Design of double-walled carbon nanotubes for biomedical applications

Double-walled carbon nanotubes (DWNTs) prepared by catalytic chemical vapour deposition were functionalized in such a way that they were optimally designed as a nano-vector for the delivery of small interfering RNA (siRNA), which is of great interest for biomedical research and drug development. DWNTs were initially oxidized and coated with a polypeptide (Poly(Lys:Phe)), which was then conjugated to thiol-modified siRNA using a heterobifunctional cross-linker. The obtained oxDWNT–siRNA was characterized by Raman spectroscopy inside and outside a biological environment (mammalian cells). Uptake of the custom designed nanotubes was not associated with detectable biochemical perturbations in cultured cells, but transfection of cells with DWNTs loaded with siRNA targeting the green fluorescent protein (GFP) gene, serving as a model system, as well as with therapeutic siRNA targeting the survivin gene, led to a significant gene silencing effect, and in the latter case a resulting apoptotic effect in cancer cells

Incidence of Hajj-associated febrile cough episodes among French pilgrims: a prospective cohort study on the influence of statin use and risk factors

AbstractA prospective epidemiological study was conducted to evaluate the incidence of febrile cough episodes among adult Muslims travelling from Marseille to Saudi Arabia during the Hajj pilgrimage and to assess if use of statin had an influence on this incidence. In total, 580 individuals were presented with a questionnaire. A significant proportion of individuals had chronic medical disorders, e.g. diabetes mellitus (132, 22.8%) and hypertension (147, 25.3%). Pilgrims had a low level of education and a low employment rate. Sixty (10.3%) were treated with statins for hypercholesterolemia. Four hundred and fourty-seven pilgrims were presented a questionnaire on returning home. A total of 74 travellers (16.6%) experienced fever during their stay in Saudi Arabia (67 attended a doctor) and 271 (60.6%) had cough (259 attended a doctor); 70 travellers with cough were febrile (25.9%). Seventy per cent of the travellers who suffered cough episodes developed their first symptoms within 3 days, suggesting a human to human transmission of the responsible pathogen, with short incubation time as evidenced by a bimodal distribution of cough in two peaks at a 24 h interval. None of demographical and socioeconomic characteristics, underlying diseases or vaccination against influenza significantly affected the occurrence of cough. Diabetes correlated with an increased risk of febrile cough (OR = 2.02 (1.05–3.89)) as well as unemployment (OR = 2.22 (0.91–5.53)). Use of statins had no significant influence on the occurrence of cough and/or fever during the pilgrimage. This result suggests that while treatment with a statin has been demonstrated to reduce the mortality from severe sepsis associated with respiratory tract infections, it probably does not play a role in the outcome of regular febrile cough episodes as observed in the cohort studied here

Endovascular retrieval of two migrated venous stents by means of balloon catheters

AbstractThe usefulness of vascular stenting was demonstrated in both arterial and venous applications to restore patency and improve suboptimal results after percutaneous transluminal angioplasty. Dislodgment of venous stents with an embolization into the right cavities or the pulmonary artery, however, is one of the most feared complications of this procedure. Percutaneous removal of these migrated stents is an appealing method of replacing more invasive operative intervention with cardiopulmonary bypass, which may be very hazardous in these often severely ill patients. We describe the cases of two patients with stents that migrated into the right ventricle and the pulmonary artery. In one patient, we were able to successfully remove these stents by using an angioplasty balloon with an operative extraction from the iliac vein, thereby obviating the need for a major operative procedure. (J Vasc Surg 1998;28:541-6.

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Background: In the past few years, the issue of \u2018microdosing\u2019 psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is. Aim: This critique paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies. Approach: Owing to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics, our focus is predominantly on psilocybin. Psilocybin is allegedly, next to lysergic acid diethylamide (LSD), one of the two most frequently used psychedelics to microdose. Where relevant and available, data for other psychedelic drugs are also mentioned. Conclusion: It is concluded that while most anecdotal reports focus on the positive experiences with microdosing, future research should also focus on potential risks of (multiple) administrations of a psychedelic in low doses. To that end, (pre)clinical studies including biological (e.g. heart rate, receptor turnover and occupancy) as well as cognitive (e.g. memory, attention) parameters have to be conducted and will shed light on the potential negative consequences microdosing could have

Chloroquine-enhanced gene delivery mediated by carbon nanotubes

Polyethyleneimine-coated double-walled carbon nanotubes (DWCNTs) were used for dual gene and drug delivery, after loading the DWCNTs with the drug chloroquine, a lysosomotropic compound that is able to promote escape from the lysosomal compartment. Different forms of functionalization of the DWCNTs were examined in order to optimize this system. They included the testing of different treatments on DWCNTs to optimize the loading and delivery of chloroquine and the selection of a cationic polymer for coating the DWCNTs for optimum DNA binding and delivery. An acid oxidation treatment of DWCNTs was selected for optimum chloroquine loading together with polyethyleneimine as optimum cationic coating agent for plasmid DNA binding. Optimization of the conditions for choroquine-enhanced gene delivery were developed using luciferase expression as a model system. We have demonstrated that chloroquine-loading increases the ability of polyethyleneimine-coated DWCNTs to deliver functional nucleic acid to human cells. Cell viability tests have shown no cytotoxicity of the functionalized DWCNTs at the concentrations needed for optimum gene delivery. These results support the potential applications of this methodology in gene therapy

How Gibbs distributions may naturally arise from synaptic adaptation mechanisms. A model-based argumentation

This paper addresses two questions in the context of neuronal networks dynamics, using methods from dynamical systems theory and statistical physics: (i) How to characterize the statistical properties of sequences of action potentials ("spike trains") produced by neuronal networks ? and; (ii) what are the effects of synaptic plasticity on these statistics ? We introduce a framework in which spike trains are associated to a coding of membrane potential trajectories, and actually, constitute a symbolic coding in important explicit examples (the so-called gIF models). On this basis, we use the thermodynamic formalism from ergodic theory to show how Gibbs distributions are natural probability measures to describe the statistics of spike trains, given the empirical averages of prescribed quantities. As a second result, we show that Gibbs distributions naturally arise when considering "slow" synaptic plasticity rules where the characteristic time for synapse adaptation is quite longer than the characteristic time for neurons dynamics.Comment: 39 pages, 3 figure

Relativistic electron beams above thunderclouds

Non-luminous relativistic electron beams above thunderclouds have been detected by the radio signals of low frequency ∼40–400 kHz which they radiate. The electron beams occur ∼2–9 ms after positive cloud-to-ground lightning discharges at heights between ∼22–72 km above thunderclouds. Intense positive lightning discharges can also cause sprites which occur either above or prior to the electron beam. One electron beam was detected without any luminous sprite which suggests that electron beams may also occur independently of sprites. Numerical simulations show that beams of electrons partially discharge the lightning electric field above thunderclouds and thereby gain a mean energy of ∼7 MeV to transport a total charge of ∼−10 mC upwards. The impulsive current ∼3 × 10<sup>−3</sup> Am<sup>−2</sup> associated with relativistic electron beams above thunderclouds is directed downwards and needs to be considered as a novel element of the global atmospheric electric circuit

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Carbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT–RNA) is presented. Fixed cells, previously exposed to oxDWNT–RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT–RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT–RNA with the small GTP-binding protein (Rab 11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network

The mesospheric inversion layer and sprites

The vertical structure of temperature observed by SABER (Sounding of Atmosphere using Broadband Emission Radiometry) aboard TIMED (Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics) and sprites observations made during the Eurosprite 2003 to 2007 observational campaign were analyzed. Sprite observations were made at two locations in France, namely Puy de Dome in the French Massif Central and at the Pic du Midi in the French Pyrenees. It is observed that the vertical structure of temperature shows evidence for a Mesospheric Inversion Layer (MIL) on those days on which sprites were observed. A few events are also reported in which sprites were not recorded, although there is evidence of a MIL in the vertical structure of the temperature. It is proposed that breaking gravity waves produced by convective thunderstorms facilitate the production of (a) sprites by modulating the neutral air-density and (b) MILs via the deposition of energy. The same proposition has been used to explain observations of lightings as well as both MILs and lightning arising out of deep convections.Comment: 34 pages, 5figures. Accepted in Journal of Geophysical Research, US