Downeyfletcher2906

These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2-/- mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.Dupuytren's disease (DD) is a common fibro-proliferative disorder of the palm. We estimated the risk of serious local and systemic complications and re-operation after DD surgery. We queried England's Hospital Episode Statistics database and included all adult DD patients who were surgically treated. A longitudinal cohort study and self-controlled case series were conducted. Between 1 April 2007 and 31 March 2017, 121,488 adults underwent 158,119 operations for DD. The cumulative incidence of 90-day serious local complications was low at 1.2% (95% CI 1.1-1.2). However, the amputation rate for re-operation by limited fasciectomy following dermofasciectomy was 8%. 90-day systemic complications were also uncommon at 0.78% (95% CI 0.74-0.83), however operations routinely performed under general or regional anaesthesia carried an increased risk of serious systemic complications such as myocardial infarction. Re-operation was lower than previous reports (33.7% for percutaneous needle fasciotomy, 19.5% for limited fasciectomy, and 18.2% for dermofasciectomy). Overall, DD surgery performed in England was safe; however, re-operation by after dermofasciectomy carries a high risk of amputation. Furthermore, whilst serious systemic complications were unusual, the data suggest that high-risk patients should undergo treatment under local anaesthesia. These data will inform better shared decision-making regarding this common condition.Thiol-lignocellulose sodium bentonite (TLSB) nanocomposites can effectively remove heavy metals from aqueous solutions. TLSB was formed by using -SH group-modified lignocellulose as a raw material, which was intercalated into the interlayers of hierarchical sodium bentonite. Characterization of TLSB was then performed with BET, FTIR, XRD, TGA, PZC, SEM, and TEM analyses. The results indicated that thiol-lignocellulose molecules may have different influences on the physicochemical properties of sodium bentonite, and an intercalated-exfoliated structure was successfully formed. The TLSB nanocomposite was subsequently investigated to validate its adsorption and desorption capacities for the zinc subgroup ions Zn(II), Cd(II) and Hg(II). The optimum adsorption parameters were determined based on the TLSB nanocomposite dosage, concentration of zinc subgroup ions, solution pH, adsorption temperature and adsorption time. The results revealed that the maximum adsorption capacity onto TLSB was 357.29 mg/g for Zn(II), 458.32 mg/g for Cd(II) and 208.12 mg/g for Hg(II). The adsorption kinetics were explained by the pseudo-second-order model, and the adsorption isotherm conformed to the Langmuir model, implying that the dominant chemical adsorption mechanism on TLSB is monolayer coverage. Thermodynamic studies suggested that the adsorption is spontaneous and endothermic. Desorption and regeneration experiments revealed that TLSB could be desorbed with HCl to recover Zn(II) and Cd(II) and with HNO3 to recover Hg(II) after several consecutive adsorption/desorption cycles. The adsorption mechanism was investigated through FTIR, EDX and SEM, which demonstrated that the introduction of thiol groups improved the adsorption capacity. All of these results suggested that TLSB is an eco-friendly and sustainable adsorbent for the extraction of Zn(II), Cd(II) and Hg(II) ions in aqueous media.Glutamate dehydrogenase (GDH) is a key enzyme interlinking carbon and nitrogen metabolism. Recent discoveries of the GDH specific role in breast cancer, hyperinsulinism/hyperammonemia (HI/HA) syndrome, and neurodegenerative diseases have reinvigorated interest on GDH regulation, which remains poorly understood despite extensive and long standing studies. Notwithstanding the growing evidence of the complexity of allosteric network behind GDH regulation, identifications of allosteric factors and associated mechanisms are paramount to deepen our understanding of the complex dynamics that regulate GDH enzymatic activity. Combining structural analyses of cryo-electron microscopy data with molecular dynamic simulations, here we show that the cofactor NADH is a key player in the GDH regulation process. Our structural analysis indicates that, binding to the regulatory sites in proximity of the antenna region, NADH acts as a positive allosteric modulator by enhancing both the affinity of the inhibitor GTP binding and inhibition of GDH catalytic activity. We further show that the binding of GTP to the NADH-bound GDH activates a triangular allosteric network, interlinking the inhibitor with regulatory and catalytic sites. This allostery produces a local conformational rearrangement that triggers an anticlockwise rotational motion of interlinked alpha-helices with specific tilted helical extension. This structural transition is a fundamental switch in the GDH enzymatic activity. It introduces a torsional stress, and the associated rotational shift in the Rossmann fold closes the catalytic cleft with consequent inhibition of the deamination process. In silico mutagenesis examinations further underpin the molecular basis of HI/HA dominant mutations and consequent over-activity of GDH through alteration of this allosteric communication network. These results shed new light on GDH regulation and may lay new foundation in the design of allosteric agents.Remote imaging photoplethysmography (iPPG) senses the cardiac pulse in outer skin layers and is responsive to mean arterial pressure and pulse pressure in critically ill patients. Whether iPPG is sufficiently sensitive to monitor cutaneous perfusion is not known. This study aimed at determining the response of iPPG to changes in cutaneous perfusion measured by Laser speckle imaging (LSI). Thirty-seven volunteers were engaged in a cognitive test known to evoke autonomic nervous activity and a Heat test. Simultaneous measurements of iPPG and LSI were taken at baseline and during cutaneous perfusion challenges. A perfusion index (PI) was calculated to assess iPPG signal strength. The response of iPPG to the challenges and its relation to LSI were determined. PI of iPPG significantly increased in response to autonomic nervous stimuli and to the Heat test by 5.8% (p = 0.005) and 11.1% (p  less then  0.001), respectively. PI was associated with LSI measures of cutaneous perfusion throughout experiments (p  less then  0.001). iPPG responses to study task correlated with those of LSI (r = 0.62, p  less then  0.001) and were comparable among subjects. iPPG is sensitive to autonomic nervous activity in volunteers and is closely associated with cutaneous perfusion.Fungal infections represent a worrisome complication in hematologic cancer patients and in the absence of disease specific symptoms, it is important to establish new biological indicators, which can be used during mould-active prophylaxis. Recently, miRNAs have appeared as candidate diagnostic and prognostic markers of several diseases. A pilot clinical study was performed to evaluate the diagnostic utility of 14 microRNAs which can be related to invasive fungal infections. Based on our data miR-142-3p, miR-142-5p, miR-26b-5p and miR-21-5p showed significant overexpression (p  less then  0.005) due to invasive aspergillosis in hemato-oncology patients with profound neutropenia. A tetramiR assay was designed to monitor peripheral blood specimens. Optimal cut-off was estimated by using the median value (fold change 1.1) of the log10 transformed gene expressions. The biomarker panel was evaluated on two independent sample cohorts implementing different antimicrobial prophylactic strategies. The receiver operating characteristic analysis with area under the curve proved to be 0.97. Three miRNAs (miR-142-5p, miR-142-3p, miR-16-5p) showed significant expression alterations in episodes with sepsis. In summary, the tetramiR assay proved to be a promising diagnostic adjunct with sufficient accuracy and sensitivity to trace invasive aspergillosis in hemato-oncology patients.We report for the first time the theory of optical tweezers of spherical dielectric particles embedded in a chiral medium. We develop a partial-wave (Mie) expansion to calculate the optical force acting on a dielectric microsphere illuminated by a circularly-polarized, highly focused laser beam. When choosing a polarization with the same handedness of the medium, the axial trap stability is improved, thus allowing for tweezing of high-refractive-index particles. When the particle is displaced off-axis by an external force, its equilibrium position is rotated around the optical axis by the mechanical effect of an optical torque. Both the optical torque and the angle of rotation are greatly enhanced in the presence of a chiral host medium when considering radii a few times larger than the wavelength. In this range, the angle of rotation depends strongly on the microsphere radius and the chirality parameter of the host medium, opening the way for a quantitative characterization of both parameters. Measurable angles are predicted even in the case of naturally occurring chiral solutes, allowing for a novel all-optical method to locally probe the chiral response at the nanoscale.Slope aspect plays a critical role in influencing vegetation pattern in semiarid area. The dry valleys of the Hengduan Mountains Region, southwestern China, are striking geographical landscape, suffering from severe ecological degradation. Here, we comprehensively investigated how slope aspect affects vegetation attributes in one of these valleys- the dry valley in the upper reaches of Min River. Three sites were selected along the valley and we quantitively examined the vegetation difference between slope aspects at the whole valley scale and each site level. We found significant vegetation differences between slope aspects in species composition, vegetative structure, and biodiversity pattern, which were in accordance with the observed significant difference in soil nutrient. Generally, north-facing slopes are associated with higher biomass, coverage and height, and species diversity than south-facing slopes. We also found between-aspect differences varied among the study sites, resulting in increased biomass, height, and β diversity differences, decreased density and coverage differences, and opposite trend observed in α diversity at relatively wet site. In conclusion, slope aspect had significant effect on vegetation attributes, which was significantly influenced by local climate (aridity) in terms of both strength and direction depending on the specific attributes investigated.A method for rapid and objective assessment of ocular lens density and transmittance is needed for research and clinical practice. The aim of this study was to determine whether the Purkinje image-based technique can be used for objective and accurate quantification of spectral density and transmittance of ocular media (the mainly crystalline lens) in visible light. Twenty-six individuals (10 young, 9 middle-aged and 7 older individuals) participated in this study. Spectral lens density was evaluated by detecting the intensity of the IVth Purkinje image for different wavelengths. Subsequently, optical density index (ODI), the area under the curve in the lens density spectrum, was calculated and ODIs were compared with clinical lens opacification scales assessed subjectively using a slit lamp. Spectral lens transmittance was estimated from the lens density spectrum. Lens densities were higher in the short wavelength region of the visible spectrum across all age groups. ODI was highly correlated with the clinical opacification scale, while lens transmittance decreased with aging.