A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany.

BACKGROUND: Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. METHODS: In a cohort of 11,982 BC patients diagnosed in 1998-2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. RESULTS: Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94-1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98-1.01, P = .68). CONCLUSIONS: Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

Emission of methylene diphenyl diisocyanate and methylene dianiline during use of cure-in-place methylene diphenyl diisocyanate-based consumer products.

The aim of this study was to provide realistic isocyanate and amine emission data when using different methylene diphenyl diisocyanate (MDI)-based polyurethane consumer products. Emission testing (air sampling) of diisocyanates and corresponding diamines was performed in a full-scale controlled-environment chamber during different work operations, such as gluing, mixing and foaming. The polyurethane products used were construction glue, one-component foam and two different two-component adhesives used in parquet flooring. Air sampling for isocyanates and amines was performed in the breathing zone of the worker and at different positions inside the controlled-environment chamber while the work operations were performed. Air sampling was also performed after the application, at different positions inside the chamber, to cover the post curing phase. Low air concentrations (0.1-0.7 µg MDI/m3, 0.03-0.2 µg isocyanate group (NCO)/m3) were found in the breathing zone and close to the work operation for some of the gluing applications. No methylene diphenyl diamine (MDA) concentrations above the limit of quantification were found for any of the applications in the breathing zone air. These results indicated that inhalation exposure to MDA or MDI would be expected to be minimal during application of do-it-yourself consumer products containing MDI.

Conformational control of benzophenone-sensitized charge transfer in dinucleotides.

Charge transfer in DNA cannot be understood without addressing the complex conformational flexibility, which occurs on a wide range of timescales. In order to reduce this complexity four dinucleotide models 1X consisting of benzophenone linked by a phosphodiester to one of the natural nucleosides X = A, G, T, C were studied in water and methanol. The theoretical work focuses on the dynamics and electronic structure of 1G. Predominant conformations in the two solvents were obtained by molecular dynamics simulations. 1G in MeOH adopts mainly an open geometry with a distance of 12­16 Å between the two aromatic parts. In H2O the two parts of 1G form primarily a stacked conformation yielding a distance of 5­6 Å. The low-lying excited states were investigated by electronic structure theory in a QM/MM environment for representative snapshots of the trajectories. Photo-induced intramolecular charge transfer in the S1 state occurs exclusively in the stacked conformation. Ultrafast transient absorption spectroscopy with 1X reveals fast charge transfer from S1 in both solvents with varying yields. Significant charge transfer from the T1 state is only found for the nucleobases with the lowest oxidation potential: in H2O, charge transfer occurs with 3.2 × 10(9) s(-1) for 1A and 6.0 × 10(9) s(-1) for 1G. The reorganization energy remains nearly unchanged going from MeOH to the more polar H2O. The electronic coupling is rather low even for the stacked conformation with H(AB) = 3 meV and explains the moderate charge transfer rates. The solvent controls the conformational distribution and therefore gates the charge transfer due to differences in distance and stacking.

Severe soft tissue infection caused by a non-beta-hemolytic Streptococcus pyogenes strain harboring a premature stop mutation in the sagC gene.

We recovered a non-beta-hemolytic Streptococcus pyogenes strain from a severe soft tissue infection. In this isolate, we detected a premature stop codon within the sagC gene of the streptolysin S (SLS) biosynthetic operon. Reintroduction of full-length sagC gene on a plasmid vector restored the beta-hemolytic phenotype to our clinical isolate, indicating that the point mutation in sagC accounted for loss of hemolytic activity. To the best of our knowledge, this is the first report to demonstrate that a severe soft tissue infection can be caused by a non-beta-hemolytic S. pyogenes strain lacking a functional SagC.

Why BLUF photoreceptors with roseoflavin cofactors lose their biological functionality.

The photophysics of roseoflavin in three different environments is investigated by using ab initio and quantum mechanics/molecular mechanics methods. Intramolecular charge transfer is shown to be responsible for the quenching of the fluorescence in the gas phase, and in the water environment. However, for the roseoflavin incorporated into the blue light using flavin (BLUF) protein environment (substituting the native flavin) no such deactivation is found. The conical intersection between the locally excited state of the chromophore and the charge transfer state involving the tyrosine residue, which in the native BLUF domain is responsible for initiating the photocycle, is missing for the roseoflavin substituted protein. This explains the experimental observations of the lack of any photocycle, and the loss of the biological function of the BLUF photoreceptor reported earlier.

Fungating Wounds - Multidimensional Challenge in Palliative Care.

SUMMARY: The management of fungating, malignant wounds is a challenge for the palliative care team. Open, malodorous, poorly healing lesions are obvious signs of underlying disease. In addition, pain and functional impairment remind the patients of their incurable illness. A multidimensional approach is necessary to meet the needs of these patients and to improve quality of life. Although achieving wound closure is rarely a realistic goal, modern techniques of wound management can help to minimize odours and exudates. Specialist knowledge in palliative care is needed to provide adequate pain control. Psychosocial support may help patients to cope with the situation and their limited abilities.

Theoretical study on the repair mechanism of the (6-4) photolesion by the (6-4) photolyase.

UV irradiation of DNA can lead to the formation of mutagenic (6-4) pyrimidine-pyrimidone photolesions. The (6-4) photolyases are the enzymes responsible for the photoinduced repair of such lesions. On the basis of the recently published crystal structure of the (6-4) photolyase bound to DNA [Maul et al. 2008] and employing quantum mechanics/molecular mechanics techniques, a repair mechanism is proposed, which involves two photoexcitations. The flavin chromophore, initially being in its reduced anionic form, is photoexcited and donates an electron to the (6-4) form of the photolesion. The photolesion is then protonated by the neighboring histidine residue and forms a radical intermediate. The latter undergoes a series of energy stabilizing hydrogen-bonding rearrangements before the electron back transfer to the flavin semiquinone. The resulting structure corresponds to the oxetane intermediate, long thought to be formed upon DNA-enzyme binding. A second photoexcitation of the flavin promotes another electron transfer to the oxetane. Proton donation from the same histidine residue allows for the splitting of the four-membered ring, hence opening an efficient pathway to the final repaired form. The repair of the lesion by a single photoexcitation was shown not to be feasible.

The thermal isomerization of the GFP chromophore: A computational study.

We present a density functional theory (B3LYP) study of the isomerization of 4-hydroxybenzylidene-1,2-dimethyl-imidazolinone (HOBDI), which is to mimic the green fluorescent protein (GFP) chromophore, in the ground state promoted by a nucleophile. Four solvents with different polarity, water, DMSO, methanol, and benzene, have been used to characterize the nucleophile assisted mechanism. The former three solvents have been used as nucleophile to participate in the reaction, while in benzene, we use n-propylamine as the nucleophile. When water, methanol and n-propylamine are used as nucleophile, the isomerization is characterized as a three-step process and the addition of the nucleophile is the rate-determining step. A proton transfer from the nucleophile to the oxygen of imidazolinone (O(1)) is observed during the addition step, which stabilizes the negative charge on O(1) due to the reduction of the C(1)[double bond, length as m-dash]C(2) double bond. The energy barrier to the reaction increases in the order of CH(3)OH

Comment on "Minimax approximation for the decomposition of energy denominators in Laplace-transformed Møller-Plesset perturbation theories" [J. Chem. Phys. 129, 044112 (2008)].

The recently proposed minimax quadrature for Laplace-transformed energy denominators in second order Møller-Plesset perturbation theory is compared to the conventionally used least-squares quadrature. Our test calculations show that the quality of the least-squares quadrature is not inferior compared to minimax. Its computational overhead (required to determine points and weights of the quadrature) is clearly insignificant relative to the subsequent MP2 calculation. For high accuracy and all-electron calculations (correlated core) good starting guesses for the roots are essential.

Visible and subclinical skin changes in male and female dispatch department workers of newspaper printing plants.

UNLABELLED: BACKGROUND AND PROBLEM: Wet work and skin exposure to detergents or solvents are well-established causes of irritant hand dermatitis. In contrast, physical irritation of the skin as another potential cause of occupational hand dermatitis has been investigated less. MATERIAL AND METHODS: Our study included 71 individuals exposed to physical irritation during work in the dispatch department of two newspaper printing plants. Clinical examination and measurements of transepidermal water loss (TEWL), capacitance and skin surface pH of the skin of hands and forearms was performed. RESULTS: Erythema and/or scaliness of the hands were unexpectedly common: 26 of the 38 female inlay workers, 11 of the 13 male inlay workers and 15 of the 20 male machine operators were affected, compared to 18 of 28 printers exposed to solvents who had been investigated in a previous study. A significantly higher skin surface pH on the hands (P < 0.05) and, less pronounced, on the forearms (P > 0.05) was found in females. There was no association between domestic skin exposure, according to questionnaire data, and the bioengineering results. Skin cleansing and skin care differed between male and female workers, but were again not associated with the outcomes. CONCLUSIONS: The point prevalence of skin changes in dispatch department workers in the present study is unexpectedly high, which points to the importance of physical irritation by paper dust. Significant differences in bioengineering parameters between male and female inlay workers were found only for skin surface pH at the exposed back of hands. Future studies should (i) try to elucidate the role of skin surface pH changes and (ii) pay more attention to physical trauma to the skin.