A comparison of the chemo- and radiotoxicity of thorium and uranium at different enrichment grades.

Uranium and thorium are heavy metals, and all of their isotopes are radioactive, so it is impossible to study chemical effects entirely independent of the radiation effects. In the present study, we tried to compare the chemo- and radiotoxicity of both metals, taking into account deterministic radiation damages reflected by acute radiation sickness and stochastic radiation damages leading to long-term health impairments (e.g., tumor induction). We made at first a literature search on acute median lethal doses that may be expected to be caused by chemical effects, as even acute radiation sickness as a manifestation of acute radiotoxicity occurs with latency. By simulations based on the biokinetic models of the International Commission on Radiological Protection and using the Integrated Modules for Bioassay Analysis software, we determined the amounts of uranium at different enrichment grades and thorium-232 leading to a short-term red bone marrow equivalent dose of 3.5 Sv considered to cause 50% lethality in humans. Different intake pathways for incorporation were considered, and values were compared to the mean lethal doses by chemotoxicity. To assess stochastic radiotoxicity, we calculated the uranium and thorium amounts leading to a committed effective dose of 200 mSv that is often considered critical. Mean lethal values for uranium and thorium are in the same order of magnitude so that the data do not give evidence for substantial differences in acute chemical toxicity. When comparing radiotoxicity, the reference units (activity in Bq or weight in g) must always be taken into account. The mean lethal equivalent dose to the red bone marrow of 3.5 Sv is reached by lower activities of thorium compared to uranium in soluble compounds. However, for uranium as well as thorium-232, acute radiation sickness is expected only after incorporation of amounts exceeding the mean lethal doses by chemotoxicity. Thus, acute radiation sickness is not a relevant clinical issue for either metal. Concerning stochastic radiation damages, thorium-232 is more radiotoxic than uranium if incorporating the same activities. Using weight units for comparison show that for soluble compounds, thorium-232 is more radiotoxic than low-enriched uranium in the case of ingestion but even more toxic than high-enriched uranium after inhalation or intravenous administration. For insoluble compounds, the situation differs as the stochastic radiotoxicity of thorium-232 ranges between depleted and natural uranium. For acute effects, the chemotoxicity of uranium, even at high enrichment grades, as well as thorium-232 exceeds deterministic radiotoxicity. Simulations show that thorium-232 is more radiotoxic than uranium expressed in activity units. If the comparison is based on weight units, the rankings depend on the uranium enrichment grades and the route of intake.

The anatomy of past abrupt warmings recorded in Greenland ice.

Data availability and temporal resolution make it challenging to unravel the anatomy (duration and temporal phasing) of the Last Glacial abrupt climate changes. Here, we address these limitations by investigating the anatomy of abrupt changes using sub-decadal-scale records from Greenland ice cores. We highlight the absence of a systematic pattern in the anatomy of abrupt changes as recorded in different ice parameters. This diversity in the sequence of changes seen in ice-core data is also observed in climate parameters derived from numerical simulations which exhibit self-sustained abrupt variability arising from internal atmosphere-ice-ocean interactions. Our analysis of two ice cores shows that the diversity of abrupt warming transitions represents variability inherent to the climate system and not archive-specific noise. Our results hint that during these abrupt events, it may not be possible to infer statistically-robust leads and lags between the different components of the climate system because of their tight coupling.

Racial differences in myocardial deformation in obese children: Significance of inflammatory state.

BACKGROUND AND AIMS: The association between racial differences in myocardial deformation and cardiometabolic risk factors is unknown in obese children. Our objective was to: 1) investigate for racial differences in myocardial deformation between white and black obese children and 2) identify biomarkers associated with these observed racial differences. We hypothesized that decreased myocardial deformation observed in black obese children could be accounted for by the differences in the markers of metabolic syndrome between the groups. METHODS AND RESULTS: Obese children were recruited prospectively. All clinical and laboratory tests for the metabolic syndrome were conducted during a single assessment using a standardized protocol. Speckle-tracking echocardiography was performed to obtain longitudinal and circumferential measures of deformation. 310 patients were included in the analysis; 158 (51%) white and 152 (49%) black. The median age was 11.3 years (IQR 5.9). Blacks demonstrated worse longitudinal strain (-14.7 ± 2.7% vs. -15.4 ± 2.9%, p = 0.04). There was no difference in circumferential strain between the groups. Multivariable linear regression showed a significant relationship between longitudinal strain and hsCRP (ß = 0.16, p = 0.03) and HOMA-IR (ß = 0.15, p = 0.04); there was no independent association between longitudinal strain and race. CONCLUSION: Black subjects demonstrated worse longitudinal strain than whites. Only hsCRP and HOMA-IR levels, not race, had an independent association with longitudinal strain, suggesting that the observed racial differences in longitudinal strain may be secondary to differences in inflammation and insulin resistance between the groups.

Dosimetric effect of photon beam energy on volumetric modulated arc therapy treatment plan quality due to body habitus in advanced prostate cancer.

PURPOSE: The purpose of this study was to dosimetrically compare 6- and 10-MV photon beam energies in high-risk prostate cancer patients of various body habitus using a volumetric modulated arc therapy (VMAT) radiation delivery technique. The objectives of the study were to evaluate whether dosimetric differences exist and to investigate whether differences are dependent on patient body habitus. METHODS AND MATERIALS: Forty patients with various body habitus who had previously received treatment to the prostate and pelvic lymph nodes with VMAT techniques were chosen. Patients were planned in the Pinnacle(3) treatment planning system with double or triple SmartArc plans with 6- and 10-MV photon energies. All patients were optimized with the same planning objectives and normalized such that 95% of the planning target volume (PTV) received the prescription dose. Patients were evaluated for PTV and organ at risk (OAR) parameters for the bladder, rectum, small bowel, penile bulb, and sigmoid colon. Metrics used for comparison were D2%, D98%, homogeneity, conformity, and dose falloff for the PTV and D(2%), D(mean), V(80%), V(60%), and V(40%) for OARs. Statistical differences were evaluated with a paired-sample Wilcoxon signed rank test with a significance level of .05. RESULTS: For the PTV, there were no statistically significant differences in D(mean), D(2cc), conformation number, and homogeneity index values, but the dose falloff parameters, R50 and R25, showed a median improvement of 6.7% (P<.01) and 6.2% (P<.01), respectively, with 10 MV. A correlation between patient anterior-posterior distance (d(AP)) and percentage reduction in R50 of 0.436% per centimeter (P<.01) was determined. For OARs, statistically significant reductions in dose metrics were found in the small bowel and bladder, but increases in the D(2cc) of 3.5% in the penile bulb (P<.01) and 0.2% in the rectum (P=.02) were shown with 10 MV. The use of 10 MV also demonstrated a statistically significant reduction in the total number of monitor units of 15.9% (P<.01) compared with 6 MV. CONCLUSIONS: The study showed that 10 MV provides a faster dose falloff than 6 MV for patients whose prostate and pelvic lymph nodes are treated using a VMAT technique irrespective of body habitus; however, the improvement in dose falloff is dependent on body habitus and increases as the patient body habitus increases.

TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma.

Bone marrow-derived human mesenchymal stem cells (hMSCs) have become valuable candidates for cell-based therapeutical applications including neuroregenerative and anti-tumor strategies. Yet, the molecular mechanisms that control hMSC trans-differentiation to neural cells and hMSC tropism toward glioma remain unclear. Here, we demonstrate that hMSCs incubated with 50 ng/ml tumor necrosis factor alpha (TNF-α) acquired astroglial cell morphology without affecting proliferation, which was increased at 5 ng/ml. TNF-α (50 ng/ml) upregulated expression of numerous genes important for neural cell growth and function including LIF (leukemia inhibitory factor), BMP2 (bone morphogenetic protein 2), SOX2 (SRY box 2), and GFAP (glial fibrillary acidic protein), whereas NES (human nestin) transcription ceased suggesting a premature neural phenotype in TNF-α-differentiated hMSCs. Studies on intracellular mitogen-activated protein kinase (MAPK) signaling revealed that inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity abolished the TNF-α-mediated regulation of neural genes in hMSCs. In addition, TNF-α significantly enhanced expression of the chemokine receptor CXCR4 (CXC motive chemokine receptor 4), which facilitated the chemotactic invasiveness of hMSCs toward stromal cell-derived factor 1 (SDF-1) alpha. TNF-α-pretreated hMSCs not only exhibited an increased ability to infiltrate glioma cell spheroids dependent on matrix metalloproteinase activity in vitro, but they also showed a potentiated tropism toward intracranial malignant gliomas in an in vivo mouse model. Taken together, our results provide evidence that culture-expansion of hMSCs in the presence of TNF-α triggers neural gene expression and functional capacities, which could improve the use of hMSCs in the treatment of neurological disorders including malignant gliomas.

[Transcriptome analyses in renal cell carcinoma. Combination of laser microdissection and microarrays]. / Transkriptomanalysen beim Nierenzellkarzinom. Kombination von Lasermikrodissektion und Microarrays.

BACKGROUND: The objective of this study was to test the feasibility of combined laser microdissection and microarray-based expression analysis in renal cell carcinoma (RCC) and to detect the most strongly deregulated genes. METHODS: Laser microdissection of tumor areas and subsequent gene expression analysis (47,000 transcripts) was performed on snap-frozen primary tumor samples from 15 patients with clear cell RCC. Four normal kidney samples served as controls. Validation was performed for one gene with quantitative RT-PCR on additional samples. RESULTS: Isolation of intact RNA from microdissected tissue was successful; 179 transcripts were significantly deregulated by a factor of 5 or more. Upregulation of FABP7 was confirmed by quantitative RT-PCR. CONCLUSION: In RCC the combination of laser microdissection and subsequent microarray analysis provides reliable data from precisely defined material. This is an optimal starting point for the development of novel therapeutic and diagnostic options.

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Nonsurgical treatment for a Class III dental relationship: a case report.

The purpose of this report is to review the orthodontic treatment of a patient with a Class III malocclusion who was treated nonsurgically with extraction of the mandibular first premolars. The basis for this treatment approach is presented, and the final treatment result reviewed. Important factors to consider when establishing a Class III molar relationship are discussed.

Pulpal response to orthodontic tooth movement in adolescents: a radiographic study.

The purpose of this study was to examine the effect of routine orthodontic treatment on the pulp and periodontal ligament. In a group of adolescent patients who were treated consecutively, radiographs were taken before orthodontic intervention, at the end of retention, and approximately 5 years out of retention. These were compared with radiographs taken at comparable time intervals of a group of patients who had not received orthodontic treatment. Damage to the pulp and the periodontal ligament similar to that seen after traumatic injury was observed only occasionally. A narrowing of the pulp canal was observed from before to after appliance therapy and during the follow-up period in the experimental group. A narrowing of the pulp canal was also seen in the untreated group. Thus this narrowing was interpreted as a normal aging process.