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This article discusses the relationship between the timing of tocilizumab (TCZ) introduction and its glucocorticoid-sparing effects on adult-onset Still's disease (AOSD). A retrospective observational study was conducted on AOSD patients who received TCZ and high-dose glucocorticoids for remission-induction therapy. The study found that early introduction of TCZ within 3 weeks of initiating glucocorticoid treatment effectively reduced the glucocorticoid dose requirement without increasing adverse events or the risk of macrophage activation syndrome. However, further research is needed to determine the efficacy of early TCZ introduction in AOSD treatment. [Extracted from the article]

Objective This study aimed to validate the Japanese version of the LupusPRO questionnaire for use with systemic lupus erythematosus patients. Methods Participants were 205 lupus patients recruited from three rheumatology centers in Japan. Demographic data were collected and quality of life was assessed using the LupusPRO and the Short Form Health Survey-12. Disease activity was evaluated by physicians using the Systemic Lupus Erythematosus Activity Index. Some participants completed questionnaires 10–14 days after the first survey. Internal consistency reliability, test-retest reliability, content validity and convergent validity were examined, and confirmatory factor analysis was performed. Results Participants’ mean age was 47.8 ± 13.6 years. Older participants scored lower on physical quality of life and higher on coping than younger participants. The LupusPRO showed satisfactory test-retest reliability (n = 111). Test-retest reliability was lower for the mental and social aspects of quality of life, indicating fluctuations in quality of life during the two-week interval. Internal consistency reliability was good and convergent validity with the corresponding domains of the Short Form Health Survey-12 was satisfactory. Confirmatory factor analysis showed a good model fit. Conclusion The Japanese LupusPRO is a reliable and valid measure to evaluate treatment interventions for systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

A sensitive radioimmunoassay showed that circulating α-interferon in the plasma of healthy individuals was low in children and reached the highest level in the young adult, then declined gradually with age. Circulating α-interferon was 0.201±0.059 ng/ml in males (n=19) and 0.184±0.076 ng/ml in females (n=14) at ages 30-39 years old. It was noted that circulating α-interferon was maintained up to a certain level even in elderly individuals. [ABSTRACT FROM AUTHOR]

Background: Construction of an intervention method for the cognitive dysfunction of patients with acute coronary syndrome (ACS) is needed. Exercise-based comprehensive cardiac rehabilitation is a potentially effective approach that can improve cognitive function in ACS patients. This study aimed to investigate the effect of cardiac rehabilitation on cognitive function in ACS patients through a systematic review., Methods: A systematic review was conducted of studies on PubMed, MEDLINE, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on September 13, 2022, to identify those reporting the effects of cardiac rehabilitation on cognitive function in ACS patients. Data that reported exercise-based comprehensive cardiac rehabilitation and cognitive function (even if not main results and any type of cognitive function assessment was used) were extracted., Results: In total, six studies were included that comprised a total of 1085 ACS patients. Overall positive effects of cardiac rehabilitation on cognitive function in ACS patients were reported across the six studies. All studies included aerobic exercise, resistance exercise, and patient education in cardiac rehabilitation. Meta-analysis could not be undertaken because each dataset used different methods to evaluate cognitive function, and the outcomes were different., Conclusions: This systematic review showed that cardiac rehabilitation could have positive effects on cognitive function in ACS patients. Our results support the efficacy of cardiac rehabilitation for cognitive function in ACS patients. Additional well-designed clinical trials of exercise-based comprehensive cardiac rehabilitation should be conducted to clarify the true effect on cognitive function in ACS patients., Competing Interests: 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., (© 2024 The Authors.)

Background: Current strategies that target cytokines (e.g., tumor necrosis factor (TNF)-α), or signaling molecules (e.g., Janus kinase (JAK)) have advanced the management for allergies and autoimmune diseases. Nevertheless, the molecular mechanism that underpins its clinical efficacy have largely remained elusive, especially in the local tissue environment. Here, we aimed to identify the genetic, epigenetic, and immunological targets of JAK inhibitors (JAKis), focusing on their effects on synovial fibroblasts (SFs), the major local effectors associated with destructive joint inflammation in rheumatoid arthritis (RA)., Methods: SFs were activated by cytokines related to inflammation in RA, and were treated with three types of JAKis or a TNF-α inhibitor (TNFi). Dynamic changes in transcriptome and chromatin accessibility were profiled across samples to identify drug targets. Furthermore, the putative targets were validated using luciferase assays and clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing., Results: We found that both JAKis and the TNFi targeted the inflammatory module including IL6. Conversely, specific gene signatures that were preferentially inhibited by either of the drug classes were identified. Strikingly, RA risk enhancers for CD40 and TRAF1 were distinctively regulated by JAKis and the TNFi. We performed luciferase assays and CRISPR-based genome editing, and successfully fine-mapped the single causal variants in these loci, rs6074022-CD40 and rs7021049-TRAF1., Conclusions: JAKis and the TNFi had a direct impact on different RA risk enhancers, and we identified nucleotide-resolution targets for both drugs. Distinctive targets of clinically effective drugs could be useful for tailoring the application of these drugs and future design of more efficient treatment strategies., (© 2024. The Author(s).)

Objective: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA)., Methods: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models., Results: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens., Conclusion: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complication caused by antithyroid drugs, particularly propylthiouracil (PTU). Most patients experience organ failure due to the affects of the treatment regimen. We herein report the case of an 89-year-old woman whose severe AAV induced by PTU resulted in various instances of organ failure that eventually led to death after 9 years of PTU therapy. During autopsy, we identified five types of organ failure. As AAV is a potentially fatal disease, the development of various vasculitis symptoms during PTU therapy should therefore be carefully monitored.

Pregnant women are encouraged to reduce sitting time and replace it with physical activity. Complications arising during pregnancy include gestational hypertension, preeclampsia, gestational diabetes mellitus (GDM), and prenatal and postpartum depression. In this systematic review, we examined effects of sedentary behavior on the health of pregnant women. We conducted a systematic review with PubMed from year 2000 to identify the relationship between a sedentary lifestyle and psychological effects, occurrence of GDM, gestational hypertension, and preeclampsia. Data extracted included sedentary time of pregnant women, psychological effects, occurrence of GDM, gestational hypertension, and preeclampsia as outcomes. Among the 200 studies retrieved, 11 were finally included after screening. The mean age of eligible pregnant women ranged from 28.5 to 32.9 years. Five studies were extracted with outcomes of psychological effects on the mother, five with GDM, and one with gestational hypertension/preeclampsia. Longer sedentary time was associated with increased risks of prepartum/postpartum depression in three of five studies and GDM in three of five studies. No association was found between sedentary behavior and the risk for gestational hypertension/preeclampsia. Higher sedentary behavior in the second trimester of pregnancy was likely to be associated with postpartum depression. Longer sitting time may increase the risk of prenatal or postnatal depression and GDM, but no relationship was proven for gestational hypertension and preeclampsia in one study. High sedentary behavior in the second trimester may have psychological impacts. The number of studies was small and further research is needed to statistically evaluate impacts of sedentary behavior during pregnancy., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Various studies have shown the effectiveness of motor interventions for children with neurodevelopmental disorders (NDDs). Web-based interventions may provide an opportunity for remote access to effective interventions with less burden on therapists. This systematic review aimed to examine the effects of web-based exercise interventions for children with NDDs. We searched PubMed for relevant articles published in English since 1994 and included intervention studies focusing on NDDs in children aged ≤18 years, who received web-based exercise interventions. We categorized the extracted information by outcome measure and intervention type and assessed the risk of bias of the included studies. We selected five articles whose subjects had autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental coordination disorder (DCD). The exercise interventions used active video games, a Zoom-based intervention, and a WhatsApp-based intervention. Three papers showed improvements in physical activity, motor function, and executive function, whereas two papers on DCD showed no improvements in motor coordination or physical activity. Web-based exercise intervention for children with ASD and ADHD may improve their motor function, executive function, and physical activity rather than for children with NDDs. An intervention may be more effective when the content of the intervention is based on objectives and symptoms, when guidance is provided by specialists, or when sufficient explanation and support are provided to parents. However, more research is needed to statistically evaluate the effectiveness of web-based exercise interventions for children with NDDs.

The mhg1 (NCU02695/ada-23) gene encodes the mitochondrial high-mobility group box (HMG-box or HMGB) protein in Neurospora crassa. The mhg1 KO strain (mhg1 KO ) has mitochondrial DNA (mtDNA) instability and a short lifespan; however, the function of MHG1 remains unclear. To investigate the role of this protein in the maintenance of mtDNA, domain deleted MHG1 proteins were expressed in the mhg1 KO strain, and their effects were analyzed. We identified two putative HMG-domains, HMGBI and HMGBII. Although deletion of the HMG-box did not abolish MHG1's mitochondrial localization, the mhg1 KO phenotype of a severe growth defect and a high sensitivity to mutagens could not be restored by introduction of HMG-box deleted mhg1 gene into the KO strain. It was indicated that recombinant full-length MHG1, i.e., mitochondrial targeting sequence (MTS) containing protein, did not exhibit explicit DNA binding, whereas the MHG1 protein truncated for the MTS sequence did in vitro by an electrophoretic mobility shift assay. Furthermore, recombinant MHG1 protein lacking MTS and HMG-domains, either HMGBI or HMGBII, had DNA affinity and an altered band shift pattern compared with MTS-truncated MHG1 protein. These results suggest that cleavage of MTS and appropriate DNA binding via HMG-domains are indispensable for maintaining mtDNA in N. crassa., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2022 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Background: Spontaneous thrombosis of a saccular, unruptured, intracranial aneurysm is rare in nongiant aneurysms. Herein, the authors present a case of acute middle cerebral artery occlusion (MCO) caused by spontaneous thrombus of a small internal carotid artery (ICA) aneurysm., Observations: A 68-year-old woman presented with increased somnolence, right-sided hemiplegia, hemispatial neglect, and total aphagia. Left MCO and a small left ICA aneurysm were suspected based on magnetic resonance angiography (MRA). The authors detected early ischemic lesions from diffusion-weighted imaging (DWI). The DWI-Alberta Stroke Program Early Computed Tomography Score was 6. T2*-weighted imaging (T2*WI) showed a thrombus, the so-called susceptibility vessel sign, at the left MCO site. Another suspected thrombus was also found in the ipsilateral ICA aneurysm. The authors treated acute phase MCO with mechanical thrombectomy (MT), after which secondary stroke prophylaxis consisting of warfarin potassium was started. Since follow-up T2*WI showed the thrombus had disappeared from the left ICA aneurysm and the whole aneurysm was clarified by MRA, coil embolization was performed. After coil embolization, there was no ischemic recurrence., Lessons: Aneurysms are infrequently found proximal to occlusion sites during MT. If the proximal aneurysm is a potential embolic source, treatment of the said aneurysm may prevent stroke.

The Cucurbitaceae family accumulates dioxin-like compounds in its fruits. We previously showed that A20/AN1 zinc finger protein (ZFP) genes were highly expressed in the zucchini (Cucurbita pepo) subspecies pepo, which accumulates dioxin-like compounds at high concentrations. Transgenic tobacco (Nicotiana tabacum) plants overexpressing A20/AN1 ZFP genes show accumulation of dioxin-like compounds in their upper parts. However, the mechanisms underlying the accumulation of dioxin-like compounds regulated by the A20/AN1 ZFPs remain unclear. Here, we show that A20/AN1 ZFPs positively regulate the expression of the major latex-like protein (MLP) and its homolog genes in N. tabacum and C. pepo. MLPs are involved in the transport of dioxin-like compounds from the roots to the upper parts of C. pepo. Overexpression of A20/AN1 ZFP genes in N. tabacum leads to the upregulation of pathogenesis-related protein class-10 genes with the binding ability toward dioxin-like compounds. Our results demonstrated that A20/AN1 ZFPs upregulate MLP and its homolog genes in N. tabacum and C. pepo, resulting in the accumulation of dioxin-like compounds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Although more children with congenital heart disease (CHD) are reaching adulthood, they generally have some impairment compared to their healthy peers. Few studies have investigated the effect of exercise training on health-related quality of life (HRQOL) and/or physical activity in children with CHD., Purpose: The purpose of this study was to systematically review the effect of exercise training on HRQOL and/or physical activity and the types of training used in general., Methods: We searched relevant articles published from 2000 to 2021 in English and included intervention studies for children with CHD younger than 20 years who underwent exercise training. Afterwards, we excluded the studies not using HRQOL or physical activity as outcome measures, classified the extracted information according to outcome measures and types of interventions, and assessed the risk of bias of the included studies., Results: Finally, 10 articles were selected, and HRQOL in 3 articles and physical activity in 3 articles showed improvement after exercise training. However, 4 articles did not show improvement in these outcome measures, and 9 of the articles had a high risk of bias in blinding. Sport-based or play-based interventions were used in 5 articles, and prescribed or structured ones were used in 5 articles., Conclusion: Although exercise training for children with CHD may improve their HRQOL and/or physical activity, more studies are needed to assess the effect statistically. In children with CHD, sport-based or play-based interventions could be used as well as prescribed or structured interventions., Competing Interests: 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., (© 2022 The Authors.)

Main Conclusion: MLP-PG1, identified in Cucurbita pepo, plays a crucial role in resistance against fungal pathogens through the induction of pathogenesis-related genes., Astract: MLP-PG1, a major latex-like protein (MLP) from zucchini (Cucurbita pepo), was identified as a transporting factor for hydrophobic organic pollutants. MLPs are members of the Bet v 1 family, similar to pathogenesis-related class 10 proteins (PR-10s). However, the biological functions of MLPs remain unclear. Herein, we show that MLP-PG1 induces the expression of pathogenesis-related (PR) genes and indirectly promotes resistance against pathogens. The activity of the MLP-PG1 promoter in leaves of transgenic tobacco plants was significantly enhanced by inoculation with Pseudomonas syringae pv. tabaci. However, MLP-PG1 did not induce direct resistance through RNase activity. Therefore, we examined the possibility that MLP-PG1 is indirectly involved in resistance; indeed, we found that MLP-PG1 induced the expression of defense-related genes. Overexpression of MLP-PG1 highly upregulated PR-2 and PR-5 and decreased the area of lesions caused by Botrytis cinerea in the leaves of transgenic tobacco plants. Our results demonstrate that MLP-PG1 is involved in indirect resistance against plant diseases, especially caused by fungal pathogens, through the induction of PR genes. This study is the first report to show the induction of PR genes by the expression of MLP from the RNA sequencing analysis and the involvement of MLP-PG1 in the resistance., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Idiopathic spinal cord herniation (ISCH) is very rare. Some reports have described postoperative ventral cerebrospinal fluid (CSF) collections in patients with ISCH; however, such collections are asymptomatic in most patients, and there is no consensus regarding whether they are part of the natural history or a complication., Observations: A 30-year-old man with ISCH underwent direct closure of a duplicated dura mater. Eight months postoperatively, he developed reworsening of right lower limb paresis and new severe right arm pain and paresis. Three-dimensional magnetic resonance imaging revealed ventral CSF collections, which the authors judged as the responsible lesions. The authors initially considered these collections to be present in the epidural space, extradurally compressing the dural sac and resulting in myelopathy. An epidural blood patch failed; however, a CSF drainage test resulted in dramatic improvement. The authors therefore determined that the CSF collections were located in the interdural space, not the epidural space. A lumboperitoneal (LP) shunt was performed to reduce the CSF pressure. The patient's symptoms improved immediately postoperatively. He had developed no recurrence of symptoms 6 months after surgery., Lessons: Ventral interdural CSF collections after ISCH surgery can cause reworsening of myelopathy and may be cured by a LP shunt to control CSF pressure.

Photoreactivation is a mechanism in which photolyase directly repairs either cyclobutane pyrimidine dimers (CPDs) or (6-4) photoproducts [(6-4) PPs] caused by ultraviolet (UV) light. In the filamentous fungus Neurospora crassa, some UV-sensitive mutants such as mus-44 have been reported to exhibit a partial photoreactivation defect (PPD) phenotype, but its mechanism has not been elucidated for a long time. In this study, the N. crassa CPD photolyase PHR was overexpressed in the Δmus-44 strain, but photoreactivation ability was not increased. Furthermore, Escherichia coli CPD photolyase or Arabidopsis thaliana (6-4) PP photolyase was also introduced into Δmus-44; however, the PPD phenotype was not complemented. These results suggested that the PPD phenotype in N. crassa is not caused by residual unrepaired pyrimidine dimers, which are the main type of DNA damage caused by UV irradiation. Finally, we revealed that Δmus-44, but not the Δmus-43 strain, which does not show the PPD phenotype, displayed higher sensitivity with increasing dose rate of UV. Moreover, Δmus-44 was also sensitive to an interstrand crosslinking agent. This indicates that the high dose of UV in our experimental condition induces DNA damage other than pyrimidine dimers, and that such damage is a likely cause of the PPD phenotype.

Objective: In parent artery occlusion (PAO) for ruptured vertebral artery dissecting aneurysms (RVADA), target embolization using coils in a short segment to occlude only the vasodilated area containing the rupture point is selected as a first-choice procedure at our institute. We focused on RVADA involving the posterior inferior cerebellar artery (PICA) and evaluated the treatment results., Methods: This study consisted of eight cases with RVADA involving the PICA which were treated between October 2007 and January 2020. Based on radiological findings such as the bleb, the rupture points were located at the affected vertebral artery (VA) distal to PICA in all cases. Target embolization, by which only coiling at the dilated segment distal to the VA was performed. We aimed to preserve blood flow to the PICA. The incidence and extent of medullary infarctions, and neurological outcome were retrospectively assessed., Results: Regarding the diameter of bilateral VA, there were no differences in six cases while the affected VA with RVADA were larger in the remaining two cases. PICA was preserved in all cases but one in which occlusion of complementary PICA was observed. Postoperative medullary infarction was not noted. There was no rebleeding during the follow-up period. However, recanalization of the VA was observed in four cases and additional coil embolization was performed. All patients were discharged with a good outcome (modified Rankin Scale [mRS] 0; seven patients, mRS 2; one patient)., Conclusion: Target embolization preserving the PICA in PICA-involved type RVADA was considered to be an effective treatment method for cases whose rupture point was located in the VA distal to PICA orifice., Competing Interests: The author completed self-reporting of conflicts of interest to the Japanese Society for Neuroendovascular Therapy. The authors declare no conflicts of interest., (©2021 The Japanese Society for Neuroendovascular Therapy.)

Hydrophobic pollutants have become widely distributed across the world. From an agricultural perspective, their accumulation in crops from contaminated soil threatens food security and quality, leading to many diseases in humans. The Cucurbitaceae family can accumulate high concentrations of hydrophobic pollutants in their aerial parts. The Cucurbitaceae family contains major latex-like proteins (MLPs) as transporting factors for hydrophobic pollutants. MLP genes are expressed in the roots in which the MLPs bind hydrophobic pollutants. MLPs transport these hydrophobic pollutants to the aerial parts of the plant through the xylem vessels. As a result, hydrophobic pollutant contamination occurs in the Cucurbitaceae family. In this study, we suppressed the expression of MLP genes in the roots and reduced the amounts of MLPs with pesticide treatments. First, the fungicides Benlate and Daconil that deceased the hydrophobic pollutant, perylene, concentration in the xylem sap of zucchini plants were selected. Daconil suppressed the transcription activity of MLP in the roots. In the Daconil treatment, the amount of MLPs in the roots and xylem sap of zucchini plants was decreased, and the concentrations of the hydrophobic pollutants, pyrene and dieldrin, were significantly decreased. Our research contributes to the production of safer crops., 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 © 2020 Elsevier B.V. All rights reserved.)

Wild-type filamentous fungus Neurospora crassa continues to grow its hyphae for a very lengthy period of time (>2 years), whereas mutations at the natural death (nd) locus shorten life span (approximately 20 days). By positional cloning based on heat augmented mutagen sensitivity of the nd strain, we identified a nonsense mutation in the msh1 gene, an eukaryotic homolog of bacterial MutS, and this mutation resulted in encoding non-functional polypeptide. By tagging with GFP, subcellular localization of the MSH1 protein in the mitochondria was observed, and knock out of the msh1 gene caused severe growth deficiency accompanying mitochondrial DNA (mtDNA) aberrations such as large-scale mtDNA deletions and rearrangements as seen in the nd strain. These results suggested that MSH1 may maintain mtDNA integrity. Thus, loss of function compromises mtDNA, leading to the acceleration of cellular aging., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: We examined the relationship between cytomegalovirus (CMV) reactivation and serious infections., Method: We conducted a single-center retrospective chart review study with 43 autoimmune disease patients experiencing CMV reactivation. We investigated the risk factors for serious infections among the patients using logistic regression analysis., Results: We identified that the maximum count of CMV antigenemia during the course of infection (CMV Ag MAX) was significantly associated with serious infection by multivariate analysis (adjusted odds ratio: 1.509; 95% confidence interval: 1.071-2.125). The receiver operating characteristic curve of CMV Ag MAX count showed a predictive value for serious infections (76.9% in sensitivity and 93.3% in specificity) and death (83.3% in sensitivity and 91.9% in specificity), and the cut-off count of serious infections and death was 6 and 10 per 10 5 white blood cell count, respectively., Conclusion: We suggest that the counts of CMV Ag MAX can reflect the extent of compromise in the immune system, and can be a predictive marker for serious infections and death., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)