Is fatigue a cause of work disability in systemic lupus erythematosus? Results from a systematic literature review.

OBJECTIVE: Fatigue affects the almost totality of Systemic Lupus Erythematous (SLE) patients impairing physical function and leading to a strong reduction of health-related quality of life (HRQoL). Similarly, SLE patients have an increased rate of work loss and work limitations. The aim of our paper was to systematically assess the relationship between fatigue and work disability in SLE. MATERIALS AND METHODS: We performed a systematic review using the terms "fatigue" and "employment", "work disability", "work impairment", "presenteeism" and "absenteeism." RESULTS: 19 studies were identified. Fatigue was involved in the development of work loss. In employed patients, fatigue led to impairment of work productivity and presenteeism with a parallel increase of both direct and indirect health costs. Fatigue also affected parenting and household productivity. CONCLUSIONS: An adequate control of fatigue could improve physical and work performance in SLE patients thus reducing rates of work loss.

Fibrils or globules? Tuning the morphology of peptide aggregates from helical building blocks.

The aggregation propensity of helical oligopeptides formed exclusively by the conformationally constrained α-aminoisobutyric acid (Aib or U in a three- or single-letter code, respectively) was studied in methanol and methanol/water solutions by spectroscopic methods (UV-vis absorption, steady-state and time-resolved fluorescence, and FT-IR absorption) and atomic force microscopy (AFM) imaging. The peptides investigated have the general formula UnN, where n = 6, 12, and 15 and N stands for a naphthyl chromophore introduced with the dual aim to serve as a spectroscopic probe and to analyze the effect of an extended aromatic group on the aggregation process. Experiments showed that the aggregation propensity in (70/30)v/v and (50/50)v/v methanol/water solutions increases with increasing the length of the peptide chain, i.e., U6N < U12N < U15N. When the peptides are immobilized on mica as a dried film, the interplay of aromatic-aromatic and interhelix interactions, the latter becoming more and more important with the elongation of the peptide chain, governs the morphology of the resulting mesoscopic aggregates. AFM imaging revealed the formation of globular or fibrillar structures, the predominance of which is controlled by the helix length of the peptide building block.

Fluctuations and the rate-limiting step of peptide-induced membrane leakage.

Peptide-induced vesicle leakage is a common experimental test for the membrane-perturbing activity of antimicrobial peptides. The leakage kinetics is usually very slow, requiring minutes to hours for complete release of vesicle contents, and exhibits a biphasic behavior. We report here that, in the case of the peptaibol trichogin GA IV, all processes involved in peptide-membrane interaction, such as peptide-membrane association, peptide aggregation, and peptide translocation, take place on a timescale much shorter than the leakage kinetics. On the basis of these findings, we propose a stochastic model in which the leakage kinetics is determined by the discrete nature of a vesicle suspension: peptides are continuously exchanging among vesicles, producing significant fluctuations over time in the number of peptide molecules bound to each vesicle, and in the formation of pores. According to this model, the fast initial leakage is caused by vesicles that contain at least one pore after the peptides are randomly distributed among the liposomes, whereas the slower release is associated with the time needed to occasionally reach in an intact vesicle the critical number of bound peptides necessary for pore formation. Fluctuations due to peptide exchange among vesicles therefore represent the rate-limiting step of such a slow mechanism.

Structural features and conformational equilibria of 310-helical peptides in solution by spectroscopic and molecular mechanics studies.

The structural features and conformational equilibria of a series of short, linear Calpha-methylvaline [(alphaMe)Val]-based peptides in methanol were investigated by combining fluorescence resonance energy transfer measurements and molecular mechanics data. IR spectra were employed to determine their secondary structure, which exhibits an intramolecularly H-bonded, 3(10)-helix conformation that is affected by backbone distortions that are enhanced by the shortness of the main chain.

Structural features of linear (alphaMe)Val-based peptides in solution by photophysical and theoretical conformational studies.

In continuation of our studies on the determination of the structural features of functionalized peptides in solution by combining time-resolved fluorescence data and molecular mechanics results, the conformational features of a series of linear, L-(alphaMe)Val-based peptides have been investigated in methanol. These foldamers have the general formula F[(alphaMe)Val](r)-T-[(alphaMe)Val](2)NHtBu, where (alphaMe)Val = C(alpha)-methylvaline and r = 0-3, while F [= fluoren-9-ylmethoxycarbonyl (Fmoc)] and T [= 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-carboxylic (Toac)] are a fluorophoric N(alpha)-protecting group and a nitroxide-based alpha-amino acid quencher, respectively. According to ir and CD spectra, the longest term of the series (r = 3) attains a 3(10)-helical structure, while the other peptides populate an intramolecularly H-bonded, 3(10)-helix-like conformation affected by dynamic helical distortions, which are enhanced by the shortness of the backbone chain. Such distortions are reflected in both the energy of the stretching mode and the molar extinction coefficient of the H-bonded N-H groups, the former being higher and the latter smaller than those of a stable 3(10)-helix. Steady-state and time-resolved fluorescence measurements in methanol show a strong quenching of Fmoc by the Toac residue, located at different helix positions, depending on the r value. Comparison of quenching efficiencies and lifetime preexponents with those theoretically obtained from the deepest energy minimum conformers, assuming a Förster mechanism, is satisfactory. The computed structures exhibit a rather compact arrangement, which accounts for the few sterically favored conformations for each peptide, in full agreement with the time-resolved fluorescence data. Orientational effects between the probes must be taken into account for a correct interpretation of the fluorescence decay results, implying that interconversion among conformational substates involving the probes is slower than the energy transfer rate.