Long-term association between physical activity and global functioning in patients with axial spondyloarthritis: results of a two-year prospective study.

OBJECTIVES: To assess the longitudinal association between physical activity and global functioning in patients with axial spondyloarthritis (axSpA), and to identify the subtype of physical activity that is longitudinally related to global functioning. METHOD: Physical activity was measured using Global Physical Activity Questionnaire. Global functioning was assessed using the Assessment of SpondyloArthritis international Society Health Index (ASAS HI). The amount and subtype (work, transport, and recreation) of physical activity, disease activity, and ASAS HI were assessed at baseline, and at 1 and 2 year follow-up. Physical activity levels were categorized as low, moderate, or high. The longitudinal association between physical activity and ASAS HI scores was analysed using a generalized estimating equation. RESULTS: The study evaluated 160 patients. Univariate analysis identified physical activity at moderate level and higher, Ankylosing Spondylitis Disease Activity Score (ASDAS), and syndesmophyte number as being longitudinally associated with ASAS HI over 2 years. Multivariate analysis identified physical activity at moderate level and higher as being longitudinally associated with ASAS HI. Physical activity above moderate levels was associated independently with good global functioning. In the analysis stratified by radiographic axSpA and non-radiographic axSpA, a positive association between physical activity and global functioning was observed in both groups. Only recreational activity, but not work- and transport-related activity, showed an independent longitudinal relationship with the ASAS HI score. CONCLUSIONS: Physical activity at moderate level and higher was associated independently with global functioning in axSpA. Therefore, patients should maintain physical activity above moderate levels to preserve global function.

On-Demand Semiconductor Source of Entangled Photons Which Simultaneously Has High Fidelity, Efficiency, and Indistinguishability.

An outstanding goal in quantum optics and scalable photonic quantum technology is to develop a source that each time emits one and only one entangled photon pair with simultaneously high entanglement fidelity, extraction efficiency, and photon indistinguishability. By coherent two-photon excitation of a single InGaAs quantum dot coupled to a circular Bragg grating bull's-eye cavity with a broadband high Purcell factor of up to 11.3, we generate entangled photon pairs with a state fidelity of 0.90(1), pair generation rate of 0.59(1), pair extraction efficiency of 0.62(6), and photon indistinguishability of 0.90(1) simultaneously. Our work will open up many applications in high-efficiency multiphoton experiments and solid-state quantum repeaters.

Transfer printing of vertical-type microscale light-emitting diode array onto flexible substrate using biomimetic stamp.

We report the transfer printing of GaN-based microscale vertical-type light-emitting diodes (µ-VLEDs) using a functional layer and a biomimetic stamp. An oxide-based functional layer is inserted onto the structure of a µ-VLED and used to separate the chip from the µ-VLED wafer by absorbing the pulse of a UV pulse laser during pick-up of the transfer printing process. Polydimethylsiloxane (PDMS)-based biomimetic stamps have been fabricated to mimic the gecko lizard cilia for improved adhesion and repeatability. The biomimetic stamp has an adhesion force of 25.6 N/cm2, which is 12 times the adhesion of a flat stamp; an adhesion force of 10 N/cm2 or more was maintained after 100,000 repeated adhesion tests. A flexible 10 × 10 prototype array on a polyimide substrate was fabricated, and its bending test results indicated that the strain effect on the forward voltage and the output power was less than 1%. The stable bending test results of the prototype indicate that µ-VLEDs using biomimetic stamps allow the necessary stability for practical transfer printing.

Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs.

Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring's adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father's LPD treatment in both, liver and testis tissues. Our results point to a 'heritable epigenetic response' of the sons to the fathers' dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming ('metabolic shift'). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.

RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC.

RUNX3, runt-domain transcription factor, is a master regulator of gene expression in major developmental pathways. It acts as a tumor suppressor in many cancers but is oncogenic in certain tumors. We observed upregulation of RUNX3 mRNA and protein expression in nasal-type extranodal natural killer (NK)/T-cell lymphoma (NKTL) patient samples and NKTL cell lines compared to normal NK cells. RUNX3 silenced NKTL cells showed increased apoptosis and reduced cell proliferation. Potential binding sites for MYC were identified in the RUNX3 enhancer region. Chromatin immunoprecipitation-quantitative PCR revealed binding activity between MYC and RUNX3. Co-transfection of the MYC expression vector with RUNX3 enhancer reporter plasmid resulted in activation of RUNX3 enhancer indicating that MYC positively regulates RUNX3 transcription in NKTL cell lines. Treatment with a small-molecule MYC inhibitor (JQ1) caused significant downregulation of MYC and RUNX3, leading to apoptosis in NKTL cells. The growth inhibition resulting from depletion of MYC by JQ1 was rescued by ectopic MYC expression. In summary, our study identified RUNX3 overexpression in NKTL with functional oncogenic properties. We further delineate that MYC may be an important upstream driver of RUNX3 upregulation and since MYC is upregulated in NKTL, further study on the employment of MYC inhibition as a therapeutic strategy is warranted.

Antibiotic resistance and repetitive-element PCR fingerprinting in Aeromonas veronii isolates.

This study evaluated antibiotic resistance and the related genes in total 47 Aeromonas veronii isolates from pet fish, eel (Anguilla japonica) and koi (Cyprinus carpio) in Korea. In comparison with the antibiotic susceptibilities of isolates from eel and koi, those of pet fish were more resistant to ceftiofur, aminoglycosides, tetracycline and nitrofurantoin. And isolates from pet fish showed high prevalences of class 1 integron, quinolones and tetracycline resistance determinants than those from eel and koi. Repetitive-element palindromic PCR (rep-PCR) showed larger diversities among A. veronii isolates. Collectively, pet fish may be a reservoir for multiple clones of A. veronii involved in antibiotic resistance. In this aspect, imported fish in the aquaculture trade should be steadily and continually screened for bacterial antibiotic resistance and related genes.

Elevated leukocyte count is associated with periodontitis in Korean adults: the 2012-2014 KNHANES.

OBJECTIVE: Both an elevated leukocyte count and periodontitis share well-recognized associations with cardiometabolic diseases. This cross-sectional study aimed to identify whether the leukocyte count is associated with periodontitis in a nationally representative Korean adult population. MATERIALS AND METHODS: Data from 9391 participants (3659 males and 5732 females) enrolled in 2012-2014 Korean National Health and Nutrition Examination Survey were analyzed. Leukocyte quartiles were categorized as follows: 3000 ≤ Q1 ≤ 4870, 4880 ≤ Q2 ≤5790, 5800 ≤ Q3 ≤ 6840, and 6850 ≤ Q4 ≤ 10000 cells/µl. Periodontitis was defined as scoring greater than or equal to 'code 3' in at least one site according to the WHO's Community Periodontal Index. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for periodontitis in each leukocyte count quartile were calculated using multiple logistic regression analyses. RESULTS: The prevalence of periodontitis was directly correlated with increasing leukocyte quartiles: 19%, 20.4%, 24.3%, and 30.3%. Compared with the lowest leukocyte quartile group, the OR (95% CI) for periodontitis of the highest leukocyte quartile was 1.558 (1.285-1.891) after controlling for confounding factors. CONCLUSION: An elevated leukocyte count was positively associated with the presence of periodontitis.

Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells.

Cold atmospheric helium plasma jets were fabricated and utilized for plasma-cell interactions. The effect of operating parameters and jet design on the generation of specific reactive oxygen and nitrogen species (RONS) within cells and cellular response were investigated. It was found that plasma treatment induced the overproduction of RONS in various cancer cell lines selectively. The plasma under a relatively low applied voltage induced the detachment of cells, a reduction in cell viability, and apoptosis, while the plasma under higher applied voltage led to cellular necrosis in our case. To determine whether plasma-induced reactive oxygen species (ROS) generation occurs through interfering with mitochondria-related cellular response, we examined the plasma effects on ROS generation in both parental A549 cells and A549 ρ(0) cells. It was observed that cancer cells were more susceptible to plasma-induced RONS (especially nitric oxide (NO) and nitrogen dioxide (NO2(-)) radicals) than normal cells, and consequently, plasma induced apoptotic cell responses mainly in cancer cells.

Gene signature combinations improve prognostic stratification of multiple myeloma patients.

Multiple myeloma (MM) is a plasma cell neoplasm with significant molecular heterogeneity. Gene expression profiling (GEP) has contributed significantly to our understanding of the underlying biology and has led to several prognostic gene signatures. However, the best way to apply these GEP signatures in clinical practice is unclear. In this study, we investigated the integration of proven prognostic signatures for improved patient risk stratification. Three publicly available MM GEP data sets that encompass newly diagnosed as well as relapsed patients were analyzed using standardized estimation of nine prognostic MM signature indices and simulations of signature index combinations. Cox regression analysis was used to assess the performance of simulated combination indices. Taking the average of multiple GEP signature indices was a simple but highly effective way of integrating multiple GEP signatures. Furthermore, although adding more signatures in general improved performance substantially, we identified a core signature combination, EMC92+HZDCD, as the top-performing prognostic signature combination across all data sets. In this study, we provided a rationale for gene signature integration and a practical strategy to choose an optimal risk score estimation in the presence of multiple prognostic signatures.

Effect of additive oxygen gas on cellular response of lung cancer cells induced by atmospheric pressure helium plasma jet.

The atmospheric pressure helium plasma jet driven by pulsed dc voltage was utilized to treat human lung cancer cells in vitro. The properties of plasma plume were adjusted by the injection type and flow rate of additive oxygen gas in atmospheric pressure helium plasma jet. The plasma characteristics such as plume length, electric current and optical emission spectra (OES) were measured at different flow rates of additive oxygen to helium. The plasma plume length and total current decreased with an increase in the additive oxygen flow rate. The electron excitation temperature estimated by the Boltzmann plot from several excited helium emission lines increased slightly with the additive oxygen flow. The oxygen atom density in the gas phase estimated by actinometry utilizing argon was observed to increase with the additive oxygen flow. The concentration of intracellular reactive oxygen species (ROS) measured by fluorescence assay was found to be not exactly proportional to that of extracellular ROS (measured by OES), but both correlated considerably. It was also observed that the expression levels of p53 and the phospho-p53 were enhanced in the presence of additive oxygen flow compared with those from the pure helium plasma treatment.

Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia.

INTRODUCTION: The dysregulation of maternal-fetal immune tolerance is one of the proposed mechanisms leading to preeclampsia. Galectins are key regulator proteins of the immune response in vertebrates and maternal-fetal immune tolerance in eutherian mammals. Previously we found that three genes in a Chr19 cluster encoding for human placental galectin-13 (PP13), galectin-14 and galectin-16 emerged during primate evolution and may confer immune tolerance to the semi-allogeneic fetus. MATERIALS AND METHODS: This study involved various methodologies for gene and protein expression profiling, genomic DNA methylation analyses, functional assays on differentiating trophoblasts including gene silencing, luciferase reporter and methylation assays. These methods were applied on placental specimens, umbilical cord blood cells, primary trophoblasts and BeWo cells. Genomic DNA sequences were analyzed for transposable elements, transcription factor binding sites and evolutionary conservation. RESULTS AND DISCUSSION: The villous trophoblastic expression of Chr19 cluster galectin genes is developmentally regulated by DNA methylation and induced by key transcription factors of villous placental development during trophoblast fusion and differentiation. This latter mechanism arose via the co-option of binding sites for these transcription factors through promoter evolution and the insertion of an anthropoid-specific L1PREC2 transposable element into the 5' untranslated region of an ancestral gene followed by gene duplication events. Among placental Chr19 cluster galectin genes, the expression of LGALS13 and LGALS14 is down-regulated in preterm severe preeclampsia associated with SGA. We reveal that this phenomenon is partly originated from the dysregulated expression of key transcription factors controlling trophoblastic functions and galectin gene expression. In addition, the differential DNA methylation of these genes was also observed in preterm preeclampsia irrespective of SGA. CONCLUSIONS: These findings reveal the evolutionary origins of the placental expression of Chr19 cluster galectins. The complex dysregulation of these genes in preeclampsia may alter immune tolerance mechanisms at the maternal-fetal interface.

p53 haploinsufficiency and functional abnormalities in multiple myeloma.

Hemizygous deletion of 17p13, which harbors the TP53 gene, has been identified in >10% of newly diagnosed multiple myeloma (MM) patients and is associated with poor prognosis. To date, there is no conclusive evidence that TP53 is the critical gene. Furthermore, the functional effect of TP53 haploinsufficiency is not well characterized. By utilizing human myeloma cell lines, we showed that TP53 hemizygous loss was associated with decreased basal expression level with a partially or severely inactivated p53 response upon genotoxic and non-genotoxic stress. The pathway deficiency was manifested as defective p53 transcriptional activities, together with significant resistance to apoptosis. In some cases with p53 WT/- and no p53 protein expression, the remaining allele was silenced by promoter hypermethylation. We also developed a p53 target gene signature to summarize the complexity of the p53 pathway abnormalities in MM and showed that it is strongly associated with genomic complexity and patient survival. In conclusion, this study identified TP53 as the critical gene located in 17p13, and revealed its haploinsufficiency properties in MM. Furthermore, we have elucidated that multiple mechanisms can deregulate the p53 functions and that this has important prognostic impact in MM.

Metabolic syndrome is associated with increased risk of recurrent colorectal adenomas in Korean men.

OBJECTIVE: Because of the high incidence of recurrent colorectal adenomas, regular surveillance by colonoscopy is recommended. However, there is still a shortage of information on the factors that influence the incidence of recurrent colorectal adenomas in patients with a history of these lesions. The aim of this study was to determine the association between the development of recurrent colorectal adenomas, metabolic syndrome and obesity. SUBJECTS AND METHODS: The hospital-based cohort was composed of 193 patients who had recurrent colorectal adenomas removed between January 2002 and December 2003. The Cox proportional hazard model was used to determine hazard ratio (HR) and 95% confidence interval (CI) between obesity, metabolic syndrome and other factors, and the incidence of recurrent adenomatous polyps. RESULTS: The mean follow-up period was 4.8 person-years. In all, 78 of the patients (40.4%) had recurrent colorectal adenomas. In the overall recurrent adenoma group, significant associations between metabolic syndrome (HR, 1.33; 95% CI, 1.02-1.73), waist circumference (WC) ≥ 90 cm (HR, 1.42; 95% CI, 1.06-1.90) and waist-hip ratio (WHR) ≥ 0.9 (HR, 2.03; 95% CI, 1.55-2.68) were found. Moreover, advanced adenomas were significantly associated with metabolic syndrome (HR, 2.81; 95% CI, 1.86-4.25), body mass index ≥ 25 kg m(-2) (HR, 2.69; 95% CI, 1.64-4.42), WC (HR, 2.16; 95% CI, 1.31-3.54) and WHR (HR, 1.99; 95% CI, 1.28-3.11). In addition, current smoking (HR, 2.60; 95% CI, 1.09-6.25) and alcohol consumption (HR, 2.20; 95% CI, 1.10-4.39) were also significantly associated with recurrent advanced adenoma. CONCLUSION: Metabolic syndrome and obesity were significantly associated with the development of recurrent colorectal adenomas in Korean adult males. Furthermore, these associations were more strongly associated with advanced adenomas.

Enhanced biological nitrogen removal in MLE combined with post-denitrification process and EF clarifier.

A modified ludzack ettinger reactor (MLE) combined with a post-denitrification reactor (PDMLE) using electroflotation (EF) as a secondary clarifier was investigated on its feasibility and process performance. Results indicated that higher mixed liquor suspended solids (MLSS) concentrations in bioreactor (5,350 ± 352 mg L(-1)) were maintained via the highly concentrated return sludge (16,771 ± 991 mg L(-1)) from the EF clarifier and the effluent suspended solids (SS) concentrations continued relatively low, representing effluent SS concentration of 1.71 ± 1.16 mg L(-1), compared with GS-A2O process during the operation of four months. The denitrification was improved by combining MLE process with post-denitrification based on endogenous decay (i.e. no additional carbon source was added), resulting in the removal efficiencies of TN were about 91 and 59% for the influent C/N ratio of 10 and 5, respectively, revealing relatively high nitrogen removal as compared with EF-A2O and gravity settling (GS)-A2O processes as a control. The nitrogen balance analysis indicates that pre-denitrification and post-denitrification contributed to 78 and 22% of TN removed, respectively.

Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma.

Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are unknown. We analyzed gene expression data sets generated on the Affymetrix U133 platform from 22 MGUS and 101 MM patients using gene-set enrichment analysis. Genes overexpressed in MM were enriched for cell cycle, proliferation and MYC activation gene sets. Upon dissecting the relationship between MYC and cell-cycle gene sets, we identified and validated an MYC activation signature dissociated from proliferation. Applying this signature, MYC is activated in 67% of myeloma, but not in MGUS. This was further confirmed by immunohistochemistry (IHC) using membrane CD138 and nuclear MYC double staining. We also showed that almost all tumors with RAS mutations expressed the MYC activation signature, and multiple mechanisms may be involved in activating MYC. MYC activation, whether assessed by gene-expression signature or IHC, is associated with hyperdiploid MM and shorter survival even in tumors that are not proliferative. Bortezomib treatment is able to overcome the survival disadvantage in patients with MYC activation.

A validation study of the Chinese wearing off questionnaire 9-symptom for Parkinson's disease.

OBJECTIVE: Development of wearing off (WO) often goes unnoticed for both patients with Parkinson's disease (PD) and physicians due to the complexity of this phenomenon. A brief 9-symptom WO questionnaire (WOQ-9) was recently found to be highly sensitive in its detection. We aimed to validate a Chinese version WOQ-9 (CWOQ-9) among Chinese patients with PD. METHODS: We recruited 101 literate Chinese PD patients among 4 different neurology or movement disorders clinics in Hong Kong to participate in this study by completing the CWOQ-9. Clinical judgment by the specialists was considered the gold standard for diagnosing WO. RESULTS: The mean age (±SD) of the patients was 61 (±9) years and 35 (34.7%) of them were female. The disease duration was 7.4 (±5.4) years and 69 (68.3%) of them were diagnosed clinically to have WO by the specialists. The positive and negative predictive values, sensitivity and specificity of CWOQ-9 were 86%, 71%, 87%, and 69% respectively. The area under curve (AUC) was 0.78 (p<0.001). CONCLUSION: This simple patient questionnaire is a valid tool for the detection of WO among Chinese PD patients.

Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma.

In this study, we correlated array-comparative genomic hybridization-defined abnormalities with survival in two different cohorts of patients treated with therapy based on high-dose melphalan with autologous stem-cell transplantation (64 from the Mayo Clinic and 67 from the University of Arkansas Medical School) and identified that several regions of genomic gains and losses were significantly associated with poorer survival. Three noncontiguous survival relevant regions covering 1p31-33 and two noncontiguous regions covering 20p12.3-12.1 were common between the two datasets. The prognostic relevance of these hotspots was validated in an independent cohort using fluorescent in situ hybridization, which showed that 1p31-32 loss is significantly associated with shorter survival (24.5 months versus 40 months, log-rank P-value=0.01), whereas 20p12 loss has a trend toward shorter survival (26.3 months versus 40 months, log-rank P-value=0.06). On multivariate analysis, 1p31-32 loss is an independent prognostic factor. On further analysis, the prognostic impact of 1p31-32 loss is due to shortening of post-relapse survival as there is no impact on complete response rates and progression-free survival.

A rapid molecular method for diagnosing epidemic dermatophytosis in a racehorse facility.

REASONS FOR PERFORMING STUDY: Identification of the species and strain of dermatophyte can play an effective role in control of disease outbreaks by establishing the source of infection. Current methods of identification are based on cultural and microscopic methods, often involving weeks before a positive identification are made. A rapid molecular diagnostic method would therefore be an important laboratory technique, but requires confirmation in equine clinical practice. OBJECTIVES: To test the sensitivity and specificity of molecular diagnostic methods applied to a racehorse herd from the Korean Racehorse Authority (KRA). METHODS: A total of 57 DNA samples were collected from hairs and crusts of skin lesions in KRA racehorses with histories and clinical signs suggestive of dermatophytosis, which was confirmed by dermatophyte-specific PCR amplification analysis using the primer pair for the chitin synthase 1 (CHS1) gene. RESULTS: Thirty-eight racehorses were definitively diagnosed with dermatophytosis using molecular and traditional diagnostic methods. PCR fingerprinting profiles using simple repetitive (GACA)4 primers showed that all diagnosed horses had the same pattern profile. Oligonucleotide sequencing of CHS1 gene PCR products confirmed Trichophyton mentagrophytes as the infectious agent. CONCLUSIONS: This study demonstrates that the PCR-based molecular diagnostic method is sensitive and specific and offers fast precise diagnosis of dermatophytosis in horses.

Topical tacrolimus (FK506) for the treatment of feline idiopathic facial dermatitis.

A 3-year-old, neutered male Persian cat with chronic ulcerative facial dermatitis was diagnosed with feline idiopathic facial dermatitis based on signalment, clinical history and diagnostic test results, including dermatohistopathological evaluation. Initial treatment started with 4 weeks of oral antifungal/antibiotic medication for severe secondary infectious dermatitis of Malassezia and bacteria. As the lesions gradually improved, the oral medication was withdrawn, leaving only 0.1% topical FK506 (tacrolimus) ointment for the remaining lesions. Topical treatment was administered just in case any new lesions developed. The patient has been managed effectively with topical tacrolimus and no side-effects were observed during treatment. Feline idiopathic facial dermatitis is known as a difficult dermatosis to manage successfully, but our experience suggests that it may respond to topical tacrolimus.

Three point method to characterize low-pressure electronegative discharges using electrostatic probe.

Electrostatic probe measurements for low-pressure inductively coupled SF(6) plasmas are performed. From the current-voltage (I-V) curves of probe, the saturation currents of the positive ions and electrons and the electron temperature are measured. The electronegativity and the negative ion density are deduced by using the ratios of these parameters at three adjacent pressure points. The positive ion density is calculated by the orbital-motion-limited theory, and the electron temperatures are given either by the slope of the I-V curves or by the electron energy distribution function with the second derivative of I-V curves. The variations in the charged species density with pressure and power are investigated.