Diabetic cardiomyopathy (DCM) is defined by progressive cardiac dysfunction driven by myocardial ATP depletion, where mitochondrial electron transport chain (ETC) Complex I dysfunction acts as a critical factor. Protein arginine methyltransferase 5 (PRMT5) maintains cardiac homeostasis, yet its function in DCM and association with Complex I remain elusive. This study aimed to investigate the function, key substrate, and mechanism of PRMT5 in DCM, and evaluate serum PRMT5 as a potential biomarker for DCM. Gain- and loss-of-function experiments of PRMT5 were conducted to explore the function of PRMT5 in DCM. IP-MS proteomics and post-translational modification analysis were applied to identify the substrates of PRMT5 and their modified sites. By employing ELISA assay, serum levels of PRMT5, lactate, and lactate/pyruvate (L/P) ratio were measured in DCM patients, and the association between serum PRMT5 level and hospital readmission risk was analyzed. PRMT5 overexpression protected against DCM pathogenesis, while its knockdown or inhibition exacerbated disease progression. PRMT5 mediated symmetric di-methylation (SDMA) of Ndufs2 at R118 to prevent its ubiquitin-proteasomal degradation and preserve mitochondrial Complex I function. DCM patients had significantly lower serum PRMT5, which correlated positively with serum lactate and L/P ratio and was associated with higher hospital readmission risk. Our findings unveil a novel PRMT5/Ndufs2 regulatory axis where arginine methylation maintains bioenergetic capacity of Complex I through methylation-ubiquitination crosstalk. PRMT5 shows potential as a therapeutic target and biomarker for DCM, which may aid the establishment of innovative diagnostic and treatment frameworks for DCM pending further translational validation.

ABSTRACT This study aimed to investigate the associations between 24‐hour urinary cortisol levels (24 h‐UFC) and alterations in left ventricular (LV) structure and function in patients with essential hypertension. A prospective cohort study was conducted, including 315 patients with essential hypertension who underwent baseline 24 h‐UFC measurement and echocardiographic evaluation of left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and the E/e′ ratio. Over a mean follow‐up period of 28.54 ± 14.21 months, patients were grouped into tertiles based on baseline 24 h‐UFC levels. Higher baseline 24 h‐UFC levels were significantly associated with greater increases in LVM and E/e′, reflecting adverse LV remodeling and diastolic dysfunction. These associations persisted after adjusting for potential confounders, including age, gender, baseline blood pressure, and their changes during follow‐up. Moreover, patients in the highest 24 h‐UFC tertile showed an increased prevalence of LV hypertrophy, contrasting with a reduction observed in the lower tertiles. These findings underscore the independent role of elevated 24 h‐UFC levels in driving adverse cardiac structural and functional changes in essential hypertension.

In the original publication [...].

Background: Low back pain (LBP) is a common condition that can affect athletes of all ages. The risk factors for LBP onset and worsening associated with the lacrosse shooting motion are not yet known. Purpose: To identify training and biomechanical factors associated with preexisting LBP and development of LBP over 6 months in youth, high school, and collegiate lacrosse players. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 128 lacrosse players were enrolled in this study between January 2016 and January 2019. Player characteristics, lacrosse experience, and participation in other sports were self-reported. At baseline and 2-, 4-, and 6-month follow-ups, the players self-rated the presence and severity of LBP using a numeric pain rating scale (0-10 points). Participants were grouped according to LBP symptoms: no LBP at any time point (n = 102), preexisting LBP (n = 17), or developed LBP within the 6-month period (n = 9). The lacrosse shooting motion was captured via 3-dimensional motion analysis, and kinematic and kinetic variables were recorded. A Low Back Stress Index was used to estimate lumbar stress as a function of pelvic acceleration at the time of maximum lateral trunk lean during the shot. Univariate analyses of covariance and logistic regression models were used to address study aims. Results: Compared with the no-LBP group, the preexisting LBP group demonstrated 13.9% to 22.9% lower maximum angular velocities at the pelvis, trunk, and shoulders in the transverse plane ( P < .05), 19.3% less collective pelvis-shoulder rotation in the transverse plane ( P = .015), and 4.5% more knee flexion excursion ( P = .063). The developed-LBP group produced 2.3% to 11.1% higher angular velocities in the pelvis, trunk, and shoulder and generated maximum pelvic acceleration values 36% to 42% higher than the remaining groups ( P < .05 for both). Mean Low Back Stress Index values were not statistically significant among the groups (no LBP: 12,504 ± 13,076 deg2/s2; preexisting LBP: 8808 ± 10,174 deg2/s2; developed LBP: 19,389 ± 13,590 deg2/s2; P = .157). Conclusion: Preexisting LBP was associated with significantly restricted motion of the pelvis, trunk, and shoulders during a lacrosse shot. Excessive pelvic acceleration may be related to the development of LBP in lacrosse players.

Aims/hypothesis Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies. Methods Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals’ left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF. Results Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p =0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF. Conclusions/interpretation ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes. Data availability The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org . Graphical Abstract

Sanfilippo syndrome Type-B, also known as mucopolysaccharidosis IIIB (MPS IIIB), accounts for approximately one-third of all Sanfilippo syndrome patients and is characterized by a similar natural history as Type-A. Patients suffer from developmental regression, bone malformation, organomegaly, GI distress, and profound neurological deficits. Despite human trials of enzyme replacement therapy (ERT) (SBC-103, AX250) in MPS IIIB, there is currently no FDA approved treatment and a few palliative options. The major concerns of ERT and gene therapy for the treatment of bone malformation are the inadequate biodistribution of the missing enzyme, N-acetyl-α-glucosaminidase (NAGLU), and that the skeleton is a poorly hit target tissue in ERT and gene therapy. Each of the four known human types of MPS III (A, B, C, and D) is usually regarded as having mild bone manifestations, yet it remains poorly characterized. This study aimed to determine bone mineral content (BMC), volumetric bone mineral density (vBMD), and biomechanical properties in femurs MPS IIIB C57BL/6 mice compared to phenotypic control C57BL/6 mice. Significant differences were observed in MPS IIIB mice within various cortical and cancellous bone parameters for both males and females (p < 0.05). Here, we establish some osteogenic manifestations of MPS IIIB within the mouse model by radiographic and biomechanical tests, which are also differentially affected by age and sex. This suggests that some skeletal features of the MPS IIIB mouse model may be used as biomarkers of peripheral disease correction for preclinical treatment of MPS IIIB.

Background The quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative. Methods We collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student’s unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs’ ability to identify breakthrough infected individuals in the vaccinated population. Results The breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p <0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population. Conclusion Our study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.

Pathological cardiac remodeling plays an essential role in the progression of cardiovascular diseases, and numerous microRNAs have been reported to participate in pathological cardiac remodeling. However, the potential role of microRNA-455-5p (miR-455-5p) in this process remains to be elucidated. In the present study, we focused on clarifying the function and searching the direct target of miR-455-5p, as well as exploring its underlying mechanisms in pathological cardiac remodeling. We found that overexpression of miR-455-5p by transfection of miR-455-5p mimic in vitro or tail vain injection of miR-455-5p agomir in vivo provoked cardiac remodeling, whereas genetic knockdown of miR-455-5p attenuated the isoprenaline-induced cardiac remodeling. Besides, miR-455-5p directly targeted to 3'-untranslated region of protein arginine methyltransferase 1 (PRMT1) and subsequently downregulated PRMT1 level. Furthermore, we found that PRMT1 protected against cardiac hypertrophy and fibrosis in vitro. Mechanistically, miR-455-5p induced cardiac remodeling by downregulating PRMT1-induced asymmetric di-methylation on R1748, R1750, R1751 and R1752 of Notch1, resulting in suppression of recruitment of Presenilin, Notch1 cleavage, NICD releasing and Notch signaling pathway. Finally, circulating miR-455-5p was positively correlated with parameters of left ventricular wall thickening. Taken together, miR-455-5p plays a provocative role in cardiac remodeling via inactivation of the PRMT1-mediated Notch signaling pathway, suggesting miR-455-5p/PRMT1/Notch1 signaling axis as potential therapeutic targets for pathological cardiac remodeling.

Abstract Objective: To evaluate the association between pre-diabetes and HF and the association of HF with changes in glycaemic status. Design and Methods: Patients newly diagnosed with AF between 2015 and 2018 were divided into 3 groups (normoglycaemia, pre-diabetes, and type 2 diabetes) according to their baseline glycaemic status. The primary outcome was incident HF. Fine and Gray model was applied, with death defined as the competing event. Results: Among 17,943 AF patients (mean age 75.5 years, 47% female), 3,711 (20.7%) had pre-diabetes and 10,127 (56.4%) had diabetes at baseline. Over a median follow-up of 4.7 years, 518 (14%) normoglycaemic, 646 (15.7%) pre-diabetic, and 1,795 (17.7%) diabetic patients developed HF. Pre-diabetes was associated with an increased risk of HF compared with normoglycaemic patients (subdistribution Hazard Ratio (SHR) =1.12, 95% confidence interval (CI): 1.03-1.22). In patients with pre-diabetes at baseline, 403 (11.1%) progressed to diabetes and 311 (8.6%) reversed to normoglycaemia at 2 years. Compared to those who remained pre-diabetic, patients who progressed to diabetes were associated with an increased risk of HF (SHR=1.50, 95% CI: 1.13-1.97), whereas those who reversed to normoglycaemia were associated with decreased risk (SHR=0.61, 95% CI: 0.42-0.94). Conclusions: Pre-diabetes was associated with an increased risk of HF in patients with AF. Compared with patients who remained pre-diabetic, those who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who reversed to normoglycaemia incurred a lower risk of HF.

Background Whether statin use can reduce the risk of heart failure (HF) remains controversial. The present study evaluates the association between statin use and HF in patients with atrial fibrillation. Methods and Results Patients with newly diagnosed atrial fibrillation from 2010 to 2018 were included. An inverse probability of treatment weighting was used to balance baseline covariates between statin users (n=23 239) and statin nonusers (n=29 251). The primary outcome was incident HF. Cox proportional hazard models with competing risk regression were used to evaluate the risk of HF between statin users and nonusers. The median age of the cohort was 74.7 years, and 47.3% were women. Over a median follow‐up of 5.1 years, incident HF occurred in 3673 (15.8%) statin users and 5595 (19.1%) statin nonusers. Statin use was associated with a 19% lower risk of HF (adjusted subdistribution hazard ratio, 0.81 [95% CI, 0.78–0.85]). Restricted to the statin users, duration of statin use was measured during follow‐up; compared with short‐term use (3 months to <2 years), there was a stepwise reduction in the risk of incident HF among those with 2 to <4 years of statin use (subdistribution hazard ratio, 0.86 [95% CI, 0.84–0.88]), 4 to <6 years of statin use (subdistribution hazard ratio, 0.74 [95% CI, 0.72–0.76]), and ≥6 years of statin use (subdistribution hazard ratio, 0.71 [95% CI, 0.69–0.74]). Subgroup analysis showed consistent reductions in the risk of HF with statin use. Conclusions Statin use was associated with a decreased risk of incident HF in a duration‐dependent manner among patients with atrial fibrillation.

This study aimed to explore the prognostic implication of N-terminal pro-brain natriuretic peptide (NT-proBNP) burden on heart failure (HF) with reduced ejection fraction (HFrEF). We performed a post hoc analysis of the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial. NT-proBNP burden was defined as the proportion of days with increased NT-proBNP (>= 1,800 pg/ml) to the whole observation time. A Cox proportional hazards regression model was used to evaluate the association with NT-proBNP burden and prognosis. A total of 815 patients with HFrEF were analyzed in our study. Patients were categorized into 4 groups accord -ing to the degree of NT-proBNP burden. In the multivariate Cox analysis, NT-proBNP burden was significantly associated with all-cause mortality, cardiovascular mortality, and HF hospitalization. Compared with patients without NT-proBNP burden, the risk for the composite outcome increased by 210% (hazard ratio [HR] 3.10, 95% confidence inter -val [CI] 1.72 to 5.58, p <0.001) in NT-proBNP burden 1 (mild) group, 432% (HR 5.32, 95% CI 2.93 to 9.67, p <0.001) in NT-proBNP burden 2 (moderate) group, and over 12 times (HR 13.15, 95% CI 7.42 to 23.33, p <0.001) in NT-proBNP burden 3 (severe) group. The sensitivity analyses stratified by age and renal function yielded similar results. A higher NT-proBNP burden was associated with a significant increase in risks of all -cause mortality, cardiovascular mortality, HF hospitalization, and composite outcome. The results suggested that NT-proBNP burden could be an important predictor of the prognosis of patients with HFrEF. (c) 2023 Elsevier Inc. All rights reserved. (Am J Car-

AimsThis study aims to evaluate the prognostic value of mean corpuscular haemoglobin concentration (MCHC) on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and resultsWe analysed HFpEF participants from the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline data (n = 1747). Patients were grouped into hypochromia or non-hypochromia group according to a MCHC cut-off level of 330 g/L. Cox proportional hazard model was used to explore the prognostic value of hypochromia on the long-term clinical outcomes (the primary endpoint [composite of cardiovascular mortality, HF hospitalization and aborted cardiac arrest], any-cause and HF hospitalization, all-cause and cardiovascular mortality). Patients were further stratified according to baseline estimated glomerular filtration rate (eGFR) to explore the impact of renal dysfunction on the prognostic value of hypochromia. Baseline hypochromia was prevalent (n = 662, 37.9%) and strongly associated with worse clinical outcomes. In patients with worse renal function (eGFR < 60 mL/min per 1.73 m(2)), hypochromia was independently associated with primary endpoint (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.23-1.98; P < 0.001), any-cause hospitalization (HR, 1.43; 95% CI, 1.20-1.71, P < 0.001) and HF hospitalization (HR, 1.40; 95% CI, 1.07-1.84; P = 0.015), whereas no significant association between hypochromia and these outcomes was found in patients with better renal function. ConclusionsAmong HFpEF patients, hypochromia (i.e. MCHC <= 330 g/L) is independently associated with adverse clinical outcomes, especially when in the presence of co-morbidity renal dysfunction.

We report the case of an 85-year-old patient who developed trifascicular block with syncope, triggered by preoperative eye drops for cataract surgery. This life-threatening situation reopens the debate over the necessity of having an anesthesiologist present during cataract surgery.Nous présentons le cas d’un patient de 85 ans, ayant présenté un bloc trifasciculaire avec syncopes déclenché par les collyres préopératoires avant une chirurgie de la cataracte. Cette situation à risque vital pour le patient relance le débat sur la nécessité d’avoir un anesthésiste disponible pour une chirurgie de cataracte.

Background Recent seasonal epidemics of influenza have been caused by human influenza A viruses of the H1N1 and H3N2 subtypes and influenza B viruses. Annual vaccination is recommended to prevent infection; however, how annual influenza vaccination influences vaccine effectiveness is largely unknown. Methods To investigate the impact of repeated vaccination on immune and protective effect, we performed a prospective seroepidemiologic study. Participants with or without prior vaccination (2018-2019) were enrolled during the 2019-2020 influenza season. Inactivated quadrivalent influenza vaccine (IIV4) was administered through the intramuscular route, and venous blood samples were collected regularly to test hemagglutination inhibition (HAI) titers. Results The geometric mean titers and proportion with titers >= 40 against the influenza vaccine components peaked at 30 days post-vaccination. At Day 30, the geometric mean titer and proportion with titers >= 40 in participants who had been previously vaccinated were higher for H3N2 but similar for both B lineages (Victoria and Yamagata) as compared with participants vaccinated for the first time. As for H1N1, the geometric mean titer was lower in repeated vaccinated participants, but the proportion with titers >= 40 was consistent in both groups. Conclusions Repeated vaccination provides similar or enhanced protection as compared with single vaccination in first-time vaccinees.

Background: Children with Juvenile Idiopathic Arthritis (JIA) may adopt different movement patterns and participate in physical activity during different states of disease. Research question: Which specific features of gait and physical function performance differ among children with active or inactive JIA compared to healthy children? Methods: Forty-three children participated (14.5 +/- 4.2 yrs; 60 % female). 3D-motion analysis methods were coupled with force measures from an instrumented treadmill captured gait mechanical measures. The 30-second Chair Rise Test (repetitions) and stair ascent-descent tests were performed, and the 11-point Wong-Baker face scale assessed pain after each test. Results: Compared to healthy controls children with active and inactive JIA had worse outcomes (12-21 % slower self-selected and fast walking speeds, 28-34 % slower stair navigation times, 28 % fewer chair rise repetitions in 30 s; all p < .05). Children with active JIA had 8-13 % slower gait speeds, 4 % fewer chair rise repetitions and 14-16 % slower stair navigation times. At faster walking speed, children with active JIA had less hip joint flexion/extension excursion in the sagittal plane during the gait cycle, produced higher leg stiffness, and demonstrated greater interlimb asymmetry in GRF vertical impulse during loading than healthy children (all p < .05). The Pedi-FABS subscore of "Duration: performing athletic activity for as long as you would like without stopping" was rated lower in children with active JIA compared to controls (p < .05). Conclusion: Gait speed, specific load-bearing functional tasks and leg stiffness features of gait may be informative 'functional biomarkers' for assessing JIA burden and tracking treatment efficacy. Additional prospective studies are needed to determine how these features change over time with pain change, and understand impact on quality of life and physical activity participation.

Background Cardiac power-to-left ventricular mass (power/mass) is an index reflecting the muscular hydraulic pump capability of the heart, and the E/e’ ratio is a specific indicator for identifying increased left ventricular filling pressure. Limited data exist regarding the prognostic value of incorporating power/mass and E/e’ ratio in heart failure with preserved ejection fraction (HFpEF). Materials and methods In total, 475 patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with complete baseline echocardiography data were included in our analysis. Patients were categorized into four groups according to power/mass and E/e’ ratio. The risk of outcomes was examined using Cox proportional hazards models and competing risk models. Results Patients with low power/mass and high E/e’ were more likely to be males (60.5%), with higher waist circumference, and had a higher prevalence of diabetes (52.1%), atrial fibrillation (50.4%), and lower estimated glomerular filtration rate (eGFR). Combined resting power/mass and E/e’ have graded correlations with left ventricular (LV) dysfunction and clinical outcomes in patients with HFpEF. After multivariable adjustments, an integrative approach combining power/mass and E/e’ remained to be a powerful prognostic predictor, with the highest HRs of clinical outcomes observed in patients with low power/mass and high E/e’ (all-cause mortality: HR 3.45; 95% CI: 1.69–7.05; P = 0.001; hospitalization for heart failure: HR 3.27; 95% CI: 1.60–6.67; P = 0.001; and primary endpoint: HR 3.07; 95% CI: 1.73–5.42; P < 0.001). Conclusion In patients with HFpEF, an echo-derived integrated approach incorporating resting power/mass and E/e’ ratio remained to be a powerful prognosis predictor and may be useful to risk-stratify patients with this heterogeneous syndrome. Clinical Trial Registration [https://clinicaltrials.gov], identifier [NCT00094302].

Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates several pathways associated with inflammation. In this study, we aimed to investigate the role of AIP1 in T2D development. Our results revealed that AIP1 was downregulated in omental adipose tissue (OAT) of obese patients with T2D compared with that in obese patients. In addition, Pearson's correlation test showed that AIP1 was negatively correlated with the homeostatic model assessment for insulin resistance (HOMA-IR, r = -0.4829) and waist-to-hip ratio (r = -0.2614), which are major clinical indexes of T2D. As revealed by the proteomic analysis, immunohistochemistry, and ELISA, the OAT and the serum of obese patients with T2D presented high inflammatory status. And the increased inflammatory factors TNF-α and C-reactive protein C (CRP) in the serum of obese patients with T2D showed a positive correlation with HOMA-IR (TNF-α, r = 0.4728; CRP, r = 0.5522). Interestingly, AIP1 deficiency in adipocytes facilitated TNF-α secretion and retarded glucose uptake. Mechanistically, AIP1 deletion in human adipocytes activated JNK, p38 MAPK, and ERK1/2 signaling. Furthermore, inhibition of these signaling pathways using specific inhibitors could suppress these signal activation and insulin resistance caused by AIP1 deficiency. In addition, AIP1 and TNF-α expression in the OAT of patients with T2D recovered to normal levels after laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings indicate that AIP1 is negatively correlated with the clinical indexes of T2D. It modulates TNF-α expression in OAT via JNK, p38 MAPK, and ERK1/2 signaling.

Abstract Background Kinesiophobia may hinder physical performance measures and functional quality of life in children with juvenile idiopathic arthritis (JIA). This study aims to quantify differences in physical function in patients with JIA compared to healthy controls, and determine the effects of kinesiophobia on physical function and physical activity. Methods This was a comparative study of participants with JIA and healthy controls (JIA n = 26, control n = 17). All children with JIA had lower extremity joint involvement. Performance-based measures included gait speed, chair and stair navigation performance. Self-reported measures included Patient Reported Outcome Measurement Information System (PROMIS®) Physical Function Mobility, and Pain Interference and the Pediatric Functional Activity Brief Scale (Pedi-FABS). The Tampa Scale of Kinesiophobia (TSK-11) assessed patient fear of movement due to pain. Linear regression models were used to determine the contribution of TSK-11 scores on performance test and Pedi-FABS scores. Results Gait speeds were 11–15% slower, chair rise repetitions were 28% fewer, and stair ascent and descent times were 26–31% slower in JIA than controls (p < .05). PROMIS® Physical Function Mobility scores were 10% lower and Pain Interference scores were 2.6 times higher in JIA than healthy controls (p = .003). TSK-11 scores were higher in JIA than controls (p < .0001). After controlling for covariates, TSK-11 scores explained 11.7–26.5% of the variance of regression models for stair climb time, chair rise performance and Pedi-FABS scores (p < .05). Conclusions Children with JIA experience difficulty with tasks related to body transfers. Kinesiophobia is a significant contributor to the functional task performance and may impact clinical outcomes.