RESUMEN

Here, we establish an approach to determine temperature-dependent aggregation rates in terms of thermostatistical quantities, which can be obtained directly from flat-histogram and statistical temperature algorithms considering the density of states of the system. Our approach is validated through simulations of an Ising-like model with anisotropically interacting particles at temperatures close to its first-order phase transition. Quantitative comparisons between the numerically obtained forward and reverse rates to approximate analytical expressions corroborate its use as a model-independent approach.

RESUMEN

CONTEXT: Although the crystallization of monosodium urate monohydrate (MSUM) has a crucial role in the occurrence of gout, which is an inflammatory arthritis disease, theoretical models have not been able to describe all features observed in its seeded growth kinetics. In contrast to previous modeling approaches, we show that our model can reproduce qualitative features typically observed in experiments. In particular, our results show that the higher the initial supersaturation and the lower the viscosity, the faster the crystallization kinetics, and they also indicate that there are distinct growth regimes for low and high concentrations of seeds. METHODS: In this work, we introduce an alternative approach based on a master equation that allows us to incorporate hypotheses for the seeded growth crystallization of MSUM in a more transparent way. Such an approach includes not only effects that are related to the finite time-dependent supersaturation and concentration of seeds, but it can also be used to determine how the viscosity of the solution can affect the crystallization kinetics of MSUM molecules.

Asunto(s)

Cristalización , Ácido Úrico , Ácido Úrico/química , Viscosidad , Cinética , Modelos Químicos

RESUMEN

The strain-induced softening behaviour observed in the differential modulus K(T,γ) of hydrogels is typically attributed to the breakage of internal network structures, such as the cross-links that bind the polymer chains. In this study, however, we consider a stress-strain relationship derived from a coarse-grained model to demonstrate that rupture of the network is not necessary for rubber-like gels to exhibit such behaviour. In particular, we show that, in some cases, the decrease of K(T,γ) as a function of the strain γ can be associated with the energy-related contribution to the elastic modulus that has been experimentally observed, e.g., for tetra-PEG hydrogels. Our findings suggest that the softening behaviour can be also attributed to the effective interaction between polymer chains and their surrounding solvent molecules, rather than the breakage of structural elements. We compare our theoretical expressions with experimental data determined for several hydrogels to illustrate and validate our approach.

RESUMEN

We consider a coarse-grained polymer model in order to investigate the origin of a recently discovered negative energy-related contribution to the elastic modulus G(T) of rubber-like gels. From this model, we are able to compute an exact expression for the free energy of the system, which allows us to evaluate a stress-strain relationship that displays a non-trivial dependence on the temperature T. We validate our approach through comparisons between the theoretical results and the experimental data obtained for tetra-PEG hydrogels, which indicate that, although simple, the present model works well to describe the experiments. Importantly, our approach unveiled aspects of the experimental analysis which turned out to be different from the conventional entropic and energetic analysis broadly used in the literature. Also, in contrast to the linear dependence predicted by the traditional, i.e., purely entropic, models, our results suggest that the general expression of the elastic modulus should be of the form [Formula: see text], with w(T) being a temperature-dependent correction factor that could be related to the interaction between the chains in the network and the solvent. Accordingly, the correction factor allows the expression found for the elastic modulus to describe both rubber and rubber-like gels.

RESUMEN

Nucleation of particles into crystalline structures can be observed in a wide range of systems from metallic and metal-organic compounds to colloidal and polymeric patch particles. Here, we perform kinetic Monte Carlo simulations to study the nucleation kinetics of particles with different ligancies z at constant supersaturation s. This approach allows one to determine several physico-chemical quantities as a function of s, including the growth probability P(n), the critical nucleus size n*, and the stationary nucleation rate Js. Our numerical results are rationalized in terms of a self-consistent nucleation theory where both n* and Js present a non-trivial dependence on s, but which can be determined from the values of effective z-dependent parameters.

Asunto(s)

Cristalización , Cinética , Método de Montecarlo , Probabilidad

RESUMEN

When the skyrmion dynamics beyond the particle-like description is considered, this topological structure can deform due to a self-induced field. In this work, we perform Monte Carlo simulations to characterize the skyrmion deformation during its steady movement. In the low-velocity regime, the deformation in the skyrmion shape is quantified by an effective inertial mass, which is related to the dissipative force. When skyrmions move faster, the large self-induced deformation triggers topological transitions. These transitions are characterized by the proliferation of skyrmions and a different total topological charge, which is obtained as a function of the skyrmion velocity. Our findings provide an alternative way to describe the dynamics of a skyrmion that accounts for the deformations of its structure. Furthermore, such motion-induced topological phase transitions make it possible to control the number of ferromagnetic skyrmions through velocity effects.

RESUMEN

We present an efficient computational methodology to obtain the viscoelastic response of dilute solutions of semiflexible filaments. By considering an approach based on the fluctuation-dissipation theorem, we were able to evaluate the dynamical properties of probe particles immersed in solutions of semiflexible filaments from relaxation simulations with a relatively low computational cost and higher precision in comparison to those based on stochastic dynamics. We used a microrheological approach to obtain the complex shear modulus and the complex viscosity of the solution through its compliance which was obtained directly from the dynamical properties of a probe particle attached to an effective medium described by a mesoscopic model, i.e., an effective filament model (EFM). The relaxation simulations were applied to assess the effects of the bending energy on the viscoelasticity of the semiflexible filament solutions, and our methodology was validated by comparing the numerical results to the experimental data on DNA and collagen solutions.

Asunto(s)

Citoesqueleto , ADN , Elasticidad , Soluciones , Viscosidad

RESUMEN

Background: We present our experience after the introduction of Advanced Trauma Life Support (ATLS)©, Trauma Team (TT) and Preperitoneal Pelvic Packing (PPP) protocols for the treatment of hemodynamically unstable pelvic blunt trauma.Methods: This is a retrospective study with historical controls: before (Control Group, CG) and after (Study Group SG) the introduction of the protocol. A single physician managed the CG and angiography was the emergency manoeuvre. A team with ATLS guidelines and PPP as an emergency manoeuvre managed the SG. Data were collected retrospectively. Patients were divided into two groups: before and after the introduction of protocols.Results: From January 2007 to October 2014, 36 patients were treated at our Centre. We consider patients from January 2007 to August 2011 (19 patients, CG) and from September 2011 to October 2014 (17 patients, SG). Median age was 54 years (43­69) in the CG vs. 47 (40­63) in the SG (p = 0.43), median initial SBP 90 mmHg (85­103) in the CG 94 (69­103) in the SG, (p = 0.60), heart rate was 90 (80­110) in the CG and 110 (95­130) in the SG, (p = 0.09). Median Injury Severity Score was 33 (21­41) in the CG and 34 (26­41) in the SG (p = 0.29). Time from arrival in the Emergency Department to first therapeutic manoeuvre was 132 minutes (109­180) in the CG and 87 minutes (51­204) in the SG (p = 0.4). The difference in mortality was statistically significant: 64.7% (11/17) in the CG and 23.5% (4/17) in the SG (p = 0.02).Conclusions: The introduction of protocols changed our approach in hemodynamically unstable pelvic trauma, achieving a remarkable improvement in early mortality

Asunto(s)

Atención de Apoyo Vital Avanzado en Trauma , Angiografía , Pacientes , Pelvis

RESUMEN

Relations between static and dynamic viscoelastic responses in gels can be very elucidating and may provide useful tools to study the behavior of bio-materials such as protein hydrogels. An important example comes from the viscoelasticity of semisolid gel-like materials, which is characterized by two regimes: a low-frequency regime, where the storage modulus G'(ω) displays a constant value Geq, and a high-frequency power-law stiffening regime, where G'(ω) ∼ ωn. Recently, by considering Monte Carlo simulations to study the formation of peptides networks, we found an intriguing and somewhat related power-law relationship between the plateau modulus and the threshold frequency, i.e., Geq∼(ω*)Δ with Δ = 2/3. Here we present a simple theoretical approach to describe that relationship and test its validity by using experimental data from a ß-lactoglobulin gel. We show that our approach can be used even in the coarsening regime where the fractal model fails. Remarkably, the very same exponent Δ is found to describe the experimental data.

Asunto(s)

Geles/química , Lactoglobulinas/química , Elasticidad , Simulación de Dinámica Molecular , Reología , Termodinámica , Viscosidad

RESUMEN

Disordered fibre networks are ubiquitous in nature and have a wide range of industrial applications as novel biomaterials. Predicting their viscoelastic response is straightforward for affine deformations that are uniform over all length scales, but when affinity fails, as has been observed experimentally, modelling becomes challenging. Here we present a numerical methodology, related to an existing framework for amorphous packings, to predict the steady-state viscoelastic spectra and degree of affinity for disordered fibre networks driven at arbitrary frequencies. Applying this method to a peptide gel model reveals a monotonic increase of the shear modulus as the soft, non-affine normal modes are successively suppressed as the driving frequency increases. In addition to being dominated by fibril bending, these low frequency network modes are also shown to be delocalised. The presented methodology provides insights into the importance of non-affinity in the viscoelastic response of peptide gels, and is easily extendible to all types of fibre networks.

Asunto(s)

Geles , Péptidos , Elasticidad

RESUMEN

It is well-known that the swelling behavior of ionic nanogels depends on their cross-link density; however, it is unclear how different topologies should affect the response of the polyelectrolyte network. Here we perform Monte Carlo simulations to obtain the equilibrium properties of ionic nanogels as a function of salt concentration Cs and the fraction f of ionizable groups in a polyelectrolyte network formed by cross-links of functionality z. Our results indicate that the network with cross-links of low connectivity result in nanogel particles with higher swelling ratios. We also confirm a de-swelling effect of salt on nanogel particles.

RESUMEN

It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain-side-chain interactions, backbone hydrogen bonding, and temperature affect amyloid fibril solubility, which might prove to be a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.

Asunto(s)

Amiloide/química , Enlace de Hidrógeno , Solubilidad

RESUMEN

Peptide hydrogels have important applications as biomaterials and in nanotechnology, but utilization often depends on their mechanical properties for which we currently have no predictive capability. Here we use a peptide model to simulate the formation of percolating amyloid fibril networks and couple these to the elastic network theory to determine their mechanical properties. We find that the time variation of network length scales can be collapsed onto master curves by using a time scaling function that depends on the peptide interaction anisotropy. The same scaling applies to network mechanics, revealing a nonmonotonic dependence of the shear modulus with time. Our structure-function relationship between the peptide building blocks, network morphology, and network mechanical properties can aid in the design of amyloid fibril networks with tailored mechanical properties.

RESUMEN

BACKGROUND: Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome. OBJECTIVE: To report the results of a long-term follow-up (mean 11 years, range 10-13) on 26 patients bilaterally implanted in two centres. METHODS: Patients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinson's Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded. RESULTS: At 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time. CONCLUSIONS: Our study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.

Asunto(s)

Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiopatología , Anciano , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Tiempo

RESUMEN

BACKGROUND AND PURPOSE: Levodopa/carbidopa intestinal gel (LCIG) infusion is nowadays becoming an established therapeutic option for advanced Parkinson's disease (PD) patients with fluctuating symptoms unresponsive to conventional oral treatment. As the implementation of LCIG therapy is increasing, there is a need for safety and efficacy data from current clinical practice. METHODS: All PD patients treated with LCIG at our centre over a 7-year period were analysed to determine the duration of treatment, retention rate, reasons for discontinuation, LCIG efficacy in motor complications, modifications of concomitant therapy and adverse events. RESULTS: Of the 59 patients, seven subjects (12%) died of causes unrelated to LCIG infusion and 11 patients (19%) discontinued therapy prior to the cut-off date. Duodopa improved motor complications and over 90% of patients reported an improvement in their quality of life, autonomy and clinical global status. The most common adverse events were dislocation and kinking of the intestinal tube. CONCLUSIONS: LCIG infusion is effective for the long-term treatment of advanced PD patients and exerts a positive and clinically significant effect on motor complications with a relatively low dropout rate.

Asunto(s)

Antiparkinsonianos/administración & dosificación , Carbidopa/administración & dosificación , Geles/administración & dosificación , Levodopa/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/uso terapéutico , Carbidopa/uso terapéutico , Combinación de Medicamentos , Femenino , Geles/uso terapéutico , Humanos , Infusiones Parenterales , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

AIM: The objectives of this study were to describe (a) the reasons why students about to start university did not choose a nursing degree, (b) the source of information/data on which they based this decision, and (c) the accuracy of this information with regard to the nursing profession in Italy. BACKGROUND: Although data are available for students who embark on a degree and the reason(s) why they choose nursing, few data are available for students at the point of matriculation who have not chosen a nursing degree. METHODS: A cross-sectional study design, including six Italian degree programmes randomly selected among the 12 available, was performed. A structured questionnaire was administered to 580 students willing to participate of the 1095 eligible (53%) in their first university lecture in autumn 2011. RESULTS: Some 507 (87.4%) questionnaires were analysed. The main reason for not having chosen a nursing degree is the lack of interest in nursing (235; 47.2%), followed by not wanting contact with ill or dying people (87; 17.5%), the fear of contact with biological material (71; 14.2%) and the lack of recognition of nursing work (44; 8.8%). Among the participants, personal experience (186; 37.1%) and relatives (124; 24.8%) are the main sources of information on the nursing profession. Moreover, only 340 participants (67.1%) recognized the degree as a necessary qualification for nursing in Italy; the majority know nothing about nursing career opportunities (452; 89.2%) or the initial salary of a nurse (250; 49.3%). Conversely, 447 (88.2%) participants indicated correctly the responsibilities imposed on nurses by the law. DISCUSSION: A considerable proportion of non-nursing students are not interested in the nursing profession and the information in their possession regarding nursing profession is incorrect. CONCLUSIONS: Multiple strategies helping potential candidates to make the best career decision on the basis of valid information should be strengthened and offered during the secondary school, through nursing students, families, teachers and networks, and not just the media. In addition, efforts to improve the working conditions of nurses must be undertaken.

Asunto(s)

Selección de Profesión , Enfermería , Estudiantes/psicología , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Humanos , Italia , Masculino , Encuestas y Cuestionarios , Universidades , Adulto Joven

RESUMEN

BACKGROUND: Sleep disorders are common in patients with advanced Parkinson's disease (PD). Nocturnal akinesia and sleep fragmentation frequently coexist with daytime sleepiness, influencing daytime functioning. Levodopa/carbidopa intestinal gel (LCIG) infusion has been shown to improve motor complications in advanced PD, and preliminary findings suggest that sleep might improve following LCIG infusion. OBJECTIVE: To analyze the impact of LCIG infusion on sleep symptoms and daytime sleepiness in patients with PD. METHODS: Twelve consecutive patients with PD completed the PD-Sleep-Scale-version-2 (PDSS-2) and the Epworth-Sleepiness-Scale (ESS) at baseline and after 2-4 months of LCIG treatment. Activities of daily living, motor symptoms and complications were assessed with the Unified-PD-rating-Scale section II, III, and IV. RESULTS: Nocturnal sleep improved substantially in all patients switched to LCIG infusion. PDSS-2 total score and subscores for 'Disturbed sleep', 'Motor symptoms at night', and 'PD symptoms at night' were significantly reduced. ESS measures of daytime sleepiness also improved. Motor complications and activities of daily living improved significantly with LCIG. CONCLUSION: Subjective measures of sleep quality and daytime sleepiness improve in patients with advanced PD undergoing LCIG infusion. Further studies with a larger number of patients and polysomnographic recordings are needed to confirm the beneficial effect on sleep and clarify the underlying mechanisms.

Asunto(s)

Antiparkinsonianos/uso terapéutico , Carbidopa/uso terapéutico , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Intrínsecos del Sueño/tratamiento farmacológico , Anciano , Antiparkinsonianos/administración & dosificación , Carbidopa/administración & dosificación , Trastornos de Somnolencia Excesiva/etiología , Trastornos de Somnolencia Excesiva/prevención & control , Vías de Administración de Medicamentos , Combinación de Medicamentos , Duodeno , Femenino , Gastrostomía , Geles , Humanos , Bombas de Infusión Implantables , Yeyuno , Levodopa/administración & dosificación , Masculino , Persona de Mediana Edad , Síndrome de Mioclonía Nocturna/tratamiento farmacológico , Síndrome de Mioclonía Nocturna/etiología , Enfermedad de Parkinson/complicaciones , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Trastornos Intrínsecos del Sueño/etiología , Resultado del Tratamiento

RESUMEN

We study the nucleation of model two-dimensional crystals formed from anisotropically interacting molecules using kinetic Monte Carlo simulations and the forward flux sampling algorithm. The growth probability P(n) of a cluster of n molecules is measured while the supersaturation s and interaction anisotropy of the molecules are varied, in order to gain insight into the nucleation mechanism. It is found that with increasing degree of interaction anisotropy the nucleus size (defined as the cluster size at which P(n) = 0.5) can increase with increasing s, with sharp jumps at certain s values. Analysis of the cluster shape reveals that nucleation in the system studied is of a non-standard form, in that it embodies elements of both the classical nucleation theory and the density functional theory frameworks.

RESUMEN

Recently, we demonstrated that TLQP-21 triggers lipolysis and induces resistance to obesity by reducing fat accumulation [1]. TLQP-21 is a 21 amino acid peptide cleavage product of the neuroprotein VGF and was first identified in rat brain. Although TLQP-21 biological activity and its molecular signaling is under active investigation, a receptor for TLQP-21 has not yet been characterized. We now demonstrate that TLQP-21 stimulates intracellular calcium mobilization in CHO cells. Furthermore, using Atomic Force Microscopy (AFM), we also provide evidence of TLQP-21 binding-site characteristics in CHO cells. AFM was used in force mapping mode equipped with a cantilever suitably functionalized with TLQP-21. Attraction of this functionalized probe to the cell surface was specific and consistent with the biological activity of TLQP-21; by contrast, there was no attraction of a probe functionalized with biologically inactive analogues. We detected interaction of the peptide with the binding-site by scanning the cell surface with the cantilever tip. The attractive force between TLQP-21 and its binding site was measured, statistically analyzed and quantified at approximately 40 pN on average, indicating a single class of binding sites. Furthermore we observed that the distribution of these binding sites on the surface was relatively uniform.

Asunto(s)

Biofisica/métodos , Obesidad/metabolismo , Fragmentos de Péptidos/química , Péptidos/química , Animales , Sitios de Unión , Células CHO , Calcio/metabolismo , Adhesión Celular , Membrana Celular/metabolismo , Cricetinae , Hipotálamo/metabolismo , Ligandos , Ratones , Microscopía de Fuerza Atómica/métodos , Microscopía de Contraste de Fase/métodos , Modelos Biológicos , Modelos Estadísticos , Ratas , Factores de Tiempo