Physiological functions of RIG-I-like receptors.

RIG-I-like receptors (RLRs) are crucial for pathogen detection and triggering immune responses and have immense physiological importance. In this review, we first summarize the interferon system and innate immunity, which constitute primary and secondary responses. Next, the molecular structure of RLRs and the mechanism of sensing non-self RNA are described. Usually, self RNA is refractory to the RLR; however, there are underlying host mechanisms that prevent immune reactions. Studies have revealed that the regulatory mechanisms of RLRs involve covalent molecular modifications, association with regulatory factors, and subcellular localization. Viruses have evolved to acquire antagonistic RLR functions to escape the host immune reactions. Finally, the pathologies caused by the malfunction of RLR signaling are described.

Endovascular Therapy for Vascular Graft Infection After Multiple Bypass Surgeries for Aorto-Iliac Occlusive Disease.

BACKGROUND: Vascular graft infection is a very complex disease. Although complete excision of the infected grafts with extra-anatomic bypass or in situ reconstruction is a general treatment strategy, some concerns including reinfection in the new graft remain. CASE REPORT: An 88 year-old man presented to the hospital with abdominal swelling and bleeding. The patient had undergone revascularization for aorto-iliac occlusive disease twice in the past. The first procedure had been performed 15 years previously, with right ilio-femoral bypass grafting for right iliac artery occlusion and stent implantation for left iliac artery stenosis. The second procedure had been performed 10 years previously, with aorta-to-left femoral and left-to-right femoro-femoral bypass grafting because the terminal aorta, the first ilio-femoral bypass graft, and the stent of the left iliac artery had been occluded. The patient was diagnosed with vascular graft infection, and endovascular therapy was selected as the revascularization method prior to graft excision. It was successfully performed using various devices and techniques, followed by graft excision without critical limb ischemia. CONCLUSION: This case demonstrates that endovascular therapy prior to graft excision can be an alternative revascularization method for vascular graft infection after bypass surgery for aorto-iliac occlusive disease.

Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity.

Chronic and aberrant nucleic acid sensing causes type I IFN-driven autoimmune diseases, designated type I interferonopathies. We found a significant reduction of regulatory T cells (Tregs) in patients with type I interferonopathies caused by mutations in ADAR1 or IFIH1 (encoding MDA5). We analyzed the underlying mechanisms using murine models and found that Treg-specific deletion of Adar1 caused peripheral Treg loss and scurfy-like lethal autoimmune disorders. Similarly, knock-in mice with Treg-specific expression of an MDA5 gain-of-function mutant caused apoptosis of peripheral Tregs and severe autoimmunity. Moreover, the impact of ADAR1 deficiency on Tregs is multifaceted, involving both MDA5 and PKR sensing. Together, our results highlight the dysregulation of Treg homeostasis by intrinsic aberrant RNA sensing as a potential determinant for type I interferonopathies.

Characterizing user demographics in posts related to breast, lung and colon cancer on Japanese twitter (X).

Various cancer-related information is spreading on social media. Our study aimed to examine the account types associated with cancer-related tweets (currently known as posts) on Twitter (currently known as X) in Japan, specifically focusing on breast, lung, and colon cancer. Using the Twitter application programming interface, we collected tweets containing keywords of the three cancers type in August-September 2022. The accounts were categorized into seven types: Survivor, Patient's family, Healthcare provider, Public organization, Private organization, News, and Other according to account name and texts. We analyzed the sources of the top 50 most liked and retweeted tweets. Out of 7753 identified tweets, breast cancer represented the majority (62.8%), followed by lung cancer (20.8%) and colon cancer (16.3%). Tweets came from 4976 accounts. Account types varied depending on the cancer type, with breast cancer topics more frequently from Survivor (16.0%) and lung cancer from Patient's family (16.3%). Healthcare provider and Public organization had minimal representation across three cancer types. The trends in the top 50 tweets mirrored the distribution of accounts for each cancer type. Breast cancer-related tweets had the highest frequency. There were few from public organizations. These findings emphasize the need to consider the characteristics of cancer-related information sources when sharing and gathering information on social media.

Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury.

IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and IL-19 gene deficient (IL-19 KO) mice. In L-arginine treated mice, the serum amylase level was significantly increased in IL-19 KO mice, and interstitial edema, analyzed using hematoxylin and eosin (H&E)-stained sections, was aggravated mildly in IL-19 KO mice compared to WT mice. Compared to WT mice treated with L-arginine, mRNA expression of tumor necrosis factor (TNF)-α was significantly upregulated in IL-19 KO mice treated with L-arginine. In WT mice, IL-19 mRNA was equally expressed in the pancreas of both control and L-arginine treated mice. The condition of lung alveoli in WT and IL-19 KO mice treated with L-arginine was then evaluated. In mice with L-arginine-induced pancreatitis, alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in IL-19 KO mice compared to WT mice. In the lungs, mRNA expressions of IL-6 and inducible nitric oxide synthase were significantly increased in IL-19 KO mice compared to WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.

Fact-Checking Cancer Information on Social Media in Japan: Retrospective Study Using Twitter.

BACKGROUND: The widespread use of social media has made it easier for patients to access cancer information. However, a large amount of misinformation and harmful information that could negatively impact patients' decision-making is also disseminated on social media platforms. OBJECTIVE: We aimed to determine the actual amount of misinformation and harmful information as well as trends in the dissemination of cancer-related information on Twitter, a representative social media platform. Our findings can support decision-making among Japanese patients with cancer. METHODS: Using the Twitter app programming interface, we extracted tweets containing the term "cancer" in Japanese that were posted between August and September of 2022. The eligibility criteria were the cancer-related tweets with the following information: (1) reference to the occurrence or prognosis of cancer, (2) recommendation or nonrecommendation of actions, (3) reference to the course of cancer treatment or adverse events, (4) results of cancer research, and (5) other cancer-related knowledge and information. Finally, we selected the top 100 tweets with the highest number of "likes." For each tweet, 2 independent reviewers evaluated whether the information was factual or misinformation, and whether it was harmful or safe with the reasons for the decisions on the misinformation and harmful tweets. Additionally, we examined the frequency of information dissemination using the number of retweets for the top 100 tweets and investigated trends in the dissemination of information. RESULTS: The extracted tweets totaled 69,875. Of the top 100 cancer-related tweets with the most "likes" that met the eligibility criteria, 44 (44%) contained misinformation, 31 (31%) contained harmful information, and 30 (30%) contained both misinformation and harmful information. Misinformation was described as Unproven (29/94, 40.4%), Disproven (19/94, 20.2%), Inappropriate application (4/94, 4.3%), Strength of evidence mischaracterized (14/94, 14.9%), Misleading (18/94, 18%), and Other misinformation (1/94, 1.1%). Harmful action was described as Harmful action (9/59, 15.2%), Harmful inaction (43/59, 72.9%), Harmful interactions (3/59, 5.1%), Economic harm (3/59, 5.1%), and Other harmful information (1/59, 1.7%). Harmful information was liked more often than safe information (median 95, IQR 43-1919 vs 75.0 IQR 43-10,747; P=.04). The median number of retweets for the leading 100 tweets was 13.5 (IQR 0-2197). Misinformation was retweeted significantly more often than factual information (median 29.0, IQR 0-502 vs 7.5, IQR 0-2197; P=.01); harmful information was also retweeted significantly more often than safe information (median 35.0, IQR 0-502 vs 8.0, IQR 0-2197; P=.002). CONCLUSIONS: It is evident that there is a prevalence of misinformation and harmful information related to cancer on Twitter in Japan and it is crucial to increase health literacy and awareness regarding this issue. Furthermore, we believe that it is important for government agencies and health care professionals to continue providing accurate medical information to support patients and their families in making informed decisions.

Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-ß Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis.

IL-19 is a cytokine discovered by homologous searching with IL-10 and is produced by non-immune cells, such as keratinocytes, in addition to immune cells, such as macrophages. Liver fibrosis results from the inflammation and activation of hepatic stellate cells via chronic liver injury. However, the participation of IL-19 in liver fibrosis remains to be sufficiently elucidated. Our group studied the immunological function of IL-19 in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. IL-19 gene-deficient (KO) mice and body weight-matched wild-type (WT) mice were used. A liver fibrosis mouse model was created via CCl4 administration (two times per week) for 8 weeks. In CCl4-induced liver fibrosis, serum analysis revealed that IL-19 KO mice had higher ALT levels compared to WT mice. IL-19 KO mice had worse fibrosis, as assessed by morphological evaluation of total area stained positive with Azan and Masson trichrome. In addition, the expression of α-SMA was increased in liver tissues of IL-19 KO mice compared to WT mice. Furthermore, mRNA expression levels of TGF-ß and α-SMA were enhanced in IL-19 KO mice compared to WT mice. In vitro assays revealed that IL-19-high expressing RAW264.7 cells inhibited the migration of NIH3T3 cells via the inhibited expression of CCL2 in the presence of CCl4 and IL-4. These findings indicate that IL-19 plays a critical role in liver fibrosis by affecting TGF-ß signaling and the migration of hepatic stellate cells during liver injury. Enhancement of the IL-19 signaling pathway is a potential treatment for liver fibrosis.

Trapa bispinosa Roxb. Pericarp Extract Exerts 5α-Reductase Inhibitory Activity in Castrated Benign Prostatic Hyperplasia Model Mice.

Trapa bispinosa Roxb. pericarp extract (TBE) has a polyphenol-rich composition and exhibits potent antioxidant and anti-glycation activities in vitro. In the present study, we investigated the inhibitory effects of TBE on 5α-reductase in vitro using LNCaP cells and in vivo using a mouse model of castrated benign prostatic hyperplasia. TBE showed concentration-dependent inhibitory effects in the 5α-reductase (5αR) activity assay. In a reporter assay using AR-Luc/LNCaP cells, TBE inhibited the activity induced by testosterone, but not that induced by dihydrotestosterone. TBE also suppressed prostate cell proliferation, prostate-specific antigens, and transmembrane protease serine 2 expression in a castrated benign prostatic hyperplasia mouse model. In addition, ellagic acid, but not gallic acid, decreased 5αR and AR-Luc activities. Together, these results suggest a potential role for TBE in benign prostatic hyperplasia through inhibition of 5αR.

Acute monocytic leukemia with KMT2A::LASP1 developed 9 months after diagnosis of acute megakaryoblastic leukemia in a 2-year-old boy.

Acute myeloid leukemia (AML) is known as one of the subsequent malignant neoplasms that can develop after cancer treatment, but it is difficult to distinguish from relapse when the preceding cancer is leukemia. We report a 2-year-old boy who developed acute megakaryoblastic leukemia (AMKL, French-American-British classification [FAB]: M7) at 18 months of age and achieved complete remission with multi-agent chemotherapy without hematopoietic stem cell transplantation. Nine months after diagnosis and 4 months after completing treatment for AMKL, he developed acute monocytic leukemia (AMoL) with the KMT2A::LASP1 chimeric gene (FAB: M5b). The second complete remission was achieved using multi-agent chemotherapy and he underwent cord blood transplantation 4 months after AMoL was diagnosed. He is currently alive and disease free at 39 and 48 months since his AMoL and AMKL diagnoses, respectively. Retrospective analysis revealed that the KMT2A::LASP1 chimeric gene was detected 4 months after diagnosis of AMKL. Common somatic mutations were not detected in AMKL or AMoL and no germline pathogenic variants were detected. Since the patient's AMoL was different from his primary leukemia of AMKL in terms of morphological, genomic, and molecular analysis, we concluded that he developed a subsequent leukemia rather than a relapse of his primary leukemia.

Efficient integrated production of bioethanol and antiviral glycerolysis lignin from sugarcane trash.

BACKGROUND: Sugarcane trash (SCT) represents up to 18% of the aboveground biomass of sugarcane, surpassing 28 million tons globally per year. The majority of SCT is burning in the fields. Hence, efficient use of SCT is necessary to reduce carbon dioxide emissions and global warming and establish agro-industrial biorefineries. Apart from its low costs, conversion of whole biomass with high production efficiency and titer yield is mandatory for effective biorefinery systems. Therefore, in this study, we developed a simple, integrated method involving a single step of glycerolysis pretreatment to produce antiviral glycerolysis lignin (AGL). Subsequently, we co-fermented glycerol with hydrolyzed glucose and xylose to yield high titers of bioethanol. RESULTS: SCT was subjected to pretreatment with microwave acidic glycerolysis with 50% aqueous (aq.) glycerol (MAG50); this pretreatment was optimized across different temperature ranges, acid concentrations, and reaction times. The optimized MAG50 (opMAG50) of SCT at 1:15 (w/v) in 1% H2SO4, 360 µM AlK(SO4)2 at 140 °C for 30 min (opMAG50) recovered the highest amount of total sugars and the lowest amount of furfural byproducts. Following opMAG50, the soluble fraction, i.e., glycerol xylose-rich solution (GXRS), was separated by filtration. A residual pulp was then washed with acetone, recovering 7.9% of the dry weight (27% of lignin) as an AGL. AGL strongly inhibited the replication of encephalomyocarditis virus (EMCV) in L929 cells without cytotoxicity. The pulp was then saccharified in yeast peptone medium by cellulase to produce a glucose concentration similar to the theoretical yield. The total xylose and arabinose recoveries were 69% and 93%, respectively. GXRS and saccharified sugars were combined and co-fermented through mixed cultures of two metabolically engineered Saccharomyces cerevisiae strains: glycerol-fermenting yeast (SK-FGG4) and xylose-fermenting yeast (SK-N2). By co-fermenting glycerol and xylose with glucose, the ethanol titer yield increased to 78.7 g/L (10% v/v ethanol), with a 96% conversion efficiency. CONCLUSION: The integration of AGL production with the co-fermentation of glycerol, hydrolyzed glucose, and xylose to produce a high titer of bioethanol paves an avenue for the use of surplus glycerol from the biodiesel industry for the efficient utilization of SCT and other lignocellulosic biomasses.

Dataset dependency of low-density lipoprotein-cholesterol estimation by machine learning.

OBJECTIVES: We evaluated the applicability of a machine learning-based low-density lipoprotein-cholesterol (LDL-C) estimation method and the influence of the characteristics of the training datasets. METHODS: Three training datasets were chosen from training datasets: health check-up participants at the Resource Center for Health Science (N = 2664), clinical patients at Gifu University Hospital (N = 7409), and clinical patients at Fujita Health University Hospital (N = 14,842). Nine different machine learning models were constructed through hyperparameter tuning and 10-fold cross-validation. Another test dataset of another 3711 clinical patients at Fujita Health University Hospital was selected as the test set used for comparing and validating the model against the Friedewald formula and the Martin method. RESULTS: The coefficients of determination of the models trained on the health check-up dataset produced coefficients of determination that were equal to or inferior to those of the Martin method. In contrast, the coefficients of determination of several models trained on clinical patients exceeded those of the Martin method. The means of the differences and the convergences to the direct method were higher for the models trained on the clinical patients' dataset than for those trained on the health check-up participants' dataset. The models trained on the latter dataset tended to overestimate the 2019 ESC/EAS Guideline for LDL-cholesterol classification. CONCLUSION: Although machine learning models provide valuable method for LDL-C estimates, they should be trained on datasets with matched characteristics. The versatility of machine learning methods is another important consideration.

Mechanisms of length-dependent recognition of viral double-stranded RNA by RIG-I.

Retinoic acid-inducible gene I (RIG-I) is the most front-line cytoplasmic viral RNA sensor and induces antiviral immune responses. RIG-I recognizes short double-stranded (dsRNA) (< 500 bp), but not long dsRNA (> 500 bp) to trigger antiviral signaling. Since RIG-I is capable of binding with dsRNA irrespective of size, length-dependent RIG-I signaling remains elusive. Here, we demonstrated that RIG-I bound to long dsRNA with slow kinetics. Remarkably, RIG-I/short dsRNA complex efficiently dissociated in an ATP hydrolysis-dependent manner, whereas RIG-I/long dsRNA was stable and did not dissociate. Our study suggests that the dissociation of RIG-I from RIG-I/dsRNA complex could be a step for efficient antiviral signaling. Dissociated RIG-I exhibited homo-oligomerization, acquiring ability to physically associate with MAVS, and biological activity upon introduction into living cells. We herein discuss common and unique mechanisms of viral dsRNA recognition by RIG-I and MDA5.

Assessment of Antibody-Titer Changes after Second and Third Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccination in Japanese Post-Kidney-Transplant Patients.

Post-renal-transplant patients have a relatively low antibody-acquisition rate following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. In this study, antibody titers were measured 5−6 months and 3 weeks to 3 months after the second and third SARS-CoV-2 mRNA vaccinations, respectively. Post-renal-transplant patients visiting our hospital who had received three SARS-CoV-2 mRNA vaccine doses were included in the study. SARS-CoV-2 immunoglobulin G antibody titers were measured three times: between 3 weeks and 3 months after the second vaccination, 5−6 months after the second vaccination, and between 3 weeks and 3 months after the third vaccination. A total of 62 (40 men and 22 women) were included, 44 of whom (71.0%) were antibody positive after their third vaccination. On comparing the antibody-acquired and antibody-non-acquired groups, body mass index (BMI, odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.07−1.93, p < 0.05) and the estimated glomerular filtration rate (eGFR, OR: 1.14, 95% CI: 1.06−1.24, p < 0.01) were associated with antibody acquisition. Therefore, in Japanese post-kidney-transplant patients, increases in the antibody-acquisition rate and absolute antibody titer after the third vaccination were observed, with BMI and eGFR associated with the antibody-acquisition rate.

Rapid Formation of an Infected Coronary Artery Aneurysm With Stent Fracture.

Infected coronary artery aneurysm (ICAA) is a rare but fatal disease. We describe a case of rapid formation of ICAA with fracture of an intracoronary stent observed on coronary angiography and cardiac computed tomography. Surgery with resection of the aneurysm and coronary artery bypass grafting was performed successfully. (Level of Difficulty: Intermediate.).

Hepatitis B Virus (HBV) Upregulates TRAIL-R3 Expression in Hepatocytes Resulting in Escape From Both Cell Apoptosis and Suppression of HBV Replication by TRAIL.

BACKGROUND: Hepatitis B virus (HBV) evades host immunity by regulating intracellular signals. To clarify this immune tolerance mechanism, we performed gene expression analysis using HBV-infected humanized mouse livers. METHODS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 3 (TRAIL-R3) was significantly upregulated in livers of HBV-infected human hepatocyte transplanted mice by cDNA microarray and next-generation sequencing. We analyzed the significance of TRAIL-R3 upregulation in HBV infection using human hepatocyte transplanted mice and HepG2 cell lines. RESULTS: TRAIL-R3 induction by HBV infection was verified by in vitro and in vivo HBV replication models, and induction was inhibited by antiviral nucleot(s)ide analogue treatment. TRAIL-R3 transcription was regulated by the TRAIL-R3 promoter at -969 to -479 nucleotides upstream from the transcription start site, and by hepatitis B x (HBx) via activation of nuclear factor-κB (NF-κB) signal. TRAIL not only induced cell apoptosis but also inhibited HBV replication. TRAIL-R3 upregulation could inhibit both TRAIL-dependent apoptosis in HBV-infected hepatocytes and TRAIL-mediated suppression of HBV replication. CONCLUSIONS: These results suggest a mechanism by which HBV persists by escaping host immunity through upregulation of TRAIL-R3. Development of novel drugs to inhibit this escape system might lead to complete HBV elimination from human hepatocytes.

Low TINAGL1 expression is a marker for poor prognosis in breast cancer.

PURPOSE: Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. METHODS: A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median follow-up period was 12.0 years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P = 0.003 and P = 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02-1.96; P = 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. CONCLUSION: Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.

Formation and Characterization of 2D Closely Packed Arrays of Bare Gold Nanoparticles without Aggregation.

Uniform 2D arrays of metal nanoparticles (NPs) have received significant attention in the field of molecular sensing using localized surface plasmon resonance. Generally, metal NPs bear organic surface-modifying molecules to prevent aggregation and form 2D metal NP arrays. However, surface-modifying molecules negatively affect molecular sensing. Previously, we developed a technique for forming a 2D bare metal NP array, denoted the sandwich (SW) technique. However, the formation mechanism of these 2D metal NP arrays remains unknown and therefore the experimental conditions of the SW technique are not optimized. Here, we observed the formation of a 2D Au NP (d: 60 nm) array using the SW technique with an optical microscope. Moderate drying conditions of the colloidal droplets sandwiched between two parallel substrates were necessary for forming 2D Au NP arrays. We then optimized the drying conditions and obtained a 2D Au NP array. This array was uniform, and the Au NPs were arranged at distances of 4.5 nm with hexagonal periodicity, without aggregation. Further, the 2D Au NP arrays exhibited excellent spot-to-spot reproducibility in surface-enhanced Raman scattering.

Double-Stranded RNA Induces Mortality in an MDA5-Mediated Type I Interferonopathy Model.

Gain-of-function mutations in the viral dsRNA sensor melanoma differentiation-associated protein 5 (MDA5) lead to autoimmune IFNopathies, including Singleton-Merten syndrome (SMS) and Aicardi-Goutières syndrome. However, much remains unclear regarding the mechanism of disease progression and how external factors such as infection or immune stimulation with vaccination can affect the immune response. With this aim, we generated mice with human MDA5 bearing the SMS-associated mutation R822Q (hM-R822Q). hM-R822Q transgenic (Tg) mice developed SMS-like heart fibrosis, aortic valve enlargement, and aortic calcification with a systemic IFN-stimulated gene signature resulting in the activation of the adaptive immune response. Although administration of the viral dsRNA mimic polyinosinic-polycytidylic acid [poly(I:C)] did not have remarkable effects on the cardiac phenotype, dramatic inflammation was observed in the intestines where IFN production was most elevated. Poly(I:C)-injected hM-R822Q Tg mice also developed lethal hypercytokinemia marked by massive IL-6 levels in the serum. Interrupting the IFN signaling through mitochondrial antiviral signaling protein or IFN-α/ß receptor alleviated hM-R822Q-induced inflammation. Furthermore, inhibition of JAK signaling with tofacitinib reduced cytokine production and ameliorated mucosal damage, enabling the survival of poly(I:C)-injected hM-R822Q Tg mice. These findings demonstrate that the MDA5 R822Q mutant introduces a critical risk factor for uncontrollable inflammation on viral infection or vaccination.

Effect of a multimodal non-pharmacological intervention on older people with dementia: a single-case experimental design study.

BACKGROUND: Older people with dementia (PWD) in nursing homes (NHs) tend to have decreased cognitive function, which may cause behavioral and psychological symptoms of dementia (BPSDs) and hinder activities of daily living (ADLs). Therefore, taking measures against the cognitive decline of PWD in NH and, in turn, the decline of BPSDs and ADLs is crucial. The purpose of this study was to test whether a multimodal non-pharmacological intervention (MNPI) is effective in maintaining and improving global cognitive function, BPSDs, and ADLs in PWD in NHs. METHODS: An intervention study using a single-case AB design was conducted in three subjects in NHs. During the non-intervention phase, participants underwent follow-up assessments, and during the intervention phase, they participated in an MNPI. The ABC Dementia Scale (which concurrently assesses ADLs ["A"], BPSDs ["B"], and cognitive function ["C"]) was used for the assessment. RESULTS: One of the three patients showed improvement in dementia severity, global cognitive function, ADLs, and BPSDs. However, the other two participants showed no improvement following the MNPI, although the possibility of a maintenance effect remained. CONCLUSION: Although there is room for improvement of the MNPI, it may be effective in maintaining and improving cognitive function, ADLs, and BPSD, in PWD in NHs. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ , No. UMIN000045858, registration date: November 1, 2021).