The Clinical Utility of Musculoskeletal Ultrasound for Disease Activity Evaluation and Therapeutic Response Prediction in Rheumatoid Arthritis Patients: A Narrative Review.

Rheumatoid arthritis (RA) is characterized by persistent synovitis and joint/bone destruction. There is an unmet need to predict the therapeutic response to disease-modifying anti-rheumatic drugs (DMARDs) and achieve a treat-to-target goal. Musculoskeletal ultrasound (MSUS) is widely used to identify structural change and assess therapeutic response in RA. This review aims to summarize the available evidence regarding the clinical application of MSUS in evaluating disease activity and predicting therapeutic responses to DMARDs. We searched the MEDLINE database using the PubMed interface and reviewed English-language literature from 2000 to 2022. This review focuses on the updated role of MSUS in assessing disease activity and predicting therapeutic responses to DMARDs in RA patients. MSUS is now widely applied to identify articular structural change and assess the disease activity of RA. Combined use of gray scale and power Doppler MSUS is also superior to clinical assessment and laboratory examination in evaluating disease activity of RA. With portable use, good viability, and high sensitivity to articular inflammation, MSUS would be useful in assessing therapeutic response to biologic/targeted synthetic DMARDs (b/tsDMARDs) in RA patients. Given MSUS could also detect subclinical inflammation in a substantial proportion of RA patients with clinical remission, it is recommended to assess b/tsDMARDs-treated RA patients who have achieved low disease activity or remission. Although substantial literature data have revealed clinical utility of MSUS for monitoring disease activity and evaluating therapeutic response in RA patients, the evidence regarding its predictive value for the effectiveness of b/tsDMARDs is limited.

Usage of point-of-care Ultrasonography for Rapid Diagnosis of Cardiac Perforation by Pacemaker Lead.

Cardiac perforation after pacemaker placement is a rare form of cardiovascular emergency. A case of an elderly adult undergoing hemodialysis that contributed to this emergency is presented. The history, clinical imaging findings, and surgical procedures for clinical assessment are briefly described. Point-of-care ultrasonography (POCUS) was used to identify, locate, and perform ultrasonography-guided pericardiocentesis. The role of POCUS in cases of tamponade has been emphasized in clinical settings.

Usage of Point-of-care Ultrasonography for Rapid Diagnosis of Acute Renal Infarction: Two Case Reports.

Acute renal infarction is a rare form of vascular emergency. Although major risk factors of renal infarction are due to cardio-embolic events such as atrial fibrillation, valvular or ischemic heart disease, renal artery thrombosis/dissection, and coagulopathy, the prevalence of idiopathic acute renal infarction can be as high as 59%. Two cases that contributed to this emergency are presented. The history, physical examination, and clinical imaging findings for clinical assessment are briefly described. Point-of-Care Ultrasonography (POCUS) was used to exclude other etiology and identify the pathological changes. The role of POCUS in rapid rule in acute renal infarction has been emphasized in clinical settings.

Rapid Detecting Brachial Plexus Injury by Point-of-Care Ultrasonography.

Brachial plexus injury (BPI) is regarded as one of the most devastating injuries of the upper extremity. Brachial plexus neuropathy can have a high morbidity by seriously affecting the motor function and sensation of upper limbs with loss of activities of daily living. The use of computed tomography myelogram and/or magnetic resonance imaging (MRI) assessing brachial plexus offers valuable details including the location, morphology, and severity of preganglionic and postganglionic injuries during the preoperative period. High-field-strength MRI with specific coil and specialized MRI sequences might be not available in every emergency setting and is time-consuming. Point-of-care ultrasonography (POCUS) comes in handy and offers good image resolution of muscles and nerves that makes early detection of neuromuscular injury possible. Here, we present a case report of BPI that POCUS provides indirect evidence of cervical root injury and expedite time to MRI.

The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis.

Although the heterogeneity of high-density lipoprotein-cholesterol (HDL-c) composition is associated with atherosclerotic cardiovascular risk, the link between electronegative subfractions of HDL-c and atherosclerosis in rheumatoid arthritis (RA) remains unknown. We examined the association of the percentage of the most electronegative subfraction of HDL-c (H5%) and RA-related atherosclerosis. Using anion-exchange purification/fast-protein liquid chromatography, we demonstrated significantly higher H5% in patients (median, 7.2%) than HC (2.8%, p < 0.005). Multivariable regression analysis revealed H5% as a significant predictor for subclinical atherosclerosis. We subsequently explored atherogenic role of H5 using cell-based assay. The results showed significantly higher levels of IL-1ß and IL-8 mRNA in H5-treated (mean ± SD, 4.45 ± 1.22 folds, 6.02 ± 1.43-folds, respectively) than H1-treated monocytes (0.89 ± 0.18-folds, 1.03 ± 0.26-folds, respectively, both p < 0.001). In macrophages, H5 upregulated the mRNA and protein expression of IL-1ß and IL-8 in a dose-dependent manner, and their expression levels were significantly higher than H1-treated macrophages (all p < 0.001). H5 induced more foam cell formation compared with H1-treated macrophages (p < 0.005). In addition, H5 has significantly lower cholesterol efflux capacity than H1 (p < 0.005). The results of nanoLC-MS/MS approach reveal that the best discriminator between high-H5% and normal-H5% is Apo(a), the main constituent of Lp(a). Moreover, Lp(a) level is a significant predictor for high-H5%. These observations suggest that H5 is involved in RA-related atherosclerosis.

To rub or not to rub? - effective rigid contact lens cleaning.

PURPOSE: To compare the efficacy of cleaning of rigid contact lenses using two care solutions with and without rubbing. METHODS: A masked randomised trial was conducted. The cleaning efficacy of two solutions recommended for rigid contact lenses, a one-step hydrogen peroxide solution (HP) and a povidone iodine-based solution (PI), were evaluated on 64 unworn orthokeratology (ortho-k) lenses subsequent to cleaning with rubbing (R) with a surfactant cleaner or without rubbing (NR). Either mascara or hand cream was applied as a contaminant to the lenses to simulate stubborn and loosely bounded deposits, respectively. For each type of deposit, the lenses were randomly assigned to four cleaning treatments: R with HP, NR with HP, R with PI, and NR with PI (n = 8 for each group). Each lens surface was assessed on site by a masked examiner under a low-magnification slit-lamp and with photo-documentation. Lenses were graded according to the deposit coverage area using a pre-set five-point scale [0 (<20% coverage) - 4 (>80% coverage)]. RESULTS: For stubborn deposits (mascara), NR failed to remove deposits from 94% of lenses, whilst R removed more than 80% of deposits from 63% of the lenses. For oily deposits, 25% of NR lenses had >80% coverage, whilst only one R lens had 60-80% coverage, with 19% having 40-60% coverage, and 38% with either 20-40% or <20%. Rubbing improved lens cleanliness for both types of deposits, but only reached statistical significance for the stubborn deposit group. There were no significant differences between the solutions. CONCLUSION: Not Rubbing and using either HP or PI solutions, is not effective in removing stubborn deposits from ortho-k lenses. It is essential to rub lenses when cleaning rigid lenses to ensure optimal lens hygiene for ocular health, especially as rigid gas permeable (RGP) lenses are intended to be reused for at least a year before replacement. Rubbing with a daily cleaner should be included in the instructions for use of the solutions tested for rigid lenses and practitioners should be encouraged to emphasise the importance of rubbing in lens care.

Cantharidin decreased viable cell number in human osteosarcoma U-2 OS cells through G2/M phase arrest and induction of cell apoptosis.

Cantharidin (CTD), a sesquiterpenoid bioactive substance, has been reported to exhibit anticancer activity against various types of cancer cells. The aim of the present study was to investigate the apoptosis effects and the underlying mechanisms of CTD on osteosarcoma U-2 OS cells. Results showed that CTD induced cell morphologic changes, reduced total viable cells, induced DNA damage, and G2/M phase arrest. CTD increased the production of reactive oxygen species and Ca2+, and elevated the activities of caspase-3 and -9, but decreased the level of mitochondrial membrane potential. Furthermore, CTD increased the ROS- and ER stress-associated protein expressions and increased the levels of pro-apoptosis-associated proteins, but decreased that of anti-apoptosis-associated proteins. Based on these observations, we suggested that CTD decreased cell number through G2/M phase arrest and the induction of cell apoptosis in U-2 OS cells and CTD could be a potential candidate for osteosarcoma treatments.

Association of muscle health impairment and atherosclerosis with major osteoporotic fracture risk in Taiwanese Vegetarians.

Objectives: Despite the beneficial effects of "vegetarian style" diet on atherosclerosis, it is also proven potentially detrimental to bone health. The influence of muscle health or atherosclerosis on major osteoporotic fracture (MOF) risk in vegetarians has rarely been explored. This prospective study aimed to investigate an association of MOF risk with muscle health and atherosclerosis in vegetarians. Materials and Methods: We conducted a questionnaire survey with the Mini-Nutritional Assessment (MNA) on 39 vegetarians. The 10-year probability of MOF was determined using the Taiwanese Fracture Risk Assessment (FRAX®) calculator. Appendicular skeletal muscle (ASM) mass and bone mineral density were measured with dual-energy X-ray absorptiometry. Physical performance was evaluated using the 6-min walk test (6MWT). Common carotid artery intima-media thickness (ccIMT) was determined using sonography. Serum levels of parathyroid hormone (PTH), Vitamin D, adiponectin, and leptin were measured. Results: Eleven (28.2%) of 39 vegetarians had a moderate-high risk of MOF, defined by FRAX-calculated risk ≥10%. These subjects had lower ASM (P < 0.005) and 6MWT distances (P < 0.01) but greater ccIMT than those with low risk. The MOF risk was negatively correlated with ASM (r = -0.51, P < 0.001) and 6MWT distances (r = -0.62, P < 0.001) but positively correlated with ccIMT (r = 0.56, P < 0.001). Linear regression analysis revealed that MOF risk scores were negatively associated with ASM and 6MWT distance while positively associated with ccIMT. There was no significant association of MOF risk with MNA scores, serum levels of PTH, Vitamin D, adiponectin, or leptin. Conclusion: Decreased ASM mass, reduced physical performance, and atherosclerosis are significantly associated with MOF risk in vegetarians.

Long term therapeutic effects of icariin-loaded PLGA microspheres in an experimental model of optic nerve ischemia via modulation of CEBP-ß/G-CSF/noncanonical NF-κB axis.

An ischemic insult at optic nerve (ON) is followed by detrimental neuroinflammation that results in progressive and long-lasting retinal ganglion cell (RGC) death and vision loss. Icariin was reported to be a safe and effective natural anti-inflammatory drug. Herein, we evaluated the long-term therapeutic effects of a single intravitreal injection of poly(lactide-co-glycolide) PLGA-icariin in a rat model of anterior ischemic optic neuropathy (rAION). Treatment with PLGA microspheres of icariin preserved the visual function and RGC density for 1 month in the rAION model. In addition, ON edema and macrophage infiltration were inhibited by treating PLGA microspheres of icariin. We found that the binding complex of icariin and CCAAT enhancer binding protein beta (CEBP-ß) significantly induced endogenous granulocyte colony-stimulating factor (G-CSF) expression to activate noncanonical nuclear factor kappa B (NF-κB) signaling pathway by promoting an alternative phosphorylation reaction of IKK-ß. Activation of noncanonical NF-κB signaling pathway promoted the M2 microglia/macrophage polarization and AKT1 activation, which prevented neuroinflammation and RGC apoptosis after ON infarct. This study concluded that protective mechanism of icariin is a CEBP-ß/G-CSF axis-induced noncanonical NF-κB activation, which provides the long-term neuroprotective effects via anti-inflammatory and antiapoptotic actions after ON ischemia.

Self-assembly of short collagen-related peptides into fibrils via cation-π interactions.

Introduction of a cationic residue at the N-terminus and an aromatic residue at the C-terminus of a collagen-related peptide can generate favorable cation-π interactions between the termini of collagen triple helices. The experimental results indicate that such cation-π interactions can promote the self-assembly of collagen triple helices into a higher-order structure in a head-to-tail manner. Our current work shows that cation-π interactions can serve as an effective force in preparing collagen-related biomaterials.

Contributions of cation-π interactions to the collagen triple helix stability.

Cation-π interactions are found to be an important noncovalent force in proteins. Collagen is a right-handed triple helix composed of three left-handed PPII helices, in which (X-Y-Gly) repeats dominate in the sequence. Molecular modeling indicates that cation-π interactions could be formed between the X and Y positions in adjacent collagen strands. Here, we used a host-guest peptide system: (Pro-Hyp-Gly)(3)-(Pro-Y-Gly-X-Hyp-Gly)-(Pro-Hyp-Gly)(3), where X is an aromatic residue and Y is a cationic residue, to study the cation-π interaction in the collagen triple helix. Circular dichroism (CD) measurements and Tm data analysis show that the cation-π interactions involving Arg have a larger contribution to the conformational stability than do those involving Lys, and Trp forms a weaker cation-π interaction with cationic residues than expected as a result of steric effects. The results also show that the formation of cation-π interactions between Arg and Phe depends on their relative positions in the strand. Moreover, the fluorinated and methylated Phe substitutions show that an electron-withdrawing or electron-donating substituent on the aromatic ring can modulate its π-electron density and the cation-π interaction in collagen. Our data demonstrate that the cation-π interaction could play an important role in stabilizing the collagen triple helix.

Increased Levels of Omega-3 Fatty Acids and DHA Are Linked to Pain Reduction in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors.

Although Janus kinase inhibitors (JAKi) could reduce patient-reported pain in rheumatoid arthritis (RA), their mechanism remains unclear. Therefore, we examined lipid metabolites change in JAKi-treated patients and evaluate their association with pain reduction. We used 1H-NMR-based lipid/metabolomics to determine serum levels of lipid metabolites at baseline and week 24 of treatment. Serum levels of significant lipid metabolites were replicated by ELISA in 24 JAKi-treated and 12 tocilizumab-treated patients. Pain was evaluated with patients' assessment on a 0-100 mm VAS, and disease activity assessed using DAS28. JAKi or tocilizumab therapy significantly reduced disease activity. Acceptable pain (VAS pain ≤20) at week 24 was observed in 66.7% of JAKi-treated patients, and pain decrement was greater than tocilizumab-treated patients (ΔVAS pain 70.0 vs. 52.5, p = 0.0595). Levels of omega-3 fatty acids and docosahexaenoic acid (DHA) were increased in JAKi-treated patients (median 0.55 mmol/L versus 0.71 mmol/L, p = 0.0005; 0.29 mmol/L versus 0.35 mmol/L, p = 0.0004; respectively), which were not observed in tocilizumab-treated patients. ELISA results showed increased DHA levels in JAKi-treated patients with acceptable pain (44.30 µg/mL versus 45.61 µg/mL, p = 0.028). A significant association of pain decrement with DHA change, not with DAS28 change, was seen in JAKi-treated patients. The pain reduction effect of JAKi probably links to increased levels of omega-3 fatty acids and DHA.

A Novel Eye Drop Formulation for Potential Treatment of Neovascular Age-Related Macular Degeneration.

Purpose: Drug delivery to posterior ocular tissues via topical eye drop administration is arduous due to the unique anatomy and physiology of the eye. Therefore, treatments for posterior eye disease have to be administered via intravitreal injection or systemic route, both of which have their drawbacks. Herein, the objective of this work was to demonstrate that a specially designed eye drop formulation could effectively deliver small-molecule vascular endothelial growth factor (VEGF) inhibitor to posterior ocular tissues for antiangiogenic therapy. Methods: The unique eye drop formulation, termed ITRI AXN eye drops, was obtained from self-assembly of (2-hydroxypropyl)-ß-cyclodextrin with a VEGF tyrosine kinase inhibitor, a hydrophilic polymer, hypromellose, and a complex stabilizer, caffeine. In vivo ocular pharmacokinetics studies were performed with New Zealand White (NZW) rabbits and Non Human Primates (NHP). The antiangiogenesis effect was evaluated on the Long-Evans rat with laser-induced choroidal neovascularization and pigmented Dutch-Belted rabbits with VEGF-induced retinal neovascularization. Results: The successful drug transport from ocular surface to posterior ocular cavity was indicated by a drug biodistribution pattern in pharmacokinetic studies. Excellent drug exposure in the choroid and retina with the concentrations of 900- and 750-fold greater than drug IC50 0.5 hours post the eye drop administration (drug level: 0.8%) was observed on the NHP study. The obtained formulation also demonstrated a comparable antiangiogenic outcome with the intravitreal injection of anti-VEGF antibody on rat and rabbit disease models. Conclusions: Our eye drop formulation has demonstrated great promise in antiangiogenic therapy against retinal and choroidal neovascularization in animal models. The results suggest that the aim of this work can be successfully achieved by the novel eye drop formulation. Translational Relevance: The preclinical results provide evidence that ITRI AXN eye drops could effectively deliver therapeutics to the choroid and retina for antiangiogenic therapy.

An evaluation of colonoscopy use: implications for health education.

In this retrospective study, we examined factors that associated with colonoscopy test use among adults who did not have colorectal cancer (CRC) in the USA. A total of 2,150 non-CRC adults >or=55 were selected from the Health Information National Trends Survey, a random-digit telephone survey that collected data in 2003-2004. Participants were classified based on receiving CRC tests within the recommended time interval. Socio-demographic and cognitive factors that are associated with colonoscopy test use were examined. The results show that adults 55-64 years old were less likely to have a colonoscopy compared with those 65 years and older. Participants with higher levels of knowledge, greater access to care, greater perceived risk, and lower psychological barriers were more likely to report receiving a colonoscopy. The findings indicate a continuous effort to increase awareness and risk perception, and reduce psychological barriers through health education.

Casticin Promotes Immune Responses, Enhances Macrophage and NK Cell Activities, and Increases Survival Rates of Leukemia BALB/c Mice.

Casticin, derived from Fructus Viticis, has anticancer properties in many human cancer cells, however, there is no report to show that casticin promotes immune responses and affects the survival rate of leukemia mice in vivo. The aim of this study is to evaluate the effects of casticin on immune responses and the survival rate of WEHI-3 cells generated in leukemia mice in vivo. Animals were divided into six groups: normal control mice, leukemia control mice, mice treated with ATRA (all-trans retinoic acid), and casticin (0.1, 0.2, and 0.4 mg/kg) treated mice. All animals were treated for 14 days and then measured for body weights, total survival rate, cell markers, the weights of liver and spleen, phagocytosis of spleen cells, NK cell activities and cell proliferation. Results show that casticin did not affect animal appearances, however, it increased body weights and decreased the weights of liver at 0.2 mg/kg and 0.4 mg/kg treatment. Casticin also decreased spleen weight at 0.2 mg/kg and 0.4 mg/kg treatment, increased CD3 at 0.1, 0.2 and 0.4 mg/kg doses and increased CD19 at 0.2 mg/kg treatment but decreased CD11b and Mac-3 at 0.1, 0.2 and 0.4 mg/kg treatment. Casticin (0.1, 0.2 and 0.4 mg/kg) increased macrophage phagocytosis from PBMC (peripheral blood mononuclear cell) and peritoneal cavity. Furthermore, casticin increased NK cells' cytotoxic activity and promoted T cell proliferation at 0.1-0.4 mg/kg treatment with or without concanavalin A (Con A) stimulation, but only increased B cell proliferation at 0.1 mg/kg treatment. Based on these observations, casticin could be used as promoted immune responses in leukemia mice in vivo.