Detecting Advanced Esophageal Cancer by Point of Care Ultrasonography.

Esophageal cancer (EC) is the 8th-most common cancer and the 6th-most common cause of death worldwide in 2020. Patients with EC might present with a variety of symptoms, such as chest tightness, retrosternal pain, acid regurgitation, heartburn sensation, dyspnea, cough, recurrent pneumonia, hoarseness, dysphagia, and weight loss, which make early diagnosing EC extremely difficult. Currently, the golden diagnostic tool of EC remains endoscopic biopsy. However, in patient suspected advanced EC, point-of-care ultrasonography (POCUS) could be a first-line screening tool. By three zones of esophageal sonography including esophageal inlet, middle third segment of esophagus just beneath the cardiac chambers, and esophagogastric junction, we could be able to detect sonographic evidence of advanced EC including heterogeneous hyperechoic esophageal mass, loss of normal wall differentiation, and mass effect to adjacent structure such as left atrium. For patients with chest pain, POCUS should be focused on cardiac, adjust mediastinum and lung survey. Here, we present a 73-year-old male presented to the emergency department with retrosternal chest pain for 3 months. POCUS revealed esophageal mass which is also proved by computer tomography and endoscopic biopsy on the same day.

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.

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.

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.

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.

An evaluation of healthcare information on the Internet: the case of colorectal cancer prevention.

Health information, provided through the Internet, has recently received attention from consumers and healthcare providers as an efficient method of motivating people to get screened for colorectal cancer (CRC). In this study, the primary purpose was to investigate the extent to which consumers were better educated about CRC screening information because of the information available on the Internet. Another purpose was to identify how better-informed consumers, with reliable and trustworthy health information, were enabled to make sound decisions regarding CRC screening. The data used in this study was taken from the 2003 Health Information National Trends Survey. People aged 55 and older were classified based on their compliance with recommended CRC screening. The study applied the PRECEDE-PROCEED model to evaluate the effects of health information taken from the Internet regarding CRC screening. The credibility and reliance of cancer related information on the Internet was significantly associated with patient compliance to be screened for CRC. Experience and knowledge of Internet use had a significant impact on the utilization of CRC screening. This analysis suggests that the design and publishing websites concerning CRC should emphasize credibility and reliance. Websites providing information about CRC must also contain the most current information so that people are able to make educated decisions about CRC screening.

Hemopexin is up-regulated in plasma from type 1 diabetes mellitus patients: Role of glucose-induced ROS.

Type 1 diabetes mellitus (T1DM) is an insulin-dependent metabolic disease in the world and often occurs in children and adolescents. Recent advances in quantitative proteomics offer potential for the discovery of plasma proteins as biomarkers for tracking disease progression and for understanding the molecular mechanisms of diabetes. Comparative proteomic analysis of the plasma proteomes from T1DM cases and healthy donors with lysine- and cysteine-labeling 2D-DIGE combining MALDI-TOF/TOF mass spectrometry revealed that 39 identified T1DM-associated plasma proteins showed significant changes in protein expression including hemopexin, and 41 in thiol reactivity. Further study showed that hemopexin can be induced in numerous cell lines by increasing the glucose concentration in the medium. Interestingly, glucose-induced hemopexin expression can be reduced by reactive oxygen species (ROS) scavengers such as glutathione, implying that hemopexin expression is linked to glucose-induced oxidative stress. In conclusion, the current work has identified potential T1DM biomarkers and one of these, hemopexin, can be modulated by glucose through a ROS-dependent mechanism.

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.

Thermodynamic and kinetic consequences of substituting glycine at different positions in a Pro-Hyp-Gly repeat collagen model peptide.

A glycine occurs at every third residue in the X-Y-Gly repeat of natural collagen. Replacing Gly residues destabilizes collagen and is often associated with many diseases. We present a comprehensive study on the thermodynamic and kinetic consequences of replacing Gly residues at different sites in collagen. For this, we prepared a series of peptides that contain a single substitution of Gly with L-Ala, D-Ala, ß-Ala, or sarcosine (Sar), at different positions in a host peptide (Pro-Hyp-Gly)(8) . Circular dichroism measurements showed that peptides with the mutation site near the C-terminus (C-terminal mutations) form a more stable collagen triple helix than those with the substitution near the N-terminus (N-terminal mutations), which is consistent with the known in vivo folding mechanism of collagen, from the C to the N-terminus. Thermodynamic analysis indicated that the destabilization in C-terminal mutations is due to entropic effects, while that in N-terminal mutations is mainly from enthalpic effects. The destabilization order is L-Ala < Sar < ß-Ala < D-Ala substitution in both the N and C-terminal mutations, suggesting that residues with normal torsion angles are less destabilizing at either position. Moreover, Sar was shown to be a better substituent than the other three amino acids at the central site of collagen strands. Kinetic studies further demonstrated that steric strains imposed by the side chains may be the most critical factor affecting the folding rate of collagen. Our data provide valuable insights into how backbone conformation, side chains, and interstrand hydrogen bonds affect the collagen triple helix at different positions.

Barriers to health care among the elderly in Japan.

Japan is undergoing a set of health care reforms aimed at cutting rising health care costs and increasing the efficiency of health care delivery. This empirical study used a large-scale community survey on 15,302 elderly people 65 years and older (56.0% women) conducted in seven municipalities in 2006, to reveal clear-cut evidence of barriers to necessary care. The reasons for not getting health care is attributed to health care cost for the elderly with lower income, while higher income counterparts reported being busy or having a condition not serious enough to seek care.

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.

The CBLB gene and Graves' disease in children.

The CBLB gene functions as a negative regulator of autoimmunity. Impairment of the Cbl-b signaling pathway may contribute to human autoimmune disease. dbSNP rs2305035 is a C/T polymorphism located in exon 10 of the CBLB gene. We report an association study of this polymorphism in children with Graves' disease. The patients were 158 unrelated children (125 girls) with Graves' disease, aged 9.8 +/- 3.3 years. The controls consisted of 237 adults without a history of autoimmune disease. The C allele and phenotype frequencies of patients and controls were 247 (78.2%) vs 356 (75.1%) (OR = 1.19, p >0.05) and 151 (95.6%) vs 221 (93.2%) (OR = 1.56, p >0.05), respectively. The allelic polymorphism in patients and controls with and without DRB1*09012 were also not significantly different. This study demonstrates that the C/T polymorphism in exon 10 of the CBLB gene is not associated with Graves' disease in children.