Proinflammatory Features of Stem Cell-like Memory T Cells from Human Patients with Rheumatoid Arthritis.

Stem cell-like memory T (Tscm) cells are a subset of memory T cells that have characteristics of stem cells. The characteristics of Tscm cells in patients with rheumatoid arthritis (RA) are not well known. The percentage of CD4+ and CD8+ Tscm cells in PBMCs and synovial fluid mononuclear cells was measured. After confirming the stem cell nature of Tscm cells, we examined their pathogenicity in RA patients and healthy controls (HCs) by assessing T cell activation markers and cytokine secretion after stimulation with anti-CD3/CD28 beads and/or IL-6. Finally, RNA transcriptome patterns in Tscm cells from RA patients were compared with those in HCs. In this study, the percentage of CD4+ and CD8+ Tscm cells in total T cells was significantly higher in RA patients than in HCs. Tscm cells self-proliferated and differentiated into memory and effector T cell subsets when stimulated. Compared with Tscm cells from HCs, Tscm cells from RA patients were more easily activated by anti-CD3/CD28 beads augmented by IL-6. Transcriptome analyses revealed that Tscm cells from RA patients showed a pattern distinct from those in HCs; RA-specific transcriptome patterns were not completely resolved in RA patients in complete clinical remission. In conclusion, Tscm cells from RA patients show a transcriptionally distinct pattern and are easily activated to produce inflammatory cytokines when stimulated by TCRs in the presence of IL-6. Tscm cells can be a continuous source of pathogenicity in RA.

Effects of winter indoor environment on the skin: Unveiling skin condition changes in Korea.

BACKGROUND: In Korea, winter can cause skin dryness due to low relative humidity (RH); moreover, indoor heating devices promote moisture loss and air pollution. If dryness persists, dead skin cells accumulate, leading to skin problems; therefore, careful skin care is required. This study aimed to compare changes in skin conditions when exposed to an indoor environment for a short period of 6 h in winter, and to suggest proper winter skin care practices. METHODS: A randomized, split-face clinical study was conducted in which healthy female participants with normal skin were exposed to an indoor environment with a heater turned on for a short period at least 6 h per day in the winter season, and cream was applied to one side of the face. Skin temperature, hydration, sebum, transepidermal water loss (TEWL), elasticity, texture, pores, redness, and wrinkles were measured at the treated and nontreated sites. RESULTS: After 6 h of exposure, skin temperature, pores, roughness, redness, and wrinkles significantly increased (p < 0.05) on the face, whereas TEWL significantly increased on the forearm (p < 0.05). However, sebum secretion appeared to function as a barrier to maintain homeostasis in the facial skin. Elasticity, pores, texture, and wrinkles in the cream-treated ceramide site improved compared to those in the nontreated site (p < 0.05). The moisture content was also significantly higher in the forearm (p < 0.05). CONCLUSION: Changes in skin parameters of participants with healthy skin were observed even after short-term exposure to an indoor environment in winter. Creams containing ceramide maintain skin homeostasis and protect the skin barrier; therefore, it is recommended to use such creams to prevent skin damage and maintain healthy skin, particularly during prolonged exposure to indoor environments during winter.

Cardiovascular risk associated with allopurinol vs. benzbromarone in patients with gout.

AIMS: With the high prevalence of gout and associated cardiovascular (CV) diseases, information on the comparative CV safety of individual urate-lowering drugs becomes increasingly important. However, few studies examined the CV risk of uricosuric agents. We compared CV risk among patients with gout who initiated allopurinol vs. benzbromarone. METHODS AND RESULTS: Using the Korean National Health Insurance claims data (2002-17), we conducted a cohort study of 124 434 gout patients who initiated either allopurinol (n = 103 695) or benzbromarone (n = 20 739), matched on propensity score at a 5:1 ratio. The primary outcome was a composite CV endpoint of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. To account for competing risk of death, we used cause-specific hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes comparing allopurinol initiators with benzbromarone. Over a mean follow-up of 1.16 years, 2258 patients developed a composite CV event. The incidence rate of the composite CV event was higher in allopurinol initiators (1.81 per 100 person-years) than benzbromarone (1.61 per 100 person-years) with a HR of 1.22 (95% CI 1.05-1.41). The HR for all-cause mortality was 1.66 (95% CI 1.43-1.93) among allopurinol initiators compared with benzbromarone. CONCLUSION: In this large population-based cohort of gout patients, allopurinol was associated with an increased risk of composite CV events and all-cause mortality compared to benzbromarone. Benzbromarone may reduce CV risk and mortality in patients with gout, although more studies are necessary to confirm our findings and to advance our understanding of the underlying mechanisms.

Goal-directed interaction of stimulus and task demand in the parahippocampal region.

The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The "dual-stream model" was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual-stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal-directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal-directed Interaction of Stimulus and Task-demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices-the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects-with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non-navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non-navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.

Nanoparticle-Mediated Blocking of Excessive Inflammation for Prevention of Heart Failure Following Myocardial Infarction.

Severe cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post-MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time-consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L-Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen-specific regulatory T cells (Tregs). Impressively, intradermal injection of L-Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory-to-reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle-mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post-MI heart failure.

Baseline disease activity influences subsequent achievement of patient acceptable symptom state in Sjögren's syndrome.

OBJECTIVES: To investigate longitudinal changes of the EULAR SS Patient-Reported Index (ESSPRI) and EULAR SS Disease Activity Index (ESSDAI), and identify factors associated with patient acceptable symptom state (PASS) in patients with primary SS (pSS). METHODS: We assessed ESSPRI, ESSDAI, clinical ESSDAI (ClinESSDAI), EULAR Sicca Score, EuroQoL 5-dimension (EQ-5D), Fatigue Severity Score, Beck Depression Inventory, and patient global assessment (PGA) for pSS, and visual analogue scale (VAS) scores for glandular and extra-glandular symptoms at baseline and follow-up. The responses to the currently available standards of care were evaluated by the PASS, the minimal clinically important improvement (MCII) of ESSPRI and ESSDAI, and a modified SS Responder Index-30 (mSSRI-30) response. RESULTS: Among 115 patients enrolled, 102 (88.7%) completed a median 3-year follow-up. The ESSPRI, ClinESSDAI and EQ-5D levels remained stable, although the PGA and ESSDAI significantly improved (both P <0.05). Of the 102 patients, 52 (51.0%) patients achieved the PASS at the follow-up and tended to attain the ESSPRI-MCII and mSSRI-30 (both P < 0.001) more frequently than the non-PASS group. Multivariate analysis revealed that the PASS was significantly associated with baseline ESSPRI negatively [odds ratio (OR) 0.609] and ESSDAI positively (OR 1.224). When categorized using baseline ESSPRI and ESSDAI, a subgroup of low ESSPRI and high ESSDAI reached a PASS achievement rate of 79.3%. CONCLUSION: Although longitudinal changes in ESSPRI and ClinESSDAI are stable in pSS, baseline ESSPRI and ESSDAI could provide prognostic information on the subsequent achievement of PASS, using currently available treatments. A categorization model using ESSPRI and ESSDAI may have clinical implications.

Tocilizumab-induced anaphylaxis in patients with adult-onset Still's disease and systemic juvenile idiopathic arthritis: a case-based review.

The benefits afforded by tocilizumab (TCZ) in patients with adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) have been described in previous studies. However, few reports have evaluated severe hypersensitivity reactions (HSRs) to TCZ in patients with AOSD or SJIA. We describe three instances of TCZ-induced anaphylactic reactions in AOSD/SJIA patients, and review relevant prior reports on patients with various rheumatic diseases. Two of our cases exhibited shock and cardiovascular collapse; TCZ was discontinued in all three cases. All events occurred within 20 min of TCZ infusion, after at least three prior infusions, indicating an IgE-mediated mechanism and previous sensitization to TCZ. In all three cases, mild HSRs had been observed about 1 month before the anaphylactic events, but pre-medication with antihistamines and corticosteroids failed to prevent anaphylaxis. All three cases had active AOSD or SJIA disease, and were refractory to other immunosuppressive agents. It is essential to be aware that severe anaphylaxis to TCZ can develop in patients with active refractory AOSD or SJIA, and to be cautious when medicating certain patients. Anaphylaxis is a serious condition that can be fatal; TCZ infusion should not be re-challenged via pre-medication in patients who exhibited mild HSRs before TCZ without desensitization.

Diffuse large B-cell lymphoma involving the left sternoclavicular joint mimicking rheumatoid arthritis flare: a case-based review.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting primarily joints and an increased risk of developing malignant lymphomas in RA has been well reported. However, primary lymphoma in a joint in RA patient is rare. We report the case of a 65-year-old man with RA suffering from pain and swelling of left sternoclavicular (SC) joint, which was not relieved by adding low-dose glucocorticoid. Magnetic resonance imaging (MRI) showed a para-osseous soft tissue swelling around the SC joint and a fracture of proximal clavicle. Histology of the soft tissue demonstrated diffuse large B-cell lymphoma and the patient subsequently underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. He was successfully treated with six cycles of R-CHOP chemotherapy, with discontinuation of MTX, resulting in a complete response. We performed a literature review and identified nine cases of lymphoma which involved joints in patients with rheumatoid arthritis. This is the first described case of a primary large B-cell lymphoma involving the unilateral SC joint in a patient with RA, which was initially confused with aggravation of RA. Therefore, malignant lymphoma should be considered in the differential diagnosis when a RA patient develops monoarthritis with spontaneous fracture, even without B symptoms.

Practical Utility of D-dimer Test for Venous Thromboembolism in Systemic Lupus Erythematosus Depends on Disease Activity: a Retrospective Cohort Study.

BACKGROUND: The D-dimer test is a screening tool for venous thromboembolism (VTE); however, its utility for patients with systemic lupus erythematosus (SLE) remains unclear. Here, we examined the utility of the D-dimer test as a screening tool for VTE in SLE patients. METHODS: SLE patients (n = 276) and age- and sex-matched patients with non-rheumatic disease (n = 1,104), all of whom underwent D-dimer testing to screen for VTE, were enrolled. The sensitivity and specificity and receiver operating characteristics curve of the D-dimer test were compared in both groups. Then, subgroup of SLE patients in whom the D-dimer test can be useful was sought. RESULTS: The incidence of VTE was more common in SLE patients than controls (10.9% vs. 4.0%). Although the sensitivity of the D-dimer test was comparable between SLE patients and controls (93.3% vs. 90.9%), the specificity of the test was profoundly lower in SLE patients compared to controls (28.4% vs. 84.4%). The area under the curve (AUC) of the D-dimer for VTE was 0.669 in SLE patients and 0.90 in control group. Multiple linear regression analysis demonstrated that SLE disease activity index-2000 (SLEDAI-2K) was significantly associated with D-dimer levels in SLE patients (ß = 0.155; P = 0.022). Subgroup analysis showed that the AUC is moderate (0.768) with low disease activity, while it is low (0.518) with high SLEDAI-2K. CONCLUSION: The D-dimer test may not be a useful screening tool for VTE in patients with active SLE. D-dimer test for predicting VTE in SLE patients should be differentially applied according to disease activity of SLE.

Improved in vitro antioxidant properties and hepatoprotective effects of a fermented Inula britannica extract on ethanol-damaged HepG2 cells.

This study aimed to improve antioxidant effect and hepatoprotective effect of Inula britannica using fermentation. Epigallocatechin gallate (EGCG) in an I. britannica extract was found to be upregulated from 2.06 to 10.28 µg/mg during fermentation (p < 0.001). After fermentation, DPPH radical-scavenging ABTS radical-scavenging, and superoxide anion-scavenging abilities increased to 92.65%, 694.25 µM Trolox/mL, and 86.38%, respectively, at 500 µg/mL (p < 0.05). Cupric-ion-reducing capacity with formation of the Cu+-neocuproine complex increased by 5.88%, 6.38%, 3.24%, and 8.55% at 62.5 to 500 µg/mL. Ferric-ion-reducing capacity of the fermented extract increased by 20%, 7.16%, 3.85%, and 5.45% at each concentration (p < 0.05). Unfermented extracts yielded cell viability of 91.42%, 90.59%, 88.38%, and 79.17%, whereas the fermented extract yielded 100.28%, 99.66%, 96.15%, and 89.90%, respectively, at each concentration in ethanol-damaged HepG2 cells (p < 0.05). Additionally, the fermented extract decreased alanine transaminase activity from 117.2 to 61.7 U/mL in the ethanol-damaged HepG2 cell line (p < 0.01). Overall, both antioxidant and hepatoprotective effect increased by fermentation in I. britannica extract. These properties are expected to lead to new antioxidant agents via production of EGCG by fermentation.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

BACKGROUND: Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. METHODS: We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. RESULTS: In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. CONCLUSIONS: This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low dose of glucocorticoids: a prospective single-arm study.

To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients with active Takayasu arteritis (TAK). In this single-center open-label trial, patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week 54. From week 14 to week 46, patients with inadequate response received increased dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed ≤ 10 mg/day. The primary efficacy end point was the achievement of partial or complete remission at week 30. All patients underwent positron emission tomography-computed tomography (PET-CT) at baseline and week 30. Twelve patients with TAK received CT-P13; one patient with protocol violation was excluded from analysis. Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0 mg/day. At week 30, three (27.3%) patients achieved complete remission and six (54.5%) patients achieved partial remission. Statistically significant improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS-A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were seen at week 30 from baseline. PET parameters were significantly reduced from baseline to week 30, including maximum standardized uptake value, target-to-vein ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no serious adverse events. Treatment with CT-P13 may lead to improvement in clinical, radiographic, and serological activities with lower glucocorticoid requirement in TAK.Trial registration number NCT02457585.

Experience-Dependent Regulation of Dentate Gyrus Excitability by Adult-Born Granule Cells.

Behavioral studies have established a role for adult-born dentate granule cells in discriminating between similar memories. However, it is unclear how these cells mediate memory discrimination. Excitability is enhanced in maturing adult-born neurons, spurring the hypothesis that the activity of these cells "directly" encodes and stores memories. An alternative hypothesis posits that maturing neurons "indirectly" contribute to memory encoding by regulating excitation-inhibition balance. We evaluated these alternatives by using dentate-sensitive active place avoidance tasks to assess experience-dependent changes in dentate field potentials in the presence and absence of neurogenesis. Before training, X-ray ablation of adult neurogenesis-reduced dentate responses to perforant-path stimulation and shifted EPSP-spike coupling leftward. These differences were unchanged after place avoidance training with the shock zone in the initial location, which both groups learned to avoid equally well. In contrast, sham-treated mice decreased dentate responses and shifted EPSP-spike coupling leftward after the shock zone was relocated, whereas X-irradiated mice failed to show these changes in dentate function and were impaired on this test of memory discrimination. During place avoidance, excitation-inhibition coupled neural synchrony in dentate local field potentials was reduced in X-irradiated mice, especially in the θ band. The difference was most prominent during conflict learning, which is impaired in the X-irradiated mice. These findings indicate that maturing adult-born neurons regulate both functional network plasticity in response to memory discrimination and dentate excitation-inhibition coordination. The most parsimonious interpretation of these results is that adult neurogenesis indirectly regulates hippocampal information processing. SIGNIFICANCE STATEMENT: Adult-born neurons in the hippocampal dentate gyrus are important for flexibly using memories, but the mechanism is controversial. Using tests of hippocampus-dependent place avoidance learning and dentate electrophysiology in mice with normal or ablated neurogenesis, we find that maturing adult-born neurons are crucial only when memory must be used flexibly, and that these neurons regulate dentate gyrus synaptic and spiking responses to neocortical input rather than directly storing information, as has been proposed. A day after learning to avoid the initial or changed locations of shock, the dentate synaptic responses are enhanced or suppressed, respectively, unlike mice lacking adult neurogenesis, which did not change. The contribution of adult neurogenesis to memory is indirect, by regulating dentate excitation-inhibition coupling.

Sector-Based Assessment of Infarct Size on Late-Gadolinium-Enhancement MRI in a Mouse Model of Acute Myocardial Infarction.

Scoring of myocardial infarction (MI) disease extent in cardiac magnetic resonance (CMR) images has been generally presented in terms of area-based infarct size. However, gradual thinning of the infarcted wall and compensatory hypertrophy of the noninfarcted remote wall during left ventricular (LV) remodeling after MI complicate the accuracy of infarct size measurement. In this study, we measured and compared infarct sizes in mice on late gadolinium enhancement (LGE) images using area-, length-, and radial sector-based methods.MI was induced by permanent ligation of the left coronary artery (n = 6). LGE images were acquired 30 minutes after intravenous injection of Gd-DTPA-BMA. Percentages of infarct size (%Area, %Length, and %Sector) on the LGE images were calculated and compared with histological findings.Infarct sizes obtained by an area-based approach were smaller than those obtained by other measurements. The area-based approach underestimated infarct size compared with the length-based approach. Most infarct sizes measured by each method demonstrated a similar trend, with maximum values determined by sector-based measurements using a mean + SD threshold. Spearman's rank correlation coefficients indicated that the 3 measurements were strongly correlated (P < 0.05) to each other. Significant differences and trends were observed between sector-based infarct sizes with different thresholds when 16 or more sectors were used.In conclusion, our study demonstrated that methods used for the histological calculation of infarct size could be applied to CMR analysis. Moreover, our results showed a similar trend to histological assessment. Sector-based CMR approaches can be useful for infarct size measurement.

Crystal structure analysis of a bacterial aryl acylamidase belonging to the amidase signature enzyme family.

The atomic structure of a bacterial aryl acylamidase (EC 3.5.1.13; AAA) is reported and structural features are investigated to better understand the catalytic profile of this enzyme. Structures of AAA were determined in its native form and in complex with the analgesic acetanilide, p-acetaminophenol, at 1.70 Å and 1.73 Å resolutions, respectively. The overall structural fold of AAA was identified as an α/ß fold class, exhibiting an open twisted ß-sheet core surrounded by α-helices. The asymmetric unit contains one AAA molecule and the monomeric form is functionally active. The core structure enclosing the signature sequence region, including the canonical Ser-cisSer-Lys catalytic triad, is conserved in all members of the Amidase Signature enzyme family. The structure of AAA in a complex with its ligand reveals a unique organization in the substrate-binding pocket. The binding pocket consists of two loops (loop1 and loop2) in the amidase signature sequence and one helix (α10) in the non-amidase signature sequence. We identified two residues (Tyr(136) and Thr(330)) that interact with the ligand via water molecules, and a hydrogen-bonding network that explains the catalytic affinity over various aryl acyl compounds. The optimum activity of AAA at pH > 10 suggests that the reaction mechanism employs Lys(84) as the catalytic base to polarize the Ser(187) nucleophile in the catalytic triad.

Greater virulence of highly pathogenic H5N1 influenza virus in cats than in dogs.

Highly pathogenic H5N1 influenza virus continues to infect animals and humans. We compared the infectivity and pathogenesis of H5N1 virus in domestic cats and dogs to find out which animal is more susceptible to H5N1 influenza virus. When cats and dogs were infected with the H5N1 virus, cats suffered from severe outcomes including death, whereas dogs did not show any mortality. Viruses were shed in the nose and rectum of cats and in the nose of dogs. Viruses were detected in brain, lung, kidney, intestine, liver, and serum in the infected cats, but only in the lung in the infected dogs. Genes encoding inflammatory cytokines and chemokines, Toll-like receptors, and apoptotic factors were more highly expressed in the lungs of cats than in those of dogs. Our results suggest that the intensive monitoring of dogs is necessary to prevent human infection by H5N1 influenza virus, since infected dogs may not show clear clinical signs, in contrast to infected cats.

A novel strain of porcine epidemic diarrhea virus in Vietnamese pigs.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and dehydration in suckling pigs and has caused high rates of death among piglets and substantial economic loss in Vietnam since 2009. To investigate the genotypes of prevailing PEDVs, intestinal and fecal samples from piglets from central and northern Vietnam were collected and analyzed. Phylogenetic analysis of the nucleotide sequences of complete spike genes of PEDVs from Vietnam resulted in the identification of two divergent groups. PEDVs (HUA-PED45 and HUA-PED47) belonged to the G2b group, along with Chinese, US, and Korean strains occurring at the end of 2010, in May 2013 and in November 2013, respectively. Six strains from the Quang Tri region were assigned to the G1b group, along with Chinese and US strains. The Vietnamese PEDVs detected in infected piglets had a nationwide distribution and belonged to the G2b and G1b genotypes.

Influence of message error type on Korean adults' attitudes toward an individual who uses augmentative and alternative communication.

The aim of this study was to investigate the influence of types of message errors on the attitudes of Korean adults toward a person who uses AAC. The attitudes of 72 adults who speak native Korean were examined through attitude questionnaires completed after viewing videotaped conversations between a boy with cerebral palsy and an adult without disabilities. Each interaction video involved a message with one of six error types, including various types of syntactic, semantic, and pragmatic errors. The participants provided information on their attitude towards the person who used AAC, and ranked their preferences among the six messages. The results provide evidence that attitudes towards the individual using AAC were most positive (in comparison with other conditions) when a pragmatic error was observed. Messages containing a syntactic error were ranked most favorably. Spearman's correlation analyses revealed some relationship between attitudes rating and preferences ranking. Our results provide evidence that specific language and cultural contexts may play an important role in shaping attitudes toward those who use AAC.

A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis.

Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/ß-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of ß-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31(+) vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.