Investigating the mechanism of acoustically activated uptake of drugs from Pluronic micelles

BACKGROUND: This paper examines the mechanism of ultrasonic enhanced drug delivery from Pluronic micelles. In previous publications by our group, fluorescently labeled Pluronic was shown to penetrate HL-60 cells with and without the action of ultrasound, while drug uptake was increased with the application of ultrasound. METHODS: In this study, the amount of uptake of two fluorescent probes, Lysosensor Green (a pH-sensitive probe) and Cell Tracker Orange CMTMR (a pH-independent probe), was measured in HL-60 and HeLa cells. RESULTS: The results of our experiments show that the increase in drug accumulation in the cells as a result of ultrasonication is not due to an increase in endocytosis due to ultrasonication. CONCLUSIONS: We hypothesize that sonoporation plays an important role in the acoustically activated drug delivery of chemotherapy drugs delivered from Pluronic micelles

Gender Differences in Carbohydrate Metabolism and Carbohydrate Loading

Prior to endurance competition, many endurance athletes participate in a carbohydrate loading regimen in order to help delay the onset of fatigue. The "classic" regimen generally includes an intense glycogen depleting training period of approximately two days followed by a glycogen loading period for 3–4 days, ingesting approximately 60–70% of total energy intake as carbohydrates, while the newer method does not consist of an intense glycogen depletion protocol. However, recent evidence has indicated that glycogen loading does not occur in the same manner for males and females, thus affecting performance. The scope of this literature review will include a brief description of the role of estradiol in relation to metabolism and gender differences seen in carbohydrate metabolism and loading

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

The XMM cluster survey: Testing chameleon gravity using the profiles of clusters

The chameleon gravity model postulates the existence of a scalar field that couples with matter to mediate a fifth force. If it exists, this fifth force would influence the hot X-ray emitting gas filling the potential wells of galaxy clusters. However, it would not influence the clusters weak lensing signal. Therefore, by comparing X-ray and weak lensing profiles, one can place upper limits on the strength of a fifth force. This technique has been attempted before using a single, nearby cluster (Coma, z = 0.02). Here we apply the technique to the stacked profiles of 58 clusters at higher redshifts (0.1 R0| R0| on cosmological scales. We hope to improve this constraint in future by extending the study to hundreds of clusters using data from the Dark Energy Survey

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Experiencing visual impairment in a lifetime home: an interpretative phenomenological inquiry

Lifetime home standards (LTHS) are a set of standards aimed at making homes more accessible. Previous research, however, indicates that LTHS do not adequately meet the needs of those with sensory impairments. Now, with visual impairment set to increase globally and acknowledging the recognised link between quality of dwelling and wellbeing, this article aims to examine the experiences of visually impaired people living in lifetime homes. The objectives are to investigate existing lifetime homes and to identify whether LTHS meet occupants’ needs. Qualitative semi-structured interviews were carried out with six visually impaired people living in homes designed to LTHS in Northern Ireland. Collected data was analysed using interpretative phenomenological analysis identifying three super-ordinate themes: (1) living with visual impairment; (2) design considerations and (3) coping strategies. A core theme of balance between psychological and physical needs emerged through interconnection of super-ordinate themes. Although there are benefits to living in lifetime homes, negative aspects are also apparent with occupants employing several coping strategies to overcome difficulties. Whilst residents experience negative emotions following visual impairment diagnoses, results suggest that occupants still regard their homes as key places of security and comfort in addition to then highlighting the need for greater consideration of specific individual needs within general guidelines

The effect of turbulent viscous shear stress on red blood cell hemolysis

[[abstract]]Non-physiologic turbulent flow occurs in medical cardiovascular devices resulting in hemodynamic stresses that may damage red blood cells (RBC) and cause hemolysis. Hemolysis was previously thought to result from Reynolds shear stress (RSS) in turbulent flows. A more recent hypothesis suggests that turbulent viscous shear stresses (TVSS) at spatial scales similar in size to RBCs are related to their damage. We applied two-dimensional digital particle image velocimetry to measure the flow field of a free-submerged axisymmetric jet that was utilized to hemolyze porcine RBCs in selected locations. Assuming a dynamic equilibrium for the sub-grid scale (SGS) energy flux between the resolved and the sub-grid scales, the SGS energy flux was calculated from the strain rate tensor computed from the resolved velocity fields. The SGS stress was determined by the Smagorinsky model, from which the turbulence dissipation rate and then TVSS were estimated. Our results showed the hemolytic threshold of the Reynolds stresses was up to 517 Pa, and the TVSSs were at least an order of magnitude less than the RSS. The results provide further insight into the relationship between turbulence and RBC damage.[[incitationindex]]SCI[[booktype]]紙本[[countrycodes]]JP

Functional characterisation and antimicrobial efficiency assessment of smart nanohydrogels containing natamycin incorporated into polysaccharide-based films

The potential application of polysaccharide-based films containing smart nanohydrogels for the controlled release of food preservatives is demonstrated here. Smart active packaging is the most promising alternative to traditional packaging as it provides a controlled antimicrobial effect, which allows reducing the amount of preservatives in the food bulk, releasing them only on demand. This work evaluates the usefulness of smart thermosensitive poly(N-isopropylacrylamide) (PNIPA) nanohydrogels with or without acrylic acid (AA) incorporated into polysaccharide-based films (GA) to transport natamycin and release it as a response to environmental triggers. Release kinetics in liquid medium from GA films containing PNIPA/AA nanohydrogels (GA-PNIPA(5) and GA-PNIPA-20AA(5)) presented a characteristic feature regarding the films without nanohydrogels that was the appearance of a lag time in natamycin release, able to reach values of around 35 h. Another important feature of natamycin release kinetics was the fact that the release from GA-PNIPA/AA films only occurred when temperature was increased, so that the natamycin release was restricted to when there is a risk of growth of microorganisms that cause food spoilage or the development of pathogenic microorganisms. Additionally, it could be observed that the relative fraction of natamycin released from GA-PNIPA/AA films was significantly (p<0.05) higher than that released from GA films loaded with the same amount of free natamycin. It can be hypothesised that the encapsulation of natamycin into nanohydrogels helped it to be released from GA films, creating reservoirs of natamycin into the films and, therefore, facilitating its diffusion through the film matrix when the nanohydrogel collapses. In a solid medium, the low water availability limited natamycin release from GA-PNIPA/AA films restricting the on/off release mechanism of PNIPA/AA nanohydrogels and favouring the hydrophobic interactions between natamycin and polymer chains at high temperatures. Despite the low natamycin release in solid media, antimicrobial efficiency of GA-PNIPA(5) films containing natamycin in acidified agar plates was higher than that obtained with GA films without natamycin and GA films with free natamycin, probably due to the protecting effect against degradation when natamycin was included in the nanohydrogels, allowing its release only when the temperature increased.Clara Fucinos and Miguel A. Cerqueira are recipients of a fellowship (SFRH/BPD/87910/2012 and SFRH/BPD/72753/2010, respectively) from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN, and FSE Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes", Ref. NORTE-07-0124-FEDER-000028 co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER and the project from the "Ministerio de Educacion y Ciencia" (Spain) "Nanohidrogeles inteligentes sensibles a cambios de pH y Temperatura: Diseno, sintesis y aplicacion en terapia del cancer y el envasado activo de alimentos", Ref. MAT2010-21509-C03-01

Association Patterns in Saproxylic Insect Networks in Three Iberian Mediterranean Woodlands and Their Resistance to Microhabitat Loss

The assessment of the relationship between species diversity, species interactions and environmental characteristics is indispensable for understanding network architecture and ecological distribution in complex networks. Saproxylic insect communities inhabiting tree hollow microhabitats within Mediterranean woodlands are highly dependent on woodland configuration and on microhabitat supply they harbor, so can be studied under the network analysis perspective. We assessed the differences in interacting patterns according to woodland site, and analysed the importance of functional species in modelling network architecture. We then evaluated their implications for saproxylic assemblages’ persistence, through simulations of three possible scenarios of loss of tree hollow microhabitat. Tree hollow-saproxylic insect networks per woodland site presented a significant nested pattern. Those woodlands with higher complexity of tree individuals and tree hollow microhabitats also housed higher species/interactions diversity and complexity of saproxylic networks, and exhibited a higher degree of nestedness, suggesting that a higher woodland complexity positively influences saproxylic diversity and interaction complexity, thus determining higher degree of nestedness. Moreover, the number of insects acting as key interconnectors (nodes falling into the core region, using core/periphery tests) was similar among woodland sites, but the species identity varied on each. Such differences in insect core composition among woodland sites suggest the functional role they depict at woodland scale. Tree hollows acting as core corresponded with large tree hollows near the ground and simultaneously housing various breeding microsites, whereas core insects were species mediating relevant ecological interactions within saproxylic communities, e.g. predation, competitive or facilitation interactions. Differences in network patterns and tree hollow characteristics among woodland sites clearly defined different sensitivity to microhabitat loss, and higher saproxylic diversity and woodland complexity showed positive relation with robustness. These results highlight that woodland complexity goes hand in hand with biotic and ecological complexity of saproxylic networks, and together exhibited positive effects on network robustness.The research Projects I+D CGL2011-23658 y CGL2012-31669 of the Spanish Minister of Science provided economic support