Anthropometric measures and physical examination could be used to assess phenotypic GLIM (Global leadership initiative on malnutrition) criteria in heart failure patients.

BACKGROUND AND AIMS: The assessment of muscle mass using technology-based methods is less commonly performed when applying the Global Leadership Initiative on Malnutrition (GLIM) criteria due to the lack of skilled clinical nutrition practitioners and/or equipment. Based on the predictive validity of poor health outcomes and feasibility in clinical practice, this study aimed to analyze whether the measurement of calf circumference (CC), mid-upper arm circumference (MAC), and the physical examination could be used as substitutes for muscle mass assessment, as well as handgrip strength (HGS) used as a substitution when applying the GLIM criteria in hospitalized HF patients. METHODS AND RESULTS: From June 2022 to January 2023, a single-center prospective study including 216 patients was performed. Additionally, covariates were identified by a directed acyclic graph. The multivariate logistic regression analysis was also used to analyze and compare the association between poor health outcomes and malnutrition (based on 5 types of GLIM criteria). Cohen-kappa coefficient and TELOS-feasibility score were calculated. The prevalence of malnutrition ranged from 35.2% to 42.6%, depending on the tool used. After adjusting for covariates, malnutrition assessed using CC, MAC, or physical examination within the GLIM criteria was independently associated with poor clinical outcomes (90-day HF-related readmission or all-cause mortality and prolonged hospital stay) but not with HGS. CONCLUSION: CC, MAC and results from physical examination but not HGS may serve as a substitutive metric of muscle mass contained in the GLIM criteria to diagnose malnutrition and predict poor clinical outcomes among HF patients. REGISTRATION NUMBER: This study was registered at Chinese Clinical Trial Registry. (ChiCTR2200057876) on 20 Mar. 2022.

Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling.

Objective: To explore the underlying mechanism of the sonic hedgehog (Shh) signaling pathway in promoting cell proliferation and migration in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Method: FLS were collected from 8 patients with RA and 3 patients with osteoarthritis (OA). The expression of smoothened (Smo, the Shh pathway activator) was quantified by real-time PCR and western blot. FLS were incubated with cyclopamine (a Smo antagonist), purmorphamine (a Smo agonist), Y27632 (a Rho/ROCK signaling inhibitor), or a combination of purmorphamine and Y27632, respectively. Cell proliferation was examined using cell counting kit-8 and cell cycle assays while cell migration was measured with Transwell and wound healing assays. Results: The expression of Smo was higher in FLS from RA patients than from OA patients (p < 0.05). RA-FLS treated with purmorphamine showed significantly activated proliferation (119.69 vs. 100.0) and migration (252.38 vs. 178.57) compared to untreated cells (both p < 0.001). RA-FLS incubated with cyclopamine or a combination of purmorphamine and Y27632 exhibited significant suppression of proliferation (81.55 vs. 100.0 and 85.84 vs. 100.0) and migration (100 vs. 178.57 and 109.52 vs. 185) ability (all p < 0.001). Conclusion: Our results demonstrated that Shh promoted cell growth and migration of FLS in RA patients through the Rho/ROCK signaling pathway.

Multi-modal retinal scanning to measure retinal thickness and peripheral blood vessels in multiple sclerosis.

Our purpose was to investigate changes to the retina in multiple sclerosis (MS) using established and novel modes of retinal image acquisition and analysis. 72 participants with MS and 80 healthy volunteers underwent retinal scanning with optical coherence tomography (OCT) and ultra-widefield (UWF) scanning laser ophthalmoscopy (SLO), over a two-year period. Changes in retinal nerve fibre layer (RNFL) thickness, macular volume and retinal blood vessel diameter were measured and parameters were then tested for associations with MS. Measurements from OCT showed that individuals with MS had a thinner RNFL and reduced macular volume when compared to healthy volunteers. On UWF images, participants with MS had reduced arterial widths in the inferior nasal quadrant of both eyes and reduced venous widths in the inferior nasal quadrant of right eyes. Longitudinal analysis showed that participants with MS had an accelerated annual rate of RNFL thinning in several regions of the retina. In conclusion, the assessment of OCT showed thinning of the RNFL and macula in concordance with previous reports on MS, while analysis of blood vessels in the retinal periphery from UWF-SLO images revealed novel changes.

Longitudinal retinal imaging study of newly diagnosed relapsing-remitting multiple sclerosis in Scottish population: baseline and 12 months follow-up profile of FutureMS retinal imaging cohort.

OBJECTIVE: Multiple sclerosis (MS) is an inflammatory degenerative condition of central nervous system. The disease course and presentation of MS is highly heterogeneous. Advanced retinal imaging techniques such as optic coherence tomography (OCT) can capture abnormalities of anterior visual pathway with high resolution, which may contribute greater insights into the pathophysiology of MS. METHODS: People with newly diagnosed relapsing-remitting MS were recruited for FutureMS retinal imaging study from two study centres in Scotland. The baseline visit was completed within 6 months of diagnosis with initial follow-up 12 months after the baseline visit. The assessments included in FutureMS retinal imaging study were visual acuity test, self-reported eye questionnaire and OCT scan. RESULTS: A total of 196 FutureMS participants completed the retinal imaging study of FutureMS with 185 participants at M0 and 155 at M12. A total of 144 participants completed both M0 and M12 visits. At the whole cohort level, the distribution of retinal measures is generally consistent between baseline and follow-up. CONCLUSION: The FutureMS retinal imaging study aims to demonstrate that patient with MS present with different extent of retinal abnormalities that can be captured by retinal imaging modalities such as OCT soon after diagnosis. These changes may sensitively mirror the brain atrophy or serve as predictors for disease activity. By developing sensitive, quantifiable and objective retinal biomarkers, FutureMS retinal imaging study will provide an opportunity to stratify patient with MS at an early stage and support future therapeutic strategies for a better outcome.

FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries is the most common cause of progressive neurological disability in working age persons. While treatable, there is substantial interindividual heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate or aggressive disease course is very limited. There is, therefore, a need for integrated predictive tools to inform individualised treatment decision making. PARTICIPANTS: Established with the aim of addressing this need for individualised predictive tools, FutureMS is a nationally representative, prospective observational cohort study of 440 adults with a new diagnosis of relapsing-remitting MS living in Scotland at the time of diagnosis between May 2016 and March 2019. FINDINGS TO DATE: The study aims to explore the pathobiology and determinants of disease heterogeneity in MS and combines detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow-up at year 1 is complete. Here, we describe the cohort design and present a profile of the participants at baseline and 1 year of follow-up. FUTURE PLANS: A third follow-up wave for the cohort has recently begun at 5 years after first visit and a further wave of follow-up is funded for year 10. Longer-term follow-up is anticipated thereafter.

Airborne particulate metals in the New York City subway: a pilot study to assess the potential for health impacts.

A prior study in New York City observed that airborne concentrations of three metals found in steel - iron, manganese, and chromium - are more than 100 times higher in the subway system than in aboveground air. To investigate the potential for health effects of exposure at these levels, we conducted a pilot study of subway workers comparing personal exposures to steel dust with biomarkers of metal exposure, oxidative stress, and DNA damage in blood and urine samples. Workers wore a personal air sampler operating at 4L/m for one to three work shifts with blood and urine samples collected at the end of the final shift. We found that PM(2.5) exposures varied among subway workers on the basis of job title and job activity. The subway workers' mean time-weighted PM(2.5) exposure was 52 microg/m3, with a median of 27 microg/m3, and a range of 6-469 microg/m3. The observed concentrations of PM(2.5), iron, manganese, and chromium fell well below occupational standards. Biomarker concentrations among the 39 subway workers were compared with a group of 11 bus drivers, and a group of 25 suburban office workers. Concentrations of DNA-protein crosslinks and chromium in plasma were significantly higher in subway workers than in bus drivers, but no significant difference was observed for these biomarkers between subway workers and office workers. Urinary isoprostane concentrations were significantly correlated with the number of years working in the subway system, and were detected at higher, though not significantly higher, concentrations in subway workers than in bus drivers or office workers. At the group level, there was no consistent pattern of biomarker concentrations among subway workers significantly exceeding those of the bus drivers and office workers. At the individual level, steel dust exposure was not correlated with any of the biomarkers measured.

Sonic Hedgehog Regulates Proliferation, Migration and Invasion of Synoviocytes in Rheumatoid Arthritis via JNK Signaling.

Activated fibroblast-like synoviocytes (FLSs) play a central role in the formation of synovial pannus and joint destruction in rheumatoid arthritis (RA). Targeting FLSs could be a potential therapeutic strategy. The objective of this study is to explore the role of c-Jun N-terminal kinase (JNK) in proliferation, migration and invasion of FLSs promoted by the sonic hedeghog (SHH) signaling pathway in patients with RA. Activation of SHH signaling was evaluated by real-time PCR and Western Blot. Levels of phosphorylation of JNK and c-Jun were detected by Western Blot. FLSs proliferation was quantified by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Cell migration and invasion were assessed by wound healing assay and Transwell chamber assay. Invasiveness of FLSs in vivo was evaluated using a humanized synovitis animal model. We observed that treatment of SHH agonist (SAG) significantly increased the levels of phosphorylation of JNK and c-Jun, while SHH antagonist (cyclopamine) significantly decreased the expression of phospho-JNK and phospho-c-Jun in FLSs. The elevated level of phospho-c-Jun stimulated by SAG was decreased in the presence of JNK inhibitor (SP600125) (P < 0.001). FLSs proliferation, migration and invasion were promoted by SHH agonist (P < 0.05). However, the enhanced aggressiveness of FLSs was abolished in the presence of JNK inhibitor (P < 0.05). In vivo study showed that the invasion of FLSs into cartilage was increased by SHH overexpression and the excessive invasiveness was inhibited by blockade of JNK signaling (P < 0.01). These results suggest that JNK is one of the downstream molecules mediating the effect of SHH signaling in FLSs. These findings indicate that SHH-JNK signaling could be a potential therapeutic target to suppress the aggressiveness of FLSs and prevent articular damage of RA.

The abnormal high expression of B cell activating factor belonging to TNF superfamily (BAFF) and its potential role in kidney transplant recipients.

B cell activating factor belonging to TNF superfamily (BAFF) is a critical regulator of B cell maturation and survival. In this present study, the expression characteristic of BAFF in kidney transplantation recipients was investigated, its potential significance was analyzed and peripheral blood of follow-up kidney transplant recipients was studied. Flow cytometric assay results showed that, cell-surface BAFF was significantly highly expressed on peripheral CD3(+) T lymphocytes in > or = 5 yrs group of kidney transplant recipients, compared with other groups (p < 0.05). BAFF expression could be found on CD4(+) T cells and CD8(+) T cells. The BAFF mRNA levels in peripheral mononuclear cells were consistent with the protein levels. However, serum soluble BAFF levels were inter-individually different in each group. Stratified by renal function, it was found that cell-surface BAFF levels were significantly higher in those with abnormal renal function, compared with recipients with normal renal function (p < 0.05). ELISA assay results showed that expression levels of cell surface BAFF were significantly correlated with anti-HLA I & II antibodies. These results indicate that BAFF may be involved in the development of graft-loss and influences the long-time outcome of kidney allograft, likely mediated by interfering with immune response.