Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Regorafenib and reactive metabolite of sunitinib activate inflammasomes: Implications for multi tyrosine kinase inhibitor-Iiduced immune related adverse events.

Multi-targeted tyrosine kinase inhibitors have been developed for the treatment of various cancers, but they are associated with a significant incidence of idiosyncratic drug reactions (IDRs). There is compelling evidence that most IDRs are immune mediated. Activation of inflammasomes is often one of the early steps in the initiation of an immune response. This activation could involve the pharmacological effect of the drug, or it could involve the release of damage associated molecular patters (DAMPs) caused by a reactive metabolite. We tested whether sunitinib, regorafenib, lenvatinib and cabozantinib can directly activate inflammasomes in differentiated THP-1 cells. We found that regorafenib activated the inflammasome of differentiated THP-1 cells directly. We also found that the supernatant from the incubation of sunitinib with FLC-4 cells, which have a high capacity to metabolize drugs, led to activate the inflammasome of differentiated THP-1 cells. In the supernatant of FLC-4 cells with sunitinib, the heat shock protein (HSP) 90 was significantly increased. Sunitinib is known to be oxidized to generate a reactive, potentially toxic quinone imine. These results support the hypothesis that the reactive metabolite of sunitinib can cause the release of DAMPs from hepatocytes, which leads to activation of inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by regorafenib and sunitinib, which in some patients, can cause IDRs.

Large Diamagnetism and Electromagnetic Duality in Two-Dimensional Dirac Electron System.

A Dirac electron system in solids mimics relativistic quantum physics that is compatible with Maxwell's equations, with which we anticipate unified electromagnetic responses. We find a large orbital diamagnetism only along the interplane direction and a nearly temperature-independent electrical conductivity of the order of e^{2}/h per plane for the new 2D Dirac organic conductor, α-(BETS)_{2}I_{3}, where BETS is bis(ethylenedithio)tetraselenafulvalene. Unlike conventional electrons in solids whose nonrelativistic effects bifurcate electric and magnetic responses, the observed orbital diamagnetism scales with the electrical conductivity in a wide temperature range. This demonstrates that an electromagnetic duality that is valid only within the relativistic framework is revived in solids.

Sarcopenia Is Associated with Fecal Incontinence in Patients with Dysphagia: Implication for Anal Sarcopenia.

OBJECTIVES: To examine the relationship between sarcopenia and fecal incontinence in patients with dysphagia. DESIGN: Cross-sectional study using the Japanese sarcopenic dysphagia database. SETTING: 19 hospitals including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation center. PARTICIPANTS: 460 dysphagic patients, aged 20 years and older. MEASUREMENTS: Sarcopenia was diagnosed by the 2019 criteria of the Asian Working Group for Sarcopenia. Fecal incontinence was assessed by health care professionals at baseline according to the definition of the Japanese Practice Guidelines for Fecal Incontinence. We examined whether there was a significant difference between the rate of fecal incontinence in patients with/without sarcopenia. Age, sex, type of dwelling, Barthel index, Charlson comorbidity index (CCI), calf circumference, handgrip strength, body mass index, malnourishment, C-reactive protein level, serum albumin level, and delivery of enteral nutrition by nasogastric and/or gastrostomy tube were measured. To examine the relationship between sarcopenia and fecal incontinence, logistic regression analysis was performed with adjustments for age, sex, sarcopenia, CCI, enteral nutrition, and dwelling. RESULTS: The mean age of patients was 81 ± 10 years. Of the 460 study patients, 404 (88%) patients had sarcopenia and 104 had fecal incontinence (23%). The rate of fecal incontinence was higher in the sarcopenia group than the non-sarcopenia group (25% vs. 7%, P = 0.003). Logistic regression analysis showed that sarcopenia was independently associated with fecal incontinence (odds ratio: 3.114, 95% confidence interval: 1.045, 9.282). CONCLUSION: The prevalence of fecal incontinence was 23% in patients with dysphagia. Sarcopenia was independently associated with fecal incontinence, which suggests the presence of anal sarcopenia. Defecation control should be assessed in patients with sarcopenia.

Construction and Quality Evaluation of the Japanese Sarcopenic Dysphagia Database.

OBJECTIVES: To describe the activity and evaluate the quality of the Japanese sarcopenic dysphagia database. DESIGN: Cohort registry study. SETTING: 19 hospitals including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation team. PARTICIPANTS: 467 dysphagic patients, aged 20 years and older. MEASUREMENTS: The following indices were assessed at baseline: age, sex, main disease, sarcopenic dysphagia, whole body sarcopenia, Food Intake Level Scale (FILS), malnutrition diagnosed by the Global Leadership Initiative on Malnutrition criteria, oral status assessed by the Revised Oral Assessment Guide or the Oral Health Assessment Tool, activities of daily living assessed by the Functional Independence Measure (FIM) or the Barthel Index (BI), Charlson comorbidity index, C-reactive protein and serum albumin levels, dysarthria, hoarseness, aphasia, pressure ulcers, bladder, bowel, and kidney function, respiratory status, polypharmacy, number of drugs, and involvement of health care professionals and rehabilitation nutrition team. FILS, FIM or BI, and outcome including discharge destination were assessed at follow-up. A simple comparison of cases and evaluation of the quality of data were performed. RESULTS: The mean age was 80.4 ± 11.4 yr. The variable input error was 0. The number of patients with missing data was high for estimated glomerular filtration rate, C-reactive protein, serum albumin, skeletal mass index, and tongue pressure. The prevalence of either probable, possible, or no sarcopenic dysphagia was 105 (23%), 182 (39%), or 179 (38%), respectively. Doctors including physiatrists, nurses, physical therapists, and registered dietitians were involved with most patients, while the rehabilitation nutrition team was involved in only 16% of patients. CONCLUSIONS: The quality of the database was relatively high. Sarcopenic dysphagia is common in patients with dysphagia.

The SARC-F Score on Admission Predicts Falls during Hospitalization in Older Adults.

OBJECTIVES: Community-dwelling older adults with sarcopenia are likely to fall. However, few studies have investigated whether sarcopenia is associated with falls during hospitalization in older adults. The purpose of this study was to determine whether the SARC-F when used as a simple screening tool for sarcopenia at the time of admission, predicts in-hospital falls. DESIGN: A retrospective, observational study. SETTING: A 900-bed university hospital. PARTICIPANTS: A total of 9,927 patients aged 65 years and older were hospitalized at the hospital between April 2019 and March 2020. MEASUREMENTS: The SARC-F contains five items: strength, assistance in walking, rise from a chair, climb stairs, and falls were evaluated at hospital admission. To investigate the relationship between the SARC-F score and falls, a ROC curve analysis was performed. Multivariate analysis adjusted for fall-related confounding factors such as age, gender, ADL, and disease were performed. RESULTS: Mean age: 75.9±6.7 years; male: 56.2% were analyzed, and 159 patients (1.6%) fell during hospitalization. SARC-F scores at admission were significantly higher in the fall group than in the control group (3 [1-6] points vs. 0 [¬0-2] point, p<0.001). Statistical association was observed between the SARC-F and in-hospital fall (area under the curve = 0.721 [0.678-0.764], p < 0.001). The cut-off value for the highest sensitivity and specificity of the SARC-F score for in-hospital falls was two (sensitivity = 0.679, specificity = 0.715). Among the subitem of the SARC-F, the hazard ratios for climbing stairs were significantly higher (HR = 1.52 [1.10-2.09], p = 0.011) and for a history of fall was significantly higher (HR = 1.41 [1.02-1.95], p = 0.036). A SARC-F score ≥ 2 had a significantly higher incidence of in-hospital falls compared to a SARC-F score <2 (3.7% vs. 0.7%, p < 0.001). Also, a SARC-F score ≥ 2 had a significantly higher hazard ratio for falls (2.11 [1.37-3.26], p < 0.001). CONCLUSION: SARC-F can help predict falls among hospitalized older adults.

SARC-F as a Screening Tool for Sarcopenia and Possible Sarcopenia Proposed by AWGS 2019 in Hospitalized Older Adults.

OBJECT: The SARC-F questionnaire is a sarcopenia screening tool. However, the validity of the SARC-F score ≥4 (SARC-F≥4) for the evaluation of sarcopenia in the hospital setting has not been investigated. This study investigated the validity of SARC-F≥4 as a screening tool for sarcopenia among hospitalized older adults. DESIGN: Cross-sectional retrospective study. SETTING: A university hospital. PARTICIPANTS: This study included older adult patients (age ≥65 years) who were hospitalized at, and subsequently discharged from, the hospital between April and September 2019 and underwent a nutritional assessment by the nutrition support team during their hospitalization. MEASUREMENTS: SARC-F was recorded at the time of admission, and the criteria specified by the Asia Working Group for Sarcopenia in 2019 (AWGS 2019) were applied to diagnose sarcopenia and possible sarcopenia. Appendicular muscle mass was estimated through validated equations, and three different models were developed for sarcopenia diagnosis. The sensitivity, specificity, and positive/negative likelihood ratios were calculated to analyze the accuracy of the SARC-F≥4 for sarcopenia and possible sarcopenia. Receiver-operating characteristic analyses were conducted to calculate the area under the curve (AUC). RESULTS: In total, 1,689 patients (mean age: 77.2±7.3 years; male: 54.4%) were analyzed, and 636 patients (37.7%) had SARC-F≥4. Patients with SARC-F≥4 had a statistically significant higher prevalence of AWGS 2019-defined sarcopenia than patients with SARC-F <4 in the models (65.4-78.9% vs 40.9-45.2%, p<0.001). The sensitivity, specificity, and positive/negative likelihood ratios of SARC-F≥4 for sarcopenia and possible sarcopenia were 49.1-51.3%, 73.9-81.2%, and 1.88-2.72/0.60-0.69 and 48.0%, 84.5%, and 3.11/0.62, respectively. The AUC for sarcopenia and possible sarcopenia were 0.644-0.695 and 0.708, respectively. The AUC of SARC-F for possible sarcopenia was equivalent to or larger than that for sarcopenia (DeLong test p=0.438, 0.088, and <0.001 vs the three models). CONCLUSIONS: SARC-F≥4 is suitable as a screening tool for sarcopenia in hospitalized older adults. SARC-F assessment could facilitate the detection and exclusion of sarcopenia at hospitalization and may lead to early adoption of a therapeutic and preventive approach.

Burden of Premorbid Consumption of Texture Modified Diets in Daily Life on Nutritional Status and Outcomes of Hospitalization.

OBJECTIVES: Due to the water-rich cooking process required to soften texture modified diets (TMDs), TMDs may have poorer nutrition. The aim of this study was to investigate the associations between daily premorbid TMD consumption and nutritional status at the time of hospitalization, and its burden on hospitalization outcomes. DESIGN: Retrospective observational study. SETTING: An academic hospital. PARTICIPANTS: The cohort comprised 3,594 older adult patients aged ≥65 years admitted to the hospital. MEASUREMENTS: Patients were interviewed on admission using a premorbid daily consumption meal form to determine whether the patient ate a TMD. Nutritional status was examined using nutritional screening tools (Mini-Nutritional Assessment Short Form [MNA-SF], Malnutrition Universal Screening Tool [MUST], Geriatric Nutritional Risk Index [GNRI]) and the European Society of Clinical Nutrition and Metabolism (ESPEN)-defined criteria of malnutrition at admission. Length of hospital stay (LOS) and in-hospital mortality were considered outcomes of hospitalization. Multivariate analyses were performed to detect associations between premorbid TMD consumption and nutritional status and outcomes. RESULTS: The mean age of the subjects was 75.9±7.0 years, including 58% males. Overall, 110 (3.1%) patients consuming a premorbid TMD were identified. They were older (p<0.001), had poor nutritional status (lower MNA-SF score [p<0.001] and GNRI value [p<0.001], higher MUST score [p<0.001], and more prevalent ESPEN-defined malnutrition [61.8% vs. 14.0%, p<0.001] than did patients without a TMD. The mortality rate and LOS of patients with TMD was higher (7.3% vs. 2.9%, p=0.017) and longer (19 days vs. 8 days, p<0.001) than those without TMD. Multivariate analyses showed that TMD consumption was independently associated with poor nutritional status and prolonged LOS after adjusting confounders. CONCLUSION: Daily consumption of a TMD during the premorbid period affects nutritional status at the time of hospitalization and outcomes. Further studies are necessary to investigate whether nutritional intervention can improve outcomes for people on a TMD.

Topological charge transport by mobile dielectric-ferroelectric domain walls.

The concept of topology has been widely applied in condensed matter physics, leading to the identification of peculiar electronic states on three-dimensional (3D) surfaces or 2D lines separating topologically distinctive regions. In the systems explored so far, the topological boundaries are built-in walls; thus, their motional degrees of freedom, which potentially bring about new paradigms, have been experimentally inaccessible. Here, working with a quasi-1D organic material with a charge-transfer instability, we show that mobile neutral-ionic (dielectric-ferroelectric) domain boundaries with topological charges carry strongly 1D-confined and anomalously large electrical conduction with an energy gap much smaller than the one-particle excitation gap. This consequence is further supported by nuclear magnetic resonance detection of spin solitons, which are required for steady current of topological charges. The present observation of topological charge transport may open a new channel for broad charge transport-related phenomena such as thermoelectric effects.

Fragmented Electronic Spins with Quantum Fluctuations in Organic Mott Insulators Near a Quantum Spin Liquid.

Magnetic structures of organic Mott insulators X[Pd(dmit)_{2}]_{2} (X=Me_{4}P, Me_{4}Sb), of which electronic states are located near a quantum spin liquid (X=EtMe_{3}Sb), are demonstrated by ^{13}C nuclear magnetic resonance. Antiferromagnetic spectra and nuclear relaxations show two distinct magnetic moments within each Pd(dmit)_{2} molecule, which cannot be described by single band dimer-Mott model and requires intramolecular electronic correlation. This unconventional fragmentation of S=1/2 electron spin with strong quantum fluctuation is presumably caused by nearly degenerated intramolecular multiple orbitals, and shares a notion of quantum liquids where electronic excitations are fractionalized and S=1/2 spin is no longer an elementary particle.

Correction to: Lower grip strength and dynamic body balance in women with distal radial fractures.

The article Lower grip strength and dynamic body balance in women with distal radial fractures, written by. K. Fujita, H. Kaburagi, A. Nimura, T. Miyamoto, Y. Wakabayashi, Y. Seki, H. Aoyama, H. Shimura, R. Kato, A. Okawa was originally published electronically on the publisher's internet portal.

Lower grip strength and dynamic body balance in women with distal radial fractures.

In this case-control study, we concluded that women with distal radial fractures who were surgically treated showed lower grip strength and dynamic body balancing than those of controls. These results suggest that measurements of grip strength and dynamic body balance may be useful screening tools to assess future fracture risk. INTRODUCTION: Patients with distal radial fractures (DRFs) are at risk of future fragility fractures. However, their physical characteristics and tendencies for falls remain unclear. We aimed to compare the physical characteristics of women with and without distal radial fractures. METHODS: We included 128 women with a DRF as their first fragility fracture (fracture group) who underwent surgical treatment. Concurrently, 128 age- and sex-matched participants without a history of fragility fractures were selected as controls (control group). The participants underwent assessments of grip strength and the body balancing ability test. Measurements were taken twice in the fracture group, at 2 weeks and 6 months postoperatively, and once in the control group. The body balancing ability test included the Functional Reach Test, Timed Up and Go test (TUG), 2-Step test (2ST), and Timed Uni-pedal Stance test. The participants also completed questionnaires about their health. RESULTS: There were no significant differences (p > 0.05) in patient characteristics between the groups. The fracture group showed lower grip strength across all age groups. In the DRF group, prolonged TUG time was observed at 2 weeks postoperatively in all age groups and at 6 months in participants aged 55-74 years; the 2ST score was significantly lower in participants aged between 65 and 74 years. CONCLUSIONS: Women with DRF demonstrated lower grip strength and dynamic body balancing ability. Lower grip strength and dynamic body balancing ability were identified as significant risk factors in women with DRF, suggesting that these may be useful screening tools to assess fracture risk.

Absence of Magnetic Thermal Conductivity in the Quantum Spin Liquid Candidate EtMe_{3}Sb[Pd(dmit)_{2}]_{2}.

We present the ultralow-temperature specific heat and thermal conductivity measurements on single crystals of triangular-lattice compound EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, which has long been considered as a gapless quantum spin liquid candidate. In specific heat measurements, a finite linear term is observed, consistent with the previous work [S. Yamashita et al., Nat. Commun. 2, 275 (2011)NCAOBW2041-172310.1038/ncomms1274]. However, we do not observe a finite residual linear term in the thermal conductivity measurements, and the thermal conductivity does not change in a magnetic field of 6 T. These results are in sharp contrast to previous thermal conductivity measurements on EtMe_{3}Sb[Pd(dmit)_{2}]_{2} [M. Yamashita et al., Science 328, 1246 (2010)SCIEAS0036-807510.1126/science.1188200], in which a huge residual linear term was observed and attributed to highly mobile gapless excitations, likely the spinons of a quantum spin liquid. In this context, the true ground state of EtMe_{3}Sb[Pd(dmit)_{2}]_{2} has to be reconsidered.

Evidence for solitonic spin excitations from a charge-lattice-coupled ferroelectric order.

Topological defects have been explored in different fields ranging from condensed matter physics and particle physics to cosmology. In condensed matter, strong coupling between charge, spin, and lattice degrees of freedom brings about emergent excitations with topological characteristics at low energies. One-dimensional (1D) systems with degenerate dimerization patterns are typical stages for the generation of topological defects, dubbed "solitons"; for instance, charged solitons are responsible for high electrical conductivity in doped trans-polyacetylene. Here, we provide evidence based on a nuclear magnetic resonance (NMR) study for mobile spin solitons deconfined from a strongly charge-lattice-coupled spin-singlet ferroelectric order in a quasi-1D organic charge-transfer complex. The NMR spectral shift and relaxation rate associated with static and dynamic spin susceptibilities indicate that the ferroelectric order is violated by dilute solitonic spin excitations, which were further demonstrated to move diffusively by the frequency dependence of the relaxation rate. The traveling solitons revealed here may promise the emergence of anomalous electrical and thermal transport.

Quantum spin liquids unveil the genuine Mott state.

The localization of charge carriers by electronic repulsion was suggested by Mott in the 1930s to explain the insulating state observed in supposedly metallic NiO. The Mott metal-insulator transition has been subject of intense investigations ever since1-3-not least for its relation to high-temperature superconductivity4. A detailed comparison to real materials, however, is lacking because the pristine Mott state is commonly obscured by antiferromagnetism and a complicated band structure. Here we study organic quantum spin liquids, prototype realizations of the single-band Hubbard model in the absence of magnetic order. Mapping the Hubbard bands by optical spectroscopy provides an absolute measure of the interaction strength and bandwidth-the crucial parameters that enter calculations. In this way, we advance beyond conventional temperature-pressure plots and quantitatively compose a generic phase diagram for all genuine Mott insulators based on the absolute strength of the electronic correlations. We also identify metallic quantum fluctuations as a precursor of the Mott insulator-metal transition, previously predicted but never observed. Our results suggest that all relevant phenomena in the phase diagram scale with the Coulomb repulsion U, which provides a direct link to unconventional superconductivity in cuprates and other strongly correlated materials.

Low-Energy Excitations in Quantum Spin Liquids Identified by Optical Spectroscopy.

The electrodynamic response of organic spin liquids with highly frustrated triangular lattices has been measured in a wide energy range. While the overall optical spectra of these Mott insulators are governed by transitions between the Hubbard bands, distinct in-gap excitations can be identified at low temperatures and frequencies, which we attribute to the quantum-spin-liquid state. For the strongly correlated ß^{'}-EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, we discover enhanced conductivity below 175 cm^{-1}, comparable to the energy of the magnetic coupling J≈250 K. For ω→0, these low-frequency excitations vanish faster than the charge-carrier response subject to Mott-Hubbard correlations, resulting in a dome-shaped band peaked at 100 cm^{-1}. Possible relations to spinons, magnons, and disorder are discussed.

Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury.

BACKGROUND: Hydrogen (H2) and carbon monoxide (CO) gas are both reported to reduce reactive oxygen species and alleviate tissue ischemia-reperfusion (I-R) injury. The present study was conducted to evaluate the effects of a mixture of H2 gas and CO gas (dual gas) in comparison with hydrogen gas (H2: 2%) alone on I-R renal injury (composition of dual gas; N2: 77.8%; O2: 20.9%; H2: 1.30%; CO: 250 parts per million). METHODS: Adult male Sprague-Dawley rats (body weight 250-280 g) were divided into 5 groups: (1) sham operation control, (2) dual gas inhalation (dual treatment) without I-R treatment, (3) I-R renal injury, (4) H2 gas alone inhalation (H2 treatment) with I-R renal injury, and (5) dual treatment with I-R renal injury. I-R renal injury was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, and then contralateral nephrectomy was performed 2 weeks later. Renal function was markedly decreased at 24 hours after reperfusion, and thereafter the effects of dual gas were assessed by histologic examination and determination of the superoxide radical, together with functional and molecular analyses. RESULTS: Pathologic examination of the kidney of I-R rats revealed severe renal damage. Importantly, cytoprotective effects of the dual treatment in comparison with H2 treatment and I-R renal injury were observed in terms of superoxide radical scavenging activity and histochemical features. Rats given dual treatment and I-R renal injury showed significant decreases in blood urea nitrogen. Increased expression of several inflammatory cytokines (tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, nuclear factor-κB, hypoxia inducible factor-1α, and heme oxygenase-1) was attenuated by the dual treatment. CONCLUSIONS: Dual gas inhalation decreases oxidative stress and markedly improves I-R-induced renal injury.