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1.
Inorg Chem ; 63(22): 10386-10396, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38758612

RESUMEN

Scheelite-type metal oxides are a notable class of functional materials, with applications including ionic conductivity, photocatalysis, and the safe storage of radioactive waste. To further engineer these materials for specific applications, a detailed understanding of how their properties can change under different conditions is required─not just in the long-range average structure but also in the short-range local structure. This paper outlines a detailed investigation of the metal oxide CsReO4, which exhibits an uncommon orthorhombic Pnma pseudo-scheelite-type structure at room temperature. Using synchrotron X-ray diffraction, the average structure of CsReO4 is found to undergo a transformation from the orthorhombic Pnma pseudo-scheelite-type structure to the tetragonal I41/a scheelite-type structure at ∼440 K. In the X-ray pair distribution function analysis, lattice strain and rotations of the ReO4 tetrahedra are apparent above 440 K despite the increase in long-range average symmetry, revealing a disconnect between the structural models at different length scales. This study demonstrates how the bonding requirements and ionic radii of the A-site cation can induce disorder that is detectable at different length scales, affecting the physical properties of the material.

2.
Inorg Chem ; 63(33): 15433-15442, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39110061

RESUMEN

The structures and high-temperature phase transition of CaUNb2O8 were studied in situ using synchrotron X-ray and neutron powder diffraction. Rietveld refinements provided an accurate description of the crystal structures of both the monoclinic fergusonite-type I2/b structure observed at room temperature and the tetragonal scheelite-type I41/a structure found at high temperatures. Bond valence sum analysis showed Nb5+ to be octahedrally coordinated in the monoclinic fergusonite-type structure, akin to other ANbO4 materials. Rietveld analysis of the variable temperature data allowed for the determination of accurate unit cell parameters and atomic coordinates, as well as revealing a reversible phase transition around ∼750 °C. The Nb-O bond distances display anomalous behavior, with a discontinuity in the longer Nb-O(1') distance coinciding with the phase transition suggestive of a reconstructive phase transition. Mode analysis identified the Γ2+ mode as the primary mode that drives the phase transition; this is linearly coupled to the induced spontaneous strain within the monoclinic fergusonite-type structure. Analysis of the temperature dependence of the Nb(z) positional parameter, as well as of the ϵ1-ϵ2 and ϵ6 strain parameters, showed that the phase transition is not strictly second order, with the critical exponent ß ≠ 1/2. This study demonstrates the complex structural features of mixed cation metal oxides at elevated temperatures.

3.
Inorg Chem ; 63(24): 11176-11186, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38767205

RESUMEN

Pair distribution function (PDF) analysis of the scheelite-type material PbWO4 reveals previously unidentified short-range structural distortions in the PbO8 polyhedra and WO4 tetrahedra not observed in the similarly structured CaWO4. These local distortions are a result of the structural influence of the Pb2+ 6s2 lone pair electrons. These are not evident from the Rietveld analysis of synchrotron X-ray or neutron powder diffraction data, nor do they strongly influence the X-ray PDF (XPDF). This illustrates the importance of neutron PDF (NPDF) in the study of such materials. First-principles density function theory (DFT) calculations show that the Pb2+ 6s2 electrons are hybridized with the O2- 2p electrons near the Fermi level. The presence of local-scale distortions has previously been neglected in studies of structure-functionality relationships in PbWO4 and other scheelite-structured photocatalytic materials, including BiVO4, and this observation opens new avenues for their optimization.

4.
Arch Sex Behav ; 53(9): 3475-3484, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39138695

RESUMEN

As some BDSM activities can carry risk of temporary or permanent marks/injury, and even death, safety is a foundational principle to BDSM participation. Given the connection between BDSM and sex for some practitioners, pornography is a likely domain for learning about BDSM safety, given its easy accessibility online. However, it is unclear whether practitioners view BDSM safety depicted in pornography as accurate and whether it influences their own practices. Therefore, the current study surveyed self-identified BDSM practitioners' perceptions of pornography's accurate representation of communication, consent, safe words, negotiation, general safety, and how these perceptions relate to their use of safe words and safety training in their own activities. Results showed that (1) demographics nor BDSM-related attributes predicted perceived accuracy of BDSM safety depictions in pornography; (2) perceived accuracy of pornography's depiction of BDSM general safety and safe words did not predict practitioners' negotiation or use of safe words; however, years of BDSM experience did predict safe word usage; (3) submissive-related BDSM roles were more likely to use safe words than dominant-related BDSM roles; (4) those who participated in BDSM only in private were less likely to have CPR and/or first-aid training and more likely to have no other safety training; (5) those who believed pornography depicted BDSM safety mostly/very accurately were more likely to have no safety training; and (6) years of BDSM experience did not predict safety training. The impact of these findings on how we understand the influence of pornography on real-world BDSM practices are discussed.


Asunto(s)
Literatura Erótica , Humanos , Masculino , Femenino , Literatura Erótica/psicología , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Masoquismo/psicología , Seguridad
5.
J Am Chem Soc ; 145(49): 26545-26549, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38019924

RESUMEN

Solid-state syntheses are generally regarded as being slow, limited by transport, and, as such, are often only stopped to check the products after many hours at high temperature. Here, using a custom-designed reactor to rapidly initiate solid-state syntheses, we are able to capture the earliest stages of a reaction using in situ X-ray scattering. For the reaction of TiO2 and Li2CO3 to form spinel lithium titanate (Li4Ti5O12)─an anode material for fast-charging applications─we capture two distinct kinetic regimes, including fast initial kinetics in the first seconds-minutes of the reaction that account for significant product formation. We use an Avrami model to compare the reaction at high temperatures (700-750 °C), which results in the rapid formation of Li4Ti5O12 within minutes, and lower temperatures (482 °C), consistent with conditions that might be chosen based on "Tamman's rule", a common heuristic. Our analysis reveals characteristic Avrami slopes (i.e., dimensionalities) for each step in the chemical transformation. We anticipate that the fast initial reaction kinetics found here are likely to be common in the synthesis of other materials used in battery electrodes, solid-state electrolytes, ion-conductive membranes, etc. where ion transport is a prerequisite for functionality.

6.
J Am Chem Soc ; 144(34): 15612-15621, 2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-35994733

RESUMEN

The stereochemical activity of lone pair electrons plays a central role in determining the structural and electronic properties of both chemically simple materials such as H2O, as well as more complex condensed phases such as photocatalysts or thermoelectrics. TlReO4 is a rare example of a non-magnetic material exhibiting a re-entrant phase transition and emphanitic behavior in the long-range structure. Here, we describe the role of the Tl+ 6s2 lone pair electrons in these unusual phase transitions and illustrate its tunability by chemical doping, which has broad implications for functional materials containing lone pair bearing cations. First-principles density functional calculations clearly show the contribution of the Tl+ 6s2 in the valence band region. Local structure analysis, via neutron total scattering, revealed that changes in the long-range structure of TlReO4 occur due to changes in the correlation length of the Tl+ lone pairs. This has a significant effect on the anion interactions, with long-range ordered lone pairs creating a more densely packed structure. This resulted in a trade-off between anionic repulsions and lone pair correlations that lead to symmetry lowering upon heating in the long-range structure, whereby lattice expansion was necessary for the Tl+ lone pairs to become highly correlated. Similarly, introducing lattice expansion through chemical pressure allowed long-range lone pair correlations to occur over a wider temperature range, demonstrating a method for tuning the energy landscape of lone pair containing functional materials.

7.
Inorg Chem ; 61(38): 15130-15137, 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36107815

RESUMEN

Oxides exhibiting the scheelite-type structure are an important class of functional materials with notable applications in photocatalysis, luminescence, and ionic conductivity. Like all materials, understanding their atomic structure is fundamental to engineering their physical properties. This study outlines a detailed structural investigation of the scheelite-type oxide RbReO4, which exhibits a rare long-range phase transition from I41/a to I41/amd upon heating. Additionally, in the long-range I41/a model, the Re-O tetrahedral distance undergoes significant contraction upon warming. Recent studies of other scheelite oxides have attributed this apparent contraction to incoherent local-scale tetrahedral rotations. In this study, we use X-ray pair distribution function analysis to show that RbReO4 undergoes a unique symmetry-lowering process on the local scale, which involves incoherent tetrahedral displacements. The rare I41/a to I41/amd long-range phase transition was found to occur via a change from static to dynamic disorder on the local scale, which is due to the combination of the size of the A-site cation and lattice expansion. This demonstrates how careful manipulation of the ionic radius of the A-site in the scheelite structure can be used to induce local-scale disorder, which has valuable implications for tailoring the physical properties of related materials.

8.
Am J Physiol Renal Physiol ; 321(2): F236-F244, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34251273

RESUMEN

Autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) is the most common nonpolycystic genetic kidney disease, but it remains unrecognized due to its clinical heterogeneity and lack of screening test. Moreover, the fact that the clinical feature is a poor predictor of disease outcome further highlights the need for the development of mechanistic biomarkers in ADTKD. However, low abundant urinary proteins secreted by thick ascending limb cells, where UMOD is synthesized, have posed a challenge for the detection of biomarkers in ADTKD-UMOD. In the CRISPR/Cas9-generated murine model and patients with ADTKD-UMOD, we found that immunoglobulin heavy chain-binding protein (BiP), an endoplasmic reticulum chaperone, was exclusively upregulated by mutant UMOD in the thick ascending limb and easily detected by Western blot analysis in the urine at an early stage of disease. However, even the most sensitive ELISA failed to detect urinary BiP in affected individuals. We therefore developed an ultrasensitive, plasmon-enhanced fluorescence-linked immunosorbent assay (p-FLISA) to quantify urinary BiP concentration by harnessing the newly invented ultrabright fluorescent nanoconstruct, termed "plasmonic Fluor." p-FLISA demonstrated that urinary BiP excretion was significantly elevated in patients with ADTKD-UMOD compared with unaffected controls, which may have potential utility in risk stratification, disease activity monitoring, disease progression prediction, and guidance of endoplasmic reticulum-targeted therapies in ADTKD.NEW & NOTEWORTHY Autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) is an underdiagnosed cause of chronic kidney disease (CKD). Lack of ultrasensitive bioanalytical tools has hindered the discovery of low abundant urinary biomarkers in ADTKD. Here, we developed an ultrasensitive plasmon-enhanced fluorescence-linked immunosorbent assay (p-FLISA). p-FLISA demonstrated that secreted immunoglobulin heavy chain-binding protein is an early urinary endoplasmic reticulum stress biomarker in ADTKD-UMOD, which will be valuable in monitoring disease progression and the treatment response in ADTKD.


Asunto(s)
Biomarcadores/orina , Estrés del Retículo Endoplásmico/fisiología , Proteínas de Choque Térmico/orina , Técnicas de Inmunoadsorción , Nefritis Intersticial/orina , Animales , Chaperón BiP del Retículo Endoplásmico , Humanos , Ratones , Nefritis Intersticial/genética , Uromodulina/genética
9.
Opt Lett ; 46(6): 1409-1412, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33720199

RESUMEN

We demonstrate an interferometric method to provide direct, single-shot measurements of cavitation bubble dynamics with nanoscale spatial and temporal resolution with results that closely match theoretical predictions. Implementation of this method reduces the need for expensive and complex ultra-high speed camera systems for the measurement of single cavitation events. This method can capture dynamics over large time intervals with sub-nanosecond temporal resolution and spatial precision surpassing the optical diffraction limit. We expect this method to have broad utility for examination of cavitation bubble dynamics, as well as for metrology applications such as optorheological materials characterization. This method provides an accurate approach for precise measurement of cavitation bubble dynamics suitable for metrology applications such as optorheological materials characterization.

10.
Inorg Chem ; 60(7): 4517-4530, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33688721

RESUMEN

The long-range average and short-range local structures in the Tm2(Ti2-xTmx)O7-x/2 (x = 0.00-0.67) series were studied using a combination of diffraction and spectroscopic techniques. The long-range average structure, established from synchrotron X-ray and neutron powder diffraction data, shows the development of multiphase regions from x = 0.134 and the formation of antisite cation disorder from x = 0.402. The crystal field splitting of the Ti4+ ions, as derived from the Ti L3-edge X-ray absorption near-edge structure (XANES) spectroscopy, decreases gradually from 2.17 to 1.92 eV with increasing Tm3+ content (x), reflecting the increase in coordination number from 6 to predominantly 7. This is consistent with a gradual evolution of the short-range local disorder from x = 0.00 to 0.67. These results suggest that local disorder develops gradually throughout the entire composition range, whereas changes in the long-range disorder occur more suddenly. Electrochemical impedance spectroscopic results show an increase in oxygen ionic conductivity at 1000 °C, by a factor of 4 upon doping at x = 0.268. This suggests that inducing small amounts of disorder into the pyrochlore structure, by stuffing, may lead to applications of this material as a solid electrolyte in solid-oxide fuel cells.

11.
Clin Oral Investig ; 24(9): 3255-3264, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31953683

RESUMEN

OBJECTIVES: The aims of this study were to (1) investigate the relative time-dependent disruption and bactericidal effects of detergent-type surfactants on single- or dual-species biofilms of root canal isolates and (2) to examine the utility of polygonal graphs for depiction of biofilm disruption and cell killing. MATERIALS AND METHODS: Single-species biofilms of Streptococcus sanguinis, Enterococcus faecalis, Fusobacterium nucleatum and Porphyromonas gingivalis were grown on nitro-cellulose membranes for 72 h and immersed in Tween®80, cetyltrimethylammoniumbromide (CTAB), and sodium dodecyl sulphate (SDS) for 1-, 5- or 10-min (n = 3 per test). The number of viable and non-viable bacteria "disrupted" from the biofilm and those "remaining-attached" was determined using a viability stain in conjunction with fluorescence microscopy. The data were analysed using non-parametric Kruskal-Wallis test with 5% significance level. RESULTS: Gram-negative obligate anaerobes were more susceptible to cell removal than gram-positive facultative anaerobes. The majority of cells were disrupted after 1-min of exposure; however, the extent varied according to the agent and species. CTAB and SDS were more effective than Tween 80™ at disrupting biofilms and killing cells but all agents failed to achieve 100% disruption/kill. CONCLUSIONS: Biofilm disruption and cell viability were influenced by the species, the test agent and the duration of exposure. CTAB and SDS were more effective in biofilm disruption than Tween 80™. Graphical depiction of biofilm disruption- and viability-outcomes provides an alternative means of simultaneously visualising and analysing relative efficacy in different domains. CLINICAL RELEVANCE: Surfactants were not as effective at biofilm disruption as NaOCl but may be added to other non-disruptive antibacterial agents to enhance this property.


Asunto(s)
Cavidad Pulpar , Irrigantes del Conducto Radicular , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas , Enterococcus faecalis , Hipoclorito de Sodio
12.
J Am Soc Nephrol ; 29(6): 1690-1705, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29739813

RESUMEN

Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined.Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo, in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids.Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro, stimulation of purified human kidney SCs and human kidney organoids with IL-1ß recapitulated the molecular events observed in vivo, inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1ß stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury.Conclusions Our findings define a connection between IL-1ß and metabolic switch in fibrosis initiation and progression and highlight IL-1ß and MYC as potential therapeutic targets in tubulointerstitial diseases.


Asunto(s)
Lesión Renal Aguda/patología , Interleucina-1beta/farmacología , Riñón/citología , Riñón/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Lesión Renal Aguda/metabolismo , Animales , Autofagia/efectos de los fármacos , Azepinas/farmacología , Proteínas Portadoras/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Progresión de la Enfermedad , Matriz Extracelular/metabolismo , Fibrosis , Glucólisis/efectos de los fármacos , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/antagonistas & inhibidores , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Túbulos Renales Proximales/patología , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Organoides , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/genética , Proteína Sequestosoma-1/genética , Proteína Sequestosoma-1/metabolismo , Transducción de Señal , Células del Estroma/metabolismo , Hormonas Tiroideas/metabolismo , Triazoles/farmacología , Proteínas de Unión a Hormona Tiroide
13.
Int Endod J ; 51(4): 489-497, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29106737

RESUMEN

AIM: To evaluate the efficacy of sonic irrigation (EndoActivator® ) using various polymer tips and power settings in a stained collagen ex vivo model. METHODOLOGY: The root canals of fifty human, straight single-rooted extracted teeth were prepared to size 40, .08 taper. The roots were split longitudinally; stained collagen applied to the canal surfaces, photographed and re-assembled. The canals were subjected to syringe without supplementary (group 1, n = 10) or with supplementary sonic (groups 2-5, n = 10) irrigation. EndoActivator® tip sizes (size 15, .02 taper for groups 2 and 3; size 35, .04 taper for groups 4 and 5) and power settings (low for groups 2 and 4; high for groups 3 and 5) were tested. After irrigation, the canals were re-photographed and the area of residual stained collagen was quantified using the UTHSCA Image Tool program (Version 3.0). The data were analysed using Wilcoxon signed rank test and general linear mixed models. RESULTS: Supplementary sonic irrigation using EndoActivator® resulted in significantly (P < 0.0001) less residual collagen compared with syringe irrigation only. Agitation of irrigant using the large EndoActivator® tip with high power resulted in significantly less (22.4% - 29.5%) residual collagen compared to other combinations (large tip/low power P = 0.001; small tip/low power P = 0.01; small tip/high power P = 0.04). There was no significant difference amongst the latter three groups (P > 0.5). CONCLUSIONS: Supplementary sonic irrigation using the EndoActivator® system was significantly more effective in removing stained collagen from the canal surface than syringe irrigation alone. EndoActivator® used with large tip (size 35, .04 taper) and high power setting in size 40, .08 taper canals was more effective than other combinations.


Asunto(s)
Colágeno/efectos de los fármacos , Colágeno/efectos de la radiación , Ensayo de Materiales , Irrigantes del Conducto Radicular/uso terapéutico , Sonicación/métodos , Cavidad Pulpar/efectos de los fármacos , Humanos , Preparación del Conducto Radicular/instrumentación , Preparación del Conducto Radicular/métodos , Tratamiento del Conducto Radicular/métodos , Capa de Barro Dentinario , Sonicación/instrumentación , Propiedades de Superficie , Jeringas , Irrigación Terapéutica/instrumentación , Irrigación Terapéutica/métodos , Ultrasonido
14.
J Am Soc Nephrol ; 28(6): 1769-1782, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28130402

RESUMEN

Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ß-catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis.


Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo/fisiología , Enfermedades Renales/etiología , Riñón/patología , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/fisiología , Animales , Factor de Crecimiento del Tejido Conjuntivo/antagonistas & inhibidores , Fibroblastos , Fibrosis/etiología , Péptidos y Proteínas de Señalización Intercelular/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Pericitos
15.
J Am Soc Nephrol ; 27(12): 3639-3652, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27026366

RESUMEN

The identification of the cellular origins of myofibroblasts has led to the discovery of novel pathways that potentially drive myofibroblast perpetuation in disease. Here, we further investigated the role of innate immune signaling pathways in this process. In mice, renal injury-induced activation of pericytes, which are myofibroblast precursors attached to endothelial cells, led to upregulated expression of TNF receptor superfamily member 12a, also known as fibroblast growth factor-inducible 14 (Fn14), by these cells. In live rat kidney slices, administration of the Fn14 ligand, TNF-related weak inducer of apoptosis (TWEAK), promoted pericyte-dependent vasoconstriction followed by pericyte detachment from capillaries. In vitro, administration of TWEAK activated and differentiated pericytes into cytokine-producing myofibroblasts, and further activated established myofibroblasts in a manner requiring canonical and noncanonical NF-κB signaling pathways. Deficiency of Fn14 protected mouse kidneys from fibrogenesis, inflammation, and associated vascular instability after in vivo injury, and was associated with loss of NF-κB signaling. In a genetic model of spontaneous CKD, therapeutic delivery of anti-TWEAK blocking antibodies attenuated disease progression, preserved organ function, and increased survival. These results identify the TWEAK-Fn14 signaling pathway as an important factor in myofibroblast perpetuation, fibrogenesis, and chronic disease progression.


Asunto(s)
Enfermedades Renales/etiología , Riñón/patología , Miofibroblastos/fisiología , Receptores del Factor de Necrosis Tumoral/fisiología , Transducción de Señal , Factores de Necrosis Tumoral/fisiología , Animales , Citocina TWEAK , Progresión de la Enfermedad , Fibrosis/etiología , Ratones , Receptor de TWEAK
16.
HIV Med ; 17(4): 247-54, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26394818

RESUMEN

OBJECTIVES: Following national guidelines to expand HIV testing in high-prevalence areas in England, a number of pilot studies were conducted in acute general medical admission units (ACUs) and general practices (GPs) to assess the feasibility and acceptability of testing in these settings. The aim of this study was to estimate the cost per HIV infection diagnosed through routine HIV testing in these settings. METHODS: Resource use data from four 2009/2010 Department of Health pilot studies (two ACUs; two GPs) were analysed. Data from the pilots were validated and supplemented with information from other sources. We constructed possible scenarios to estimate the cost per test carried out through expanded HIV testing in ACUs and GPs, and the cost per diagnosis. RESULTS: In the pilots, cost per test ranged from £8.55 to £13.50, and offer time and patient uptake were 2 minutes and 90% in ACUs, and 5 minutes and 60% in GPs, respectively. In scenario analyses we fixed offer time, diagnostic test cost and uptake rate at 2 minutes, £6 and 80% for ACUs, and 5 minutes, £9.60 and 40% for GPs, respectively. The cost per new HIV diagnosis at a positivity of 2/1000 tests conducted was £3230 in ACUs and £7930 in GPs for tests performed by a Band 3 staff member, and £5940 in ACUs and £18 800 in GPs for tests performed by either hospital consultants or GPs. CONCLUSIONS: Expanded HIV testing may be more cost-efficient in ACUs than in GPs as a consequence of a shorter offer time, higher patient uptake, higher HIV positivity and lower diagnostic test costs. As cost per new HIV diagnosis reduces at higher HIV positivity, expanded HIV testing should be promoted in high HIV prevalence areas.


Asunto(s)
Costos y Análisis de Costo/métodos , Pruebas Diagnósticas de Rutina/economía , Infecciones por VIH/diagnóstico , Adolescente , Adulto , Anciano , Inglaterra , Medicina General/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Tamizaje Masivo/economía , Persona de Mediana Edad , Proyectos Piloto , Adulto Joven
17.
Proc Natl Acad Sci U S A ; 110(4): 1440-5, 2013 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-23302695

RESUMEN

Fibrosis of vital organs is a major public health problem with limited therapeutic options. Mesenchymal cells including microvascular mural cells (pericytes) are major progenitors of scar-forming myofibroblasts in kidney and other organs. Here we show pericytes in healthy kidneys have active WNT/ß-catenin signaling responses that are markedly up-regulated following kidney injury. Dickkopf-related protein 1 (DKK-1), a ligand for the WNT coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP-5 and LRP-6) and an inhibitor of WNT/ß-catenin signaling, effectively inhibits pericyte activation, detachment, and transition to myofibroblasts in vivo in response to kidney injury, resulting in attenuated fibrogenesis, capillary rarefaction, and inflammation. DKK-1 blocks activation and proliferation of established myofibroblasts in vitro and blocks pericyte proliferation to PDGF, pericyte migration, gene activation, and cytoskeletal reorganization to TGF-ß or connective tissue growth factor. These effects are largely independent of inhibition of downstream ß-catenin signaling. DKK-1 acts predominantly by inhibiting PDGF-, TGF-ß-, and connective tissue growth factor-activated MAPK and JNK signaling cascades, acting via LRP-6 with associated WNT ligand. Biochemically, LRP-6 interacts closely with PDGF receptor ß and TGF-ß receptor 1 at the cell membrane, suggesting that it may have roles in pathways other than WNT/ß-catenin. In summary, DKK-1 blocks many of the changes in pericytes required for myofibroblast transition and attenuates established myofibroblast proliferation/activation by mechanisms dependent on LRP-6 and WNT ligands but not the downstream ß-catenin pathway.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patología , Pericitos/metabolismo , Pericitos/patología , Animales , Becaplermina , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento del Tejido Conjuntivo/farmacología , Fibrosis , Puntos de Control de la Fase G1 del Ciclo Celular , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/farmacología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Pericitos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-sis/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Transducción de Señal , Factor de Crecimiento Transformador beta/farmacología , Vía de Señalización Wnt/genética , beta Catenina/metabolismo
18.
Soc Sci Res ; 59: 23-36, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27480369

RESUMEN

The online sexual exploitation of children is facilitated by websites that form virtual communities, via hyperlinks, to distribute images, videos, and other material. However, how these communities form, are structured, and evolve over time is unknown. Collected using a custom-designed webcrawler, we begin from known child sexual exploitation (CE) seed websites and follow hyperlinks to connected, related, websites. Using a repeated measure design we analyze 10 networks of 300 + websites each - over 4.8 million unique webpages in total, over a period of 60 weeks. Community detection techniques reveal that CE-related networks were dominated by two large communities hosting varied material -not necessarily matching the seed website. Community stability, over 60 weeks, varied across networks. Reciprocity in hyperlinking between community members was substantially higher than within the full network, however, websites were not more likely to connect to homogeneous-content websites.


Asunto(s)
Abuso Sexual Infantil , Internet , Niño , Redes Comunitarias , Humanos
19.
J R Nav Med Serv ; 100(3): 328-32, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25895415

RESUMEN

AIM: To discuss the influence of Vitamin D deficiency in the osseointegration process of a dental implant by way of a case report. SUMMARY: A 29-year-old soldier attended clinic with a fractured mandibular premolar (tooth 44) that was traumatised following head trauma related to the detonation of an Improvised Explosive Device (IED) whilst serving on operational duty. The tooth was deemed unsalvageable and was extracted with immediate placement of a dental implant. The patient experienced no problems but at assessment, five months post-operatively, no osseo-integration of the implant was found. Concurrent medical investigations revealed that he was severely Vitamin D deficient and that this may have contributed to the implant failure. CONCLUSION: Vitamin D deficiency may play a role in the failure of osseointegration in dental implants. The assessment of vitamin D status in patients who have been in long-term hospital care or rehabilitation should be considered, prior to the placement of dental implants.


Asunto(s)
Coronas , Implantación Dental Endoósea , Fracaso de la Restauración Dental , Oseointegración , Deficiencia de Vitamina D/complicaciones , Adulto , Humanos , Masculino , Personal Militar , Fracturas de los Dientes/cirugía , Deficiencia de Vitamina D/diagnóstico
20.
Acta Biomater ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39368720

RESUMEN

We introduce a method utilizing single laser-generated cavitation bubbles to stimulate cellular mechanotransduction in dermal fibroblasts embedded within 3D hydrogels. We demonstrate that fibroblasts embedded in either amorphous or fibrillar hydrogels engage in Ca2+ signaling following exposure to an impulsive mechanical stimulus provided by a single 250µm diameter laser-generated cavitation bubble. We find that the spatial extent of the cellular signaling is larger for cells embedded within a fibrous collagen hydrogel as compared to those embedded within an amorphous polyvinyl alcohol polymer (SLO-PVA) hydrogel. Additionally, for fibroblasts embedded in collagen, we find an increased range of cellular mechanosensitivity for cells that are polarized relative to the radial axis as compared to the circumferential axis. By contrast, fibroblasts embedded within SLO-PVA did not display orientation-dependent mechanosensitivity. Fibroblasts embedded in hydrogels and cultured in calcium-free media did not show cavitation-induced mechanotransduction; implicating calcium signaling based on transmembrane Ca2+ transport. This study demonstrates the utility of single laser-generated cavitation bubbles to provide local non-invasive impulsive mechanical stimuli within 3D hydrogel tissue models with concurrent imaging using optical microscopy. STATEMENT OF SIGNIFICANCE: : Currently, there are limited methods for the non-invasive real-time assessment of cellular sensitivity to mechanical stimuli within 3D tissue scaffolds. We describe an original approach that utilizes a pulsed laser microbeam within a standard laser scanning microscope system to generate single cavitation bubbles to provide impulsive mechanostimulation to cells within 3D fibrillar and amorphous hydrogels. Using this technique, we measure the cellular mechanosensitivity of primary human dermal fibroblasts embedded in amorphous and fibrillar hydrogels, thereby providing a useful method to examine cellular mechanotransduction in 3D biomaterials. Moreover, the implementation of our method within a standard optical microscope makes it suitable for broad adoption by cellular mechanotransduction researchers and opens the possibility of high-throughput evaluation of biomaterials with respect to cellular mechanosignaling.

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