594 research outputs found
Pulmonary Predictors of Incident Diabetes in Smokers.
BACKGROUND: Diabetes mellitus and its complications are a large and increasing burden for health care worldwide. Reduced pulmonary function has been observed in diabetes (both type 1 and type 2), and this reduction is thought to occur prior to diagnosis. Other measures of pulmonary health are associated with diabetes, including lower exercise tolerance, greater dyspnea, lower quality of life (as measured by the St. George's Respiratory Questionaire [SGRQ]) and susceptibility to lung infection and these measures may also predate diabetes diagnosis. METHODS: We examined 7080 participants in the COPD Genetic Epidemiology (COPDGene) study who did not report diabetes at their baseline visit and who provided health status updates during 4.2 years of longitudinal follow-up (LFU). We used Cox proportional hazards modeling, censoring participants at final LFU contact, reported mortality or report of incident diabetes to model predictors of diabetes. These models were constructed using known risk factors as well as proposed markers related to pulmonary health, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, respiratory exacerbations (RE), 6-minute walk distance (6MWD), pulmonary associated quality of life (as measured by the SGRQ), corticosteroid use, chronic bronchitis and dyspnea. RESULTS: Over 21,519 person years of follow-up, 392 of 7080 participants reported incident diabetes which was associated with expected predictors; increased body mass index (BMI), high blood pressure, high cholesterol and current smoking status. Age, gender and accumulated smoking exposure were not associated with incident diabetes. Additionally, preserved ratio with impaired spirometry (PRISm) pattern pulmonary function, reduced 6MWD and any report of serious pulmonary events were associated with incident diabetes. CONCLUSIONS: This cluster of pulmonary indicators may aid clinicians in identifying and treating patients with pre- or undiagnosed diabetes
Degradation of Cry1Ab protein from genetically modified maize (MON810) in relation to total dietary feed proteins in dairy cow digestion
To investigate the relative degradation and fragmentation pattern of the recombinant Cry1Ab protein from genetically modified (GM) maize MON810 throughout the gastrointestinal tract (GIT) of dairy cows, a 25 months GM maize feeding study was conducted on 36 lactating Bavarian Fleckvieh cows allocated into two groups (18 cows per group) fed diets containing either GM maize MON810 or nearly isogenic non-GM maize as the respective diet components. All cows were fed a partial total mixed ration (pTMR). During the feeding trial, 8 feed (4 transgenic (T) and 4 non-transgenic (NT) pTMR) and 42 feces (26 T and 18 NT) samples from the subset of cows fed T and NT diets, and at the end of the feeding trial, digesta contents of rumen, abomasum, small intestine, large intestine and cecum were collected after the slaughter of six cows of each feeding group. Samples were analyzed for Cry1Ab protein and total protein using Cry1Ab specific ELISA and bicinchoninic acid assay, respectively. Immunoblot analyses were performed to evaluate the integrity of Cry1Ab protein in feed, digesta and feces samples. A decrease to 44% in Cry1Ab protein concentration from T pTMR to the voided feces (9.40 versus 4.18 μg/g of total proteins) was recorded. Concentrations of Cry1Ab protein in GIT digesta of cows fed T diets varied between the lowest 0.38 μg/g of total proteins in abomasum to the highest 3.84 μg/g of total proteins in rumen. Immunoblot analysis revealed the extensive degradation of recombinant Cry1Ab protein into a smaller fragment of around 34 kDa in GIT. The results of the present study indicate that the recombinant Cry1Ab protein from MON810 is increasingly degraded into a small fragment during dairy cow digestion
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The polygenic nature of telomere length and the anti-ageing properties of lithium
Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p 0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy
Rapid Qualitative Urinary Tract Infection Pathogen Identification by SeptiFast® Real-Time PCR
Background
Urinary tract infections (UTI) are frequent in outpatients. Fast pathogen identification is mandatory for shortening the time of discomfort and preventing serious complications. Urine culture needs up to 48 hours until pathogen identification. Consequently, the initial antibiotic regimen is empirical.
Aim
To evaluate the feasibility of qualitative urine pathogen identification by a commercially available real-time PCR blood pathogen test (SeptiFast®) and to compare the results with dipslide and microbiological culture.
Design of study
Pilot study with prospectively collected urine samples.
Setting
University hospital.
Methods
82 prospectively collected urine samples from 81 patients with suspected UTI were included. Dipslide urine culture was followed by microbiological pathogen identification in dipslide positive samples. In parallel, qualitative DNA based pathogen identification (SeptiFast®) was performed in all samples.
Results
61 samples were SeptiFast® positive, whereas 67 samples were dipslide culture positive. The inter-methodological concordance of positive and negative findings in the gram+, gram- and fungi sector was 371/410 (90%), 477/492 (97%) and 238/246 (97%), respectively. Sensitivity and specificity of the SeptiFast® test for the detection of an infection was 0.82 and 0.60, respectively. SeptiFast® pathogen identifications were available at least 43 hours prior to culture results.
Conclusion
The SeptiFast® platform identified bacterial DNA in urine specimens considerably faster compared to conventional culture. For UTI diagnosis sensitivity and specificity is limited by its present qualitative setup which does not allow pathogen quantification. Future quantitative assays may hold promise for PCR based UTI pathogen identification as a supplementation of conventional culture methods
Dynamics of a disabled population in Morocco
BACKGROUND: The disabled population constitutes a class of people needing special care and necessitating important economic and social effort. METHODS: In this paper, using specific parameter settings, partial differential equations are used to model the temporal change of the proportion of the disabled population in Morocco. RESULTS: Combining different forms and values of the parameters, a numerical method is proposed and three scenarios are considered. These forms and values are determined by data fitting and simulation. CONCLUSIONS: The experiments show clearly the dynamical evolution of the disabled population with time and age according to each scenario
Nano-Stenciled RGD-Gold Patterns That Inhibit Focal Contact Maturation Induce Lamellipodia Formation in Fibroblasts
Cultured fibroblasts adhere to extracellular substrates by means of cell-matrix adhesions that are assembled in a hierarchical way, thereby gaining in protein complexity and size. Here we asked how restricting the size of cell-matrix adhesions affects cell morphology and behavior. Using a nanostencil technique, culture substrates were patterned with gold squares of a width and spacing between 250 nm and 2 µm. The gold was functionalized with RGD peptide as ligand for cellular integrins, and mouse embryo fibroblasts were plated. Limiting the length of cell-matrix adhesions to 500 nm or less disturbed the maturation of vinculin-positive focal complexes into focal contacts and fibrillar adhesions, as indicated by poor recruitment of α5-integrin. We found that on sub-micrometer patterns, fibroblasts spread extensively, but did not polarize. Instead, they formed excessive numbers of lamellipodia and a fine actin meshwork without stress fibers. Moreover, these cells showed aberrant fibronectin fibrillogenesis, and their speed of directed migration was reduced significantly compared to fibroblasts on 2 µm square patterns. Interference with RhoA/ROCK signaling eliminated the pattern-dependent differences in cell morphology. Our results indicate that manipulating the maturation of cell-matrix adhesions by nanopatterned surfaces allows to influence morphology, actin dynamics, migration and ECM assembly of adhering fibroblasts
Uncovering cis Regulatory Codes Using Synthetic Promoter Shuffling
Revealing the spectrum of combinatorial regulation of transcription at individual promoters is essential for understanding the complex structure of biological networks. However, the computations represented by the integration of various molecular signals at complex promoters are difficult to decipher in the absence of simple cis regulatory codes. Here we synthetically shuffle the regulatory architecture — operator sequences binding activators and repressors — of a canonical bacterial promoter. The resulting library of complex promoters allows for rapid exploration of promoter encoded logic regulation. Among all possible logic functions, NOR and ANDN promoter encoded logics predominate. A simple transcriptional cis regulatory code determines both logics, establishing a straightforward map between promoter structure and logic phenotype. The regulatory code is determined solely by the type of transcriptional regulation combinations: two repressors generate a NOR: NOT (a OR b) whereas a repressor and an activator generate an ANDN: a AND NOT b. Three-input versions of both logics, having an additional repressor as an input, are also present in the library. The resulting complex promoters cover a wide dynamic range of transcriptional strengths. Synthetic promoter shuffling represents a fast and efficient method for exploring the spectrum of complex regulatory functions that can be encoded by complex promoters. From an engineering point of view, synthetic promoter shuffling enables the experimental testing of the functional properties of complex promoters that cannot necessarily be inferred ab initio from the known properties of the individual genetic components. Synthetic promoter shuffling may provide a useful experimental tool for studying naturally occurring promoter shuffling
The Tyrosine Kinase c-Src Directly Mediates Growth Factor-Induced Notch-1 and Furin Interaction and Notch-1 Activation in Pancreatic Cancer Cells
The proteolytic activity of Furin responsible for processing full length Notch-1 (p300) plays a critical role in Notch signaling. The amplitude and duration of Notch activity can be regulated at various points in the pathway, but there has been no report regarding regulation of the Notch-1-Furin interaction, despite its importance. In the present study, we found that the Notch-1-Furin interaction is regulated by the non-receptor tyrosine kinase, c-Src. c-Src and Notch-1 are physically associated, and this association is responsible for Notch-1 processing and activation. We also found that growth factor TGF-α, an EGFR ligand, and PDGF-BB, a PDGFR ligand, induce the Notch-1-Furin interaction mediated by c-Src. Our results support three new and provocative conclusions: (1) The association between Notch-1 and Furin is a well-regulated process; (2) Extracellular growth factor signals regulate this interaction, which is mediated by c-Src; (3) There is cross-talk between the plasma growth factor receptor-c-Src and Notch pathways. Co-localization of Notch-1 and c-Src was confirmed in xenograft tumor tissues and in the tissues of pancreatic cancer patients. Our findings have implications for the mechanism by which the Notch and growth factor receptor-c-Src signaling pathways regulate carcinogenesis and cancer cell growth
Low pressure plasma nitrided CoCrMo alloy utilising HIPIMS discharge for biomedical applications
CoCrMo is a biomedical grade alloy which is widely used in the manufacturing of orthopaedic
implants such as hip and knee replacement joints because of it has high hardness, high
corrosion resistance, and excellent biocompatibility. However, the release of metal ions due to
corrosion and wear of the alloy over time may cause allergic or other adverse reactions in some
patients. To date, various surface modification techniques including nitriding, have been used
to improve the performance of CoCrMo (F75) alloy.
In the current work, a new low-pressure plasma nitriding process is described. Unlike
conventional plasma nitriding, the process utilises High Power Impulse Magnetron Sputtering
(HIPIMS) discharge, sustained on one Cr target at low power, to further enhance the ionisation
of the gas in the vacuum chamber and to avoid coating deposition. The nitriding of CoCrMo
alloy has been carried out in a wide range of nitriding voltages (from -500 V to -1100 V) at
400 °C for duration of 4 hours. The chemical and phase composition of the nitrided layer has
been studied by various advanced surface analyses techniques.
The X-ray diffraction data of all the nitrided samples revealed the formation of
expanded austenite (γN) phase. Texture analyses revealed that at lower nitriding voltages
(-700 V) the predominant crystallographic orientation of the compound layer is (200)
whereas at higher voltages (-900 V to -1100 V) the layer develops mixed (111) and (200)
texture. For samples nitrided at a lower bias voltage of - 500 V, diffraction peaks for
CrN/NbN and Cr2N were also observed due to the deposition of target materials (Cr and
Nb). However, no coating deposition on the substrate surface was observed at higher bias
voltages (-700 V and higher) due to sufficient re-sputtering effect. The results obtained
from glow discharge optical emission spectroscopy (GDOES) depth profiling showed that
the depth of nitriding increased from approximately 0.7 µm at -500 V to 6 µm at -1100 V.
In the pin-on-disc tribological test nitrided samples showed low coefficient of friction µ in
the range of 0.6 to 0.7, compared to µ= 0.8 recorded for the untreated substrate. The wear
coefficients (Kc) were found to be between 1.79 × 10-15 m3N
-1m-1
(-700 V) and 4.62 × 10-
15 m3N
-1m-1
(-1100 V), which were one order of magnitude lower than the untreated
substrate, Kc = 6 ×10-14 m3N
-1m-1
. The Knoop microhardness (HK) of nitrided samples
significantly increased by a factor of 5 (HK= 2750 at -1100 V) as compared to the untreated
substrate, HK=525, demonstrating the high efficiency of the process. The samples nitrided
at -700 V and - 900 V exhibited enhanced corrosion resistance as compared to untreated
alloy by avoiding the formation of CrN based compounds which adversely affect the
corrosion performance
Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study
Objectives We aimed to evaluate the mechanical properties
and healing patterns 6 and 9 months after implantation of the
sirolimus-eluting Fantom bioresorbable scaffold (BRS).
Background The Fantom BRS (Reva Medical, San Diego,
USA) has differentiating properties including radiopacity,
strut thickness of 125 µm, high expansion capacity and
has demonstrated favourable mid-term clinical and
angiographic outcomes.
Methods and results FANTOM II was a prospective,
single arm study with implantation of the Fantom BRS
in 240 patients with stable angina pectoris. Guidance by
optical coherence tomography (OCT) was encouraged and
was repeated at 6-month (cohort A) or 9-month follow-up
(cohort B). Matched baseline and follow-up OCT recordings
were available in 152 patients. In-scaffold mean lumen
area in cohort A was 6.8±1.7mm2
and 5.7±1.4mm2
at baseline and follow-up (p<0.0001) and was
7.2±1.6mm2
and 5.6±1.4mm2
in cohort B (p<0.0001).
Mean scaffold area remained stable from 7.1±1.5mm2
at baseline to 7.2±1.4mm2
at 6 months (p=0.12), and
from 7.4±1.5mm2
to 7.3±1.4mm2
at 9 months. Strut
malapposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR
0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both
groups at 6-month and 9-month follow-up. Strut tissue
coverage was 98.1 (IQR 95.9;99.4)% at 6 months and
98.9 (IQR 98.3;100.0)% at 9 months.
Conclusions The novel Fantom BRS had favourable
healing patterns at 6-month and 9-month follow-up as
malapposition was effectively resolved and strut coverage
was almost complete. The scaffold remained stable
through follow-up with no signs of systematic late recoil
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