Diagnosis of Partial Body Radiation Exposure in Mice Using Peripheral Blood Gene Expression Profiles

In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB) can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI). However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals. Here, we identified gene expression profiles in the PB that were characteristic of anterior hemibody-, posterior hemibody- and single limb-irradiation at 0.5 Gy, 2 Gy and 10 Gy in C57Bl6 mice. These PB signatures predicted the radiation status of partially irradiated mice with a high level of accuracy (range 79–100%) compared to non-irradiated mice. Interestingly, PB signatures of partial body irradiation were poorly predictive of radiation status by site of injury (range 16–43%), suggesting that the PB molecular response to partial body irradiation was anatomic site specific. Importantly, PB gene signatures generated from TBI-treated mice failed completely to predict the radiation status of partially irradiated animals or non-irradiated controls. These data demonstrate that partial body irradiation, even to a single limb, generates a characteristic PB signature of radiation injury and thus may necessitate the use of multiple signatures, both partial body and total body, to accurately assess the status of an individual exposed to radiation

Effect of lifestyle intervention for people with diabetes or prediabetes in real-world primary care: propensity score analysis

<p>Abstract</p> <p>Background</p> <p>Many lifestyle interventions for patients with prediabetes or type 2 diabetes mellitus (T2DM) have been investigated in randomised clinical trial settings. However, the translation of these programmes into primary care seems challenging and the prevalence of T2DM is increasing. Therefore, there is an urgent need for lifestyle programmes, developed and shown to be effective in real-world primary care. We evaluated a lifestyle programme, commissioned by the Dutch government, for patients with prediabetes or type 2 diabetes in primary care.</p> <p>Methods</p> <p>We performed a retrospective comparative medical records analysis using propensity score matching. Patients with prediabetes or T2DM were selected from ten primary healthcare centres. Patients who received the lifestyle intervention (n = 186) were compared with a matched group of patients who received usual care (n = 2632). Data were extracted from the electronic primary care records. Propensity score matching was used to control for confounding by indication. Outcome measures were exercise level, BMI, HbA1c, fasting glucose, systolic and diastolic blood pressure, total cholesterol, HDL and LDL cholesterol and triglycerides and the follow-up period was one year.</p> <p>Results</p> <p>There was no significant difference at follow-up in any outcome measure between either group. The reduction at one year follow-up of HbA1c and fasting glucose was positive in the intervention group compared with controls, although not statistically significant (-0.12%, <it>P </it>= 0.07 and -0.17 mmol/l, <it>P </it>= 0.08 respectively).</p> <p>Conclusions</p> <p>The effects of the lifestyle programme in real-world primary care for patients with prediabetes or T2DM were small and not statistically significant. The attention of governments for lifestyle interventions is important, but from the available literature and the results of this study, it must be concluded that improving lifestyle in real-world primary care is still challenging.</p

Laser-Induced Acoustic Desorption/ Atmospheric Pressure Chemical Ionization Mass Spectrometry

Laser-induced acoustic desorption (LIAD) was successfully coupled to a conventional atmospheric pressure chemical ionization (APCI) source in a commercial linear quadrupole ion trap mass spectrometer (LQIT). Model compounds representing a wide variety of different ypes, including basic nitrogen and oxygen compounds, aromatic and aliphatic compounds, as well as unsaturated and saturated hydrocarbons, were tested separately and as a mixture. These model compounds were successfully evaporated into the gas phase by using LIAD and then ionized by using APCI with different reagents. From the four APCI reagent systems tested, neat carbon disulfide provided the best results. The mixture of methanol and water produced primarily protonated molecules, as expected. However, only the most basic compounds yielded ions under these conditions. In sharp contrast, using APCI with either neat benzene or neat carbon disulfide as the reagent resulted in the ionization of all the analytes studied to predominantly yield stable molecular ions. Benzene yielded a larger fraction of protonated molecules than carbon disulfide, which is a disadvantage. A similar but minor amount of fragmentation was observed for these two reagents. When the experiment was performed without a liquid reagent (nitrogen gas was the reagent), more fragmentation was observed. Analysis of a known mixture as well as a petroleum cut was also carried out. In summary, the new experiment presented here allows the evaporation of thermally labile compounds, both polar and nonpolar, without dissociation or aggregation, and their ionization to predominantly form stable molecular ions

Carbon Disulfide Reagent Allows the Characterization of Nonpolar Analytes by Atmospheric Pressure Chemical Ionization Mass Spectrometry

While atmospheric pressure ionization methodologies have revolutionized the mass spectrometric analysis of nonvolatile analytes, limitations native to the chemistry of these methodologies hinder or entirely inhibit the analysis of certain analytes, specifically, many nonpolar compounds. Examination of various analytes, including asphaltene and lignin model compounds as well as saturated hydrocarbons, demonstrates that atmospheric pressure chemical ionization (APCI) using CS2 as the reagent produces an abundant and stable molecular ion (M+•) for all model compounds studied, with the exception of completely saturated aliphatic hydrocarbons and the two amino acids tested, arginine and phenylalanine. This reagent substantially broadens the applicability of mass spectrometry to nonvolatile nonpolar analytes and also facilitates the examination of radical cation chemistry by mass spectrometry

Development of a High-Throughput Laser-Induced Acoustic Desorption Probe and Raster Sampling For Laser-Induced Acoustic Desorption/Atmospheric Pressure Chemical Ionization

Laser-induced acoustic desorption (LIAD) was recently coupled to atmospheric pressure chemical ionization (APCI) and shown to be of great utility for the analysis of a variety of thermally labile nonpolar analytes that are not amenable to ionization via electrospray ionization, such as nonvolatile hydrocarbons. Despite these advancements, LIAD still suffered from several limitations, including only being able to sample a small fraction of the analyte molecules deposited on a Ti foil for desorption, poor reproducibility, as well as limited laser power throughput to the backside of the foil. These limitations severely hinder the analysis of especially challenging analytes, such as asphaltenes. To address these issues, a novel high-throughput LIAD probe and an assembly for raster sampling of a LIAD foil were designed, constructed, and tested. The new probe design allows 98% of the initial laser power to be realized at the backside of the foil over the 25% achieved previously, thus improving reproducibility and allowing for the analysis of large nonvolatile analytes, including asphaltenes. The raster assembly provided a 5.7 fold increase in the surface area of a LIAD foil that could be sampled and improved reproducibility and sensitivity for LIAD experiments. The raster assembly can also improve throughput as foils containing multiple analytes can be prepared and analyzed