Mapping the Sensitive Volume of an Ion-Counting Nanodosimeter

We present two methods of independently mapping the dimensions of the sensitive volume in an ion-counting nanodosimeter. The first method is based on a calculational approach simulating the extraction of ions from the sensitive volume, and the second method on probing the sensitive volume with 250 MeV protons. Sensitive-volume maps obtained with both methods are compared and systematic errors inherent in both methods are quantified.Comment: 27 pages, 8 figures. Submitted to JINST, Jan. 16 200

Design of a novel flow-and-shoot microbeam

Presented here is a novel microbeam technology—the Flow-And-ShooT (FAST) microbeam—under development at RARAF. In this system, cells undergo controlled fluidic transport along a microfluidic channel intersecting the microbeam path. They are imaged and tracked in real-time, using a high-speed camera and dynamically targeted, using a magnetic Point and Shoot system. With the proposed FAST system, RARAF expects to reach a throughput of 100 000 cells per hour, which will allow increasing the throughput of experiments by at least one order of magnitude. The implementation of FAST will also allow the irradiation of non-adherent cells (e.g. lymphocytes), which is of great interest to many of the RARAF users. This study presents the design of a FAST microbeam and results of first tests of imaging and tracking as well as a discussion of the achievable throughput

Acquired constriction ring syndrome as a cause of inconsolable cry in a child: a case report

Acute constriction ring syndrome (ACRS) is a rare clinical condition characterized by formation of a circumferential constriction ring around an appendage or genitalia. Cases are mostly reported in infants and young children. Early recognition and a definitive treatment are of paramount importance in order to avoid irreversible ischemia and possible auto-amputation. We describe a case of a 14-month-old child presented to casualty with a history of refusal to feed and inconsolable cry. Parents noticed a recent swelling of left third toe. On careful examination the child was found to have an acquired constriction ring secondary to a tightly wrapped hair around left third toe. An urgent surgical decompression was done by the orthopaedic team with complete resolution of symptoms. We summarized the pathophysiology of ACRS underlining the need of awareness in treating physicians. The possible medico legal implications should be kept in mind bearing a suggested link with non-accidental injury

DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1-1.2 Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91 Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08 Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX MFI as a biomarker for dosimetry in a protracted, environmental exposure scenario

Outdoor particulate matter and childhood asthma admissions in Athens, Greece: a time-series study

<p>Abstract</p> <p>Background</p> <p>Particulate matter with diameter less than 10 micrometers (PM₁₀) that originates from anthropogenic activities and natural sources may settle in the bronchi and cause adverse effects possibly via oxidative stress in susceptible individuals, such as asthmatic children. This study aimed to investigate the effect of outdoor PM₁₀concentrations on childhood asthma admissions (CAA) in Athens, Greece.</p> <p>Methods</p> <p>Daily counts of CAA from the three Children's Hospitals within the greater Athens' area were obtained from the hospital records during a four-year period (2001-2004, n = 3602 children). Mean daily PM₁₀concentrations recorded by the air pollution-monitoring network of the greater Athens area were also collected. The relationship between CAA and PM₁₀concentrations was investigated using the Generalized Linear Models with Poisson distribution and logistic analysis.</p> <p>Results</p> <p>There was a statistically significant (95% CL) relationship between CAA and mean daily PM₁₀concentrations on the day of exposure (+3.8% for 10 μg/m³increase in PM₁₀concentrations), while a 1-day lag (+3.4% for 10 μg/m³increase in PM₁₀concentrations) and a 4-day lag (+4.3% for 10 μg/m³increase in PM₁₀concentrations) were observed for older asthmatic children (5-14 year-old). High mean daily PM₁₀concentration (the highest 10%; >65.69 μg/m³) doubled the risk of asthma exacerbations even in younger asthmatic children (0-4 year-old).</p> <p>Conclusions</p> <p>Our results provide evidence of the adverse effect of PM₁₀on the rates of paediatric asthma exacerbations and hospital admissions. A four-day lag effect between PM₁₀peak exposure and asthma admissions was also observed in the older age group.</p

Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up of 23 patients in a single tertiary center

© 2007 Russo and Katsicas; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Chronic Nicotine Modifies Skeletal Muscle Na,K-ATPase Activity through Its Interaction with the Nicotinic Acetylcholine Receptor and Phospholemman

Our previous finding that the muscle nicotinic acetylcholine receptor (nAChR) and the Na,K-ATPase interact as a regulatory complex to modulate Na,K-ATPase activity suggested that chronic, circulating nicotine may alter this interaction, with long-term changes in the membrane potential. To test this hypothesis, we chronically exposed rats to nicotine delivered orally for 21–31 days. Chronic nicotine produced a steady membrane depolarization of ∼3 mV in the diaphragm muscle, which resulted from a net change in electrogenic transport by the Na,K-ATPase α2 and α1 isoforms. Electrogenic transport by the α2 isoform increased (+1.8 mV) while the activity of the α1 isoform decreased (−4.4 mV). Protein expression of Na,K-ATPase α1 or α2 isoforms and the nAChR did not change; however, the content of α2 subunit in the plasma membrane decreased by 25%, indicating that its stimulated electrogenic transport is due to an increase in specific activity. The physical association between the nAChR, the Na,K-ATPase α1 or α2 subunits, and the regulatory subunit of the Na,K-ATPase, phospholemman (PLM), measured by co-immuno precipitation, was stable and unchanged. Chronic nicotine treatment activated PKCα/β2 and PKCδ and was accompanied by parallel increases in PLM phosphorylation at Ser63 and Ser68. Collectively, these results demonstrate that nicotine at chronic doses, acting through the nAChR-Na,K-ATPase complex, is able to modulate Na,K-ATPase activity in an isoform-specific manner and that the regulatory range includes both stimulation and inhibition of enzyme activity. Cholinergic modulation of Na,K-ATPase activity is achieved, in part, through activation of PKC and phosphorylation of PLM

Protein Phosphatase 2A Interacts with the Na+,K+-ATPase and Modulates Its Trafficking by Inhibition of Its Association with Arrestin

Background: The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na +,K +-ATPase. The catalytic subunit of the Na +,K +-ATPase includes several functional domains that determine its enzymatic and trafficking properties. Methodology/Principal Findings: Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na +,K +-ATPase interacting protein. PP-2A C-subunit interacted with the Na +,K +-ATPase, but not with the homologous sequences of the H +,K +-ATPase. We confirmed that the Na +,K +-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na +,K +-ATPase trafficking through direct association. PP2A inhibits association between the Na +,K +-ATPase and arrestin, and diminishes the effect of arrestin on Na +,K +-ATPase trafficking. GRK phosphorylates the Na +,K +-ATPase and PP2A can at least partially reverse this phosphorylation. Conclusions/Significance: Taken together, these data demonstrate that the sodium pump belongs to a growing list of io

An ultrasoft X-ray multi-microbeam irradiation system for studies of DNA damage responses by fixed- and live-cell fluorescence microscopy

Localized induction of DNA damage is a valuable tool for studying cellular DNA damage responses. In recent decades, methods have been developed to generate DNA damage using radiation of various types, including photons and charged particles. Here we describe a simple ultrasoft X-ray multi-microbeam system for high dose-rate, localized induction of DNA strand breaks in cells at spatially and geometrically adjustable sites. Our system can be combined with fixed- and live-cell microscopy to study responses of cells to DNA damage