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  • Corneal endothelial (CE) dysfunction is the main indication for corneal transplantation, an invasive procedure with several limitations. Developing novel strategies to re-activate CE regenerative capacity is, therefore, of fundamental importance. This goal has proved to be challenging as corneal endothelial cells (CEnC) are blocked in the G0/G1 phase of the cell cycle in vivo and, albeit retaining proliferative capacity in vitro, this is further hindered by endothelial-to-mesenchymal transition. Herein we investigated the mechanisms regulating CEnC proliferation in vitro. Comparing the proteome of non-proliferating (in vivo-G0/G1) and proliferating (in vitro-G2/M) rabbit CEnC (rCEnC), 77 proteins, out of 3,328 identified, were differentially expressed in the two groups (p  less then  0.005). Literature and Gene Ontology analysis revealed β-catenin and transforming growth factor (TGF-β) pathways to be correlated with the identified proteins. Treatment of rCEnC with a β-catenin activator and inhibitor showed that β-catenin activation was necessary during rCEnC proliferation, but not sufficient for its induction. Furthermore, both pro-proliferative activity of basic fibroblast growth factor and anti-proliferative effects of TGF-β were regulated through β-catenin. Overall, these results provide novel insights into the molecular basis underlying the proliferation process that CEnC re-activate in vitro, consolidating the role of β-catenin and TGF-β.Antibodies have been explored extensively as a potential therapeutic for Alzheimer's disease, where amyloid-β (Aβ) peptides and the tau protein deposit in patient brains. While the major focus of antibody-based therapy development was on Aβ, arguably with limited success in clinical trials, targeting tau has become an emerging strategy, possibly extending therapies to dementias with isolated tau pathology. Interestingly, low titres of autoantibodies to pathological tau have been described in humans and transgenic mouse models, but their pathophysiological relevance remained elusive. Here, we used two independent approaches to deplete the B-cell lineage and hence antibody formation in human P301S mutant tau transgenic ****, TAU58/2. TAU58/2 **** were either crossed with the B-cell-deficient Ighm knockout line (muMT-/-) or treated with anti-CD20 antibodies that target B-cell precursors. In both models, B-cell depletion significantly reduced astrocytosis in TAU58/2 ****. Only when B-cells were absent throughout life, in TAU58/2.muMT-/- ****, were spatial learning deficits moderately aggravated while motor performance improved as compared to B-cell-competent TAU58/2 ****. This was associated with changes in brain region-specific tau solubility. No other relevant behavioural or neuropathological changes were observed in TAU58/2 **** in the absence of B-cells/antibodies. Taken together, our data suggests that the presence of antibodies throughout life contributes to astrocytosis in TAU58/2 **** and limits learning deficits, while other deficits and neuropathological changes appear to be independent of the presence of B-cells/antibodies.Microorganisms are fundamental drivers of biogeochemical cycling, though their contribution to coral reef ecosystem functioning is poorly understood. Here, we infer predictors of bacterioplankton community dynamics across surface-waters of the Great Barrier Reef (GBR) through a meta-analysis, combining microbial with environmental data from the eReefs platform. Nutrient dynamics and temperature explained 41.4% of inter-seasonal and cross-shelf variation in bacterial assemblages. Bacterial families OCS155, Cryomorphaceae, Flavobacteriaceae, Synechococcaceae and Rhodobacteraceae dominated inshore reefs and their relative abundances positively correlated with nutrient loads. In contrast, Prochlorococcaceae negatively correlated with nutrients and became increasingly dominant towards outershelf reefs. Cyanobacteria in Prochlorococcaceae and Synechococcaceae families occupy complementary cross-shelf biogeochemical niches; their abundance ratios representing a potential indicator of GBR nutrient levels. One Flavobacteriaceae-affiliated taxa was putatively identified as diagnostic for ecosystem degradation. Establishing microbial observatories along GBR environmental gradients will facilitate robust assessments of microbial contributions to reef health and inform tipping-points in reef condition.We report on a potential method to separate sugars by using the specific interaction between fullerenes and saccharides in liquid chromatography (LC). Aromatic rings with high electron density are believed to interact strongly with saccharides due to CH-π and/or OH-π interactions. In this study, the fullerene-bonded columns were used to separate saccharides by LC under aqueous conditions. https://www.selleckchem.com/products/azd6738.html As a result, 2-aminobenzamide-labeled glucose homopolymer (Glcs) was effectively separated by both C60 and C70 columns in the range of Glc-1 to Glc-20 and high blood glucose level being retained in greater quantity. Furthermore, similar separations were identified by LC-mass spectrometry with non-labeled glucose homopolymers. Theoretical study based on molecular dynamics and DFT calculation demonstrated that a supramolecular complex of saccharide-fullerene was formed through CH-π and/or OH-π interactions, and that the interactions between saccharide and fullerene increase with the increase units of the saccharide. Additionally, the C60 column retained disaccharides containing maltose, trehalose, and sucrose. In this case, it was assumed that the retention rates were determined by the difference of the dipole moment in each saccharide. These results suggest that the dipole-induced dipole interaction was dominant, and that maltose-with the higher dipole moment-was more strongly retained compared to other disaccharides having lower dipole moment.There is an increasing need to control light phase with tailored precision via simple means in both fundamental science and industry. One of the best candidates to achieve this goal are electro-optical materials. In this work, a novel technique to modulate the spatial phase profile of a propagating light beam by means of liquid crystals (LC), electro-optically addressed by indium-tin oxide (ITO) grating microstructures, is proposed and experimentally demonstrated. A planar LC cell is assembled between two perpendicularly placed ITO gratings based on microstructured electrodes. By properly selecting only four voltage sources, we modulate the LC-induced phase profile such that non-diffractive Bessel beams, laser stretching, beam steering, and 2D tunable diffraction gratings are generated. In such a way, the proposed LC-tunable component performs as an all-in-one device with unprecedented characteristics and multiple functionalities. The operation voltages are very low and the aperture is large. Moreover, the device operates with a very simple voltage control scheme and it is lightweight and compact.
    Corneal endothelial (CE) dysfunction is the main indication for corneal transplantation, an invasive procedure with several limitations. Developing novel strategies to re-activate CE regenerative capacity is, therefore, of fundamental importance. This goal has proved to be challenging as corneal endothelial cells (CEnC) are blocked in the G0/G1 phase of the cell cycle in vivo and, albeit retaining proliferative capacity in vitro, this is further hindered by endothelial-to-mesenchymal transition. Herein we investigated the mechanisms regulating CEnC proliferation in vitro. Comparing the proteome of non-proliferating (in vivo-G0/G1) and proliferating (in vitro-G2/M) rabbit CEnC (rCEnC), 77 proteins, out of 3,328 identified, were differentially expressed in the two groups (p  less then  0.005). Literature and Gene Ontology analysis revealed β-catenin and transforming growth factor (TGF-β) pathways to be correlated with the identified proteins. Treatment of rCEnC with a β-catenin activator and inhibitor showed that β-catenin activation was necessary during rCEnC proliferation, but not sufficient for its induction. Furthermore, both pro-proliferative activity of basic fibroblast growth factor and anti-proliferative effects of TGF-β were regulated through β-catenin. Overall, these results provide novel insights into the molecular basis underlying the proliferation process that CEnC re-activate in vitro, consolidating the role of β-catenin and TGF-β.Antibodies have been explored extensively as a potential therapeutic for Alzheimer's disease, where amyloid-β (Aβ) peptides and the tau protein deposit in patient brains. While the major focus of antibody-based therapy development was on Aβ, arguably with limited success in clinical trials, targeting tau has become an emerging strategy, possibly extending therapies to dementias with isolated tau pathology. Interestingly, low titres of autoantibodies to pathological tau have been described in humans and transgenic mouse models, but their pathophysiological relevance remained elusive. Here, we used two independent approaches to deplete the B-cell lineage and hence antibody formation in human P301S mutant tau transgenic mice, TAU58/2. TAU58/2 mice were either crossed with the B-cell-deficient Ighm knockout line (muMT-/-) or treated with anti-CD20 antibodies that target B-cell precursors. In both models, B-cell depletion significantly reduced astrocytosis in TAU58/2 mice. Only when B-cells were absent throughout life, in TAU58/2.muMT-/- mice, were spatial learning deficits moderately aggravated while motor performance improved as compared to B-cell-competent TAU58/2 mice. This was associated with changes in brain region-specific tau solubility. No other relevant behavioural or neuropathological changes were observed in TAU58/2 mice in the absence of B-cells/antibodies. Taken together, our data suggests that the presence of antibodies throughout life contributes to astrocytosis in TAU58/2 mice and limits learning deficits, while other deficits and neuropathological changes appear to be independent of the presence of B-cells/antibodies.Microorganisms are fundamental drivers of biogeochemical cycling, though their contribution to coral reef ecosystem functioning is poorly understood. Here, we infer predictors of bacterioplankton community dynamics across surface-waters of the Great Barrier Reef (GBR) through a meta-analysis, combining microbial with environmental data from the eReefs platform. Nutrient dynamics and temperature explained 41.4% of inter-seasonal and cross-shelf variation in bacterial assemblages. Bacterial families OCS155, Cryomorphaceae, Flavobacteriaceae, Synechococcaceae and Rhodobacteraceae dominated inshore reefs and their relative abundances positively correlated with nutrient loads. In contrast, Prochlorococcaceae negatively correlated with nutrients and became increasingly dominant towards outershelf reefs. Cyanobacteria in Prochlorococcaceae and Synechococcaceae families occupy complementary cross-shelf biogeochemical niches; their abundance ratios representing a potential indicator of GBR nutrient levels. One Flavobacteriaceae-affiliated taxa was putatively identified as diagnostic for ecosystem degradation. Establishing microbial observatories along GBR environmental gradients will facilitate robust assessments of microbial contributions to reef health and inform tipping-points in reef condition.We report on a potential method to separate sugars by using the specific interaction between fullerenes and saccharides in liquid chromatography (LC). Aromatic rings with high electron density are believed to interact strongly with saccharides due to CH-π and/or OH-π interactions. In this study, the fullerene-bonded columns were used to separate saccharides by LC under aqueous conditions. https://www.selleckchem.com/products/azd6738.html As a result, 2-aminobenzamide-labeled glucose homopolymer (Glcs) was effectively separated by both C60 and C70 columns in the range of Glc-1 to Glc-20 and high blood glucose level being retained in greater quantity. Furthermore, similar separations were identified by LC-mass spectrometry with non-labeled glucose homopolymers. Theoretical study based on molecular dynamics and DFT calculation demonstrated that a supramolecular complex of saccharide-fullerene was formed through CH-π and/or OH-π interactions, and that the interactions between saccharide and fullerene increase with the increase units of the saccharide. Additionally, the C60 column retained disaccharides containing maltose, trehalose, and sucrose. In this case, it was assumed that the retention rates were determined by the difference of the dipole moment in each saccharide. These results suggest that the dipole-induced dipole interaction was dominant, and that maltose-with the higher dipole moment-was more strongly retained compared to other disaccharides having lower dipole moment.There is an increasing need to control light phase with tailored precision via simple means in both fundamental science and industry. One of the best candidates to achieve this goal are electro-optical materials. In this work, a novel technique to modulate the spatial phase profile of a propagating light beam by means of liquid crystals (LC), electro-optically addressed by indium-tin oxide (ITO) grating microstructures, is proposed and experimentally demonstrated. A planar LC cell is assembled between two perpendicularly placed ITO gratings based on microstructured electrodes. By properly selecting only four voltage sources, we modulate the LC-induced phase profile such that non-diffractive Bessel beams, laser stretching, beam steering, and 2D tunable diffraction gratings are generated. In such a way, the proposed LC-tunable component performs as an all-in-one device with unprecedented characteristics and multiple functionalities. The operation voltages are very low and the aperture is large. Moreover, the device operates with a very simple voltage control scheme and it is lightweight and compact.
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  • In the present work, an extensive and detailed theoretical investigation is reported on the thermomechanical, electronic and thermodynamic properties of zinc-blende (sphalerite, zb-ZnS) and rock-salt zinc sulfide (rs-ZnS) over a wide range of pressure, by means of ab initio Density Functional Theory, Gaussian type orbitals and the well known B3LYP functional. For the first time, vibrational frequencies, phonon dispersion relations, elasto-piezo-dielectric tensor, thermodynamic and thermomechanical properties of rs-ZnS were calculated with a consistent approach that allows a direct comparison with the low-pressure polymorph. Special attention was paid to the evaluation of the thermodynamic pressure-temperature stability of the mineral phases between 0-25 GPa and 0-800 K. The static (T = 0 K) bulk moduli of sphalerite and rock-salt ZnS were 72.63 (3) GPa and 84.39 (5) GPa, respectively. The phase transition in static conditions calculated from the equation of state was about 15.5 GPa, whereas the elastic constants data resulted in Ptrans = 14.6 GPa. At room temperature (300 K), the zb-rs transition occurs at 14.70 GPa and a negative Clapeyron slope (dP)/(dT) = 0.0023 was observed up to 800 K. The electronic band structure showed a direct band gap for zb-ZnS (Eg = 4.830 eV at equilibrium geometry), which became an indirect one by increasing pressure above 11 GPa. The results were found to be in good agreement with the available experimental and theoretical data, further extending the knowledge of important properties of zinc sulfide, in particular the thermomechanical ones of the rock-salt polymorph here extensively explored for the first time.Perovskite-like oxides AB'1/2B''1/2O3 may experience different degrees of ordering of the B cations that can be varied by suitable synthesis conditions or post-synthesis treatment. In this work the earlier proposed statistical model of order-disorder phase transitions of B cations is extended to account for the effect of pressure. Depending on the composition, pressure is found to either increase or decrease the order-disorder phase transition temperature. The change in transition temperature due to pressure in many cases reaches several hundred kelvin at pressures accessible in the laboratory, which may significantly change the degree of atomic ordering. The work is intended to help in determining how pressure influences the degree of atomic ordering and to stimulate research into the effect of pressure on atomic order-disorder phase transitions in perovskites.Structural features and kinetics of the transition between ordered metastable ****c.-derived D03 and equilibrium f.c.c.-derived L12 phases of Fe-xGa alloys (x = 27.2% and 28.0%) have been analyzed by in situ real-time neutron diffraction during isothermal annealing in the temperature range 405-470°C. It has been revealed that the transition proceeds with alternation of the first- and second-order phase transformations according to a D03 → A2 → A1 → L12 scheme, where A2 and A1 are disordered ****c. and f.c.c. structures. Deformations of the crystal lattice that arise due to these transitions are determined. The kinetics of the L12 phase nucleation and growth were analyzed in the frame of the Johnson-Mehl-Avrami-Kolmogorov (JMAK) model; however, only the early stage of the D03 → L12 transition is well described by the JMAK equation. The value of the Avrami exponent corresponds to the constant growth rate of the new L12 phase and decreasing nucleation rate in the Fe-27.2Ga alloy and indicates the presence of pre-existing nucleation centres of the L12 phase in the Fe-28.0Ga alloy.Investigation into the temperature dependence of the mechanical behavior of ultra-coarse grained cemented carbide materials is highly demanded due to its service conditions of concurrent applied stress and high temperature. In the present study, based on the designed experiments and microstructural characterization combined with crystallographic analysis, the evolution of slip systems, motion and interaction of dislocations with temperature are quantified for the WC hard phase. Mechanisms are proposed for the formation of the sessile dislocations in the main slip systems at the room temperature and the glissile dislocations in the new slip systems activated at high temperatures. Furthermore, the correlation of the plastic strain and fracture toughness with the temperature-dependent slip activation, dislocation reaction and transformation is explained quantitatively. Enlightened by the present findings, potential approach to enhance the high-temperature strength of ultra-coarse cemented carbides based on WC strengthening was suggested.Crystal structures of six new salts of 2-methyl-5-nitroaniline with inorganic acids [(H2Me5NA)Br, (H2Me5NA)I, (H2Me5NA)NO3, (H2Me5NA)Cl, (H2Me5NA)HSO4 and (H2Me5NA)I3·0.5H2O] are determined by single-crystal X-ray diffraction. The most important hydrogen-bonding patterns are formed by the ammonio group and respective anions composing 1D or 2D networks. The patterns are analysed using the graph-set approach and mathematical interrelations between graph-set descriptors are shown for comparative purposes. Analysis of IR spectra enables the strength of hydrogen bonds in the crystals to be assessed. The frequency of N-H and O-H stretching vibrations and NH3 group libration indicates that the strongest hydrogen bonds are present in (H2Me5NA)HSO4, whereas the weakest ones occur in (H2Me5NA)I3·0.5H2O. Hirshfeld surface analysis reveals that apart from obvious N-H...anion hydrogen bonds, the molecules are also connected to each other by exclusive C-H...ONO2 interactions. The opposite occurs in the crystal structure of 2-methyl-4-nitroaniline salts, where a variety of ONO2...π(N)NO2 non-hydrogen bonding interactions are observed.There is intensive searching for superhard materials in both theoretical and experimental studies. Refractory and transition metal carbides are typical materials with high hardness. https://www.selleckchem.com/products/skl2001.html In this study, first-principles calculations were performed first to analyze the electronic structures and mechanical properties of the tungsten-carbide-based compounds. The results indicated that tungsten carbide could be hardened by alloying elements with high work functions to tailor the Fermi level and electron density. Guided by the calculations, a new type of tungsten carbide alloyed with Re was synthesized. The Young's modulus and hardness of the Re-alloyed tungsten carbide are increased by 31% and 44%, respectively, as compared with those of tungsten carbide. This study provides a new methodology to design superhard materials on a feasible electronic base using work function as a simple guiding parameter.
    In the present work, an extensive and detailed theoretical investigation is reported on the thermomechanical, electronic and thermodynamic properties of zinc-blende (sphalerite, zb-ZnS) and rock-salt zinc sulfide (rs-ZnS) over a wide range of pressure, by means of ab initio Density Functional Theory, Gaussian type orbitals and the well known B3LYP functional. For the first time, vibrational frequencies, phonon dispersion relations, elasto-piezo-dielectric tensor, thermodynamic and thermomechanical properties of rs-ZnS were calculated with a consistent approach that allows a direct comparison with the low-pressure polymorph. Special attention was paid to the evaluation of the thermodynamic pressure-temperature stability of the mineral phases between 0-25 GPa and 0-800 K. The static (T = 0 K) bulk moduli of sphalerite and rock-salt ZnS were 72.63 (3) GPa and 84.39 (5) GPa, respectively. The phase transition in static conditions calculated from the equation of state was about 15.5 GPa, whereas the elastic constants data resulted in Ptrans = 14.6 GPa. At room temperature (300 K), the zb-rs transition occurs at 14.70 GPa and a negative Clapeyron slope (dP)/(dT) = 0.0023 was observed up to 800 K. The electronic band structure showed a direct band gap for zb-ZnS (Eg = 4.830 eV at equilibrium geometry), which became an indirect one by increasing pressure above 11 GPa. The results were found to be in good agreement with the available experimental and theoretical data, further extending the knowledge of important properties of zinc sulfide, in particular the thermomechanical ones of the rock-salt polymorph here extensively explored for the first time.Perovskite-like oxides AB'1/2B''1/2O3 may experience different degrees of ordering of the B cations that can be varied by suitable synthesis conditions or post-synthesis treatment. In this work the earlier proposed statistical model of order-disorder phase transitions of B cations is extended to account for the effect of pressure. Depending on the composition, pressure is found to either increase or decrease the order-disorder phase transition temperature. The change in transition temperature due to pressure in many cases reaches several hundred kelvin at pressures accessible in the laboratory, which may significantly change the degree of atomic ordering. The work is intended to help in determining how pressure influences the degree of atomic ordering and to stimulate research into the effect of pressure on atomic order-disorder phase transitions in perovskites.Structural features and kinetics of the transition between ordered metastable b.c.c.-derived D03 and equilibrium f.c.c.-derived L12 phases of Fe-xGa alloys (x = 27.2% and 28.0%) have been analyzed by in situ real-time neutron diffraction during isothermal annealing in the temperature range 405-470°C. It has been revealed that the transition proceeds with alternation of the first- and second-order phase transformations according to a D03 → A2 → A1 → L12 scheme, where A2 and A1 are disordered b.c.c. and f.c.c. structures. Deformations of the crystal lattice that arise due to these transitions are determined. The kinetics of the L12 phase nucleation and growth were analyzed in the frame of the Johnson-Mehl-Avrami-Kolmogorov (JMAK) model; however, only the early stage of the D03 → L12 transition is well described by the JMAK equation. The value of the Avrami exponent corresponds to the constant growth rate of the new L12 phase and decreasing nucleation rate in the Fe-27.2Ga alloy and indicates the presence of pre-existing nucleation centres of the L12 phase in the Fe-28.0Ga alloy.Investigation into the temperature dependence of the mechanical behavior of ultra-coarse grained cemented carbide materials is highly demanded due to its service conditions of concurrent applied stress and high temperature. In the present study, based on the designed experiments and microstructural characterization combined with crystallographic analysis, the evolution of slip systems, motion and interaction of dislocations with temperature are quantified for the WC hard phase. Mechanisms are proposed for the formation of the sessile dislocations in the main slip systems at the room temperature and the glissile dislocations in the new slip systems activated at high temperatures. Furthermore, the correlation of the plastic strain and fracture toughness with the temperature-dependent slip activation, dislocation reaction and transformation is explained quantitatively. Enlightened by the present findings, potential approach to enhance the high-temperature strength of ultra-coarse cemented carbides based on WC strengthening was suggested.Crystal structures of six new salts of 2-methyl-5-nitroaniline with inorganic acids [(H2Me5NA)Br, (H2Me5NA)I, (H2Me5NA)NO3, (H2Me5NA)Cl, (H2Me5NA)HSO4 and (H2Me5NA)I3·0.5H2O] are determined by single-crystal X-ray diffraction. The most important hydrogen-bonding patterns are formed by the ammonio group and respective anions composing 1D or 2D networks. The patterns are analysed using the graph-set approach and mathematical interrelations between graph-set descriptors are shown for comparative purposes. Analysis of IR spectra enables the strength of hydrogen bonds in the crystals to be assessed. The frequency of N-H and O-H stretching vibrations and NH3 group libration indicates that the strongest hydrogen bonds are present in (H2Me5NA)HSO4, whereas the weakest ones occur in (H2Me5NA)I3·0.5H2O. Hirshfeld surface analysis reveals that apart from obvious N-H...anion hydrogen bonds, the molecules are also connected to each other by exclusive C-H...ONO2 interactions. The opposite occurs in the crystal structure of 2-methyl-4-nitroaniline salts, where a variety of ONO2...π(N)NO2 non-hydrogen bonding interactions are observed.There is intensive searching for superhard materials in both theoretical and experimental studies. Refractory and transition metal carbides are typical materials with high hardness. https://www.selleckchem.com/products/skl2001.html In this study, first-principles calculations were performed first to analyze the electronic structures and mechanical properties of the tungsten-carbide-based compounds. The results indicated that tungsten carbide could be hardened by alloying elements with high work functions to tailor the Fermi level and electron density. Guided by the calculations, a new type of tungsten carbide alloyed with Re was synthesized. The Young's modulus and hardness of the Re-alloyed tungsten carbide are increased by 31% and 44%, respectively, as compared with those of tungsten carbide. This study provides a new methodology to design superhard materials on a feasible electronic base using work function as a simple guiding parameter.
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  • First, the authors' method is performed only in a single stage. Second, the flap is based on a rich vascular supply from the angular artery, which eliminates the possibility of flap necrosis through multiple turnovers. Third, because the turnover nasolabial flap is a construct of the epidermis, dermis, and subcutaneous fat, the flap is quite stiff thus reducing the possibility of nostril collapse. Fourth, the procedure leaves no scars in the superior area of the nose other than the nasolabial fold scar.
    To (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI).

    Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material.

    The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential.

    A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation.
    A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation.
    Within the context of xerostomia, there is evidence that adipose-derived stem cells (ASCs) can differentiate into salivary gland cells in the appropriate environment. The purpose of this study was to preliminarily investigate whether fat grafting as practiced in the United States would be an effective treatment for xerostomia.

    Patients were selected for the study if they were seeking treatment for xerostomia after radiation treatment to the head and neck for cancer treatment. Fat grafting was performed in bilateral parotid and submandibular glands. Visual Analog Scale (VAS) of xerostomia was used both preoperatively and postoperatively to assess the effect upon xerostomia symptoms.

    Nine patients were included in this study. All patients had complaints of long-standing xerostomia. The average preoperative VAS score was 9.1. All patients tolerated all rounds of fat grafting with no complications. The average postoperative VAS score was 6.0. Compared to preoperative scores, all patients had improvement in VAS scores. The decrease in average VAS score postoperatively (9.1 versus 6.0) was statistically significant (P = 0.007).

    Our study showed that there was improvement in xerostomia symptoms with autologous fat transfer alone. This is a novel finding for fat grafting demonstrating regenerative potential. There has been extensive basic research that has shown that adipose-derived mesenchymal stem cells can have a protective and restorative role after salivary gland radiation damage. Our case series is the first report of fat grafting having a similar reported outcome.

    4.
    4.
    The purpose of this study was to investigate the advantages of endoscopic lateral osteotomy, to evaluate the effects of the periosteal elevation on ecchymosis and to search the reasons for the ecchymosis and the intranasal mucosal tears.

    On a randomly chosen side a subperiosteal tunnel was elevated, on the other side a subperiosteal tunnel was not elevated. Bilateral lateral osteotomies were performed. Internal nasal packing was not used. The post-operative care was similar for all patients. The patients were evaluated on the third post-operative day. The intranasal mucosal tears, the lateral osteotomy cut on the periosteal elevation side were examined using endoscopes. The degree of ecchymosis was determined by 2 other surgeons, who were unaware of the elevated side, using the grading system adapted from Hoffman et al. RESULTS The intranasal mucosal injury was seen in 16 of non-elevated side whereas it was 14 on the periosteal elevated side. Endoscopy showed the perforating arteries and elevation of the ot due to the trauma of the angular artery. https://www.selleckchem.com/products/img-7289.html Intramucosal tears do not increase the severity of the ecchymosis.
    The aim of our study was to analyze the aesthetic and functional outcome in the radial forearm free flap donor site using a simple split thickness skin grafting (STSG) closure compared with the use of dermal scaffold supporting the STSG closure.

    The study analyzed 18 patients, divided in 2 groups based on the donor site closure modality. In STSG group, a simple STSG was used to cover the defect. In the DS + STSG group, the defect was covered by the use of dermal substitute (MatriDerm) supporting the STSG. Groups were compared on the following outcome variable scar status; hand function; circumferences at most proximal and most distal point of the graft. All patients were followed up 1, 6, and 12 months post-operative.

    Nine patients from STSG group showed a difference in circumference between the operated and contralateral limbs respectively of 2.9 mm proximal and 1.2 mm distal; in the 9 patients of DS + STGS group the difference was respectively of 1.2 mm proximal and 1.3 mm distal. Welch unequal variances t-test demonstrated statistical significance of the values with P < 0.004 (P < 0.5). The average VSS was 1.82 ±â€Š0.2 for STSG group and 1.75 ±â€Š0.2 for DS + STGS group. The DASH score was 21.8% in STSG group and 19.4% in DS + STGS group.

    Our study shows that patients treated with Matriderm + STSG obtained a better result both in esthetic and functional outcomes.
    Our study shows that patients treated with Matriderm + STSG obtained a better result both in esthetic and functional outcomes.
    First, the authors' method is performed only in a single stage. Second, the flap is based on a rich vascular supply from the angular artery, which eliminates the possibility of flap necrosis through multiple turnovers. Third, because the turnover nasolabial flap is a construct of the epidermis, dermis, and subcutaneous fat, the flap is quite stiff thus reducing the possibility of nostril collapse. Fourth, the procedure leaves no scars in the superior area of the nose other than the nasolabial fold scar. To (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI). Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material. The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential. A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation. A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation. Within the context of xerostomia, there is evidence that adipose-derived stem cells (ASCs) can differentiate into salivary gland cells in the appropriate environment. The purpose of this study was to preliminarily investigate whether fat grafting as practiced in the United States would be an effective treatment for xerostomia. Patients were selected for the study if they were seeking treatment for xerostomia after radiation treatment to the head and neck for cancer treatment. Fat grafting was performed in bilateral parotid and submandibular glands. Visual Analog Scale (VAS) of xerostomia was used both preoperatively and postoperatively to assess the effect upon xerostomia symptoms. Nine patients were included in this study. All patients had complaints of long-standing xerostomia. The average preoperative VAS score was 9.1. All patients tolerated all rounds of fat grafting with no complications. The average postoperative VAS score was 6.0. Compared to preoperative scores, all patients had improvement in VAS scores. The decrease in average VAS score postoperatively (9.1 versus 6.0) was statistically significant (P = 0.007). Our study showed that there was improvement in xerostomia symptoms with autologous fat transfer alone. This is a novel finding for fat grafting demonstrating regenerative potential. There has been extensive basic research that has shown that adipose-derived mesenchymal stem cells can have a protective and restorative role after salivary gland radiation damage. Our case series is the first report of fat grafting having a similar reported outcome. 4. 4. The purpose of this study was to investigate the advantages of endoscopic lateral osteotomy, to evaluate the effects of the periosteal elevation on ecchymosis and to search the reasons for the ecchymosis and the intranasal mucosal tears. On a randomly chosen side a subperiosteal tunnel was elevated, on the other side a subperiosteal tunnel was not elevated. Bilateral lateral osteotomies were performed. Internal nasal packing was not used. The post-operative care was similar for all patients. The patients were evaluated on the third post-operative day. The intranasal mucosal tears, the lateral osteotomy cut on the periosteal elevation side were examined using endoscopes. The degree of ecchymosis was determined by 2 other surgeons, who were unaware of the elevated side, using the grading system adapted from Hoffman et al. RESULTS The intranasal mucosal injury was seen in 16 of non-elevated side whereas it was 14 on the periosteal elevated side. Endoscopy showed the perforating arteries and elevation of the ot due to the trauma of the angular artery. https://www.selleckchem.com/products/img-7289.html Intramucosal tears do not increase the severity of the ecchymosis. The aim of our study was to analyze the aesthetic and functional outcome in the radial forearm free flap donor site using a simple split thickness skin grafting (STSG) closure compared with the use of dermal scaffold supporting the STSG closure. The study analyzed 18 patients, divided in 2 groups based on the donor site closure modality. In STSG group, a simple STSG was used to cover the defect. In the DS + STSG group, the defect was covered by the use of dermal substitute (MatriDerm) supporting the STSG. Groups were compared on the following outcome variable scar status; hand function; circumferences at most proximal and most distal point of the graft. All patients were followed up 1, 6, and 12 months post-operative. Nine patients from STSG group showed a difference in circumference between the operated and contralateral limbs respectively of 2.9 mm proximal and 1.2 mm distal; in the 9 patients of DS + STGS group the difference was respectively of 1.2 mm proximal and 1.3 mm distal. Welch unequal variances t-test demonstrated statistical significance of the values with P < 0.004 (P < 0.5). The average VSS was 1.82 ±â€Š0.2 for STSG group and 1.75 ±â€Š0.2 for DS + STGS group. The DASH score was 21.8% in STSG group and 19.4% in DS + STGS group. Our study shows that patients treated with Matriderm + STSG obtained a better result both in esthetic and functional outcomes. Our study shows that patients treated with Matriderm + STSG obtained a better result both in esthetic and functional outcomes.
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  • uropean ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake.
    We identified multiple suggestive loci for sodium and potassium intake near genes associated with eating behavior, nervous system development and function, and blood pressure regulation in individuals of European ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake.Given ever increasing ease of access to technology, the majority of adults first turn to the internet for medical advice. The world wide web is filled with user-generated content within multiple social media platforms that lack a governing body to validate the information's accuracy and reliability. The authors performed a qualitative review of first-aid burn resources available on YouTube using two validated scales Modified Discern and Global Quality Scale. A search was conducted using the term "burn treatment" on September 18, 2019. Of 120 reviewed videos, 59 met their inclusion criteria. 36% (n = 21) of the speakers had formal medical training, with only 12% (n = 7) identified as burn care professionals. The mean views originating from nonmedical speakers (162,675) were more than eight times that originating from burn centers (14,975). The quality of the videos was compared by video source, speaker, and specialty. Burn centers had the highest Modified Discern and Global Quality Scale scores, 2.91 and 2.86, respectively (P less then .05). Additionally, the authors were able to demonstrate that there was a statistically significant higher quality of videos when the speaker was a burn care professional or had formal medical training. Unfortunately, their review demonstrated that videos originating from hospital systems and burn centers made up a minority of the online media content. These results illustrate an opportunity for improvement by way of increased content creation to bolster the online presence of the burn community and provide patients with more accurate information.
    Interval cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising oncologic outcomes for patients with advanced ovarian cancer, but a large-scale, multicenter study to evaluate the efficacy of HIPEC combined with primary cytoreductive surgery (PCS) has yet to be conducted.

    To compare survival outcomes between PCS with HIPEC vs PCS alone for patients with stage III epithelial ovarian cancer.

    This cohort study was conducted from January 2010 to May 2017 at 5 high-volume institutions in China. A total of 584 patients with stage III primary epithelial ovarian cancer were treated with either PCS alone or PCS with HIPEC. The median (interquartile range) follow-up period was 42.2 (33.3-51.0) months. Data analysis was conducted from August to December 2019.

    PCS with HIPEC vs PCS alone.

    Primary outcomes were median survival time and 3-year overall survival. The inverse probability of treatment weighting (IPTW) method, based on propensity score, was used to controsurvival. When complete PCS is possible, this approach could be a valuable therapy for patients with stage III epithelial ovarian cancer.
    Stress among health care professionals is well documented. The use of mindfulness-based interventions to reduce stress has shown promising results; however, the time commitment of typical programs can be a barrier to successful implementation in health care settings.

    To determine the efficacy and feasibility of a brief mindfulness-based program to reduce stress during work hours among health care professionals.

    This intent-to-treat randomized clinical trial was conducted among full-time health care professionals at the Clinical Center at the National Institutes of Health in Bethesda, Maryland, between September 2017 and May 2018. Participants were randomized to receive mindfulness-based self-care (MBSC) training or life-as-usual control. Data were analyzed from June 2018 to January 2020.

    The MBSC intervention included 5 weekly, 1.5-hour in-class mindfulness practice sessions.

    Stress level was the primary outcome, assessed with the Perceived Stress Scale 10-Item version. Secondary outcomes included a.001), and mindful self-care (mean [SD] score, 7.29 [2.44] vs 5.54 [2.77]; P < .001). Burnout, negative affect, and trait mindfulness levels did not differ between groups. Changes within the MBSC group through follow-up included sustained reductions in stress (change, -6.14; 95% CI, -7.84 to -4.44; P < .001), anxiety (change, -1.46; 95% CI, -1.97 to -0.94; P < .001), trait mindfulness (change, 0.63; 95% CI, 0.36 to 0.90; P < .001), and state mindfulness (change, 1.89; 95% CI, 1.39 to 2.39; P < .001).

    This randomized clinical trial found that this brief mindfulness-based intervention was an effective and feasible means to reduce stress in health care professionals. Larger studies are needed to assess the effects on clinical care and patient outcomes.

    ClinicalTrials.gov Identifier NCT03781336.
    ClinicalTrials.gov Identifier NCT03781336.
    Two 2018 randomized controlled trials (DAWN and DEFUSE 3) demonstrated the clinical benefit of mechanical thrombectomy (MT) more than 6 hours after onset in acute ischemic stroke (AIS). https://www.selleckchem.com/products/Mubritinib-TAK-165.html Health-economic evidence is needed to determine whether the short-term health benefits of late MT translate to a cost-effective option during a lifetime in the United States.

    To compare the cost-effectiveness of 2 strategies (MT added to standard medical care [SMC] vs SMC alone) for various subgroups of patients with AIS receiving care more than 6 hours after symptom onset.

    This economic evaluation study used the results of the DAWN and DEFUSE 3 trials to populate a cost-effectiveness model from a US health care perspective combining a decision tree and Markov trace. The DAWN and DEFUSE 3 trials enrolled 206 international patients from 2014 to 2017 and 182 US patients from 2016 to 2017, respectively. Patients were followed until 3 months after stroke. The clinical outcome at 3 months was available for 29 subgroups of patients with AIS and anterior circulation large vessel occlusions.
    uropean ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake. We identified multiple suggestive loci for sodium and potassium intake near genes associated with eating behavior, nervous system development and function, and blood pressure regulation in individuals of European ancestry. Further research is needed to replicate these findings and to provide insight into the underlying genetic mechanisms by which these genomic regions influence sodium and potassium intake.Given ever increasing ease of access to technology, the majority of adults first turn to the internet for medical advice. The world wide web is filled with user-generated content within multiple social media platforms that lack a governing body to validate the information's accuracy and reliability. The authors performed a qualitative review of first-aid burn resources available on YouTube using two validated scales Modified Discern and Global Quality Scale. A search was conducted using the term "burn treatment" on September 18, 2019. Of 120 reviewed videos, 59 met their inclusion criteria. 36% (n = 21) of the speakers had formal medical training, with only 12% (n = 7) identified as burn care professionals. The mean views originating from nonmedical speakers (162,675) were more than eight times that originating from burn centers (14,975). The quality of the videos was compared by video source, speaker, and specialty. Burn centers had the highest Modified Discern and Global Quality Scale scores, 2.91 and 2.86, respectively (P less then .05). Additionally, the authors were able to demonstrate that there was a statistically significant higher quality of videos when the speaker was a burn care professional or had formal medical training. Unfortunately, their review demonstrated that videos originating from hospital systems and burn centers made up a minority of the online media content. These results illustrate an opportunity for improvement by way of increased content creation to bolster the online presence of the burn community and provide patients with more accurate information. Interval cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising oncologic outcomes for patients with advanced ovarian cancer, but a large-scale, multicenter study to evaluate the efficacy of HIPEC combined with primary cytoreductive surgery (PCS) has yet to be conducted. To compare survival outcomes between PCS with HIPEC vs PCS alone for patients with stage III epithelial ovarian cancer. This cohort study was conducted from January 2010 to May 2017 at 5 high-volume institutions in China. A total of 584 patients with stage III primary epithelial ovarian cancer were treated with either PCS alone or PCS with HIPEC. The median (interquartile range) follow-up period was 42.2 (33.3-51.0) months. Data analysis was conducted from August to December 2019. PCS with HIPEC vs PCS alone. Primary outcomes were median survival time and 3-year overall survival. The inverse probability of treatment weighting (IPTW) method, based on propensity score, was used to controsurvival. When complete PCS is possible, this approach could be a valuable therapy for patients with stage III epithelial ovarian cancer. Stress among health care professionals is well documented. The use of mindfulness-based interventions to reduce stress has shown promising results; however, the time commitment of typical programs can be a barrier to successful implementation in health care settings. To determine the efficacy and feasibility of a brief mindfulness-based program to reduce stress during work hours among health care professionals. This intent-to-treat randomized clinical trial was conducted among full-time health care professionals at the Clinical Center at the National Institutes of Health in Bethesda, Maryland, between September 2017 and May 2018. Participants were randomized to receive mindfulness-based self-care (MBSC) training or life-as-usual control. Data were analyzed from June 2018 to January 2020. The MBSC intervention included 5 weekly, 1.5-hour in-class mindfulness practice sessions. Stress level was the primary outcome, assessed with the Perceived Stress Scale 10-Item version. Secondary outcomes included a.001), and mindful self-care (mean [SD] score, 7.29 [2.44] vs 5.54 [2.77]; P < .001). Burnout, negative affect, and trait mindfulness levels did not differ between groups. Changes within the MBSC group through follow-up included sustained reductions in stress (change, -6.14; 95% CI, -7.84 to -4.44; P < .001), anxiety (change, -1.46; 95% CI, -1.97 to -0.94; P < .001), trait mindfulness (change, 0.63; 95% CI, 0.36 to 0.90; P < .001), and state mindfulness (change, 1.89; 95% CI, 1.39 to 2.39; P < .001). This randomized clinical trial found that this brief mindfulness-based intervention was an effective and feasible means to reduce stress in health care professionals. Larger studies are needed to assess the effects on clinical care and patient outcomes. ClinicalTrials.gov Identifier NCT03781336. ClinicalTrials.gov Identifier NCT03781336. Two 2018 randomized controlled trials (DAWN and DEFUSE 3) demonstrated the clinical benefit of mechanical thrombectomy (MT) more than 6 hours after onset in acute ischemic stroke (AIS). https://www.selleckchem.com/products/Mubritinib-TAK-165.html Health-economic evidence is needed to determine whether the short-term health benefits of late MT translate to a cost-effective option during a lifetime in the United States. To compare the cost-effectiveness of 2 strategies (MT added to standard medical care [SMC] vs SMC alone) for various subgroups of patients with AIS receiving care more than 6 hours after symptom onset. This economic evaluation study used the results of the DAWN and DEFUSE 3 trials to populate a cost-effectiveness model from a US health care perspective combining a decision tree and Markov trace. The DAWN and DEFUSE 3 trials enrolled 206 international patients from 2014 to 2017 and 182 US patients from 2016 to 2017, respectively. Patients were followed until 3 months after stroke. The clinical outcome at 3 months was available for 29 subgroups of patients with AIS and anterior circulation large vessel occlusions.
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  • The unusual α-amino, β-hydroxy acid MeBmt is a key structural feature of cyclosporin A, an important naturally occurring immunosuppressant and antiviral agent. We present a convergent synthesis of MeBmt which relies on new aspects of dynamic kinetic resolution (DKR) to establish simultaneously the chirality at C(2) and C(3). We also show that this route is applicable to the synthesis of other derivatives.This Correspondence article is a counterstatement to a Brief Report published by Lachenmeier and co-workers on 17th February 2020 in F1000Research "Are side effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?". This counterstatement proposes that the authors of that article neither present proof or evidence for the alleged side effects of CBD products (no case reports presented with utilisable data), nor do they show that side effects are due to the presence of THC. https://www.selleckchem.com/products/bip-inducer-x-bix.html Primarily, there is no clear definition of THC because the authors do not explain whether they mean Delta9-THC only (without its precursor tetrahydrocannabinolic acid (THCA)) or total-THC (the sum of Delta9-THC and its precursor THCA, normalised to THC); indeed EU Recommendation 2016/2115 on the monitoring of cannabinoids in food requires the measurement and documentation of the precursor acids complementary to the decarboxylated cannabinoids. The key part of the authors' work - Table 2 with the assessment of the CBD products - leaves the reader in the dark about the nature of "THC". This is all the more concerning because acid-free Delta9-THC is psychotropic but THCA is not. Additionally, the classification of the CBD products ("toxicity assessment") presented is based on the assignment of the quantitative relation to the LOAEL (lowest observed adverse effect level) of THC (2.5 mg of acid-free Delta9-THC per adult and day as assigned by EFSA, 2015). However, many assumptions by Lachenmeier et al. on daily intake of CBD products are questionable, in particular food supplements, where the recommended daily consumption was missing on the label. Finally, the authors of the paper also compare their findings with the German recommendations on maximum levels of total-THC in food, ignoring that those limits refer to total-THC and the ready-to-eat products, and not to the food ingredient itself - in particular hemp tea products.Primary rectal squamous cell carcinoma is rare compared to adenocarcinoma, which is the predominant histologic type most commonly discovered at the time of colorectal carcinoma diagnosis. Due to the infrequent nature of this malignancy, data on tumor pathogenesis and risk factors remains sparse. Moreover, no standardized therapeutic regimen exists. This report describes a case of advanced rectal squamous cell carcinoma diagnosed in a 46-year-old female who initially presented with abdominal pain. Her clinical course was uncomplicated and she responded well to the selected therapy. **** work remains to be accomplished for patients with rectal squamous cell carcinoma.Background School closures have been a recommended non-pharmaceutical intervention in pandemic response owing to the potential to reduce transmission of infection between children, school staff and those that they contact. However, given the many roles that schools play in society, closure for any extended period is likely to have additional impacts. Literature reviews of research exploring school closure to date have focused upon epidemiological effects; there is an unmet need for research that considers the multiplicity of potential impacts of school closures. Methods We used systematic searching, coding and synthesis techniques to develop a systems-based logic model. We included literature related to school closure planned in response to epidemics large and small, spanning the 1918-19 'flu pandemic through to the emerging literature on the 2019 novel coronavirus. We used over 170 research studies and a number of policy documents to inform our model. Results The model organises the concepts used by authors into seven higher level domains children's health and wellbeing, children's education, impacts on teachers and other school staff, the school organisation, considerations for parents and families, public health considerations, and broader economic impacts. The model also collates ideas about potential moderating factors and ethical considerations. While dependent upon the nature of epidemics experienced to date, we aim for the model to provide a starting point for theorising about school closures in general, and as part of a wider system that is influenced by contextual and population factors. Conclusions The model highlights that the impacts of school closures are **** broader than those related solely to health, and demonstrates that there is a need for further concerted work in this area. The publication of this logic model should help to frame future research in this area and aid decision-makers when considering future school closure policy and possible mitigation strategies.Background Improving maternal health and reducing maternal mortality are part of the United Nations global Sustainable Development Goals for 2030. Ensuring every woman's right to safe delivery is critical for reducing the maternal mortality rate. Our study aimed to identify determinants of safe delivery utilization among women in the eastern Indonesia. Methods This study was cross-sectional and used a secondary data from the 2017 Indonesian Demographic and Health Survey (IDHS). A total of 2,162 women who had their last child in the five years preceding the survey and lived in the eastern part of Indonesia were selected as the respondents. Chi-squared test and binary logistic regression were used to understand the determinants of safe delivery. Results Higher child rank and interval ≤2 years (OR 0.30, 95% CI 0.19-0.47), unwanted pregnancy at time of becoming pregnant (OR 1.48, 95% CI 1.05-2.08), richest wealth quintile (OR 5.59, 95% CI 3.37-9.30), more than four antenatal care visits (OR 3.62, 95% CI 2.73-4.79), rural residence, good composite labor force participation, and a good attitude towards domestic violence were found to be significantly associated with delivery at health facility. Higher child rank and interval ≤2 years (OR 0.49, 95% CI 0.29-0.83), husband/partner having completed secondary or higher education (OR 2.18, 95% CI 1.48-3.22), being in the richest wealth quintile, and four other factors were found to be significantly associated with the assistance of skilled birth attendants. Conclusions This research extends our knowledge on the determinants of safe delivery among women in the eastern part of Indonesia. This study revealed that the economic status of household remains an important issue in improving safe delivery among women in eastern part of Indonesia. An open innovation and partnership process to improve safe delivery program that engages the full range of stakeholders should be developed based on economic situation.
    The unusual α-amino, β-hydroxy acid MeBmt is a key structural feature of cyclosporin A, an important naturally occurring immunosuppressant and antiviral agent. We present a convergent synthesis of MeBmt which relies on new aspects of dynamic kinetic resolution (DKR) to establish simultaneously the chirality at C(2) and C(3). We also show that this route is applicable to the synthesis of other derivatives.This Correspondence article is a counterstatement to a Brief Report published by Lachenmeier and co-workers on 17th February 2020 in F1000Research "Are side effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?". This counterstatement proposes that the authors of that article neither present proof or evidence for the alleged side effects of CBD products (no case reports presented with utilisable data), nor do they show that side effects are due to the presence of THC. https://www.selleckchem.com/products/bip-inducer-x-bix.html Primarily, there is no clear definition of THC because the authors do not explain whether they mean Delta9-THC only (without its precursor tetrahydrocannabinolic acid (THCA)) or total-THC (the sum of Delta9-THC and its precursor THCA, normalised to THC); indeed EU Recommendation 2016/2115 on the monitoring of cannabinoids in food requires the measurement and documentation of the precursor acids complementary to the decarboxylated cannabinoids. The key part of the authors' work - Table 2 with the assessment of the CBD products - leaves the reader in the dark about the nature of "THC". This is all the more concerning because acid-free Delta9-THC is psychotropic but THCA is not. Additionally, the classification of the CBD products ("toxicity assessment") presented is based on the assignment of the quantitative relation to the LOAEL (lowest observed adverse effect level) of THC (2.5 mg of acid-free Delta9-THC per adult and day as assigned by EFSA, 2015). However, many assumptions by Lachenmeier et al. on daily intake of CBD products are questionable, in particular food supplements, where the recommended daily consumption was missing on the label. Finally, the authors of the paper also compare their findings with the German recommendations on maximum levels of total-THC in food, ignoring that those limits refer to total-THC and the ready-to-eat products, and not to the food ingredient itself - in particular hemp tea products.Primary rectal squamous cell carcinoma is rare compared to adenocarcinoma, which is the predominant histologic type most commonly discovered at the time of colorectal carcinoma diagnosis. Due to the infrequent nature of this malignancy, data on tumor pathogenesis and risk factors remains sparse. Moreover, no standardized therapeutic regimen exists. This report describes a case of advanced rectal squamous cell carcinoma diagnosed in a 46-year-old female who initially presented with abdominal pain. Her clinical course was uncomplicated and she responded well to the selected therapy. Much work remains to be accomplished for patients with rectal squamous cell carcinoma.Background School closures have been a recommended non-pharmaceutical intervention in pandemic response owing to the potential to reduce transmission of infection between children, school staff and those that they contact. However, given the many roles that schools play in society, closure for any extended period is likely to have additional impacts. Literature reviews of research exploring school closure to date have focused upon epidemiological effects; there is an unmet need for research that considers the multiplicity of potential impacts of school closures. Methods We used systematic searching, coding and synthesis techniques to develop a systems-based logic model. We included literature related to school closure planned in response to epidemics large and small, spanning the 1918-19 'flu pandemic through to the emerging literature on the 2019 novel coronavirus. We used over 170 research studies and a number of policy documents to inform our model. Results The model organises the concepts used by authors into seven higher level domains children's health and wellbeing, children's education, impacts on teachers and other school staff, the school organisation, considerations for parents and families, public health considerations, and broader economic impacts. The model also collates ideas about potential moderating factors and ethical considerations. While dependent upon the nature of epidemics experienced to date, we aim for the model to provide a starting point for theorising about school closures in general, and as part of a wider system that is influenced by contextual and population factors. Conclusions The model highlights that the impacts of school closures are much broader than those related solely to health, and demonstrates that there is a need for further concerted work in this area. The publication of this logic model should help to frame future research in this area and aid decision-makers when considering future school closure policy and possible mitigation strategies.Background Improving maternal health and reducing maternal mortality are part of the United Nations global Sustainable Development Goals for 2030. Ensuring every woman's right to safe delivery is critical for reducing the maternal mortality rate. Our study aimed to identify determinants of safe delivery utilization among women in the eastern Indonesia. Methods This study was cross-sectional and used a secondary data from the 2017 Indonesian Demographic and Health Survey (IDHS). A total of 2,162 women who had their last child in the five years preceding the survey and lived in the eastern part of Indonesia were selected as the respondents. Chi-squared test and binary logistic regression were used to understand the determinants of safe delivery. Results Higher child rank and interval ≤2 years (OR 0.30, 95% CI 0.19-0.47), unwanted pregnancy at time of becoming pregnant (OR 1.48, 95% CI 1.05-2.08), richest wealth quintile (OR 5.59, 95% CI 3.37-9.30), more than four antenatal care visits (OR 3.62, 95% CI 2.73-4.79), rural residence, good composite labor force participation, and a good attitude towards domestic violence were found to be significantly associated with delivery at health facility. Higher child rank and interval ≤2 years (OR 0.49, 95% CI 0.29-0.83), husband/partner having completed secondary or higher education (OR 2.18, 95% CI 1.48-3.22), being in the richest wealth quintile, and four other factors were found to be significantly associated with the assistance of skilled birth attendants. Conclusions This research extends our knowledge on the determinants of safe delivery among women in the eastern part of Indonesia. This study revealed that the economic status of household remains an important issue in improving safe delivery among women in eastern part of Indonesia. An open innovation and partnership process to improve safe delivery program that engages the full range of stakeholders should be developed based on economic situation.
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  • For the field of virology, perhaps one of the most paradigm-shifting events so far in the 21st century was the identification of the giant double-stranded DNA virus that infects amoebae. https://www.selleckchem.com/products/ABT-263.html Remarkably, this virus, known as Mimivirus, has a genome that encodes for nearly 1,000 proteins, some of which are involved in the biosynthesis of unusual sugars. Indeed, the virus is coated by a layer of glycosylated fibers that contain d-glucose, N-acetyl-d-glucosamine, l-rhamnose, and 4-amino-4,6-dideoxy-d-glucose. Here we describe a combined structural and enzymological investigation of the protein encoded by the open-reading frame L780, which corresponds to an l-rhamnose synthase. The structure of the L780/NADP+ /UDP-l-rhamnose ternary complex was determined to 1.45 Å resolution and refined to an overall R-factor of 19.9%. Each subunit of the dimeric protein adopts a bilobal-shaped appearance with the N-terminal domain harboring the dinucleotide-binding site and the C-terminal domain positioning the UDP-sugar into the active site. The overall molecular architecture of L780 places it into the short-chain dehydrogenase/reductase superfamily. Kinetic analyses indicate that the enzyme can function on either UDP- and dTDP-sugars but displays a higher catalytic efficiency with the UDP-linked substrate. Site-directed mutagenesis experiments suggest that both Cys 108 and Lys 175 play key roles in catalysis. This structure represents the first model of a viral UDP-l-rhamnose synthase and provides new details into these fascinating enzymes.Protein-protein interactions (PPIs) in all the molecular aspects that take place both inside and outside cells. However, determining experimentally the structure and affinity of PPIs is expensive and time consuming. Therefore, the development of computational tools, as a complement to experimental methods, is fundamental. Here, we present a computational suite MODPIN, to model and predict the changes of binding affinity of PPIs. In this approach we use homology modeling to derive the structures of PPIs and score them using state-of-the-art scoring functions. We explore the conformational space of PPIs by generating not a single structural model but a collection of structural models with different conformations based on several templates. We apply the approach to predict the changes in free energy upon mutations and splicing variants of large datasets of PPIs to statistically quantify the quality and accuracy of the predictions. As an example, we use MODPIN to study the effect of mutations in the interaction between colicin endonuclease 9 and colicin endonuclease 2 immune protein from Escherichia coli. Finally, we have compared our results with other state-of-art methods.Immunoglobulin (Ig) domains are the most prevalent protein domain structure and share a highly conserved folding pattern; however, this structural family of proteins is also the most diverse in terms of biological roles and tissue expression. Ig domains vary significantly in amino acid sequence but share a highly conserved tryptophan in the hydrophobic core of this beta-stranded protein. Palladin is an actin binding and bundling protein that has five Ig domains and plays an important role in normal cell adhesion and motility. Mutation of the core tryptophan in one Ig domain of palladin has been identified in a pancreatic cancer cell line, suggesting a crucial role for this sole tryptophan in palladin Ig domain structure, stability, and function. We found that actin binding and bundling was not completely abolished with removal of this tryptophan despite a partially unfolded structure and significantly reduced stability of the mutant Ig domain as shown by circular dichroism investigations. In addition, this mutant palladin domain displays a tryptophan-like fluorescence attributed to an anomalous tyrosine emission at 341 nm. Our results indicate that this emission originates from a tyrosinate that may be formed in the excited ground state by proton transfer to a nearby aspartic acid residue. Furthermore, this study emphasizes the importance of tryptophan in protein structural stability and illustrates how tyrosinate emission contributions may be overlooked during the interpretation of the fluorescence properties of proteins.Since December 2019, we have been in the battlefield with a new threat to the humanity, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), characterized by viral pneumonia. It may be asymptomatic or cause various symptoms, ranging from flu-like symptoms to acute respiratory distress syndrome and eventually death. At present, the only reliable test for COVID-19 diagnosis is quantitative reverse transcriptase-polymerase chain reaction. Assessing the immune response against SARS-CoV-2 could increase the detection sensitivity of infected population. Hereby, we report the performances of a fully automated chemiluminescent immunoassay (CLIA) on 276 serum samples. One hundred samples obtained from COVID-19 negative subjects (COVID-19 free) were analyzed to evaluate the diagnostic specificity of antibody (Ab) detection. Thereafter, 176 samples obtained from 125 patients with confirmed COVID-19 (COVID-19 patients) were selected to assess the diagnostic sensitivity of the CLIA. All samples were analyzed on MAGLUMI 800 platform. All COVID-19 free samples had Ab levels below the cutoff values. Hence, the diagnostic specificity was estimated at 100% (95% confidence interval [CI] = 96.3-100.0; positive predictive value = 100%). By the 18th day from the onset of symptoms, we reached an optimal diagnostic sensitivity (more than 95.0%) In fact, the diagnostic sensitivity increased over time and between 15 and 25 days after symptoms onset, reached 95.5% (95% CI = 84.9-99.2). The new automated CLIA analyzer appeared to be a robust and reliable method to measure specific Ab against COVID-19 at high throughput. Our data suggest that combining Ab and nucleic acid detection could increase diagnostic sensitivity.Worldwide, over 70.8 million people are forcibly displaced from their homes as a result of persecution, conflict, violence, or human rights violation. In humanitarian crises, protection and the provision of basic needs are often prioritized. Research may be seen as opportunistic. However, without documenting and researching humanitarian responses, knowledge is not shared and does not accumulate, limiting the application of evidence-based interventions where they are most needed. Research in humanitarian crises is complex, both ethically and methodologically. Community-engaged research, and specifically community-based participatory research (CBPR), can address some of the challenges of research in these settings. Using case studies of research we have conducted with communities affected by humanitarian crises, we highlight challenges and opportunities of the application of the ten core principles of CBPR in humanitarian settings. Despite some challenges and barriers, CBPR is a highly effective approach to use when engaging these populations in research.
    For the field of virology, perhaps one of the most paradigm-shifting events so far in the 21st century was the identification of the giant double-stranded DNA virus that infects amoebae. https://www.selleckchem.com/products/ABT-263.html Remarkably, this virus, known as Mimivirus, has a genome that encodes for nearly 1,000 proteins, some of which are involved in the biosynthesis of unusual sugars. Indeed, the virus is coated by a layer of glycosylated fibers that contain d-glucose, N-acetyl-d-glucosamine, l-rhamnose, and 4-amino-4,6-dideoxy-d-glucose. Here we describe a combined structural and enzymological investigation of the protein encoded by the open-reading frame L780, which corresponds to an l-rhamnose synthase. The structure of the L780/NADP+ /UDP-l-rhamnose ternary complex was determined to 1.45 Å resolution and refined to an overall R-factor of 19.9%. Each subunit of the dimeric protein adopts a bilobal-shaped appearance with the N-terminal domain harboring the dinucleotide-binding site and the C-terminal domain positioning the UDP-sugar into the active site. The overall molecular architecture of L780 places it into the short-chain dehydrogenase/reductase superfamily. Kinetic analyses indicate that the enzyme can function on either UDP- and dTDP-sugars but displays a higher catalytic efficiency with the UDP-linked substrate. Site-directed mutagenesis experiments suggest that both Cys 108 and Lys 175 play key roles in catalysis. This structure represents the first model of a viral UDP-l-rhamnose synthase and provides new details into these fascinating enzymes.Protein-protein interactions (PPIs) in all the molecular aspects that take place both inside and outside cells. However, determining experimentally the structure and affinity of PPIs is expensive and time consuming. Therefore, the development of computational tools, as a complement to experimental methods, is fundamental. Here, we present a computational suite MODPIN, to model and predict the changes of binding affinity of PPIs. In this approach we use homology modeling to derive the structures of PPIs and score them using state-of-the-art scoring functions. We explore the conformational space of PPIs by generating not a single structural model but a collection of structural models with different conformations based on several templates. We apply the approach to predict the changes in free energy upon mutations and splicing variants of large datasets of PPIs to statistically quantify the quality and accuracy of the predictions. As an example, we use MODPIN to study the effect of mutations in the interaction between colicin endonuclease 9 and colicin endonuclease 2 immune protein from Escherichia coli. Finally, we have compared our results with other state-of-art methods.Immunoglobulin (Ig) domains are the most prevalent protein domain structure and share a highly conserved folding pattern; however, this structural family of proteins is also the most diverse in terms of biological roles and tissue expression. Ig domains vary significantly in amino acid sequence but share a highly conserved tryptophan in the hydrophobic core of this beta-stranded protein. Palladin is an actin binding and bundling protein that has five Ig domains and plays an important role in normal cell adhesion and motility. Mutation of the core tryptophan in one Ig domain of palladin has been identified in a pancreatic cancer cell line, suggesting a crucial role for this sole tryptophan in palladin Ig domain structure, stability, and function. We found that actin binding and bundling was not completely abolished with removal of this tryptophan despite a partially unfolded structure and significantly reduced stability of the mutant Ig domain as shown by circular dichroism investigations. In addition, this mutant palladin domain displays a tryptophan-like fluorescence attributed to an anomalous tyrosine emission at 341 nm. Our results indicate that this emission originates from a tyrosinate that may be formed in the excited ground state by proton transfer to a nearby aspartic acid residue. Furthermore, this study emphasizes the importance of tryptophan in protein structural stability and illustrates how tyrosinate emission contributions may be overlooked during the interpretation of the fluorescence properties of proteins.Since December 2019, we have been in the battlefield with a new threat to the humanity, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), characterized by viral pneumonia. It may be asymptomatic or cause various symptoms, ranging from flu-like symptoms to acute respiratory distress syndrome and eventually death. At present, the only reliable test for COVID-19 diagnosis is quantitative reverse transcriptase-polymerase chain reaction. Assessing the immune response against SARS-CoV-2 could increase the detection sensitivity of infected population. Hereby, we report the performances of a fully automated chemiluminescent immunoassay (CLIA) on 276 serum samples. One hundred samples obtained from COVID-19 negative subjects (COVID-19 free) were analyzed to evaluate the diagnostic specificity of antibody (Ab) detection. Thereafter, 176 samples obtained from 125 patients with confirmed COVID-19 (COVID-19 patients) were selected to assess the diagnostic sensitivity of the CLIA. All samples were analyzed on MAGLUMI 800 platform. All COVID-19 free samples had Ab levels below the cutoff values. Hence, the diagnostic specificity was estimated at 100% (95% confidence interval [CI] = 96.3-100.0; positive predictive value = 100%). By the 18th day from the onset of symptoms, we reached an optimal diagnostic sensitivity (more than 95.0%) In fact, the diagnostic sensitivity increased over time and between 15 and 25 days after symptoms onset, reached 95.5% (95% CI = 84.9-99.2). The new automated CLIA analyzer appeared to be a robust and reliable method to measure specific Ab against COVID-19 at high throughput. Our data suggest that combining Ab and nucleic acid detection could increase diagnostic sensitivity.Worldwide, over 70.8 million people are forcibly displaced from their homes as a result of persecution, conflict, violence, or human rights violation. In humanitarian crises, protection and the provision of basic needs are often prioritized. Research may be seen as opportunistic. However, without documenting and researching humanitarian responses, knowledge is not shared and does not accumulate, limiting the application of evidence-based interventions where they are most needed. Research in humanitarian crises is complex, both ethically and methodologically. Community-engaged research, and specifically community-based participatory research (CBPR), can address some of the challenges of research in these settings. Using case studies of research we have conducted with communities affected by humanitarian crises, we highlight challenges and opportunities of the application of the ten core principles of CBPR in humanitarian settings. Despite some challenges and barriers, CBPR is a highly effective approach to use when engaging these populations in research.
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  • n those who went a few days later for receiving the missed/late dose. Conclusion The adherence rate to BPG injection among RHD patients was found to be high (80.60%). Patients' admission status and their action on missed and/or late doses were found to be important determinants of adherence in this study. © 2020 Mekonen et al.Purpose Counselees' preferences are considered important for the choice of risk communication format and for improving patient-centered care. We here report on counselees' preferences for how risks are presented in familial breast cancer counseling and the impact of this preferred format on their understanding of risk. Patients and Methods As part of a practice-based randomized controlled trial, 326 unaffected women with a family history of breast cancer received their lifetime risk in one of five presentation formats after standard genetic counseling in three Dutch familial cancer clinics 1) in percentages, 2) in frequencies ("X out of 100"), 3) in frequencies plus graphical format (10×10 human icons), 4) in frequencies and 10-year age-related risk and 5) in frequencies and 10-year age-related risk plus graphical format. Format preferences and risk understanding (accuracy) were assessed at 2-week follow-up by a questionnaire, completed by 279/326 women. https://www.selleckchem.com/products/JNJ-7706621.html Results The most preferred risk communication formats were numbers combined with verbal descriptions (37%) and numbers only (26%). Of the numerical formats, most (55%) women preferred percentages. The majority (73%) preferred to be informed about both lifetime and 10-year age-related risk. Women who had received a graphical display were more likely to choose a graphical display as their preferred format. There was no significant effect between the intervention groups with regard to risk accuracy. Overall, women given risk estimates in their preferred format had a slightly better understanding of risk. Conclusion The results suggest that the accuracy of breast cancer risk estimation is slightly better for women who had received this information in their preferred format, but the risk format used had no effect on women's risk accuracy. To meet the most frequent preference, counselors should consider providing a time frame of reference (eg, risk in the next 10 years) in a numerical format, in addition to lifetime risk. © 2020 Henneman et al.Objective Pharmacological interventions remain the cornerstone of chronic pain treatment; however, nearly 40% of the prescription medicines are not taken as prescribed. The present study aims at understanding and describing non-adherence from the perspective of chronic pain patients during a 1-year follow-up study. Methods A cohort of 950 consecutive patients referred to a first consultation in Multidisciplinary Chronic Pain Clinics was followed with a standardized protocol for 1 year. This included assessment of pain characteristics; prescribed medication; therapeutic adherence; effectiveness of treatment, non-adherence and its perceived reasons; clinical outcomes and quality of life. We used a mixed methods approach, including qualitative and quantitative analyses. Results Forty-nine percent of the 562 patients who responded to all assessments during follow-up were adherent after 1 year of chronic pain treatment. The core associations between each "non-adherence reason" and Anatomical Therapeutic Chemical Code (ATC) group were perceived side effects (p=0.019) and delayed start (p=0.022) for narcotic analgesics (opioids); perceived non-efficacy (p=0.017) and delayed start (p=0.004) for antiepileptics and anticonvulsants; perceived low necessity (p=0.041) and delayed start (p=0.036) for analgesics antipyretics; change in prescriptions because of a new clinical condition for antidepressants (p=0.024); high concerns (p=0.045) and change in prescriptions because of a new clinical condition (p less then 0.001) for non-steroidal anti-inflammatory drugs; delayed start (p=0.016) and financial constraints (p=0.018) for other medications. Discussion This study emphasizes the patient's perspective regarding non-adherence to pharmacological treatment of chronic pain, providing valuable and novel information to be used in future interventions to help patients make an informed choice about their adherence behavior. © 2020 Sampaio et al.Purpose This study is aiming to investigate cardiovascular patients' attitudes towards self-management during hospitalization in China. Patients and Methods Twenty-nine individuals living with cardiovascular disease from one designated Cardiology Department in Hangzhou, China, were recruited through a purposive sampling procedure. A qualitative descriptive methodology was used. Semi-structured interviews were also used to gain attitudes toward self-management. The interviews were audio-recorded, transcribed and analyzed by thematic analysis to develop the results. Results Four themes were identified from the qualitative data (1) Responsibilities of self-management; (2) Reflections on self-management; (3) Acknowledgement of self-management support; (4) Challenges in implementing and adherence to self-management. Additionally, interview data were also given to illustrate these main themes emerging during the analysis. Patients gradually took their responsibilities to manage chronic symptoms. During their self-management process, they did reflections to help correct their regiments through supportive interactions. Health system responsiveness, health disparities, social capital, and cultural setting were the main external factors influencing better self-management implementation and adherence. Conclusion This study revealed the hospitalized cardiovascular patients' attitudes towards self-management in China. These findings emphasized the importance of patients' responsibility, reflections, and various social support receiving and pointed out specific external factors influencing the health outcomes and their quality of life. This study also proves the guide for the policymakers and health system better instructions to develop individually and culturally tailored advanced self-management interventions and programs. © 2020 Qiu et al.
    n those who went a few days later for receiving the missed/late dose. Conclusion The adherence rate to BPG injection among RHD patients was found to be high (80.60%). Patients' admission status and their action on missed and/or late doses were found to be important determinants of adherence in this study. © 2020 Mekonen et al.Purpose Counselees' preferences are considered important for the choice of risk communication format and for improving patient-centered care. We here report on counselees' preferences for how risks are presented in familial breast cancer counseling and the impact of this preferred format on their understanding of risk. Patients and Methods As part of a practice-based randomized controlled trial, 326 unaffected women with a family history of breast cancer received their lifetime risk in one of five presentation formats after standard genetic counseling in three Dutch familial cancer clinics 1) in percentages, 2) in frequencies ("X out of 100"), 3) in frequencies plus graphical format (10×10 human icons), 4) in frequencies and 10-year age-related risk and 5) in frequencies and 10-year age-related risk plus graphical format. Format preferences and risk understanding (accuracy) were assessed at 2-week follow-up by a questionnaire, completed by 279/326 women. https://www.selleckchem.com/products/JNJ-7706621.html Results The most preferred risk communication formats were numbers combined with verbal descriptions (37%) and numbers only (26%). Of the numerical formats, most (55%) women preferred percentages. The majority (73%) preferred to be informed about both lifetime and 10-year age-related risk. Women who had received a graphical display were more likely to choose a graphical display as their preferred format. There was no significant effect between the intervention groups with regard to risk accuracy. Overall, women given risk estimates in their preferred format had a slightly better understanding of risk. Conclusion The results suggest that the accuracy of breast cancer risk estimation is slightly better for women who had received this information in their preferred format, but the risk format used had no effect on women's risk accuracy. To meet the most frequent preference, counselors should consider providing a time frame of reference (eg, risk in the next 10 years) in a numerical format, in addition to lifetime risk. © 2020 Henneman et al.Objective Pharmacological interventions remain the cornerstone of chronic pain treatment; however, nearly 40% of the prescription medicines are not taken as prescribed. The present study aims at understanding and describing non-adherence from the perspective of chronic pain patients during a 1-year follow-up study. Methods A cohort of 950 consecutive patients referred to a first consultation in Multidisciplinary Chronic Pain Clinics was followed with a standardized protocol for 1 year. This included assessment of pain characteristics; prescribed medication; therapeutic adherence; effectiveness of treatment, non-adherence and its perceived reasons; clinical outcomes and quality of life. We used a mixed methods approach, including qualitative and quantitative analyses. Results Forty-nine percent of the 562 patients who responded to all assessments during follow-up were adherent after 1 year of chronic pain treatment. The core associations between each "non-adherence reason" and Anatomical Therapeutic Chemical Code (ATC) group were perceived side effects (p=0.019) and delayed start (p=0.022) for narcotic analgesics (opioids); perceived non-efficacy (p=0.017) and delayed start (p=0.004) for antiepileptics and anticonvulsants; perceived low necessity (p=0.041) and delayed start (p=0.036) for analgesics antipyretics; change in prescriptions because of a new clinical condition for antidepressants (p=0.024); high concerns (p=0.045) and change in prescriptions because of a new clinical condition (p less then 0.001) for non-steroidal anti-inflammatory drugs; delayed start (p=0.016) and financial constraints (p=0.018) for other medications. Discussion This study emphasizes the patient's perspective regarding non-adherence to pharmacological treatment of chronic pain, providing valuable and novel information to be used in future interventions to help patients make an informed choice about their adherence behavior. © 2020 Sampaio et al.Purpose This study is aiming to investigate cardiovascular patients' attitudes towards self-management during hospitalization in China. Patients and Methods Twenty-nine individuals living with cardiovascular disease from one designated Cardiology Department in Hangzhou, China, were recruited through a purposive sampling procedure. A qualitative descriptive methodology was used. Semi-structured interviews were also used to gain attitudes toward self-management. The interviews were audio-recorded, transcribed and analyzed by thematic analysis to develop the results. Results Four themes were identified from the qualitative data (1) Responsibilities of self-management; (2) Reflections on self-management; (3) Acknowledgement of self-management support; (4) Challenges in implementing and adherence to self-management. Additionally, interview data were also given to illustrate these main themes emerging during the analysis. Patients gradually took their responsibilities to manage chronic symptoms. During their self-management process, they did reflections to help correct their regiments through supportive interactions. Health system responsiveness, health disparities, social capital, and cultural setting were the main external factors influencing better self-management implementation and adherence. Conclusion This study revealed the hospitalized cardiovascular patients' attitudes towards self-management in China. These findings emphasized the importance of patients' responsibility, reflections, and various social support receiving and pointed out specific external factors influencing the health outcomes and their quality of life. This study also proves the guide for the policymakers and health system better instructions to develop individually and culturally tailored advanced self-management interventions and programs. © 2020 Qiu et al.
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  • Enterobacterales and other non-fermenting Gram-negative bacteria have become a threat worldwide owing to the frequency of multidrug resistance in these pathogens. On the other hand, efficacious therapeutic options are quickly diminishing. The aims of this study were to describe the susceptibility of 50 multiresistant Gram-negative bacteria, mostly pan-resistant, against old and less-used antimicrobial drugs and to investigate the presence of antimicrobial resistance genes.

    A total of 50 genetically distinct isolates were included in this study, including 14 Acinetobacter baumannii (belonging to ST79, ST317, ST835 and ST836), 1 Pseudomonas aeruginosa (ST245), 8 Serratia marcescens and 27 Klebsiella pneumoniae (belonging to ST11, ST340, ST258, ST16, ST23, ST25, ST101, ST234, ST437 and ST442). The isolates were submitted to antimicrobial susceptibility testing and whole-genome sequencing to evaluate lineages and resistance genes.

    Our results showed that some strains harboured carbapenemase genes, e.g. bla
    mannii, ceftazidime/avibactam against Enterobacterales, and fosfomycin against S. marcescens.The potent aroma compounds in butter from four kinds of Chinese butter hotpot seasoning were first investigated by analyzing the isolates from solid-phase microextraction. A total of 49 aroma compounds were identified, and 23 of them were highly correlated with the aroma profiles of the butter by partial least squares regression analysis. Aroma extract dilution analysis and odor activity value calculations were applied to further reveal the dominant odorants. Fifty-three odorants with flavor dilution factors between 1 and 1024 were identified and OAVs of 17 odorants were greater than 1. Finally, an aroma recombination experiment was prepared by mixing the aroma-active compounds (OAVs > 1), and the aroma profile of the recombination showed good agreement with that of the original sample. Omission tests showed that 2-furfurylthiol, 2-acetylthiazole, anethole, (E)-2-decenal, and 1,8-cineole were the key odorants for the overall aroma of butter.The fatty acid content of flour is an important indicator for determining the deterioration of flour. We propose a novel rapid measurement method for fatty acid content during flour storage based on a self-designed color-sensitive gas sensor array. First, a color-sensitive gas sensor array was prepared to capture the odor changes during flour storage. The sensor features were then optimized using genetic algorithm (GA), ant colony optimization (ACO) and particle swarm optimization (PSO). Finally, **** propagation neural network (BPNN) models were established to measure the fatty acid content during flour storage. Experimental results showed that the optimization effects of the three algorithms improved in the following order GA less then ACO less then PSO, for the sensor features optimization. https://www.selleckchem.com/products/MK-1775.html In the validation set, the determination coefficient of the best PSO-BPNN model was 0.9837. The overall results demonstrate that the models established on the optimized features can realize rapid measurements of fatty acid content during flour storage.In bottled wines, haze and turbidity are phenomena to be avoided. Since bentonite fining is a common process to clarify wines removing heat unstable proteins, a theoretical study on the adsorption of three Charged Model Molecules (CMMs, egg albumin, polyphenols and riboflavin) was carried out to deep comprehend this chemical phenomenon. Four bentonites were adopted and finely characterized together with the potential release of Na+ and Ca2+ cations, revealing suitable for RT albumin removal within 120 min. Better results in terms of adsorbed quantity were achieved by adopting 12%v/v EtOH/H2O solvent and by swelling bentonites for 24 h before use. With the most performing sample (Na/Ca_0.27), a comprehensive study on simultaneous adsorption of the three CMMs was performed, resulting in polyphenols adsorption increase due to their interactions with albumin. Notwithstanding the majority of albumin and riboflavin was successfully removed, ca. 40-50% of tested polyphenols was preserved.Cadmium, inorganic arsenic and, potentially, dimethyl arsenic acid are carcinogens widely elevated in rice. Here it was identified that the food-safe and common cadmium chelator citric acid efficiently removed cadmium from intact grain via pre-soaking procedure, while also reducing arsenic species. A twostep pre-soaking stage was developed whereby rice was first incubated, at ambient temperature, in 1 M citric acid for 12 h, and then in 1 M calcium carbonate for another 12 h, the latter step to neutralize pH, followed by cooking. When 10 different individual types of rice were processed in such a way this resulted in removal rates of 79% for cadmium, 81% for inorganic arsenic and a 66% for DMA. The technology is particularly suitable for bulk food processing and could be deployed in the most cadmium and arsenic impacted regions where rice is a staple.Cyclodextrin (CD)-metal-organic frameworks (MOFs) are developed as a new type of food-acceptable multi-porous material, which shows a great potential for controlled volatile compound release. This study aimed to synthesize CD-MOFs from potassium nitrate, crystallized with α-cyclodextrin (α-CD), β-CD or γ-CD, and their complex capacities were further evaluated using menthol encapsulation. Compared with CD, all the CD-MOFs had highly ordered crystal structures and more regular shapes. β-CD-MOF showed better thermal stability, with an initial thermal degradation temperature of 253 °C, higher than the other two CD-MOFs. The CD-MOFs were used for menthol encapsulation and the resulting menthol concentration within the inclusion complexes (ICs) was determined. The menthol concentration in ICs followed the order β-CD-MOF > β-CD > γ-CD-MOF > γ-CD > α-CD ≥ α-CD-MOF. The menthol content and encapsulation efficiency of β-CD-MOF were 21.76% (w/w) and 22.54% (w/w) respectively, significantly higher than those of other reported solid materials, such as amylose, CD and V-type starch.Ochratoxin A (OTA) is a toxic metabolite that is widely distributed in food products. Herein, we proposed a new fluorescent aptasensor for OTA detection by using cascade strand displacement reaction. The binding of OTA and OTA aptamer on magnetic beads surface inhibited its hybridization with complementary DNA, and subsequently initiated the strand displacement reaction that induced amplified fluorescence signal. By tracing fluorescence response, our method demonstrated an improved detection limit of 0.63 ng/mL, a short assay time of 110 min, and a satisfactory detection specificity by using ochratoxin B, aflatoxin B1, and zearalenone as control toxins. Recovery studies were conducted by spiking OTA in real food samples, including white wine, red wine, cereal drink, coffee beverage and tea beverage, and confirmed desirable accuracy and practical applicability of our method. Therefore, our method may have a great potential use in the food quality control in the future.
    Enterobacterales and other non-fermenting Gram-negative bacteria have become a threat worldwide owing to the frequency of multidrug resistance in these pathogens. On the other hand, efficacious therapeutic options are quickly diminishing. The aims of this study were to describe the susceptibility of 50 multiresistant Gram-negative bacteria, mostly pan-resistant, against old and less-used antimicrobial drugs and to investigate the presence of antimicrobial resistance genes. A total of 50 genetically distinct isolates were included in this study, including 14 Acinetobacter baumannii (belonging to ST79, ST317, ST835 and ST836), 1 Pseudomonas aeruginosa (ST245), 8 Serratia marcescens and 27 Klebsiella pneumoniae (belonging to ST11, ST340, ST258, ST16, ST23, ST25, ST101, ST234, ST437 and ST442). The isolates were submitted to antimicrobial susceptibility testing and whole-genome sequencing to evaluate lineages and resistance genes. Our results showed that some strains harboured carbapenemase genes, e.g. bla mannii, ceftazidime/avibactam against Enterobacterales, and fosfomycin against S. marcescens.The potent aroma compounds in butter from four kinds of Chinese butter hotpot seasoning were first investigated by analyzing the isolates from solid-phase microextraction. A total of 49 aroma compounds were identified, and 23 of them were highly correlated with the aroma profiles of the butter by partial least squares regression analysis. Aroma extract dilution analysis and odor activity value calculations were applied to further reveal the dominant odorants. Fifty-three odorants with flavor dilution factors between 1 and 1024 were identified and OAVs of 17 odorants were greater than 1. Finally, an aroma recombination experiment was prepared by mixing the aroma-active compounds (OAVs > 1), and the aroma profile of the recombination showed good agreement with that of the original sample. Omission tests showed that 2-furfurylthiol, 2-acetylthiazole, anethole, (E)-2-decenal, and 1,8-cineole were the key odorants for the overall aroma of butter.The fatty acid content of flour is an important indicator for determining the deterioration of flour. We propose a novel rapid measurement method for fatty acid content during flour storage based on a self-designed color-sensitive gas sensor array. First, a color-sensitive gas sensor array was prepared to capture the odor changes during flour storage. The sensor features were then optimized using genetic algorithm (GA), ant colony optimization (ACO) and particle swarm optimization (PSO). Finally, back propagation neural network (BPNN) models were established to measure the fatty acid content during flour storage. Experimental results showed that the optimization effects of the three algorithms improved in the following order GA less then ACO less then PSO, for the sensor features optimization. https://www.selleckchem.com/products/MK-1775.html In the validation set, the determination coefficient of the best PSO-BPNN model was 0.9837. The overall results demonstrate that the models established on the optimized features can realize rapid measurements of fatty acid content during flour storage.In bottled wines, haze and turbidity are phenomena to be avoided. Since bentonite fining is a common process to clarify wines removing heat unstable proteins, a theoretical study on the adsorption of three Charged Model Molecules (CMMs, egg albumin, polyphenols and riboflavin) was carried out to deep comprehend this chemical phenomenon. Four bentonites were adopted and finely characterized together with the potential release of Na+ and Ca2+ cations, revealing suitable for RT albumin removal within 120 min. Better results in terms of adsorbed quantity were achieved by adopting 12%v/v EtOH/H2O solvent and by swelling bentonites for 24 h before use. With the most performing sample (Na/Ca_0.27), a comprehensive study on simultaneous adsorption of the three CMMs was performed, resulting in polyphenols adsorption increase due to their interactions with albumin. Notwithstanding the majority of albumin and riboflavin was successfully removed, ca. 40-50% of tested polyphenols was preserved.Cadmium, inorganic arsenic and, potentially, dimethyl arsenic acid are carcinogens widely elevated in rice. Here it was identified that the food-safe and common cadmium chelator citric acid efficiently removed cadmium from intact grain via pre-soaking procedure, while also reducing arsenic species. A twostep pre-soaking stage was developed whereby rice was first incubated, at ambient temperature, in 1 M citric acid for 12 h, and then in 1 M calcium carbonate for another 12 h, the latter step to neutralize pH, followed by cooking. When 10 different individual types of rice were processed in such a way this resulted in removal rates of 79% for cadmium, 81% for inorganic arsenic and a 66% for DMA. The technology is particularly suitable for bulk food processing and could be deployed in the most cadmium and arsenic impacted regions where rice is a staple.Cyclodextrin (CD)-metal-organic frameworks (MOFs) are developed as a new type of food-acceptable multi-porous material, which shows a great potential for controlled volatile compound release. This study aimed to synthesize CD-MOFs from potassium nitrate, crystallized with α-cyclodextrin (α-CD), β-CD or γ-CD, and their complex capacities were further evaluated using menthol encapsulation. Compared with CD, all the CD-MOFs had highly ordered crystal structures and more regular shapes. β-CD-MOF showed better thermal stability, with an initial thermal degradation temperature of 253 °C, higher than the other two CD-MOFs. The CD-MOFs were used for menthol encapsulation and the resulting menthol concentration within the inclusion complexes (ICs) was determined. The menthol concentration in ICs followed the order β-CD-MOF > β-CD > γ-CD-MOF > γ-CD > α-CD ≥ α-CD-MOF. The menthol content and encapsulation efficiency of β-CD-MOF were 21.76% (w/w) and 22.54% (w/w) respectively, significantly higher than those of other reported solid materials, such as amylose, CD and V-type starch.Ochratoxin A (OTA) is a toxic metabolite that is widely distributed in food products. Herein, we proposed a new fluorescent aptasensor for OTA detection by using cascade strand displacement reaction. The binding of OTA and OTA aptamer on magnetic beads surface inhibited its hybridization with complementary DNA, and subsequently initiated the strand displacement reaction that induced amplified fluorescence signal. By tracing fluorescence response, our method demonstrated an improved detection limit of 0.63 ng/mL, a short assay time of 110 min, and a satisfactory detection specificity by using ochratoxin B, aflatoxin B1, and zearalenone as control toxins. Recovery studies were conducted by spiking OTA in real food samples, including white wine, red wine, cereal drink, coffee beverage and tea beverage, and confirmed desirable accuracy and practical applicability of our method. Therefore, our method may have a great potential use in the food quality control in the future.
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  • n of these components with an interdisciplinary approach would help to manage hand disability properly.
    A growing body of experimental evidence suggests that hemin released from heme is a potent oxidant and accumulates in intracranial hematomas. Hemopexin (Hpx) decreases hemin accumulation and catabolism by nerve cells. In previous study, we observed that Hpx gene knockout aggravated striatal injury and worsened behavioral deficits of **** subjected to intracerebral hemorrhage.

    To examine the effect of Hpx on oxidative damage and apoptosis in cultured nerve cells with blood clot.

    Neuron and glial cells were transfected with adenoviral Hpx gene. Transfected primary neuron-glial cells were co-cultured with 50 μl of arterial blood clot using insert transwells. The sham group was co-coulture with 50 μl of DMEM/F12, which contained 28 μl of serum; the control group was transfected with adenoviral vector. At 12 and 24 h, the level of malonaldehyde (MDA), surperoxide dismutase (***) concentration, glutathione (GSH), apoptosis, expression of HO-1 and caspase-3 were detected.

    MDA level was decreased (P < 0.01) whereas *** and GSH concentration were increased in the Hpx group (P < 0.05 and P < 0.01, respectively). Results of flow cytometry revealed no significant difference in apoptosis between the Hpx group and model group at 12 h. However, the percentage of cells undergoing apoptosis in the Hpx group was decreased at 24 h compared with the model group (P < 0.01). HO-1 expression decreased in the Hpx group at 24 h (P < 0.01) while caspase-3 expression decreased at both 12 and 24 h (P < 0.011 and P < 0.05, respectively) compared with the model group.

    Hpx protected nerve cells exposed to blood from injury by anti-oxidation and a decrease in the expression of HO-1 and caspase-3.
    Hpx protected nerve cells exposed to blood from injury by anti-oxidation and a decrease in the expression of HO-1 and caspase-3.Malignant melanoma has a propensity for the development of hepatic and pulmonary metastases. MicroRNAs (miRs) are small, noncoding RNA molecules containing about 22 nucleotides that mediate protein expression and can contribute to cancer progression. We aim to identify clinically useful differences in miR expression in metastatic melanoma tissue. RNA was extracted from formalin-fixed, paraffin-embedded samples of hepatic and pulmonary metastatic melanoma, benign, nevi, and primary cutaneous melanoma. Assessment of miR expression was performed on purified RNA using the NanoString nCounter miRNA assay. miRs with greater than twofold change in expression when compared to other tumor sites (P value ≤ 0.05, modified t-test) were identified as dysregulated. Common gene targets were then identified among dysregulated miRs unique to each metastatic site. https://www.selleckchem.com/products/MK-1775.html Melanoma metastatic to the liver had differential expression of 26 miRs compared to benign nevi and 16 miRs compared to primary melanoma (P  less then  0.048). Melanoma metastatic to the lung had differential expression of 19 miRs compared to benign nevi and 10 miRs compared to primary melanoma (P  less then  0.024). Compared to lung metastases, liver metastases had greater than twofold upregulation of four miRs, and 4.2-fold downregulation of miR-200c-3p (P  less then  0.0081). These findings indicate that sites of metastatic melanoma have unique miR profiles that may contribute to their development and localization. Further investigation of the utility of these miRs as diagnostic and prognostic biomarkers and their impact on the development of metastatic melanoma is warranted.Melanoma disseminates to the skeletal system where it is then difficult to treat. Yet, there remains limited research investigating metastatic bone disease (MBD) in melanoma. Here, we evaluate whether there are distinct clinicopathologic variables at the time of primary melanoma diagnosis that predispose metastases to engraft bone, and we test the hypothesis that patients with MBD have different responses to treatment. Cutaneous melanoma patients enrolled in a prospective database were studied. Individuals with metastatic melanoma and bone metastases (M-Bone) were compared to those with metastatic disease but no M-Bone. Of the 463 (42.7%) patients, 198 with unresectable metastatic melanoma had M-Bone and 98 developed bone metastasis (bone mets) as first site. Progression-free survival and overall survival were significantly worse in patients with M-Bone compared to those without M-Bone (P less then 0.001) independent of treatment modalities, and in patients whose melanoma spread to bone first, compared to those who developed first mets elsewhere (P less then 0.001). Interestingly, patients with bone mets presented with primary tumors that had more tumor infiltrating lymphocytes (P less then 0.001) and less often a nodular histologic subtype compared to patients without M-Bone (P less then 0.001). Our data suggest that melanoma bone metastasis is a distinct clinical and biological entity that cannot be explained by generalized metastatic phenotype in all patients. The observed dichotomy between more favorable primary histopathologic characteristics and a grave overall prognosis requires more studies to elucidate the molecular processes by which melanomas infiltrate bone and to build a mechanistic understanding of how melanoma bone metastases yield such detrimental outcomes.Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive neoplasm typically presenting with widespread involvement of the abdominopelvic peritoneum of adolescent males, usually without organ-based primary. Although it is believed to originate from the serous (mainly peritoneal) membranes, intracranial, sinonasal, intraosseous, and other soft tissue sites are also documented. A chromosomal translocation t(1122)(p13;q12) signature that fuses EWSR1 and WT1 genes results in the production of a chimeric protein with transcriptional regulatory activity that drives oncogenesis. Integration of clinical, morphologic, immunohistochemical, and genetic data is necessary to arrive at the correct diagnosis, especially when the tumor arises in an atypical site. A 15-year-old male presented with hematuria and was found to have a large renal tumor associated with adrenal, liver, lung, and bone metastases. Histopathologic and immunophenotypic features were distinctive for DSRCT. This diagnosis was confirmed by means of fluorescence in situ hybridization and cytogenetic analysis, which documented the pathognomonic t(11;22) translocation, and by reverse transcription polymerase chain reaction on snap-frozen tissue, which revealed the EWSR1/WT1-specific chimeric transcript.
    n of these components with an interdisciplinary approach would help to manage hand disability properly. A growing body of experimental evidence suggests that hemin released from heme is a potent oxidant and accumulates in intracranial hematomas. Hemopexin (Hpx) decreases hemin accumulation and catabolism by nerve cells. In previous study, we observed that Hpx gene knockout aggravated striatal injury and worsened behavioral deficits of mice subjected to intracerebral hemorrhage. To examine the effect of Hpx on oxidative damage and apoptosis in cultured nerve cells with blood clot. Neuron and glial cells were transfected with adenoviral Hpx gene. Transfected primary neuron-glial cells were co-cultured with 50 μl of arterial blood clot using insert transwells. The sham group was co-coulture with 50 μl of DMEM/F12, which contained 28 μl of serum; the control group was transfected with adenoviral vector. At 12 and 24 h, the level of malonaldehyde (MDA), surperoxide dismutase (SOD) concentration, glutathione (GSH), apoptosis, expression of HO-1 and caspase-3 were detected. MDA level was decreased (P < 0.01) whereas SOD and GSH concentration were increased in the Hpx group (P < 0.05 and P < 0.01, respectively). Results of flow cytometry revealed no significant difference in apoptosis between the Hpx group and model group at 12 h. However, the percentage of cells undergoing apoptosis in the Hpx group was decreased at 24 h compared with the model group (P < 0.01). HO-1 expression decreased in the Hpx group at 24 h (P < 0.01) while caspase-3 expression decreased at both 12 and 24 h (P < 0.011 and P < 0.05, respectively) compared with the model group. Hpx protected nerve cells exposed to blood from injury by anti-oxidation and a decrease in the expression of HO-1 and caspase-3. Hpx protected nerve cells exposed to blood from injury by anti-oxidation and a decrease in the expression of HO-1 and caspase-3.Malignant melanoma has a propensity for the development of hepatic and pulmonary metastases. MicroRNAs (miRs) are small, noncoding RNA molecules containing about 22 nucleotides that mediate protein expression and can contribute to cancer progression. We aim to identify clinically useful differences in miR expression in metastatic melanoma tissue. RNA was extracted from formalin-fixed, paraffin-embedded samples of hepatic and pulmonary metastatic melanoma, benign, nevi, and primary cutaneous melanoma. Assessment of miR expression was performed on purified RNA using the NanoString nCounter miRNA assay. miRs with greater than twofold change in expression when compared to other tumor sites (P value ≤ 0.05, modified t-test) were identified as dysregulated. Common gene targets were then identified among dysregulated miRs unique to each metastatic site. https://www.selleckchem.com/products/MK-1775.html Melanoma metastatic to the liver had differential expression of 26 miRs compared to benign nevi and 16 miRs compared to primary melanoma (P  less then  0.048). Melanoma metastatic to the lung had differential expression of 19 miRs compared to benign nevi and 10 miRs compared to primary melanoma (P  less then  0.024). Compared to lung metastases, liver metastases had greater than twofold upregulation of four miRs, and 4.2-fold downregulation of miR-200c-3p (P  less then  0.0081). These findings indicate that sites of metastatic melanoma have unique miR profiles that may contribute to their development and localization. Further investigation of the utility of these miRs as diagnostic and prognostic biomarkers and their impact on the development of metastatic melanoma is warranted.Melanoma disseminates to the skeletal system where it is then difficult to treat. Yet, there remains limited research investigating metastatic bone disease (MBD) in melanoma. Here, we evaluate whether there are distinct clinicopathologic variables at the time of primary melanoma diagnosis that predispose metastases to engraft bone, and we test the hypothesis that patients with MBD have different responses to treatment. Cutaneous melanoma patients enrolled in a prospective database were studied. Individuals with metastatic melanoma and bone metastases (M-Bone) were compared to those with metastatic disease but no M-Bone. Of the 463 (42.7%) patients, 198 with unresectable metastatic melanoma had M-Bone and 98 developed bone metastasis (bone mets) as first site. Progression-free survival and overall survival were significantly worse in patients with M-Bone compared to those without M-Bone (P less then 0.001) independent of treatment modalities, and in patients whose melanoma spread to bone first, compared to those who developed first mets elsewhere (P less then 0.001). Interestingly, patients with bone mets presented with primary tumors that had more tumor infiltrating lymphocytes (P less then 0.001) and less often a nodular histologic subtype compared to patients without M-Bone (P less then 0.001). Our data suggest that melanoma bone metastasis is a distinct clinical and biological entity that cannot be explained by generalized metastatic phenotype in all patients. The observed dichotomy between more favorable primary histopathologic characteristics and a grave overall prognosis requires more studies to elucidate the molecular processes by which melanomas infiltrate bone and to build a mechanistic understanding of how melanoma bone metastases yield such detrimental outcomes.Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive neoplasm typically presenting with widespread involvement of the abdominopelvic peritoneum of adolescent males, usually without organ-based primary. Although it is believed to originate from the serous (mainly peritoneal) membranes, intracranial, sinonasal, intraosseous, and other soft tissue sites are also documented. A chromosomal translocation t(1122)(p13;q12) signature that fuses EWSR1 and WT1 genes results in the production of a chimeric protein with transcriptional regulatory activity that drives oncogenesis. Integration of clinical, morphologic, immunohistochemical, and genetic data is necessary to arrive at the correct diagnosis, especially when the tumor arises in an atypical site. A 15-year-old male presented with hematuria and was found to have a large renal tumor associated with adrenal, liver, lung, and bone metastases. Histopathologic and immunophenotypic features were distinctive for DSRCT. This diagnosis was confirmed by means of fluorescence in situ hybridization and cytogenetic analysis, which documented the pathognomonic t(11;22) translocation, and by reverse transcription polymerase chain reaction on snap-frozen tissue, which revealed the EWSR1/WT1-specific chimeric transcript.
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