First Report of Tomato Yellow Mottle-Associated Virus Infecting Tobacco in China.

Tomato yellow mottle-associated virus (TYMaV) belongs to the genus Cytorhabdovirus in the family Rhabdoviridae and has been reported to infect a variety of Solanaceae crops, such as Solanum lycopersicum, S. nigrum, Capsicum annuum and Nicotiana benthamiana (Li et al. 2022, Li et al. 2023, Xu et al. 2017, Zhou et al. 2019). In August 2022, about 500 out of 2000 tobacco (N. tabacum) plants showing leaf distortion, crinkling and mosaic symptoms were found in one tobacco growing field in Xingren City, Guizhou Province, China. To identify the causal pathogen(s), leaves from 20 symptomatic tobacco plants were collected and pooled to perform small RNA deep sequencing (sRNA-Seq) and assembly. Briefly, total RNA was extracted with TRIzol Reagent (Takara, Kusatsu, Japan). A small RNA cDNA library was constructed by the small RNA Sample Pre Kit. sRNA-Seq was performed with an Illumina NovaSeq 6000 platform. About 29 million reads were obtained and 334 contigs generated after removal of host-derived sequences. Among them, 31 unique contigs mapped to the TYMaV genome (NC_034240.1), covering 28.43% of the genome with the mean read coverage of 0.92%. Meanwhile, 226 contigs mapped to the genome of a potyvirus, chilli veinal mottle virus (ChiVMV, NC_005778.1), covering 88.79% of the genome with the mean read coverage of 0.83%. To verify the sRNA-Seq result for TYMaV identification, reverse transcription (RT)- PCR was performed with specific primers TYMaV-F (5'-CTGACGTAGTGTTGGCAGAT-3') and TYMaV-R (5'-AACCTCCATGCAGAACCATGG-3'). The expected-size 936-bp fragment was amplified from total RNA of all 20 samples. Dot enzyme-linked immunosorbent assays (Dot-ELISA) with antibody for TYMaV (kindly provided by Dr. Zhenggang Li from Guangdong Academy of Agricultural Sciences) were performed and further verified TYMaV infection. In addition, five asymptomatic tobacco plants from the same field as controls were used to detect TYMaV by RT-PCR and Dot-ELISA, and all samples showed negative test results. Subsequently, 17 primer pairs (Supplementary Table 1) were used to obtain the full-length sequence of TYMaV from a single positive tobacco sample by RT-PCR, followed by Sanger sequencing at Sangon Biotech (Shanghai, China). The resulting amplicon sequences were assembled into a nearly full-length genome sequence of a TYMaV isolate from tobacco in Guizhou (TYMaV-GZ). BLASTn analysis of the 13, 393 nt-long sequence (GeneBank accession number, PP444718) revealed 84.7% and 87.2% nt sequence identity with the TYMaV tomato isolate (KY075646.1) and the TYMaV S. nigrum isolate (MW527091.1), respectively. Moreover, five S. nigrum plants showing leaf crinkling and mosaic symptoms from tobacco fields tested positive for TYMaV by RT-PCR assay, suggesting a potential spread of TYMaV between tobacco and S. nigrum, which may serve as a reservoir for the virus in the tobacco fields. However, the transmission route of TYMaV remains unknown, and further verification is needed. To our knowledge, this is the first report of TYMaV infecting tobacco crop in China. It will be important to assess the potential economic importance of TYMaV to tobacco production in China and elsewhere, and to elucidate the respective roles of this virus and ChiVMV in the leaf distorting and yellowing symptoms.

Molecular mechanism of Spatholobi Caulis treatment for cholangiocarcinoma based on network pharmacology, molecular docking, and molecular dynamics simulation.

Cholangiocarcinoma (CCA) is a type of malignant tumor originating from the intrahepatic, periportal, or distal biliary system. The treatment means for CCA is limited, and its prognosis is poor. Spatholobi Caulis (SC) is reported to have effects on anti-inflammatory and anti-tumor, but its role in CCA is unclear. First, the potential molecular mechanism of SC for CCA treatment was explored based on network pharmacology, and the core targets were verified by molecular docking and molecular dynamics simulation. Then, we explored the inhibitory effect of SC on the malignant biological behavior of CCA in vitro and in vivo and also explored the related signaling pathways. The effect of combination therapy of SC and cisplatin (DDP) in CCA was also explored. Finally, we conducted a network pharmacological study and simple experimental verification on luteolin, one of the main components of SC. Network pharmacology analysis showed that the core targets of SC on CCA were AKT1, CASP3, MYC, TP53, and VEGFA. Molecular docking and molecular dynamics simulation indicated a good combination between the core target protein and the corresponding active ingredients. In vitro, SC inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. In vivo experiments, the results were consistent with in vitro experiments, and there was no significant hepatorenal toxicity of SC at our dosage. Based on KEGG enrichment analysis, we found PI3K/AKT signaling pathway might be the main signaling pathway of SC action on CCA by using AKT agonist SC79. To explore whether SC was related to the chemotherapy sensitivity of CCA, we found that SC combined with DDP could more effectively inhibit the progression of cholangiocarcinoma. Finally, we found luteolin may inhibit the proliferation and invasion of CCA cells. Our study demonstrates for the first time that SC inhibits the progression of CCA by suppressing EMT through the PI3K-AKT signaling pathway, and SC could enhance the effectiveness of cisplatin therapy for CCA.

Advances in targeted therapy of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a malignant tumor originating in the bile duct and its branching epithelium. Due to its high heterogeneity, there are no specific clinical indications at the early stage, the diagnosis is often in advanced CCA. With surgical resection, the 5-year postoperative survival rate (long-term survival rate) is very poor. The regimen of gemcitabine combined with platinum has been used as the first-line chemotherapy for advanced patients. In recent years, targeted therapy for a variety of malignant tumors has made great progress, showing good efficacy and safety in advanced CCA. However, the current targeted therapy of CCA still has many challenges, such as adverse reactions, drug resistance, and individual differences. Therefore, the researches need to further explore the targeted therapy mechanism of CCA malignancies in depth, develop more effective and safe drugs, and accurately formulate plans based on patient characteristics to further improve patient prognosis in the future. This article reviews the recent progress of targeted therapy for CCA, aiming to provide a strategy for the research and clinical work of targeted therapy for CCA.

For these patients without surgical indications, chemotherapy and radiation therapy are the main treatment options, among which gemcitabine combined with cisplatin is the standard recognized chemotherapy regimen.With the gradual maturity of gene detection technology, the molecular pathology of CCA has gradually been revealed and precision oncology has become a promising method for the treatment of CCA.

Advances in research and application of photodynamic therapy in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a disease characterized by insidious clinical manifestations and challenging to diagnose. Patients are usually diagnosed at an advanced stage and miss the opportunity for radical surgery. Therefore, effective palliative therapy is the main treatment approach for unresectable CCA. Current common palliative treatments include biliary drainage, chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, these treatments only offer limited improvement in quality of life and survival. Photodynamic therapy (PDT) is a novel local treatment method that is considered a safe tumor ablation method for numerous cancers. It has shown good efficacy in various studies of CCA and is expected to become an important treatment for CCA. In the present study, the mechanisms of PDT in the treatment of CCA were systematically explored and the progress in the research of photosensitizers was discussed. The current study focused on the various PDT protocols and their therapeutic effects in CCA, with the objective of providing a new horizon for future research and clinical applications of PDT in the treatment of CCA.

Antiviral Mechanisms of Anisomycin Produced by Streptomyces albulus SN40 on Potato Virus Y.

Microbial secondary metabolites produced by Streptomyces have diverse application prospects in the control of plant diseases. Herein, the fermentation filtrate of Streptomyces SN40 effectively inhibited the infection of tobacco mosaic virus (TMV) in Nicotiana glutinosa and systemic infection of potato virus Y (PVY) in Nicotiana benthamiana. Additionally, metabolomic analysis indicated that anisomycin (C14H19NO4) and trans-3-indoleacrylic acid (C11H9NO2) were highly abundant in the crude extract and that anisomycin effectively suppressed the infection of TMV as well as PVY. Subsequently, transcriptomic analysis was conducted to elucidate its mechanisms on the induction of host defense responses. Furthermore, the results of molecular docking suggested that anisomycin can potentially bind with the helicase domain (Hel) of TMV replicase, TMV coat protein (CP), and PVY helper component proteinase (HC-Pro). This study demonstrates new functions of anisomycin in virus inhibition and provides important theoretical significance for the development of new biological pesticides to control diverse plant viruses.

MicroRNA-194-5p/Heparin-binding EGF-like growth factor signaling mediates dexamethasone-induced activation of pseudorabies virus in rat pheochromocytoma cells.

Pseudorabies virus (PRV) is a neurotropic virus, which infects a wide range of mammals. The activity of PRV is gradually suppressed in hosts that have tolerated the primary infection. Increased glucocorticoid levels resulting from stressful stimuli overcome repression of PRV activity. However, the host cell mechanism involved in the activation processes under stressful conditions remains unclear. In this study, infection of rat PC-12 pheochromocytoma cells with neuronal properties using PRV at a multiplicity of infection (MOI) = 1 for 24 h made the activity of PRV be the relatively repressed state, and then incubation with 0.5 µM of the corticosteroid dexamethasone (DEX) for 4 h overcomes the relative repression of PRV activity. RNA-seq deep sequencing and bioinformatics analyses revealed different microRNA and mRNA profiles of PC-12 cells with/without PRV and/or DEX treatment. qRT-PCR and western blot analyses confirmed the negative regulatory relationship of miRNA-194-5p and its target heparin-binding EGF-like growth factor (Hbegf); a dual-luciferase reporter assay revealed that Hbegf is directly targeted by miRNA-194-5p. Further, miRNA-194-5p mock transfection contributed to PRV activation, Hbegf was downregulated in DEX-treated PRV infection cells, and Hbegf overexpression contributed to returning activated PRV to the repression state. Moreover, miRNA-194-5p overexpression resulted in reduced levels of HBEGF, c-JUN, and p-EGFR, whereas Hbegf overexpression suppressed the reduction caused by miRNA-194-5p overexpression. Overall, this study is the first to report that changes in the miR-194-5p-HBEGF/EGFR pathway in neurons are involved in DEX-induced activation of PRV, laying a foundation for the clinical prevention of stress-induced PRV activation.

LncRNA CA12-AS1 targets miR-133a to promote LPS-induced inflammatory response in bovine mammary epithelial cells.

Bovine mastitis seriously affects milk production and quality and causes huge economic losses in the dairy industry. Recent studies have shown that long non-coding RNAs (lncRNAs) may regulate bovine mastitis. In this study, the expression of lncRNA CA12-AS1 was significantly upregulated in LPS-induced bovine mammary epithelial cells (bMECs) but negatively correlated with the expression of miR-133a, suggesting that it may be related to the inflammatory response in bMECs. Dual luciferase reporter gene assay revealed that miR-133a is a downstream target gene of lncRNA CA12-AS1. Furthermore, lncRNA CA12-AS1 silencing negatively regulated the expression of miR-133a inhibited the secretion of inflammatory factors (IL-6, IL-8 and IL-1ß) and decreased the mRNA expression levels of nuclear factor kappa B (NF-κB) (p65/p50) and apoptosis-related genes (BAX, caspase3 and caspase9). LncRNA CA12-AS1 silencing also promoted the mRNA expression levels of the Tight junction (TJ) signaling pathway-related genes (Claudin-1, Occludin and ZO-1), apoptotic gene BCL2, proliferation-related genes (CDK2, CDK4 and PCNA) and the viability of bMECs. However, overexpression of lncRNA CA12-AS1 reversed the above effects. These results revealed that lncRNA CA12-AS1 is a pro-inflammatory regulator, and its silencing can alleviate bovine mastitis by targeting miR-133a, providing a novel strategy for molecular therapy of cow mastitis.

The role of circulating biomarkers in predicting the 30-day mortality of immune checkpoint inhibitors-related myocarditis: a retrospective cohort study.

Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.

Fabrication of antimicrobial and high-toughness poly (lactic acid) composite films using tung oil derivatives.

Tung oil derivatives are promising alternatives to traditional toxic plasticizers for improving the toughness of poly (lactic acid) (PLA) films. In this study, a tung oil-based quaternary ammonium salt (Q-ETO) was synthesized using a multi-step process involving epoxidation, ring opening, and substitution reactions. PLA based composite films with various amounts of Q-ETO were prepared by solvent casting. The impact of various amount of Q-ETO on PLA/Q-ETO composite films were evaluated with regard to their mechanical properties, hydrophilicity, water vapor permeability, optical properties, thermal stability, antibacterial properties, and leaching properties. The PLA/5%Q-ETO composite film yielded the highest elongation at break (82.52 ± 9.53 %), which was 153.67 % higher than that of pure PLA. All PLA composite films showed an antibacterial efficiency exceeding 90 % against both S. aureus and E. coli. Moreover, the PLA/Q-ETO composite film blocked the transmission of both ultraviolet and visible light while preventing the permeation of water vapor. The addition of Q-ETO only weakly affected the color and thermal stability of the PLA/Q-ETO composite film. Given the numerous advantages of the PLA composite film, it has significant potential for application as a food packaging material.

Comparison of blinatumomab and CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia: a systematic review and meta-analysis.

OBJECTIVES: This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies. RESULTS: The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy. CONCLUSIONS: The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.

Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis.

Focal iron overload is frequently observed in patients with rheumatoid arthritis (RA), yet its functional significance remains elusive. Herein, we report that iron deposition in lesion aggravates arthritis by inducing macrophage ferroptosis. We show that excessive iron in synovial fluid positively correlates with RA disease severity as does lipid hyperoxidation of focal monocyte/macrophages. Further study reveals high susceptibility to iron induced ferroptosis of the anti-inflammatory macrophages M2, while pro-inflammatory M1 are less affected. Distinct glutathione peroxidase 4 (GPX4) degradation depending on p62/SQSTM1 in the two cell types make great contribution mechanically. Of note, ferroptosis inhibitor liproxstatin-1 (LPX-1) can alleviate the progression of K/BxN serum-transfer induced arthritis (STIA) mice accompanied with increasing M2 macrophages proportion. We thus propose that the heterogeneous ferroptosis susceptibility of macrophage subtypes as well as consequent inflammation and immune disorders are potential biomarkers and therapeutic targets in RA.

Pediatric anti-NMDAR encephalitis with demyelination on brain MRI: A single center study.

OBJECTIVE: To explore the clinical characteristics, immunotherapy response, and prognosis of pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis associated with demyelination on brain magnetic resonance (MRI). METHODS: We retrospectively reviewed the medical records of children diagnosed with anti-NMDAR encephalitis in our hospital between January 2016 and December 2021. All children with evidence of demyelination on brain MRI were included. RESULTS: A total of 183 anti-NMDAR encephalitis children were included; 8.7 % (16/183) of them had demyelination on brain MRI. Nine were positive for myelin oligodendrocyte glycoprotein (MOG)-IgG, while two were positive for both MOG-IgG and glial fibrillary acidic protein (GFAP)-IgG. Four patients had a history of acquired demyelinating syndromes and encephalitis, respectively, while nine (56.3 %) had atypical symptoms of anti-NMDAR encephalitis. All children had supratentorial demyelination on brain MRI; four of them had additional infratentorial lesions. All children received first-line immunotherapy; four were administered repeated first-line immunotherapy and/or rituximab because of poor initial response. During the follow-up, 37.5 % (6/16) of the children relapsed, but all responded well to immunotherapy. There were no significant differences in mRS score before immunotherapy, response to first-line immunotherapy, and long-term prognosis between anti-NMDAR encephalitis children with and without demyelination. However, patients with demyelination were more likely to have a history of acquired demyelinating syndromes or unexplained cortical encephalitis and to relapse. CONCLUSION: Pediatric anti-NMDAR encephalitis can co-occur with demyelination and has a high rate of MOG-IgG positivity. A history of acquired demyelinating syndromes or unexplained cortical encephalitis and atypical symptoms may indicate demyelination in children with anti-NMDAR encephalitis. Pediatric anti-NMDAR encephalitis with demyelination is more likely to relapse and needs a closer follow-up. However, it remains unknown whether more intensive immunotherapy is required in these patients.

Elevated serum levels of the NLRP3 inflammasome are associated with the severity of anti-NMDAR encephalitis in children.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, mainly impacting young females and children. The involvement of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and related cytokines in pediatric individuals with this condition remains unclear. METHODS: We collected information from 27 children who had anti-NMDAR encephalitis and 12 individuals with non-inflammatory neurological disorders as controls. We used an enzyme-linked immunosorbent assay (ELISA) to identify NLRP3 inflammasome, interleukin (IL)-1ß, and IL-18 expression in cerebrospinal fluid (CSF) and matching serum samples. The modified Rankin Scale (mRS) score was performed throughout the acute phase and at the 6-month follow-up to determine the severity of the disease. The area under the curve (AUC) of the receiver operating characteristic curve was utilized to calculate the prediction efficacy. RESULTS: When compared to controls, individuals with anti-NMDAR encephalitis had significantly increased serum expression of the NLRP3 inflammasome (p < 0.001), IL-1ß (p < 0.05), and IL-18 (p < 0.01). In the acute phase, mRS scores were correlated positively with serum levels of NLRP3 inflammasome (p = 0.008), IL-1ß (p = 0.023), and IL-18 (p < 0.001). A positive connection was also found between serum levels of NLRP3 inflammasome and IL-1ß (p = 0.005). Furthermore, the expression of IL-1ß and IL-18 in serum correlated with the 6-month follow-up outcome. The AUC for NLRP3 inflammasome in distinguishing patients with severe neurologic impairments from those with moderate impairments was 0.808 (95 % CI: 0.645-0.972). CONCLUSION: In our investigation, children with anti-NMDAR encephalitis have more severe first clinical presentations when their serum concentrations of the NLRP3 inflammasome and related cytokines were higher. These findings provide a potential role for the NLRP3 inflammasome pathway in the pathogenesis of NMDAR encephalitis and provide a basis for targeted therapeutic interventions.

Effects of polymer polarity on the interface interaction of polymer/liquid metal composites.

Soft polymer/liquid metal (LM) composites have attracted considerable interest in flexible electronic energy fields. Interface interaction is a key issue that limits the improvement of their electrical performances and energy density. This paper investigates the influence of the polymer polarity on the interface interaction of composites. Four polymer matrixes-polypropylene (PP), polyethylene terephthalate (PET), polyvinylidene fluoride (PVDF), and poly(vinylidenefluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CFE)) were used. It was found that the order of interaction obeyed the order of the polymer polarity: PP/LM < PET/LM < PVDF/LM ≤ (P(VDF-TrFE-CFE))/LM. The increase in polymer polarity significantly promotes the dipole-dipole interaction between polar groups of polymers and the oxide shell of the LM. The best high-polarity PVDF/LM composites display good interface interaction to suppress the dielectric loss, facilitating the PVDF/LM films to exhibit increased capacitive storage density (+44%, 1.68 J cm-3) without degrading the energy efficiency (80%). Our findings will guide researchers to design and choose matrix materials for achieving more improved performance of LM devices.

Endoscopically guided interventional photodynamic therapy for orthotopic pancreatic ductal adenocarcinoma based on NIR-II fluorescent nanoparticles.

Rationale: Pancreatic cancer, comprising mostly pancreatic ductal adenocarcinoma (PDAC), is a highly malignant disease, typically known as a hypoxic tumor microenvironment. The application of PDT in pancreatic cancer in clinic is still hampered by several shortcomings, including the (i) deep location of pancreatic cancer, (ii) tissue damage induced by optical fibers, (iii) hypoxic microenvironment, (iv) short excitation wavelengths of traditional photosensitizers, and (v) poor delivery efficiency of photosensitizers. Methods: We designed an organic nanoparticle as photosensitizer for near-infrared II (NIR-II) fluorescent (FL) imaging that exerts a type I PDT effect on deep orthotopic pancreatic tumors under excitation by a NIR (808 nm) laser. Results: This novel photosensitizer exhibits enhanced accumulation in orthotopic pancreatic cancer in mice and could be used to effectively detect pancreatic cancer and guide subsequent laser irradiation for accurate PDT of deep pancreatic cancer. In addition, we built an endoscopic platform monitored by NIR-II FL imaging to achieve minimally invasive endoscopically guided interventional photodynamic therapy (EG-iPDT) with efficient inhibition of orthotopic pancreatic cancer, which prolonged overall survival up to 78 days compared to PBS + EG-iPDT group (*p < 0.05) in a mouse model. Conclusions: Minimally invasive EG-iPDT has promise as an intraoperative treatment for early-stage or unresectable or metastatic pancreatic cancer.

Educational disparities in joint pain within and across US states: do macro sociopolitical contexts matter?

ABSTRACT: Despite growing recognition of the importance of social, economic, and political contexts for population health and health inequalities, research on pain disparities relies heavily on individual-level data, while neglecting overarching macrolevel factors such as state-level policies and characteristics. Focusing on moderate or severe arthritis-attributable joint pain-a common form of pain that considerably harms individuals' quality of life-we (1) compared joint pain prevalence across US states; (2) estimated educational disparities in joint pain across states; and (3) assessed whether state sociopolitical contexts help explain these 2 forms of cross-state variation. We linked individual-level data on 407,938 adults (ages 25-80 years) from the 2017 Behavioral Risk Factor Surveillance System with state-level data on 6 measures (eg, the Supplemental Nutrition Assistance Program [SNAP], Earned Income Tax Credit, Gini index, and social cohesion index). We conducted multilevel logistic regressions to identify predictors of joint pain and inequalities therein. Prevalence of joint pain varies strikingly across US states: the age-adjusted prevalence ranges from 6.9% in Minnesota to 23.1% in West Virginia. Educational gradients in joint pain exist in all states but vary substantially in magnitude, primarily due to variation in pain prevalence among the least educated. At all education levels, residents of states with greater educational disparities in pain are at a substantially higher risk of pain than peers in states with lower educational disparities. More generous SNAP programs (odds ratio [OR] = 0.925; 95% confidence interval [CI]: 0.963-0.957) and higher social cohesion (OR = 0.819; 95% CI: 0.748-0.896) predict lower overall pain prevalence, and state-level Gini predicts higher pain disparities by education.