The human genome encodes several hundred microRNA (miRNA) genes that produce small (21–23n) single strand regulatory RNA molecules. Although abnormal expression of miRNAs has been linked to cancer ...progression, the mechanisms of this dysregulation are poorly understood. Malignant mesothelioma (MM) of pleura is an aggressive and highly lethal cancer resistant to conventional therapies. We and others previously linked loss of the 9p21.3 chromosome in MM with short time to tumor recurrence. In this study, we report that MM cell lines derived from patients with more aggressive disease fail to express miR-31, a microRNA recently linked with suppression of breast cancer metastases. We further demonstrate that this loss is due to homozygous deletion of the miR-31-encoding gene that resides in 9p21.3. Functional assessment of miR-31 activity revealed its ability to inhibit proliferation, migration, invasion, and clonogenicity of MM cells. Re-introduction of miR-31 suppressed the cell cycle and inhibited expression of multiple factors involved in cooperative maintenance of DNA replication and cell cycle progression, including pro-survival phosphatase PPP6C, which was previously associated with chemotherapy and radiation therapy resistance, and maintenance of chromosomal stability. PPP6C, whose mRNA is distinguished with three miR-31-binding sites in its 3′-untranslated region, was consistently down-regulated by miR-31 introduction and up-regulated in clinical MM specimens as compared with matched normal tissues. Taken together, our data suggest that tumor-suppressive propensity of miR-31 can be used for development of new therapies against mesothelioma and other cancers that show loss of the 9p21.3 chromosome.
Summary
Background
Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood.
Objective
To compare workplace productivity—absenteeism and ...presenteeism—and impairment in daily activities in severe and non‐severe asthma over time and identify characteristics associated with presenteeism in severe asthma.
Methods
The Severe Asthma Web‐based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non‐severe asthma were enrolled (18‐88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed‐up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self‐reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated.
Results
At baseline, 61.4% of participants with severe asthma and 66.2% with non‐severe asthma under 65 years were employed. At younger ages (30‐50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past‐year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non‐severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma‐related quality of life and symptoms of depression or anxiety (P < .01).
Conclusion and clinical relevance
Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.
To evaluate the occurrence, management, and clinical significance of increases in intraocular pressure (IOP) in patients with diabetic macular edema treated with dexamethasone intravitreal implant ...(DEX implant).
Randomized, multicenter, 3-year, Phase III study. Patients (N = 1,048) with diabetic macular edema were randomized to DEX implant 0.7-mg, DEX implant 0.35-mg, or sham procedure with retreatment allowed at ≥6-month intervals (seven injections maximum).
In the DEX implant 0.7-mg, DEX implant 0.35-mg, and sham groups, respectively, ≥10-mmHg IOP increases from baseline occurred in 27.7%, 24.8%, and 3.7% of patients, and their frequency did not increase with repeat injections. IOP-lowering medication was used by 41.5%, 37.6%, and 9.1% of patients. Only one patient (0.3%) in each DEX implant group had filtering surgery to manage a steroid-induced IOP increase. Among DEX implant 0.7-mg-treated patients with and without a ≥10-mmHg IOP increase, 21.9% (21 of 96) and 22.4% (57 of 255), respectively, achieved ≥15-letter best-corrected visual acuity gain at the end of the study, and mean average change in central retinal thickness from baseline was -127 μm and -106 μm, respectively.
DEX implant demonstrated clear benefit of treatment despite increases in IOP. Sequential implants had no cumulative effect on IOP.
Variation in both inter‐ and intraspecific traits affects community dynamics, yet we know little regarding the relative importance of external environmental filters versus internal biotic ...interactions that shape the functional space of communities along broad‐scale environmental gradients, such as latitude, elevation, or depth. We examined changes in several key aspects of functional alpha diversity for marine fishes along depth and latitude gradients by quantifying intra‐ and interspecific richness, dispersion, and regularity in functional trait space. We derived eight functional traits related to food acquisition and locomotion and calculated seven complementary indices of functional diversity for 144 species of marine ray‐finned fishes along large‐scale depth (50–1200 m) and latitudinal gradients (29°–51° S) in New Zealand waters. Traits were derived from morphological measurements taken directly from footage obtained using Baited Remote Underwater Stereo‐Video systems and museum specimens. We partitioned functional variation into intra‐ and interspecific components for the first time using a PERMANOVA approach. We also implemented two tree‐based diversity metrics in a functional distance‐based context for the first time: namely, the variance in pairwise functional distance and the variance in nearest neighbor distance. Functional alpha diversity increased with increasing depth and decreased with increasing latitude. More specifically, the dispersion and mean nearest neighbor distances among species in trait space and intraspecific trait variability all increased with depth, whereas functional hypervolume (richness) was stable across depth. In contrast, functional hypervolume, dispersion, and regularity indices all decreased with increasing latitude; however, intraspecific trait variation increased with latitude, suggesting that intraspecific trait variability becomes increasingly important at higher latitudes. These results suggest that competition within and among species are key processes shaping functional multidimensional space for fishes in the deep sea. Increasing morphological dissimilarity with increasing depth may facilitate niche partitioning to promote coexistence, whereas abiotic filtering may be the dominant process structuring communities with increasing latitude.
We quantified in situ inter‐specific and intra‐specific variation for deep‐sea fishes, providing novel methodology to partition community‐level trait variation into within and among species components in a multi‐trait context. Increasing morphological dissimilarity with depth may facilitate niche partitioning, promoting coexistence, whereas abiotic filtering may be the dominant process structuring communities across latitude.
Summary
A country-specific FRAX model has been developed for the Ukraine to replace the Austrian model hitherto used. Comparison of the Austrian and Ukrainian models indicated that the former ...markedly overestimated fracture probability whilst correctly stratifying risk.
Introduction
FRAX has been used to estimate osteoporotic fracture risk since 2009. Rather than using a surrogate model, the Austrian version of FRAX was adopted for clinical practice. Since then, data have become available on hip fracture incidence in the Ukraine.
Methods
The incidence of hip fracture was computed from three regional estimates and used to construct a country-specific FRAX model for the Ukraine. The model characteristics were compared with those of the Austrian FRAX model, previously used in Ukraine by using all combinations of six risk factors and eight values of BMD (total number of combinations =512).
Results
The relationship between the probabilities of a major fracture derived from the two versions of FRAX indicated a close correlation between the two estimates (
r
> 0.95). The Ukrainian version, however, gave markedly lower probabilities than the Austrian model at all ages. For a major osteoporotic fracture, the median probability was lower by 25% at age 50 years and the difference increased with age. At the age of 60, 70 and 80 years, the median value was lower by 30, 53 and 65%, respectively. Similar findings were observed for men and for hip fracture.
Conclusion
The Ukrainian FRAX model should enhance accuracy of determining fracture probability among the Ukrainian population and help to guide decisions about treatment. The study also indicates that the use of surrogate FRAX models or models from other countries, whilst correctly stratifying risk, may markedly over or underestimate the absolute fracture probability.
Abstract
We present a new broad-band radio frequency catalogue across 0.12 GHz ≤ ν ≤ 20 GHz created by combining data from the Murchison Widefield Array Commissioning Survey, the Australia Telescope ...20 GHz survey, and the literature. Our catalogue consists of 1285 sources limited by S20 GHz > 40 mJy at 5σ, and contains flux density measurements (or estimates) and uncertainties at 0.074, 0.080, 0.119, 0.150, 0.180, 0.408, 0.843, 1.4, 4.8, 8.6, and 20 GHz. We fit a second-order polynomial in log–log space to the spectral energy distributions of all these sources in order to characterize their broad-band emission. For the 994 sources that are well described by a linear or quadratic model we present a new diagnostic plot arranging sources by the linear and curvature terms. We demonstrate the advantages of such a plot over the traditional radio colour–colour diagram. We also present astrophysical descriptions of the sources found in each segment of this new parameter space and discuss the utility of these plots in the upcoming era of large area, deep, broad-band radio surveys.
Objectives Escherichia coli producing CTX-M-15 enzyme began to rapidly spread in the UK from around 2003 but other types also occur, notably CTX-M-14. We examined breasts from UK-reared (n = 62) and ...imported (n = 27) chickens as potential sources of quinolone-resistant E. coli with blaCTX-M genes. A further 40 samples for which the country of rearing could not be identified were examined. Methods During 2006, 129 fresh and frozen chicken breast fillets were purchased from retail outlets in the West Midlands. These were cultured for E. coli on CLED agar containing 8 mg/L ciprofloxacin and carrying a 10 µg cefpodoxime disc. Resistant isolates were identified and typed by RAPD fingerprinting; blaCTX-M was identified by PCR and genotyped by reverse-line hybridization. Results The country of rearing was identified from the packaging for 89 of 129 purchased samples. Only one of the 62 UK-reared chicken samples carried E. coli producing a CTX-M-1 enzyme, whereas 10 of 27 samples reared overseas had E. coli with CTX-M enzymes. Specifically, 4/10 Brazilian, 3/4 Brazilian/Polish/French, and 2/2 Dutch samples had E. coli with CTX-M-2 enzymes. Six of 40 samples for which the country of rearing was not known had producers of CTX-M enzymes, 5 of them with CTX-M-14. Conclusions Quinolone-resistant E. coli with various CTX-M β-lactamase genes that are common in human infections worldwide were found in imported chicken breasts, indicating a possible source for gut colonization. Samples from Brazil were commonly positive for E. coli with CTX-M-2, the dominant blaCTX-M genotype from human infections in South America, which is currently rare in clinical infections in the UK. CTX-M-15, the dominant CTX-M type in human infections in the UK, was not found in chicken isolates, suggesting that the UK-reared chickens are not a reservoir of CTX-M-15.
Hyaluronan-linked protein 1 (HAPLN1) which has been shown to be highly expressed in malignant pleural mesotheliomas (MPM), was detected in serum using an electrochemical surface-imprinting method. ...First, the detection method was optimized using Bovine serum albumin (BSA) as a model protein to mimic the optimal conditions required to imprint the similar molecular weight protein HAPLN1. BSA was imprinted on the gold electrode with hydroxyl terminated alkane thiols, which formed a self-assembled monolayer (SAM) around BSA. The analyte (BSA) was then washed away and its imprint (empty cavity with shape-memory) was used for detection of BSA in a solution, using electrochemical open-circuit potential method, namely potentiometry. Factors considered to optimize the conditions include incubation time, protein concentration, limit of detection and size of electrode. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to confirm selectivity of imprints. With the obtained imprinting control parameters, HAPLN1 was imprinted in duplicate and the detection of spiked HAPLN1 was successfully conducted in serum.
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