseline levels and 22 small daughter nodules disappeared, leaving only the primary tumor. Therefore, we performed resection of the primary tumor as conversion surgery, and postoperative histopathology confirmed complete tumor necrosis. No cancer recurrence has been observed until the 5-month postoperative follow-up, and the patient remains drug free. Consistent with the findings in this case, a review of previously reported cases revealed that in cases of successful conversion surgery, neoadjuvant Atezo/Bev therapy was associated with intra-tumoral bleeding, immune-related adverse events, and normalization of the tumor marker levels., (© 2023. The Author(s).)

Mitochondrial dynamic process is important for cell viability, metabolic activity, and mitochondria health. Here, we present a protocol for measuring mitochondrial size through immunofluorescence staining, confocal imaging, and analysis in ImageJ. We describe the steps for tissue processing, antigen retrieval, mitochondrial staining using an integrating immunofluorescence assay, and computerized image analysis to measure each mitochondrial size in mouse and human liver tissues. This protocol reduces tissue sample volume and processing time for the preparation of primary cells. For complete details on the use and execution of this protocol, please refer to Pearah et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coral reef ecosystems supported by environmentally sensitive reef-building corals face serious threats from human activities. Our understanding of these reef threats is hampered by the lack of sufficiently sensitive coral environmental impact assessment systems. In this study, we established a platform for metabolomic analysis at the single-coral-polyp level using state-of-the-art mass spectrometry (probe electrospray ionization/tandem mass spectrometry; PESI/MS/MS) capable of fine-scale analysis. We analyzed the impact of the organic UV filter, benzophenone (BP), which has a negative impact on corals. We also analyzed ammonium and nitrate samples, which affect the environmental sensitivity of coral-zooxanthella (Symbiodiniaceae) holobionts, to provide new insights into coral biology with a focus on metabolites. The method established in this study breaks new ground by combining PESI/MS/MS with a technique for coral polyps that can control the presence or absence of zooxanthellae in corals, enabling functions of zooxanthellae to be assessed on a polyp-by-polyp basis for the first time. This system will clarify biological mechanisms of corals and will become an important model system for environmental impact assessment using marine organisms., (© 2024. The Author(s).)

Background and Objectives: This study aimed to identify disease-related autoantibodies in the serum of patients with immune-mediated neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP) and to investigate the clinical characteristics of patients with these antibodies., Methods: Proteins extracted from mouse brain tissue were used to react with sera from patients with CIDP by western blotting (WB) to determine the presence of common bands. Positive bands were then identified by mass spectrometry and confirmed for reactivity with patient sera using enzyme-linked immunosorbent assay (ELISA) and WB. Reactivity was further confirmed by cell-based and tissue-based indirect immunofluorescence assays. The clinical characteristics of patients with candidate autoantibody-positive CIDP were analyzed, and their association with other neurologic diseases was also investigated., Results: Screening of 78 CIDP patient sera by WB revealed a positive band around 60-70 kDa identified as dihydrolipoamide S-acetyltransferase (DLAT) by immunoprecipitation and mass spectrometry. Serum immunoglobulin G (IgG) and IgM antibodies' reactivity to recombinant DLAT was confirmed using ELISA and WB. A relatively high reactivity was observed in 29 of 160 (18%) patients with CIDP, followed by patients with sensory neuropathy (6/58, 10%) and patients with MS (2/47, 4%), but not in patients with Guillain-Barré syndrome (0/27), patients with hereditary neuropathy (0/40), and healthy controls (0/26). Both the cell-based and tissue-based assays confirmed reactivity in 26 of 33 patients with CIDP. Comparing the clinical characteristics of patients with CIDP with anti-DLAT antibodies (n = 29) with those of negative cases (n = 131), a higher percentage of patients had comorbid sensory ataxia (69% vs 37%), cranial nerve disorders (24% vs 9%), and malignancy (20% vs 5%). A high DLAT expression was observed in human autopsy dorsal root ganglia, confirming the reactivity of patient serum with mouse dorsal root ganglion cells., Discussion: Reactivity to DLAT was confirmed in patient sera, mainly in patients with CIDP. DLAT is highly expressed in the dorsal root ganglion cells, and anti-DLAT antibody may serve as a biomarker for sensory-dominant neuropathies.

While microbial biogeochemical activities such as those involving denitrification and sulfate reduction have been considered to play important roles in material cycling in various aquatic ecosystems, our current understanding of the microbial community in groundwater ecosystems is remarkably insufficient. To assess the groundwater in the Ryukyu limestone aquifer of Okinawa Island, which is located in the southernmost region of Japan, we performed metagenomic analysis on the microbial communities at the three sites and screened for functional genes associated with nitrogen metabolism. 16S rRNA amplicon analysis showed that bacteria accounted for 94-98% of the microbial communities, which included archaea at all three sites. The bacterial communities associated with nitrogen metabolism shifted by month at each site, indicating that this metabolism was accomplished by the bacterial community as a whole. Interestingly, site 3 contained much higher levels of the denitrification genes such as narG and napA than the other two sites. This site was thought to have undergone denitrification that was driven by high quantities of dissolved organic carbon (DOC). In contrast, site 2 was characterized by a high nitrate-nitrogen (NO 3 -N) content and a low amount of DOC, and this site yielded a moderate amount of denitrification genes. Site 1 showed markedly low amounts of all nitrogen metabolism genes. Overall, nitrogen metabolism in the Ryukyu limestone aquifer was found to change based on environmental factors., (© 2024. The Author(s).)

Denitrification crucially regulates the attenuation of groundwater nitrate and is unlikely to occur in a fast-flowing aquifer such as the Ryukyu limestone aquifer in southern Okinawa Island, Japan. However, evidences of denitrification have been observed in several wells within this region. This study analyzed environmental isotopes (δ 15 N NO3 and ẟ 18 O NO3 ) to derive the rationale for denitrification at this site. Additionally, the presence of two subsurface dams in the study area may influence the processes involved in nitrate attenuation. Herein, we analyzed 150 groundwater samples collected spatially and seasonally to characterize the variations in the groundwater chemistry and stable isotopes during denitrification. The values of δ 15 N NO3 and δ 18 O NO3 displayed a progressive trend up to +59.7 ‰ and + 21 ‰, respectively, whereas the concentrations of NO 3 - -N decreased to 0.1 mg L -1 . In several wells, the enrichment factors of δ 15 N NO3 ranged from -6.6 to -2.1, indicating rapid denitrification, and the δ 15 N NO3 to δ 18 O NO3 ratios varied from 1.3:1 to 2:1, confirming the occurrence of denitrification. Denitrification intensively proceeds under conditions of depleted dissolved oxygen concentrations (<2 mg L -1 ), sluggish groundwater flow with longer residence times, high concentrations of dissolved organic carbon (>1.2 mg L -1 ), and low groundwater levels during the dry season with precipitation rates of <100 mm per month (Jun-Sep). SF 6 analysis indicated the exclusive occurrence of denitrification in specific wells with groundwater residence times exceeding 30 years. These wells are located in close proximity to the major NE-SW fault system in the Komesu area, where the hydraulic gradient was below 0.005. Detailed geological and lithological investigations based on borehole data revealed that subsurface dams did not cause denitrification while the major NE-SW fault system uplifted the impermeable basement rock of the Shimajiri Group, creating a lithological gap at an equivalent depth that ultimately formed a sluggish groundwater area, promoting denitrification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options., Methods: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort., Results: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities., Conclusions: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described., (© 2024. The Author(s).)

Rotavin-M1 (POLYVAC) was licensed in Vietnam in 2012. The association of Rotavin-M1 with intussusception, a rare adverse event associated with rotavirus vaccines, and with adverse events following immunization (AEFI) have not been evaluated and monitored under conditions of routine use. From February 2017 to May 2021, we conducted a pilot introduction of Rotavin-M1 into the routine vaccination program in two provinces. Surveillance for intussusception was conducted at six sentinel hospitals. AEFI reports at 30 min and 7 days after vaccination were recorded. Among 443 children <12 months of age admitted for intussusception, most (92.3%) were children ≥ 6 months. Of the 388 children who were age-eligible to receive Rotavin-M1, 116 (29.9%) had received ≥1 dose. No intussusception cases occurred in the 1-21 days after dose 1 and one case occurred on day 21 after dose 2. Among the 45,367 children who received ≥1 dose of Rotavin-M1, 9.5% of children reported at least one AEFI after dose 1 and 7.3% after dose 2. Significantly higher AEFI rates occurred among children given Rotavin-M1 with pentavalent vaccines (Quinvaxem ® , ComBE Five ® ) compared to Rotavin-M1 without pentavalent vaccines. There was no association between intussusception and Rotavin-M1. The vaccine was generally safe when administered alone and when co-administered with other vaccines.

Although it is in its early stages, canine induced pluripotent stem cells (ciPSCs) hold great potential for innovative translational research in regenerative medicine, developmental biology, drug screening, and disease modeling. However, almost all ciPSCs were generated from fibroblasts, and available canine cell sources for reprogramming are still limited. Furthermore, no report is available to generate ciPSCs under feeder-free conditions because of their low reprogramming efficiency. Here, we reanalyzed canine pluripotency-associated genes and designed canine LIN28A, NANOG, OCT3/4, SOX2, KLF4, and C-MYC encoding Sendai virus vector, called 159cf. and 162cf. We demonstrated that not only canine fibroblasts but also canine urine-derived cells, which can be isolated using a noninvasive and straightforward method, were successfully reprogrammed with or without feeder cells. ciPSCs existed in undifferentiated states, differentiating into the three germ layers in vitro and in vivo. We successfully generated ciPSCs under feeder-free conditions, which can promote studies in veterinary and consequently human regenerative medicines., Competing Interests: Declaration of interests This study was also funded by Anicom Specialty Medical Institute. T.A. and K.W. are employees of Anicom Specialty Medical Institute. M.I. and M.N. are the inventors of the patent application (JP 6770224 B2, JP 7174958 B2, US 10544431 B1, EP 3246406 B1, TW I 696700 B, CN 107109400 B, SG 11201705820U, KR 6102459458 B1)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We investigated the effect of bioactive glass and zinc oxide nanoparticles on enamel remineralization, as well as their antimicrobial effect on cariogenic microbes. This is the first study that investigated the properties of bioactive glass and zinc oxide nanoparticles with mixed materials., Methods: Fluoride gel (F), bioactive glass microparticles (µB), bioactive glass nanoparticles (nB), zinc oxide nanoparticles (Z), and a mixed suspension of nB and Z (nBZ) were prepared and characterized by scanning and transmission electron microscopy, zeta potential measurement, X-ray diffraction, and acid buffering capacity testing. Further, we performed a remineralization cycle test of 28 days, and nanoindentation testing was carried out during the immersion period, and then the enamel surfaces were examined using scanning electron microscopy. Additionally, the antimicrobial effects of the sample suspensions were evaluated by measuring their minimum microbicidal concentrations against various cariogenic microbes., Results: Our results revealed that nB had a near-circular shape with an amorphous structure and a considerably large specific surface area due to nanoparticulation. Additionally, nB possessed a rapid acid buffering capacity that was comparable to that of μB. In the remineralization test, faster recovery of mechanical properties was observed on the enamel surface immersed in samples containing bioactive glass nanoparticles (nB and nBZ). After remineralization, demineralized enamel immersed in any of the samples showed a rough and porous surface structure covered with mineralized structures. Furthermore, nBZ exhibited a broad antimicrobial spectrum., Conclusions: These results demonstrated that bioactive glass and zinc oxide nanoparticles have superior demineralization-suppressing and remineralization-promoting effects.

This study evaluated the effect of a 0.5% chloramine T solution on a chemical-cured universal adhesive by comparing the light-cured, one-step, self-etch adhesive for the bonding performance, mechanical properties, and resin-dentin interfacial characteristics. Caries-free human molars were randomly assigned into eight groups based on the bonding systems employed (Bond Force II, BF and Bondmer Lightless, BL), the immersion solutions used before bonding (0.5% chloramine T solution and distilled water), and the immersion durations (5 and 60 min). Microtensile bond strength (μTBS), nanoleakage evaluation, and nanoindentation tests were performed, and the surface morphology of the resin-dentin interface was examined using a focus ion beam/scanning ion microscopy system. Immersion in chloramine-T for 5 min significantly decreased the μTBS of Bondmer Lightless (from 22.62 to 12.87 MPa) compared with that in distilled water. Moreover, there was also a decreasing trend after immersing in chloramine-T for 60 min (from 19.11 to 13.93 MPa). Chloramine T was found to have no effect on the hardness, elastic modulus, or morphological characteristics of the ion-beam milled resin-dentin interfacial surfaces in the tested adhesives, suggesting that chloramine T might reduce the bond strength by interfering with the interaction and the sealing between the adhesive resin and dentin in the chemical-cured universal adhesive, albeit without affecting the mechanical properties.

Mitochondrial fusion plays an important role in both their structure and function. In this issue, Su et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202301091) report that a nucleoside diphosphate kinase, NME3, facilitates mitochondrial tethering prior to fusion through its direct membrane-binding and hexamerization but not its kinase activity., (© 2023 Ikeda et al.)

Objective: Parkinson's disease (PD) is characterized by various non-motor symptoms (NMS), such as constipation, olfactory disturbance, sleep disturbance, mental disorders, and motor symptoms. This study aimed to investigate factors associated with NMS in patients with PD., Methods: Symptoms of PD were evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parts I-IV. NMS was assessed using the MDS-UPDRS Part I (self-assessment of NMS) and rapid eye movement sleep behavior disorder (RBD) questionnaires. Patients were categorized by age into <70 years and ≥ 70 years (older adults) groups, according to disease duration into early-stage and advanced-stage groups with a cut-off value of 5 years for motor symptoms, and by sex into male and female groups., Results: A total of 431 patients with PD (202 males and 229 females) with a mean age of 67.7 years, a mean disease duration of 6.4 years, and a mean Part I total score of 9.9 participated in this study. The Part I total score was significantly positively correlated ( p  < 0.01) with disease duration and Part II, III, and IV scores. For Part I sub-item scores, the older group had significantly higher scores for cognitive impairment, hallucinations, sleep problems, urinary problems, and constipation than the <70 years group, whereas the advanced-stage group had significantly higher scores for hallucinations, sleep problems, daytime sleepiness, pain, urinary problems, and constipation ( p  < 0.05) than the early-stage group. Anxiety was higher in female patients than in male patients, whereas daytime sleepiness, urinary problems, and RBD were higher in male patients than in female patients ( p  < 0.05). Factors affecting Part I included disease duration, Part II total scores, Part IV total scores, and RBD., Conclusion: According to the self-questionnaire assessment, NMS was highly severe in older adult patients, those with longer illness duration, subjective and objective motor function impairments, and RBD. Sex-based differences were also observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morimoto, Iijima, Okuma, Suzuki, Yoshii, Nogawa, Osada and Kitagawa.)

Distinctive anatomical features of bones can influence not only how these structures perform in living animals but also the tendency of elements to be transported by flowing water after death. Such transport can be critical in the concentration of fossils from animals that live near freshwater habitats, providing important context for interpreting the composition of paleocommunities. Measurements of the tendency of flowing water to disperse skeletal elements have been collected for diverse taxa, including mammals, turtles, and birds. However, these extant models may not be entirely appropriate for many morphologically distinct extinct lineages, such as non-avian dinosaurs. To expand the range of models available for evaluating the influence of hydrodynamic transport on the assembly of fossil deposits, we used a flow tank to measure the water speeds that disperse bones from a subadult American alligator (Alligator mississippiensis), with the skull and mandible tested in multiple starting orientations. Alligator bones are sorted into three main dispersal groups: early (vertebrae, most girdle elements), intermediate (ribs, most limb bones), and late (pubis, femur), with the skull and mandible varying between intermediate and late depending on orientation. Late dispersing elements tended to be heavy or very flat. These results can refine interpretations of the taphonomic context for deposits of fossil crocodylians and morphologically similar taxa (e.g., choristoderes, phytosaurs) and provide an additional comparative model for deposits of non-avian dinosaurs. Moreover, variation in hydrodynamic sorting across lineages highlights how distinctive anatomical features can influence the concentration of fossils, shaping understanding of assemblage composition and paleofaunal evolution., (© 2022 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

The detection sensitivity of immunostick colorimetric assay has been increased by using a bio-nanocapsule as a scaffold for oriented immobilization of immunoglobulin Gs. This immunostick produced ∼82-folds stronger coloration in the detection of food allergens and reduced detection time by a factor of 5., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

This study aimed to evaluate the effects of phosphoproteins on bacterial mineralization. Dental calculus formation is attributed to bacterial mineralization in the oral cavity; however, the influence of phosphoproteins (which are abundant in saliva) is not clear. The model bacterium Escherichia coli was suspended in a calcification solution containing casein as a model phosphoprotein. To evaluate mineralization independent of bacterial metabolism, bacteria killed by heat treatment at 70°C were compared with viable bacteria. After incubation at 37°C for 24 h, the mode of calcification was observed using electron microscopy and energy dispersive x-ray spectroscopy. Solutions without casein produced precipitation in solution, which was identical to that in experiments without bacteria. In contrast, calcification solutions with 200 ppm casein only produced calcium phosphate deposition intracellularly. Without heat treatment, intracellular calcification rarely occurred, even when casein was added. Thus, phosphoproteins promoted intracellular calcification of dead bacteria; this is similar to the calcification of insoluble matrices, such as collagen fibrils, promoted by acidic polymers. We concluded that intracellular calcification is caused by the collagen fibril-like behavior of dead bacteria. The promotion of intracellular calcification of dead bacteria by phosphoproteins suggested a basic principle of dental calculus formation., (© 2023 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)

Aim: Although many reports have shown that Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is effective for postoperative urinary continence, the postoperative voiding status and sexual function associated with this technique have not yet been adequately compared with those associated with conventional RARP (C-RARP). In this study, the lower urinary tract function, erectile function, and cancer control after C-RARP and RS-RARP were compared chronologically., Materials and Methods: We selected 50 cases of C-RARP and RS-RARP each by propensity score matching and evaluated them over time using various questionnaires. Urinary continence recovery rates and biochemical recurrence (BCR)-free survival rates were calculated using the Kaplan-Meier method and compared between the two groups using the log-rank test., Results: When urinary continence was defined as 0 pads per day, 0 pads per day + 1 security linear, or ≤1 pad per day, the postoperative improvement in urinary continence was better with RS-RARP over the course of up to 1 year for all definitions. The International Consultation on Incontinence Questionnaire-Short Form total scores and the Overactive Bladder Symptom Scores were better in the postoperative RS-RARP group. There were no significant differences in the International Prostate Symptom Score total score, QOL score, and erectile hardness score between the two groups during the observation period. The BCR-free survival did not differ significantly between the two groups CONCLUSIONS: Postoperative urinary continence was better in the RS-RARP group than in the C-RARP group; however, the voiding function, erectile function, and cancer control did not differ significantly., (© 2023 Wiley Periodicals LLC.)

Quartz-crystal-microbalance (QCM) biosensor is a typical label-free biosensor, and its sensitivity can be greatly improved by removing electrodes and wires that would be otherwise attached to the surfaces of the quartz resonator. The wireless-electrodeless QCM biosensor was then developed using a microelectro-mechanical systems (MEMS) process, although challenges remain in the sensitivity, the coupling efficiency, and the miniaturization (or mass production). In this study, we establish a MEMS process to obtain a large number of identical ultrasensitive and highly efficient sensor chips with dimensions of 6 mm square. The fundamental shear resonance frequency of the thinned AT-cut quartz resonator packaged in the microchannel exceeds 160 MHz, which is excited by antennas deposited on inner walls of the microchannel, significantly improving the electro-mechanical coupling efficiency in the wireless operation. The high sensitivity of the developed MEMS QCM biosensors is confirmed by the immunoglobulin G (IgG) detection using protein A and ZZ-tag displaying a bionanocapsule (ZZ-BNC), where we find that the ZZ-BNC can provide more effective binding sites and higher affinity to the target molecules, indicating a further enhancement in the sensitivity of the MEMS QCM biosensor. We then perform the label-free C-reactive protein (CRP) detection using the ZZ-BNC-functionalized MEMS QCM biosensor, which achieves a detection limit of 1 ng mL -1 or less even with direct detection.

Metal allergy is a common disease that afflicts many people. Nevertheless, the mechanism underlying metal allergy development has not been completely elucidated. Metal nanoparticles might be involved in the development of a metal allergy, but the associated details are unknown. In this study, we evaluated the pharmacokinetics and allergenicity of nickel nanoparticles (Ni-NPs) compared with those of nickel microparticles (Ni-MPs) and nickel ions. After characterizing each particle, the particles were suspended in phosphate-buffered saline and sonicated to prepare a dispersion. We assumed the presence of nickel ions for each particle dispersion and positive control and orally administered nickel chloride to BALB/c mice repeatedly for 28 days. Results showed that compared with those in the Ni-MP administration group (MP group), the Ni-NP administration group (NP group) showed intestinal epithelial tissue damage, elevated serum interleukin (IL)-17 and IL-1β levels, and higher nickel accumulation in the liver and kidney. Additionally, transmission electron microscopy confirmed the accumulation of Ni-NPs in the livers of both the NP and nickel ion administration groups. Furthermore, we intraperitoneally administered a mixed solution of each particle dispersion and lipopolysaccharide to mice and then intradermally administered nickel chloride solution to the auricle after 7 days. Swelling of the auricle was observed in both the NP and MP groups, and an allergic reaction to nickel was induced. Particularly in the NP group, significant lymphocytic infiltration into the auricular tissue was observed, and serum IL-6 and IL-17 levels were increased. The results of this study showed that in mice, Ni-NP accumulation in each tissue was increased after oral administration and toxicity was enhanced, as compared to those with Ni-MPs. Orally administered nickel ions transformed into nanoparticles with a crystalline structure and accumulated in tissues. Furthermore, Ni-NPs and Ni-MPs induced sensitization and nickel allergy reactions in the same manner as that with nickel ions, but Ni-NPs induced stronger sensitization. Additionally, the involvement of Th17 cells was suspected in Ni-NP-induced toxicity and allergic reactions. In conclusion, oral exposure to Ni-NPs results in more serious biotoxicity and accumulation in tissues than Ni-MPs, suggesting that the probability of developing an allergy might increase.

RING-between RING (RBR)-type ubiquitin (Ub) ligases (E3s) such as Parkin receive Ub from Ub-conjugating enzymes (E2s) in response to ligase activation. However, the specific E2s that transfer Ub to each RBR-type ligase are largely unknown because of insufficient methods for monitoring their interaction. To address this problem, we have developed a method that detects intracellular interactions between E2s and activated Parkin. Fluorescent homotetramer Azami-Green fused with E2 and oligomeric Ash (Assembly helper) fused with Parkin form a liquid-liquid phase separation (LLPS) in cells only when E2 and Parkin interact. Using this method, we identified multiple E2s interacting with activated Parkin on damaged mitochondria during mitophagy. Combined with in vitro ubiquitination assays and bioinformatics, these findings revealed an underlying consensus sequence for E2 interactions with activated Parkin. Application of this method to other RBR-type E3s including HOIP, HHARI, and TRIAD1 revealed that HOIP forms an LLPS with its substrate NEMO in response to a proinflammatory cytokine and that HHARI and TRIAD1 form a cytosolic LLPS independent of Ub-like protein NEDD8. Since an E2-E3 interaction is a prerequisite for RBR-type E3 activation and subsequent substrate ubiquitination, the method we have established here can be an in-cell tool to elucidate the potentially novel mechanisms involved in RBR-type E3s., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteoporosis is considered a risk factor for osseointegration during implant treatment. Photofunctionalization of titanium has been shown to improve bone-based cell adhesion, proliferation, and functional expression, increasing the bone-implant contact rate and bone-implant integration strength. This study aimed to test the hypothesis that photofunctionalization is effective for implant fixation using an osteoporosis rat model. In the biomechanical push-in test, the bone-implant integration strength of the photofunctionalization treatment group was 1.53 times that of the control group (p<0.05). These values implied that photofunctionalization restored the ovariectomy-induced low bone-implant integration strength to normal states. In the micro-CT analysis, the BV/TV of the photofunctionalization treatment group was 1.32 times that of the control group (p<0.05). These values implied that photofunctionalization restored the ovariectomy-induced low peri-implant bone formation to normal states. These results indicate that photofunctionalization treatment increased peri-implant bone formation and bone-implant integration strength in ovariectomized rats.

The human mtHSP60/HSPD1-mtHSP10/HSPE1 system prevents protein misfolding and maintains proteostasis in the mitochondrial matrix. Altered activities of this chaperonin system have been implicated in human diseases, such as cancer and neurodegeneration. However, how defects in HSPD1 and HSPE1 affect mitochondrial structure and dynamics remains elusive. In the current study, we address this fundamental question in a human cell line, HEK293T. We found that the depletion of HSPD1 or HSPE1 results in fragmentation of mitochondria, suggesting a decrease in mitochondrial fusion. Supporting this notion, HSPE1 depletion led to proteolytic inactivation of OPA1, a dynamin-related GTPase that fuses the mitochondrial membrane. This OPA1 inactivation was mediated by a stress-activated metalloprotease, OMA1. In contrast, HSPD1 depletion did not induce OMA1 activation or OPA1 cleavage. These data suggest that HSPE1 controls mitochondrial morphology through a mechanism separate from its chaperonin activity., Competing Interests: The authors declare no competing financial interests., (© 2023 The Author(s).)