Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention.

Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.

Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.

IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study.

OBJECTIVES: Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. METHODS: We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). RESULTS: A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh -0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. CONCLUSION: IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting.

Both angled bony-increased offset and metal-augmented baseplates provide satisfactory bone incorporation to the glenoid in reverse total shoulder arthroplasty: a radiographic evaluation using tomosynthesis.

BACKGROUND: Angled bony-increased offset and metal-augmented baseplate have recently been used to achieve neutral to inferior inclination of the glenoid implant. Nonetheless, bone incorporation is difficult to evaluate using computed tomography or other conventional methods owing to the presence of metal artifacts; therefore, whether bone incorporation between the grafted bone and glenoid or between the graft and baseplate implant can be achieved remains unclear. Several studies have reported the effectiveness of tomosynthesis in reducing metal artifacts for the evaluation of implant loosening, bone resorption, and spot welds. We aimed to evaluate and compare the bone incorporation rates between angled bony-increased offset and metal-augmented implants using tomosynthesis with metal artifact reduction technology. We hypothesized that a high bone incorporation rate would be obtained with angled bony-increased offset and a metal-augmented baseplate. METHODS: A total of 52 patients who underwent reverse total shoulder arthroplasty (TSA) with angled bony-increased offset and 42 patients who underwent reverse total shoulder arthroplasty with metal-augmented baseplate were assessed and followed up for a minimum of 2 years. The bone incorporation and implant loosening rates were compared between the 2 groups, and the sites of spot welds and trabeculation were recorded according to zones. Bone incorporation between the bone and prosthesis was defined as a confirmation of spot welds connecting the porous area and bone in more than three zones. Bone incorporation between the native bone and grafted bone was defined as an observation of trabeculation. Glenoid loosening was defined as the presence of at least 1 mm radiolucency around the prosthesis in more than 2 zones. RESULTS: Both the angled bony-increased offset and metal-augmented baseplate groups achieved sufficient bone incorporation rates (98% [51/52 cases] vs. 100% [42/42 cases], P = 1.0) and low implant loosening rates (2% [1/52 cases] vs. 0% [0/42 cases], P = 1.0). Spot welds and trabeculation were likely to be confirmed in the lower parts of the glenoid. CONCLUSION: The two groups did not show any significant differences regarding bone incorporation rates. Considering the complexity of performing the procedure with angled bony-increased offset, the use of a metal-augmented baseplate can serve as an alternative treatment to avoid superior inclination in reverse total shoulder arthroplasty.

Scandium Ion-Promoted Electron-Transfer Disproportionation of 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO•) in Acetonitrile and Its Regeneration Induced by Water.

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO•), a persistent nitronyl nitroxide radical, has been used for the detection and trapping of nitric oxide, as a redox mediator for batteries, for the activity estimation of antioxidants, and so on. However, there is no report on the reactivity of PTIO• in the presence of redox-inactive metal ions. In this study, it is demonstrated that the addition of scandium triflate, Sc(OTf)3 (OTf = OSO2CF3), to an acetonitrile (MeCN) solution of PTIO• resulted in an electron-transfer disproportionation to generate the corresponding cation (PTIO+) and anion (PTIO-), the latter of which is suggested to be stabilized by Sc3+ to form [(PTIO)Sc]2+. The decay of the absorption band at 361 nm due to PTIO•, monitored using a stopped-flow technique, obeyed second-order kinetics. The second-order rate constant for the disproportionation, thus determined, increased with increasing the Sc(OTf)3 concentration to reach a constant value. A drastic change in the cyclic voltammogram recorded for PTIO• in deaerated MeCN containing 0.10 M Bu4NClO4 was also observed upon addition of Sc(OTf)3, suggesting that the large positive shift of the one-electron reduction potential of PTIO• (equivalent to the one-electron oxidation potential of PTIO-) in the presence of Sc(OTf)3 may result in the disproportionation. When H2O was added to the PTIO•-Sc(OTf)3 system in deaerated MeCN, PTIO• was completely regenerated. It is suggested that the complex formation of Sc3+ with H2O may weaken the interaction between PTIO- and Sc3+, leading to electron-transfer comproportionation to regenerate PTIO•. The reversible disproportionation of PTIO• was also confirmed by electron paramagnetic resonance (EPR) spectroscopy.

Enhancement of cytotoxic effects with ALA-PDT on treatment of radioresistant cancer cells.

Radiation therapy is a lower invasive local treatment than surgery and is selected as a primary treatment for solid tumors. However, when some cancer cells obtain radiotherapy tolerance, cytotoxicity of radiotherapy for cancer cells is attenuated. Photodynamic therapy (PDT) is a non-invasive cancer therapy combined with photosensitizers and laser irradiation with an appropriate wavelength. PDT is carried out for recurrent esophageal cancer patients after radiation chemotherapy and is an effective treatment for radiation-resistant tumors. However, it is not clear why PDT is effective against radioresistant cancers. In this study, we attempted to clear this mechanism using X-ray resistant cancer cells. X-ray resistant cells produce high amounts of mitochondria-derived ROS, which enhanced nuclear translocation of NF-κB, resulting in increased NO production. Moreover, the expression of PEPT1 that imports 5-aminolevulinic acid, the precursor of photosensitizers, was upregulated in X-ray resistant cancer cells. This was accompanied by an increase in intracellular 5-aminolevulinic acid-derived porphyrin accumulation, resulting in enhancement of PDT-induced cytotoxicity. Therefore, effective accumulation of photosensitizers induced by ROS and NO may achieve PDT after radiation therapy and PDT could be a promising treatment for radioresistant cancer cells.

Reactive oxygen species induced by indomethacin enhance accumulation of heme carrier protein 1 and hematoporphyrin accumulation in vitro and in vivo in a brain tumor model.

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

Genetic architecture underlying IgG-RF production is distinct from that of IgM-RF.

OBJECTIVE: HLA-DRB1 alleles, particularly the shared epitope (SE) alleles, are strongly associated with RA. Different genetic structures underlie the production of the various autoantibodies in RA. While extensive genetic analyses have been conducted to generate a detailed profile of ACPA, a representative autoantibody in RA, the genetic architecture underlying subfractions of RF other than IgM-RF, namely IgG-RF, known to be associated with rheumatoid vasculitis, is not well understood. METHODS: We enrolled a total of 743 RA subjects whose detailed autoantibody (IgG-RF, IgM-RF, and ACPA) data were available. We evaluated co-presence and correlations of the levels of these autoantibodies. We analysed associations between the presence or levels of the autoantibodies and HLA-DRB1 alleles for the 743 RA patients and 2008 healthy controls. RESULTS: We found both IgG-RF(+) and IgG-RF(-) RA subjects showed comparable associations with SE alleles, which was not observed for the other autoantibodies. Furthermore, there was a clear difference in SE allele associations between IgG-RF(+) and (-) subsets: the association with the IgG-RF(+) subsets was solely driven by HLA-DRB1*04:05, the most frequent SE allele in the Japanese population, while not only HLA-DRB1*04:05 but also HLA-DRB1*04:01, less frequent in the Japanese population but the most frequent SE allele in Europeans, were main drivers of the association in the IgG-RF(-) subset. We confirmed that these associations were irrespective of ACPA presence. CONCLUSION: We found a unique genetic architecture for IgG-RF(-) RA, which showed a strong association with a SE allele not frequent in the Japanese population but the most frequent SE allele in Europeans. The findings could shed light on uncovered RA pathology.

The impact of concomitant Sjögren's disease on rheumatoid arthritis disease activity: a systematic review and meta-analysis.

OBJECTIVES: Rheumatoid arthritis (RA) and Sjögren's syndrome (SS) frequently co-exist but the consequence for RA disease activity of having concomitant SS (RA/SS) is not well established. We conducted a systematic review and meta-analysis to investigate the impact of SS on disease outcomes in individuals with RA. METHODS: We searched Web of Science (Core Collection, FSTA, Medline), PubMed and Cochrane databases, without language restriction. Studies reporting RA disease activity scores, joint counts, visual analogue scales (VAS), disability and joint damage, and comparing RA and RA/SS were selected. Outcomes reported in at least 3 studies in which the diagnosis of SS fulfilled classification criteria underwent meta-analysis, using a random effects model where heterogeneity was detected. RESULTS: The literature search identified 2991 articles and abstracts; 23 underwent full-text review and 16 were included. The studies included a total of 29722 patients (8614 with RA/SS and 21108 with RA). Using studies eligible for meta-analysis (744 patients with RA/SS and 4450 with RA), we found higher DAS-28 ESR scores (mean difference 0.50, 95% CI -0.008-1.006; p=0.05), higher swollen joint count scores (mean difference 1.05, 95% CI 0.42-1.67; p=0.001), and greater functional disability as measured by HAQ (mean difference 0.19, 95% CI 0.05-0.34; p=0.009) in RA/SS compared to RA alone. Other outcome measures (tender joint count, fatigue VAS) showed a numerical trend towards higher scores in RA/SS but were not statistically significant. CONCLUSIONS: RA/SS patients appear to have higher disease activity and more functional disability than patients with RA alone. The aetiology and clinical implications of this are unclear and warrant further investigation.

Opening-Wedge High Tibial Osteotomy With High Hinge Position Risks Lateral Hinge Fracture in Men With Posterolateral Tibial Condyle Protrusion.

PURPOSE: The primary aim of this study was to evaluate the 3-dimensional morphology of the proximal tibia around the osteotomy plane in open-wedge high tibial osteotomy, focusing on the posterolateral (PL) and posteromedial (PM) tibial condyles, and to clarify the changes in morphologic parameters due to differences in patient characteristics and hinge position. The secondary aim was to examine whether morphologic features were associated with insufficient osteotomy, which increases the risk of lateral hinge fracture (LHF). METHODS: The PL and PM anteroposterior distance, asymmetry ratio, and discrepancy between PL and PM distances along the tibial osteotomy plane were measured. We investigated changes in the parameters due to differences in patient characteristics and hinge position. Osteotomy configurations and LHFs were evaluated using postoperative computed tomography scans. RESULTS: The 3-dimensional preoperative plans of 117 knees (male, 41 knees; female, 76 knees) were evaluated. PL distances were larger than PM distances in almost all cases. The average asymmetry ratio was 1.35, and the standard deviation was 0.22. Higher hinge position was associated with a larger asymmetry ratio and discrepancy (P < .001). The asymmetry ratio and discrepancy were independently positively correlated with male sex (P = .002 and P = .001, respectively) and gentle posterior tibial slope (P < .001 and P < .001, respectively). Osteotomies with type III LHFs showed lower osteotomy sufficiency than osteotomies without LHFs (P < .001). CONCLUSIONS: PL tibial condyle protrusion was more pronounced in male patients and those with a high hinge position, and may result in insufficient PL osteotomy, which is a risk factor for type III LHF during open-wedge high tibial osteotomy. The optimal hinge position was located approximately 15 mm and 20 mm distal to the lateral tibial plateau in female and male patients, respectively. LEVEL OF EVIDENCE: IV: retrospective case series.

Hinge fractures reaching the tibial plateau can be caused by forcible opening of insufficient posterior osteotomy during open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to use the finite element method (FEM) to reproduce fracture lines that reach the lateral tibial plateau during open-wedge high tibial osteotomy (OWHTO) in patients with Type III lateral hinge fracture (LHF). It was hypothesized that the FEM could clarify biomechanical causes of Type III LHF, enabling prevention of adverse complications. METHODS: This study used the nonlinear FEM to analyze the data of eight knees in eight patients (two males and six females) with Type III LHF among 82 patients who underwent OWHTO, as well as the data of eight individuals with no LHF. To predict the onset of Type III LHF, simulation models were also developed in which posterior osteotomy sufficiency varied from 50% to perfect, the latter defined as osteotomy reaching the hinge point. RESULTS: Real-life instances of Type III LHF caused by insufficient posterior osteotomy were reproduced in all patient-specific FEM models, and these models accurately predicted fracture types and locations. During opening of the osteotomy gap, the fracture line reached the lateral tibial plateau, and extended vertically from the end of the insufficient posterior osteotomy, avoiding the rigid proximal tibiofibular joint. In contrast, sufficient posterior osteotomy resulted in a lack of LHF. Posterior osteotomy extension ≥ 70% of the width of the osteotomy plane was the cut-off value to prevent Type III LHF. CONCLUSION: Forced opening of insufficient posterior osteotomy was found to be a biomechanical cause of Type III LHF that extended perpendicularly to the lateral tibial plateau, avoiding the proximal tibiofibular joint. The clinical significance of this study is that sufficient posterior osteotomy during OWHTO, defined as at least 70% of the width of the osteotomy plane, can prevent Type III LHF.

Evaluation of muscle strength recovery following superior capsular reconstruction using a tensor fascia lata graft: a comparison with the unaffected side.

BACKGROUND: Superior capsular reconstruction (SCR) using a tensor fascia lata graft has been performed in patients with irreparable rotator cuff tears and shoulder pseudoparalysis (PPS), and good clinical results have been reported. This procedure can be indicated for younger patients who are highly active in sports and manual labor from the viewpoint of joint preservation. However, this procedure supplements the defect with a graft that has no muscle contractility; therefore, the extent to which shoulder muscle strength is recovered after SCR remains unclear. We hypothesized that the recovery of muscle strength after SCR would not be normalized and would be only approximately 50% of that of the healthy (unaffected) side. This study aimed to evaluate muscle strength after SCR in patients with PPS due to irreparable rotator cuff tears and the extent of recovery by comparing with that of the unaffected side. METHODS: In total, 20 patients who underwent SCR for PPS using a tensor fascia lata graft with a minimum 2-year follow-up were included. Shoulder muscle strength in abduction, internal rotation, and external rotation was evaluated using a handheld dynamometer. Muscle strength was compared to that on the unaffected side, and the affected/unaffected ratio was measured. Shoulder range of motionand acromiohumeral distance were also evaluated. RESULTS: The postoperative range of motions and acromiohumeral distance (4.0 ± 1.4 mm vs. 8.4 ± 1.9 mm, P < .001) were significantly improved compared to those preoperatively. In external and internal rotation, the muscle strength of the affected side was recovered by approximately 80% compared to that of the unaffected side. However, in abduction, the muscle strength of the affected side (2.9 ± 1.5 kg) could not reach 50% (48.0 ± 15.9%, range: 25.0%-76.5%) of that of the unaffected side (5.9 ± 1.8 kg). CONCLUSION: Abduction strength was not sufficiently restored after SCR when compared to that on the unaffected side.

Clinical outcomes and temporal changes in the range of motion following reverse total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty is a definitive solution for the treatment of massive rotator cuff tear and shoulder pseudoparalysis since it can improve shoulder function, especially in elderly individuals. For many elderly individuals, the concern is when they can return to their daily lives after surgery. This study aimed to clarify the characteristics of temporal postoperative values following reverse total shoulder arthroplasty and investigate the factors that affect clinical outcomes. METHODS: This study included 52 patients (mean 79.2 years, range 70-87 years) who underwent primary reverse total shoulder arthroplasty for shoulder pseudoparalysis at a single institution by a single surgeon using the same implant between October 2014 and June 2019. We divided 52 patient into the following groups (1) female (n = 34)vs. male (n = 18) patients; (2) with (n = 19) vs. without (n = 33) arthritic changes in glenohumeral joints (Hamada grade 2, 3 vs. 4, 5); (3) with (n = 23) vs. without (n = 29) subscapularis tendon repair; and investigated the temporal changes in the range of motion (flexion, abduction, external rotation, and internal rotation) and American Shoulder and Elbow Surgeons scores. RESULTS: Significant differences were observed in postoperative shoulder flexion (P = .046) and abduction (P = .049) between the female and male groups. The male patients were able to obtain quick functional recovery. However, no significant differences were observed in postoperative American Shoulder and Elbow Surgeons scores, and the shoulder range of motion between patients with Hamada grade 2, 3 and 4, 5, and between the subscapularis repair and no repair groups. CONCLUSION: The factor that affected the final and temporal values of range of motion after reverse total shoulder arthroplasty was sex, rather than the arthritic changes in glenohumeral joint and the treatment of the subscapularis tendon.

Digital skin defect management: Hand and wrist volar flap solutions.

BACKGROUND: Selecting the optimal flap for managing digit skin defects is challenging, particularly for inexperienced surgeons, given the numerous reconstructive options and insufficient evidence supporting one flap type's superiority over another. This retrospective study introduces four efficacious hand flaps to address volar skin defects and transverse and oblique cuts, examines the optimal flap advancement distance, and discusses effective management. METHODS: Patients with digit skin defects who underwent flap surgery between 2009 and 2022 were included. Fifty-four patients treated with oblique triangular, volar VY advancement (unilateral and bilateral pedicled volar VY advancement flaps for fingers and thumbs, respectively), reverse homodigital island, and radial artery superficial palmar branch flaps were included. We evaluated the flap advancement distance, flap length, range of motion, complications, and Semmes-Weinstein monofilament test and Disabilities of the Arm, Shoulder, and Hand questionnaire results. RESULTS: The median flap advancement distances for triangular oblique (19 patients), unilateral (11 patients), and bilateral pedicled (5 patients) volar VY advancement flaps were 1.3, 1.8, and 2.0 cm, respectively. The flap lengths for the reverse digital island (8 patients) and radial artery superficial palmar branch (11 patients) flaps were 2.4 and 5.0 cm, respectively. Five, three, and one cases of proximal interphalangeal flexion contractures of ≥ -20° were observed in the VY advancement, reverse digital island, and radial artery superficial palmar branch flaps, respectively. One unilateral VY advancement flap case caused severe numbness and neuroma. All complication cases featured >15 and > 20 mm defect lengths on the fingers and thumb, respectively. CONCLUSIONS: To minimize sensory disruption and contractures, we recommend oblique triangular and unilateral pedicle volar VY advancement flaps for finger skin defects up to 12 mm and defects sized 12-15 mm, respectively. Advancement flaps are unsuitable for >15 and > 20-25 mm defects on the fingers and thumb, respectively.

Water-Induced Regeneration of a 2,2-Diphenyl-1-picrylhydrazyl Radical after Its Scandium Ion-Promoted Electron-Transfer Disproportionation in an Aprotic Medium.

A neutral, stable radical, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•), has been frequently used to estimate the activity of antioxidants for more than 60 years. However, the number of reports about the effect of metal ions on the reactivity of DPPH• is quite limited. We have recently reported a unique electron-transfer disproportionation of DPPH• to produce the DPPH cations (DPPH+) and anions (DPPH-) upon the addition of scandium triflate [Sc(OTf)3 (OTf = OSO2CF3)] to an acetonitrile (MeCN) solution of DPPH•. The driving force of this reaction is suggested to be an interaction between DPPH- and Sc3+. In this study, it is demonstrated that the addition of H2O to the DPPH•-Sc(OTf)3 system in MeCN resulted in an increase in the absorption band at 519 nm due to DPPH•. This indicated that an electron-transfer comproportionation occurred to regenerate DPPH•. The regeneration of DPPH• was also confirmed by electron paramagnetic resonance (EPR) spectroscopy. The amount of DPPH• increased with an increasing amount of added H2O to reach a constant value. The detailed mechanism of regeneration of DPPH• was proposed based on the detailed spectroscopic and kinetic analyses, in which the reaction of DPPH+ with [(DPPH)2Sc(H2O)3]+ generated upon the addition of H2O to [(DPPH)2Sc]+ is the rate-determining step.

Systemic chronic diseases coexist with and affect locomotive syndrome: The Nagahama Study.

OBJECTIVES: The concept of locomotive syndrome was proposed to highlight older adults who require nursing care services due to the malfunctioning of their locomotive organs. With the coming of a super-ageing society, there is a growing need to understand the relation between systemic chronic diseases and locomotive syndrome. METHODS: We analysed the second-visit dataset of the Nagahama Study. The association analysis was performed to identify the chronic diseases that were risk factors associated with the occurrence and the progression of locomotive syndrome in both the cross-sectional and longitudinal studies. RESULTS: Hypertension, stroke, coronary heart disease, rheumatoid arthritis, chronic renal failure, osteoporosis, anaemia, and gastroesophageal reflux disease were independently correlated with locomotive syndrome through the deterioration of body pain, social activity, and cognitive function in the cross-sectional study. Multiple chronic diseases had additive effects and significantly increased the risk of locomotive syndrome. In the longitudinal study, osteoporosis and kidney disease were significantly correlated with the worsening of the total GLFS-25 score. CONCLUSIONS: Locomotive syndrome coexisted with various systemic chronic diseases, especially cardiovascular diseases. Osteoporosis and kidney disease were significantly correlated with the progression of locomotive dysfunction. The management of various chronic diseases may be useful to prevent locomotive syndrome and vice versa.

Physical and financial impacts caused by the COVID-19 pandemic exacerbate knee pain: A longitudinal study of a large-scale general population.

OBJECTIVES: This study aimed to evaluate the changes in knee pain, a dominant cause of physical disability, following the coronavirus disease (COVID-19) pandemic, and to identify factors affecting the changes in knee pain. METHODS: We analysed the pre- and post-COVID-19 longitudinal data set of the Nagahama Study. Knee pain was assessed using the Knee Society Score (KSS). The estimated KSS from the age and sex using regression model in the pre- and post-COVID-19 data set was compared. Factors including the activity score, educational level, and various impacts of COVID-19 were analysed for correlation analyses with changes in KSS. RESULTS: Data collected from 6409 participants showed statistically significant differences in KSS, pre- (mean = 22.0; SD = 4.4) and post-COVID-19 (mean = 19.5; SD = 6.4). Low activity score (p = .008), low educational level (p < .001), and undesirable financial impact (p = .030) were independently associated with knee pain exacerbation. CONCLUSION: The harmful effects of the COVID-19 pandemic on knee pain were suggested. People should be encouraged to engage in physical activities, such as walking, despite the state of emergency. Furthermore, social support for economically disadvantaged groups may improve healthcare access, preventing the acute exacerbations of knee pain.

Management of sarcopenia in patients with rheumatoid arthritis.

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future.