The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium ...channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. Transgenic mouse models have proved useful in understanding the physiological role of individual sodium channels, and there has been significant progress in the development of subtype selective inhibitors of sodium channels. This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors.
Nucleation and crystallization have been proven to be the key steps for early stage formation of metal–organic framework nanoparticles. However, the growth mechanisms attributed to size and topology ...control at the later stages require more research. In this study, we provide new insight into an aggregative growth pattern observed for zeolitic imidazolate framework-8 (ZIF-8). Nanoscaled ZIF-8 was synthesized with an excess of organic ligands. After reaching a size limitation, ZIF-8 particles undergo an oriented attachment (OA) growth pathway to form clusters. Additional imidazole ligands as bridging agents facilitate the OA process by cross-linking smaller ZIF-8 particles. Adding a cationic surfactant disturbs the interfacial electrostatic interactions among those nanoparticles and reduced the growth rate of {100} faces. We envision that the work presented here will inspire the mechanism studies for other nanoporous crystals.
Exercise and healthy eating are proposed as a recommended lifestyle by the World Health Organization with several positive outcomes, including a decrease in pathologies such as diabetes and reduction ...in mortality rates. However, research suggests that there is the potential for exercise behaviour to become addictive among a small minority of individuals, which detrimentally impacts their lives. The risk of exercise addiction increases for endurance sports, of which cycling is considered one, given the intense physical and psychological demands, due to elevation and distance, in amateur cycling events. Understanding the risk factors specific to cycling is worthy of investigation, as it is not clear whether cycling can become an addiction. Using the ‘addiction component model’ as a framework, qualitative analysis was used to determine whether symptoms of addiction were present among a sample of eight female cyclists. Through the use of thematic analysis, the results showed that symptoms of addiction were reported by participants. Three themes were generated from research interviews comprising ‘addiction components’ (i.e. salience, conflict, mood modification, tolerance, withdrawal, and cycling despite health problems), ‘enabling infrastructure’ (i.e. supportive work, supportive family and friends), and ‘striving for excellence’ (i.e. needing to be the best, pushing too far, and having unrealistic expectation), currently measured in the ‘addiction component model’. There were also novel themes including ‘cycling above health’ where the participant continues to cycle against medical advice; ‘enabling infrastructure’ where work, family, and friends are accepting of cycling; and ‘striving for excellence’ where the participants ‘needing to be the best’ when comparing themselves to their peers, ‘pushing too far’ to achieve the goal set, and finally ‘unrealistic expectations’ resulting in negative comparison to peers. These findings suggest that addiction to cycling should be investigated further, and implications may necessitate clinical intervention to find alternative coping mechanisms when exercise is not available to an individual as there is a likelihood that individuals will continue to exercise in spite of injury and against medical advice.
Normal optic nerve axons exhibit a temperature dependence, previously explained by a membrane potential hyperpolarization on warming. We now report that near infra-red laser light, delivered via a ...fibre optic light guide, also affects axonal membrane potential and threshold, at least partly through a photo-thermal effect. Application of light to optic nerve, at the recording site, gave rise to a local membrane potential hyperpolarization over a period of about a minute, and increased the size of the depolarizing after potential. Application near the site of electrical stimulation reversibly raised current-threshold, and the change in threshold recorded over minutes of irradiation was significantly increased by the application of the I
blocker, ZD7288 (50 µM), indicating I
limits the hyperpolarizing effect of light. Light application also had fast effects on nerve behaviour, increasing threshold without appreciable delay (within seconds), probably by a mechanism independent of kinetically fast K
channels and Na
channel inactivation, and hypothesized to be caused by reversible changes in myelin function.
ABSTRACT
Background
Service members experience unique circumstances when providing medical care in austere environments. Some challenges include supply shortages and the need to perform surgery in ...extreme temperatures. As such, methods for the sanitization of medical tools are sought and efficacy of existing materiel sourced to austere medical facilities should be examined for this purpose. This study tested the efficacy of commercially available, FDA-approved wound cleansers for alternative use as a potential sanitizer of stainless-steel medical devices and instruments found at improvised medical facilities.
Methods
Escherichia coli and Staphylococcus aureus cultures were inoculated onto sterile stainless-steel carriers. After cleanser treatment, samples were held for 2 h, 24 h, or 7 days to represent different turn-around times between uses at ambient (25 °C), cold (−20 °C) and hot (50 °C) temperatures. Additional ex vivo challenges were performed using slurry harvested from porcine cecum. Colony-forming units and log reduction were calculated. Significance was determined using one-way ANOVA and multiple comparisons between treatment groups were calculated using Tukey’s multiple comparison test.
Results
All wound cleansers demonstrated statistically significant bactericidal activity against lab bacteria and ex vivo cecal slurry. E. coli and S. aureus resulted in approximately a 5-6 log reduction on average, resulting in no growth after treatment for all cleaners at 2 and 24 h. Similarly, 7-day post exposure results in a 6-log reduction after treatment for all groups at 25 °C and −25 °C. While treatment of ex vivo samples did not result in total kill, significant reductions in bacterial load were observed in all groups.
Conclusions
Wound cleansers cleared for use in surgical settings demonstrated antimicrobial effects against bacteria deposited on metal surfaces. These cleansers decreased bacterial viability when challenged against extreme temperatures and few bacteria were harvested from treated surfaces even after 7 days. FDA-approved wound cleaners show promise as a potential sanitizer in resource limited environments.
Computationally designed multi-subunit assemblies have shown considerable promise for a variety of applications, including a new generation of potent vaccines. One of the major routes to such ...materials is rigid body sequence-independent docking of cyclic oligomers into architectures with point group or lattice symmetries. Current methods for docking and designing such assemblies are tailored to specific classes of symmetry and are difficult to modify for novel applications. Here we describe RPXDock, a fast, flexible, and modular software package for sequence-independent rigid-body protein docking across a wide range of symmetric architectures that is easily customizable for further development. RPXDock uses an efficient hierarchical search and a residue-pair transform (RPX) scoring method to rapidly search through multidimensional docking space. We describe the structure of the software, provide practical guidelines for its use, and describe the available functionalities including a variety of score functions and filtering tools that can be used to guide and refine docking results towards desired configurations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increases in the current threshold occur in optic nerve axons with the application of infra-red laser light, whose mechanism is only partly understood. In isolated rat optic nerve, laser light was ...applied near the site of electrical stimulation, via a flexible fibre optic. Paired applications of light produced increases in threshold that were reduced on the second application, the response recovering with increasing delays, with a time constant of 24 s. 3-min duration single applications of laser light gave rise to a rapid increase in threshold followed by a fade, whose time-constant was between 40 and 50 s. After-effects were sometimes apparent following the light application, where the resting threshold was reduced. The increase in threshold was partially blocked by 38.6 mM Li
+
in combination with 5
μ
M bumetanide, a manoeuvre increasing refractoriness and consistent with axonal depolarization. Assessing the effect of laser light on the nerve input resistance ruled out a previously suggested fall in myelin resistance as contributing to threshold changes. These data appear consistent with an axonal membrane potential that partly relies on temperature-dependent electroneutral Na
+
influx, and where fade in the response to the laser may be caused by a gradually diminishing Na
+
pump–induced hyperpolarization, in response to falling intracellular Na
+
.
Background The feasibility and efficacy of a web-based curriculum in supplementing thoracic surgical training was previously shown. However, the impact of curricular participation on validated ...knowledge tests remains unknown. We compared in-service training examination (ITE) results among trainees, stratified by curricular use. Methods The national online curriculum was implemented in August 2013. We retrospectively reviewed trainees who participated in thoracic surgical training programs in both 2012 to 2013 and 2013 to 2014. Scores from the 2013 and 2014 ITEs were obtained, and curricular usage data were collected from site analytics. Trainees were separated into three groups according to 2013 ITE scores; within each group, changes in score for high- versus low-volume users were compared. Results 187 trainees took the ITE both years, with exposure to the online curriculum during only the second year. High-volume users’ scores trended toward greater improvement than scores of low-volume users (+18.2% versus +13.0%, p = 0.199). When stratified by 2013 score, the lowest scoring quartile improved substantially, and the highest scoring quartile improved modestly, regardless of curricular use. However, for those individuals who achieved mid-range scores in 2013, there was a trend toward much greater improvement in score with heavier use of the curriculum (+17.0% versus +7.0%, p = 0.094). Conclusions Among trainees who had access to the novel online curriculum during the second of 2 consecutive years, we evaluated the impact of curricular participation on ITE scores. The effect appears to be most pronounced in individuals with mid-range scores, in whom high curricular use led to the greatest improvement.
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