No abstract

Femtosecond time-resolved infrared spectroscopy was used to study the vibrational response of riboflavin in DMSO to photoexcitation at 387 nm. Vibrational cooling in the excited electronic state is observed and characterized by a time constant of 4.0 +/- 0.1 ps. Its characteristic pattern of negative and positive IR difference signals allows the identification and determination of excited-state vibrational frequencies of riboflavin in the spectral region between 1100 and 1740 cm (-1). Density functional theory (B3LYP), Hartree-Fock (HF) and configuration interaction singles (CIS) methods were employed to calculate the vibrational spectra of the electronic ground state and the first singlet excited pipi* state as well as respective electronic energies, structural parameters, electronic dipole moments and intrinsic force constants. The harmonic frequencies of the S 1 excited state calculated by the CIS method are in satisfactory agreement with the observed band positions. There is a clear correspondence between computed ground- and excited-state vibrations. Major changes upon photoexcitation include the loss of the double bond between the C4a and N5 atoms, reflected in a downshift of related vibrations in the spectral region from 1450 to 1720 cm (-1). Furthermore, the vibrational analysis reveals intra- and intermolecular hydrogen bonding of the riboflavin chromophore.

Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

The effects of lactulose and lactitol (2 x 10 g/d) were studied in 36 healthy volunteers in comparison to placebo. All parameters studied were affected by both treatments, lactulose in general leading to more pronounced changes compared to lactitol. Probiotic bacteria were increased, and putrefactive bacteria and potential pathogens were significantly reduced. These variations in colonic flora had the following consequences: (i) a reduced activity of pro-carcinogenic enzymes: azoreductase, 7 alpha-dehydroxylase, beta-glucuronidase, nitroreductase and urease activity; (ii) a global increase of short-chain fatty acids in faeces; (iii) an effect on pH and moisture of faeces, and (iv) also on aromatic compounds such as phenol, cresol, indole and skatol. The findings suggest that lactulose and lactitol are not comparable in their effect on the colonic microflora, its metabolism, and the consequent probiotic effects on human health. The differences found may also be of clinical relevance suggesting that neither compound is equipotent.

Purpose: The use of circulating tumor cells (CTC) as "liquid biopsy" is limited by the very low yield of CTCs available for subsequent analyses. Most in vitro approaches rely on small sample volumes (5-10 mL).Experimental Design: Here, we used a novel approach, the GILUPI CellCollector, which enables an in vivo isolation of CTCs from peripheral blood. In total, 50 lung cancer patients were screened in two subsequent device applications before and after therapy (n ¼ 185 applications).Results: By in vivo isolation, 58% (108/185) of the patients were positive for !1 CTC (median, 5 CTCs; range, 1-56 cells) as compared with 27% (23/84; range, 1-300 cells) using the FDAcleared CellSearch system. Furthermore, we could show that treatment response during therapy was associated with significant decreases in CTC counts (P ¼ 0.001). By dPCR, mutations in the KRAS and EGFR genes relevant for treatment decisions could be detected in CTCs captured by in vivo isolation and confirmed in the primary tumors of the same patients.Conclusions: In vivo isolation of CTCs overcomes blood volume limitations of other approaches, which might help to implement CTC-based "liquid biopsies" into clinical decision making.