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1.
Brain ; 147(7): 2496-2506, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38325327

RESUMEN

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.


Asunto(s)
Electrocorticografía , Humanos , Masculino , Femenino , Adulto , Electrocorticografía/métodos , Adulto Joven , Adolescente , Electroencefalografía/métodos , Persona de Mediana Edad , Epilepsia/fisiopatología , Epilepsia/cirugía , Niño , Ondas Encefálicas/fisiología , Encéfalo/fisiopatología
2.
J Am Chem Soc ; 143(15): 5805-5814, 2021 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-33851530

RESUMEN

Although micelles derived from the solution self-assembly of amphiphilic molecules and polymers have been prepared with a wide variety of shapes, examples with well-defined branched structures have remained elusive. We describe a divergent, directed self-assembly approach to low dispersity dendritic micelles with a high degree of structural perfection and tailorable branch numbers and generations. We use block copolymer amphiphiles as precursors and a crystallization-driven seeded growth approach whereby the termini of fiber-like micelles function as branching sites. Different dendrimeric generations are accessible by adjusting the ratio of added unimers to pre-existing seed micelles where the branch positions are determined by the reduced coronal chain grafting density on the surface of the micelle crystalline core. We demonstrate the spatially defined decoration of the assemblies with emissive nanoparticles and utility of the resulting hybrids as fluorescent sensors for anions where the dendritic architecture enables ultrahigh sensitivity.


Asunto(s)
Dendrímeros/química , Micelas , Aniones/química , Cristalización , Compuestos Ferrosos/química , Límite de Detección , Microscopía de Fuerza Atómica , Polivinilos/química , Puntos Cuánticos/química , Silanos/química , Espectrometría de Fluorescencia , Sulfuros/análisis , Propiedades de Superficie
3.
J Am Chem Soc ; 142(31): 13469-13480, 2020 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-32594739

RESUMEN

The creation of organic heterojunctions from conjugated polymers on the nanoscale has attracted recent attention as a consequence of their considerable potential in optoelectronic devices. Herein, we report proof-of-concept results on a versatile synthetic strategy to access various linearly segmented nanowire heterojunctions with controlled dimensions using the seeded growth "living crystallization-driven self-assembly" method followed by a secondary crystallization step. Specifically, we describe the creation of coaxial and also segmented coaxial B-A-B and A-B-A nanowires with a solvophilic poly(ethylene glycol) (PEG) corona, an inner crystalline core that consists of poly(di-n-hexylfluorene) (PDHF), which functions as a donor, and an outer crystalline core of poly(3-(2'-ethylhexyl)thiophene) (P3EHT), which acts as an acceptor. The latter is present either along the entire nanowire or solely in the central or terminal segments. These assemblies were created by seeded growth of two types of π-conjugated polymeric building blocks, the triblock copolymer PDHF-b-P3EHT-b-PEG and the diblock copolymer PDHF-b-PEG, by using fiber-like seeds derived from either material. The nanowires with both solid-state donor and acceptor blocks exhibit Förster resonance energy transfer (FRET) from the PDHF inner core to the P3EHT outer core which was characterized by fluorescence spectroscopy and laser confocal scanning fluorescence microscopy (LCSM). The FRET in the solid-state coaxial heterojunctions with an inner PDHF core and an outer P3EHT core was enhanced relative to the directly analogous system in which the P3EHT block was solvated.


Asunto(s)
Nanocables/química , Polímeros/síntesis química , Cristalización , Estructura Molecular , Tamaño de la Partícula , Polímeros/química , Propiedades de Superficie
4.
J Am Chem Soc ; 141(48): 19088-19098, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31657915

RESUMEN

Fiber-like micelles based on biodegradable and biocompatible polymers exhibit considerable promise for applications in nanomedicine, but until recently no convenient methods were available to prepare samples with uniform and controllable dimensions and spatial control of functionality. "Living" crystallization-driven self-assembly (CDSA) is a seeded growth method of growing importance for the preparation of uniform 1D and 2D core-shell nanoparticles from a range of crystallizable polymeric amphiphiles. However, in the case of poly(l-lactide) (PLLA), arguably the most widely utilized biodegradable polymer as the crystallizable core-forming block, the controlled formation of uniform fiber-like structures over a substantial range of lengths by "living" CDSA has been a major challenge. Herein, we demonstrate that via simple modulation of the solvent conditions via the addition of trifluoroethanol (TFE), DMSO, DMF and acetone, uniform fiber-like nanoparticles from PLLA diblock copolymers with controlled lengths up to 1 µm can be prepared. The probable mechanism involves improved unimer solvation by a reduction of hydrogen bonding interactions among PLLA chains. We provide evidence that this minimizes undesirable unimer aggregation which otherwise favors self-nucleation that competes with epitaxial crystallization from seed termini. This approach has also allowed the formation of well-defined segmented block comicelles with PLLA cores via the sequential seeded-growth of PLLA block copolymers with different corona-forming blocks.


Asunto(s)
Resinas Acrílicas/química , Micelas , Nanopartículas/química , Poliésteres/química , Cristalización , Enlace de Hidrógeno , Nanopartículas/ultraestructura , Tamaño de la Partícula , Solubilidad , Solventes
5.
J Am Chem Soc ; 140(49): 17127-17140, 2018 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-30392357

RESUMEN

Fiber-like block copolymer (BCP) micelles offer considerable potential for a variety of applications; however, uniform samples of controlled length and with spatially tailored chemistry have not been accessible. Recently, a seeded growth method, termed "living" crystallization-driven self-assembly (CDSA), has been developed to allow the formation of 1D micelles and block comicelles of precisely controlled dimensions from BCPs with a crystallizable segment. An expansion of the range of core-forming blocks that participate in living CDSA is necessary for this technique to be compatible with a broad range of applications. Few examples currently exist of well-defined, water-dispersible BCP micelles prepared using this approach, especially from biocompatible and biodegradable polymers. Herein, we demonstrate that BCPs containing a crystallizable polycarbonate, poly(spiro[fluorene-9,5'-[1,3]-dioxan]-2'-one) (PFTMC), can readily undergo living CDSA processes. PFTMC- b-poly(ethylene glycol) (PEG) BCPs with PFTMC:PEG block ratios of 1:11 and 1:25 were shown to undergo living CDSA to form near monodisperse fiber-like micelles of precisely controlled lengths of up to ∼1.6 µm. Detailed structural characterization of these micelles by TEM, AFM, SAXS, and WAXS revealed that they comprise a crystalline, chain-folded PFTMC core with a rectangular cross-section that is surrounded by a solvent swollen PEG corona. PFTMC- b-PEG fiber-like micelles were shown to be dispersible in water to give colloidally stable solutions. This allowed an assessment of the toxicity of these structures toward WI-38 and HeLa cells. From these experiments, we observed no discernible cytotoxicity from a sample of 119 nm fiber-like micelles to either healthy (WI-38) or cancerous (HeLa) cell types. The living CDSA process was extended to PFTMC- b-poly(2-vinylpyridine) (P2VP), and addition of this BCP to PFTMC- b-PEG seed micelles led to the formation of well-defined segmented fibers with spatially localized coronal chemistries.

6.
J Am Chem Soc ; 140(23): 7222-7231, 2018 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-29847112

RESUMEN

Chiral polymers are ubiquitous in nature, and the self-assembly of chiral materials is a field of widespread interest. In this paper, we describe the formation of chiral metallopolymers based on poly(cobaltoceniumethylene) ([PCE] n+), which have been prepared through oxidation of poly(cobaltocenylethylene) (PCE) in the presence of enantiopure N-acyl-amino-acid-derived anionic surfactants, such as N-palmitoyl-l-alanine (C16-l-Ala) and N-palmitoyl-d-alanine (C16-d-Ala). It is postulated that the resulting metallopolymer complexes [PCE][C16-l/d-Ala] n contain close ionic contacts, and exhibit chirality through the axially chiral ethylenic CH2-CH2 bridges, leading to interaction of the chromophoric [CoCp2]+ units through chiral space. The steric influence of the long palmitoyl (C16) surfactant tail is key for the transmission of chirality to the polymer, and results in a brushlike amphiphilic macromolecular structure that also affords solubility in polar organic solvents (e.g., EtOH, THF). Upon dialysis of these solutions into water, the hydrophobic palmitoyl surfactant substituents aggregate and the complex assembles into superhelical ribbons with identifiable "handedness", indicating the transmission of chirality from the molecular surfactant to the micrometer length scale, via the macromolecular complex.

7.
Soft Matter ; 14(3): 331-343, 2018 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-29164218

RESUMEN

Individual colloids often carry a charge as a result of the dissociation (or adsorption) of weakly-ionized surface groups. The magnitude depends on the precise chemical environment surrounding a particle, which in a concentrated dispersion is a function of the colloid packing fraction η. Theoretical studies have suggested that the effective charge Zeff in regulated systems could, in general, decrease with increasing η. We test this hypothesis for nonpolar dispersions by determining Zeff(η) over a wide range of packing fractions (10-5 ≤ η ≤ 0.3) using a combination of small-angle X-ray scattering and electrophoretic mobility measurements. All dispersions remain entirely in the fluid phase regime. We find a complex dependence of the particle charge as a function of the packing fraction, with Zeff initially decreasing at low concentrations before finally increasing at high η. We attribute the non-monotonic density dependence to a crossover from concentration-independent screening at low η, to a high packing fraction regime in which counterions outnumber salt ions and electrostatic screening becomes η-dependent. The efficiency of charge stabilization at high concentrations may explain the unusually high stability of concentrated nanoparticle dispersions which has been reported.

8.
Soft Matter ; 13(33): 5535-5542, 2017 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-28795175

RESUMEN

Here X-ray reflectivity has been used to determine the structure of liquid crystal monolayers for different cyanobiphenyl homologues supported on aqueous solutions of two different salt species. Sodium iodide induces homeotropic ordering for all of the monolayer forming liquid crystal homologues studied here, and forms a Stern layer of iodide ions at the liquid crystal cyano headgroup, similar to the case of lipids or surfactants supported on electrolyte solutions. The liquid crystal headgroups were also found to penetrate into the water surface when binding with iodide ions. Sodium bromide, however, does not form the same localisation of ions close to a liquid crystal monolayer, and instead appears to produce no noticeable change in the scattering length density of the liquid crystal monolayer compared to pure water. However, on further compression the X-ray reflectivity dramatically changes, revealing the emergence of the so-called "trilayer" structure for 5CB and 8CB. This transition occurs at a lower areal density for sodium bromide than for pure water, and unlike for the uncompressed film, a layer of bromide ions was found at the trilayer-water interface.

9.
J Am Chem Soc ; 138(13): 4484-93, 2016 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-27049840

RESUMEN

Cylindrical block copolymer micelles have shown considerable promise in various fields of biomedical research. However, unlike spherical micelles and vesicles, control over their dimensions in biologically relevant solvents has posed a key challenge that potentially limits in depth studies and their optimization for applications. Here, we report the preparation of cylindrical micelles of length in the wide range of 70 nm to 1.10 µm in aqueous media with narrow length distributions (length polydispersities <1.10). In our approach, an amphiphilic linear-brush block copolymer, with high potential for functionalization, was synthesized based on poly(ferrocenyldimethylsilane)-b-poly(allyl glycidyl ether) (PFS-b-PAGE) decorated with triethylene glycol (TEG), abbreviated as PFS-b-(PEO-g-TEG). PFS-b-(PEO-g-TEG) cylindrical micelles of controlled length with low polydispersities were prepared in N,N-dimethylformamide using small seed initiators via living crystallization-driven self-assembly. Successful dispersion of these micelles into aqueous media was achieved by dialysis against deionized water. Furthermore, B-A-B amphiphilic triblock comicelles with PFS-b-poly(2-vinylpyridine) (P2VP) as hydrophobic "B" blocks and hydrophilic PFS-b-(PEO-g-TEG) "A" segments were prepared and their hierarchical self-assembly in aqueous media studied. It was found that superstructures formed are dependent on the length of the hydrophobic blocks. Quaternization of P2VP was shown to cause the disassembly of the superstructures, resulting in the first examples of water-soluble cylindrical multiblock comicelles. We also demonstrate the ability of the triblock comicelles with quaternized terminal segments to complex DNA and, thus, to potentially function as gene vectors.


Asunto(s)
Micelas , Polietilenglicoles/química , Polímeros/química , Compuestos Epoxi/química , Modelos Moleculares , Poliestirenos/química , Polivinilos/química , Piridinas/química
10.
J Am Chem Soc ; 138(12): 4087-95, 2016 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-26878261

RESUMEN

Self-assembled "cross" architectures are well-known in biological systems (as illustrated by chromosomes, for example); however, comparable synthetic structures are extremely rare. Herein we report an in depth study of the hierarchical assembly of the amphiphilic cylindrical P-H-P triblock comicelles with polar (P) coronal ends and a hydrophobic (H) central periphery in a selective solvent for the terminal segments which allows access to "cross" supermicelles under certain conditions. Well-defined P-H-P triblock comicelles M(PFS-b-PtBA)-b-M(PFS-b-PDMS)-b-M(PFS-b-PtBA) (M = micelle segment, PFS = polyferrocenyldimethylsilane, PtBA = poly(tert-butyl acrylate), and PDMS = polydimethylsiloxane) were created by the living crystallization-driven self-assembly (CDSA) method. By manipulating two factors in the supermicelles, namely the H segment-solvent interfacial energy (through the central H segment length, L1) and coronal steric effects (via the PtBA corona chain length in the P segment, L2 related to the degree of polymerization DP2) the aggregation of the triblock comicelles could be finely tuned. This allowed a phase-diagram to be constructed that can be extended to other triblock comicelles with different coronas on the central or end segment where "cross" supermicelles were exclusively formed under predicted conditions. Laser scanning confocal microscopy (LSCM) analysis of dye-labeled "cross" supermicelles, and block "cross" supermicelles formed by addition of a different unimer to the arm termini, provided complementary characterization to transmission electron microscopy (TEM) and dynamic light scattering (DLS) and confirmed the existence of these "cross" supermicelles as kinetically stable, micron-size colloidally stable structures in solution.

11.
J Am Chem Soc ; 137(45): 14288-94, 2015 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-26496508

RESUMEN

A tetra(aniline)-based cationic amphiphile, TANI-NHC(O)C5H10N(CH3)3(+)Br(-) (TANI-PTAB) was synthesized, and its emeraldine base (EB) state was found to self-assemble into nanowires in aqueous solution. The observed self-assembly is described by an isodesmic model, as shown by temperature-dependent UV-vis investigations. Linear dichroism (LD) studies, combined with computational modeling using time-dependent density functional theory (TD-DFT), suggests that TANI-PTAB molecules are ordered in an antiparallel arrangement within nanowires, with the long axis of TANI-PTAB arranged perpendicular to the nanowire long axis. Addition of either S- or R- camphorsulfonic acid (CSA) to TANI-PTAB converted TANI to the emeraldine salt (ES), which retained the ability to form nanowires. Acid doping of TANI-PTAB had a profound effect on the nanowire morphology, as the CSA counterions' chirality translated into helical twisting of the nanowires, as observed by circular dichroism (CD). Finally, the electrical conductivity of CSA-doped helical nanowire thin films processed from aqueous solution was 2.7 mS cm(-1). The conductivity, control over self-assembled 1D structure and water-solubility demonstrate these materials' promise as processable and addressable functional materials for molecular electronics, redox-controlled materials and sensing.

12.
Kidney Int ; 88(4): 897-904, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26154928

RESUMEN

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.


Asunto(s)
Lesión Renal Aguda/terapia , Riñón/fisiopatología , Terapia de Reemplazo Renal , Tiempo de Tratamiento , Espera Vigilante , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/fisiopatología , Anciano , Canadá , Enfermedad Crítica , Estudios de Factibilidad , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Proyectos Piloto , Terapia de Reemplazo Renal/efectos adversos , Terapia de Reemplazo Renal/mortalidad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
13.
Biomacromolecules ; 16(6): 1784-93, 2015 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-25928444

RESUMEN

This work reports on the preparation and characterization of natural composite materials prepared from bacterial cellulose (BC) incorporated into a gelatin matrix. Composite morphology was studied using scanning electron microscopy and 2D Raman imaging revealing an inhomogeneous dispersion of BC within the gelatin matrix. The composite materials showed controllable degrees of transparency to visible light and opacity to UV light depending on BC weight fraction. By adding a 10 wt % fraction of BC in gelatin, visible (λ = 550 nm) and UV (λ = 350 nm) transmittances were found to decrease by ∼35 and 40%, respectively. Additionally, stress transfer occurring between the gelatin and BC fibrils was quantified using Raman spectroscopy. This is the first report for a gelatin-matrix composite containing cellulose. As a function of strain, two distinct domains, both showing linear relationships, were observed for which an average initial shift rate with respect to strain of -0.63 ± 0.2 cm(-1)%(-1) was observed, followed by an average shift rate of -0.25 ± 0.03 cm(-1)%(-1). The average initial Raman band shift rate value corresponds to an average effective Young's modulus of 39 ± 13 GPa and 73 ± 25 GPa, respectively, for either a 2D and 3D network of BC fibrils embedded in the gelatin matrix. As a function of stress, a linear relationship was observed with a Raman band shift rate of -27 ± 3 cm(-1)GPa(-1). The potential use of these composite materials as a UV blocking food coating is discussed.


Asunto(s)
Celulosa/química , Gelatina/química , Nanocompuestos/química , Nanocompuestos/efectos de la radiación , Estrés Mecánico , Rayos Ultravioleta
14.
BMC Nephrol ; 16: 127, 2015 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-26238520

RESUMEN

BACKGROUND: Sustained low efficiency dialysis (SLED) is increasingly used as a renal replacement modality in critically ill patients with acute kidney injury (AKI) and hemodynamic instability. SLED may reduce the hemodynamic perturbations of intermittent hemodialysis, while obviating the resource demands of CRRT. Although SLED is being increasingly used, few studies have evaluated its impact on clinical outcomes. METHODS: We conducted a cohort study comparing SLED (target 8 h/session, blood flow 200 mL/min, predominantly without anticoagulation) to CRRT in four ICUs at an academic medical centre. The primary outcome was mortality 30 days after RRT initiation, adjusted for demographics, comorbidity, baseline kidney function, and Sequential Organ Failure Assessment score. Secondary outcomes were persistent RRT dependence at 30 days and early clinical deterioration, defined as a rise in SOFA score or death 48 h after starting RRT. RESULTS: We identified 158 patients who initiated treatment with CRRT and 74 with SLED. Mortality at 30 days was 54 % and 61 % among SLED- and CRRT-treated patients, respectively [adjusted odds ratio (OR) 1.07, 95 % CI 0.56-2.03, as compared with CRRT]. Among SLED recipients, the risk of RRT dependence at 30 days (adjusted OR 1.36, 95 % CI 0.51-3.57) and early clinical deterioration (adjusted OR 0.73, 95 % CI 0.40-1.34) were not different as compared to patients who initiated CRRT. CONCLUSIONS: Notwithstanding the limitations of this small non-randomized study, we found similar clinical outcomes for patients treated with SLED and CRRT. While we await the completion of a trial that will definitively assess the non-inferiority of SLED as compared to CRRT, SLED appears to be an acceptable alternative form of renal support in hemodynamically unstable patients with AKI.


Asunto(s)
Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Diálisis Renal/métodos , Adulto , Anciano , Causas de Muerte , Enfermedad Crítica , Progresión de la Enfermedad , Femenino , Hemodiafiltración/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
15.
Am J Nephrol ; 39(6): 509-14, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24903565

RESUMEN

BACKGROUND: National guidelines recommend using anemia management protocols to guide treatment. The objective of this study was to determine if an anemia management protocol would improve hemoglobin (Hgb) indices in hemodialysis patients and to measure whether the protocol would reduce the use and cost of darbepoetin alfa (DBO) and intravenous (IV) iron in hemodialysis patients. METHODS: An anemia management protocol was created and implemented for hemodialysis patients at our institution. A retrospective observational review of the use of DBO and IV iron as well as changes in Hgb, transferrin saturation and ferritin in 174 patients was conducted 6 months before and after implementation of the anemia protocol. RESULTS: The number of Hgb measurements in the target range increased from 44.3 to 46.0% (p = 0.48) after protocol implementation. The mean weekly dose of DBO was reduced from 34.56 ± 31.12 to 31.11 ± 28.64 µg post-protocol implementation (p = 0.011), which translated to a cost savings of USD 41,649 over 6 months. The mean monthly IV iron dose also decreased from 139.56 ± 98.83 to 97.65 ± 79.05 mg (p < 0.005), a cost savings of USD 18,594 over the same time period. CONCLUSION: The use of an anemia management protocol resulted in the deprescribing of DBO and iron agents while increasing the number of patients in the target Hgb range, which led to significant cost savings in the treatment of anemia.


Asunto(s)
Anemia/tratamiento farmacológico , Ahorro de Costo , Costos de los Medicamentos , Eritropoyetina/análogos & derivados , Hematínicos/uso terapéutico , Hierro/uso terapéutico , Fallo Renal Crónico/terapia , Diálisis Renal , Adulto , Anciano , Anemia/complicaciones , Anemia/metabolismo , Protocolos Clínicos , Darbepoetina alfa , Eritropoyetina/economía , Eritropoyetina/uso terapéutico , Femenino , Ferritinas/metabolismo , Hematínicos/economía , Unidades de Hemodiálisis en Hospital , Hemoglobinas/metabolismo , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Transferrina/metabolismo
16.
Soft Matter ; 10(4): 566-77, 2014 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-24651922

RESUMEN

A highly-charged spherical colloid in a salt-free environment exerts such a powerful attraction on its counterions that a certain fraction condenses onto the surface of a particle. The degree of condensation depends on the curvature of the surface. So, for instance, condensation is triggered on a highly-charged sphere only if the radius exceeds a certain critical radius R*. R* is expected to be a simple function of the volume fraction of particles. To test these predictions, we prepare spherical particles which contain a covalently-bound ionic liquid, which is engineered to dissociate efficiently in a low-dielectric medium. By varying the proportion of ionic liquid to monomer we synthesise nonpolar dispersions of highly-charged spheres which contain essentially no free co-ions. The only ions in the system are counterions generated by the dissociation of surface-bound groups. We study the electrophoretic mobility of this salt-free system as a function of the colloid volume fraction, the particle radius, and the bare charge density and find evidence for extensive counterion condensation. At low electric fields, we observe excellent agreement with Poisson-Boltzmann predictions for counterion condensation on spheres. At high electric fields however, where ion advection is dominant, the electrophoretic mobility is enhanced significantly which we attribute to hydrodynamic stripping of the condensed layer of counterions from the surface of the particle.

17.
bioRxiv ; 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38496541

RESUMEN

Objective: Interictal epileptiform spikes, high-frequency ripple oscillations, and their co-occurrence (spike ripples) in human scalp or intracranial voltage recordings are well-established epileptic biomarkers. While clinically significant, the neural mechanisms generating these electrographic biomarkers remain unclear. To reduce this knowledge gap, we introduce a novel photothrombotic stroke model in mice that reproduces focal interictal electrographic biomarkers observed in human epilepsy. Methods: We induced a stroke in the motor cortex of C57BL/6 mice unilaterally (N=7) using a photothrombotic procedure previously established in rats. We then implanted intracranial electrodes (2 ipsilateral and 2 contralateral) and obtained intermittent local field potential (LFP) recordings over several weeks in awake, behaving mice. We evaluated the LFP for focal slowing and epileptic biomarkers - spikes, ripples, and spike ripples - using both automated and semi-automated procedures. Results: Delta power (1-4 Hz) was higher in the stroke hemisphere than the non-stroke hemisphere in all mice ( p <0.001). Automated detection procedures indicated that compared to the non-stroke hemisphere, the stroke hemisphere had an increased spike ripple ( p =0.006) and spike rates ( p =0.039), but no change in ripple rate ( p =0.98). Expert validation confirmed the observation of elevated spike ripple rates ( p =0.008) and a trend of elevated spike rate ( p =0.055) in the stroke hemisphere. Interestingly, the validated ripple rate in the stroke hemisphere was higher than the non-stroke hemisphere ( p =0.031), highlighting the difficulty of automatically detecting ripples. Finally, using optimal performance thresholds, automatically detected spike ripples classified the stroke hemisphere with the best accuracy (sensitivity 0.94, specificity 0.94). Significance: Cortical photothrombosis-induced stroke in commonly used C57BL/6 mice produces electrographic biomarkers as observed in human epilepsy. This model represents a new translational cortical epilepsy model with a defined irritative zone, which can be broadly applied in transgenic mice for cell type specific analysis of the cellular and circuit mechanisms of pathologic interictal activity. Key Points: Cortical photothrombosis in mice produces stroke with characteristic intermittent focal delta slowing.Cortical photothrombosis stroke in mice produces the epileptic biomarkers spikes, ripples, and spike ripples.All biomarkers share morphological features with the corresponding human correlate.Spike ripples better lateralize to the lesional cortex than spikes or ripples.This cortical model can be applied in transgenic mice for mechanistic studies.

19.
Neurobiol Lang (Camb) ; 4(1): 53-80, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37229140

RESUMEN

Speech requires successful information transfer within cortical-basal ganglia loop circuits to produce the desired acoustic output. For this reason, up to 90% of Parkinson's disease patients experience impairments of speech articulation. Deep brain stimulation (DBS) is highly effective in controlling the symptoms of Parkinson's disease, sometimes alongside speech improvement, but subthalamic nucleus (STN) DBS can also lead to decreases in semantic and phonological fluency. This paradox demands better understanding of the interactions between the cortical speech network and the STN, which can be investigated with intracranial EEG recordings collected during DBS implantation surgery. We analyzed the propagation of high-gamma activity between STN, superior temporal gyrus (STG), and ventral sensorimotor cortices during reading aloud via event-related causality, a method that estimates strengths and directionalities of neural activity propagation. We employed a newly developed bivariate smoothing model based on a two-dimensional moving average, which is optimal for reducing random noise while retaining a sharp step response, to ensure precise embedding of statistical significance in the time-frequency space. Sustained and reciprocal neural interactions between STN and ventral sensorimotor cortex were observed. Moreover, high-gamma activity propagated from the STG to the STN prior to speech onset. The strength of this influence was affected by the lexical status of the utterance, with increased activity propagation during word versus pseudoword reading. These unique data suggest a potential role for the STN in the feedforward control of speech.

20.
Langmuir ; 28(5): 2502-9, 2012 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-22208500

RESUMEN

For the first time a series of anionic surfactant ionic liquids (SAILs) has been synthesized based on organic surfactant anions and 1-butyl-3-methyl-imidazolium cations. These compounds are more environmentally friendly and chemically tunable as compared to other common ionic liquids. A detailed investigation of physicochemical properties highlights potential applications from battery design to reaction control, and studies into aqueous aggregation behavior, as well as structuring in pure ILs, point to possible uses in electrochemistry.


Asunto(s)
Imidazoles/química , Líquidos Iónicos/química , Tensoactivos/química , Aniones/síntesis química , Aniones/química , Cationes/química , Líquidos Iónicos/síntesis química , Estructura Molecular , Tensoactivos/síntesis química
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