THE IMPACT OF SLEEP ON PHYSICAL AND MENTAL HEALTH: IMPORTANCE OF HEALTHY SLEEP HABITS.

Sleep is an important part of health, and when you go to sleep, how long you sleep, and how well you sleep all have a big impact on your health. Sleep may be required for regulating the body's metabolism, feelings, function, memory storage, brain recovery, and learning. Because of how important these processes are, sleep should be seen as just as important to health as what you eat and how much you exercise. Adults' sleep generally gets shorter and less restful, their sleep starts later and is more broken up, they have more sleep problems, and their rest-activity rhythms get weaker. In addition to receiving enough sleep (quality), healthy sleep habits also include maintaining a consistent sleep schedule. Ninety male college students with varying sleep schedules were analyzed for their physical and emotional well-being. By using factor analysis to categorize individuals' sleeping patterns across three dimensions regularity, quality, and quantity. We were able to develop sleep-habit measures. Clustering identified four distinct patterns of sleep behavior: good sleep was defined by regular, high-quality sleep despite being of comparatively brief duration; long sleep was predictable, fairly lengthy, but of minimal quality; short sleep was of excellent quality despite being short and irregular; and poor sleep was erratic, low-quality, and relatively long. The excellent sleepers also had reduced diastolic and systolic and a smaller means waist measurement. In addition, the poor sleepers had the lowest average MCS scores of all of the study groups. Poor sleepers also had the lowest mean scores on the Subjective Depression Scale (SDS). Issues involving glucose or lipid absorption were also more common in the short-term and long poor-sleep categories. Without restful sleep and a regular bedtime routine, it is impossible to maintain excellent mental and physical wellness, even if time and sleep are maintained constantly. Therefore, to produce suitable sleep recommendations for enhanced mental and physical health, we evaluated not only the quantity of sleep but also its consistency and high quality.

Melittin exerts opposing effects on short- and long-range dynamics in bicontinuous microemulsions.

Bicontinuous microemulsions (BµEs) are a promising biomembrane mimetic system for investigating the behavior of antimicrobial peptides (AMPs) and their delivery to open wounds to combat antibiotic-resistant microorganisms. The properties of the BµE host are in turn affected by the guest AMP and can deviate from those of the unperturbed BµEs, especially at higher AMP concentrations. Here we report the effect of an archetypal AMP, melittin, over a wide range of concentrations, on the nanoscopic dynamics of BµEs formed by water/sodium dodecyl sulfate (SDS)/1-pentanol/dodecane, investigated using quasi-elastic neutron scattering (QENS). Two distinct motions are observed, namely, (i) the lateral motion of the surfactant on the surface of the oil channels and (ii) the internal motion of the surfactants. It is found that melittin restricts both the lateral and the internal motion, thereby acting as a stiffening agent. The lateral motion is more strongly affected, at low concentration of melittin. The lateral diffusion coefficient decreased sharply, approaching a constant value at higher melittin concentration. These results are in sharp contrast with the recent dynamic light scattering and neutron spin echo results which showed that at the length and time scales longer than those probed in the current work, melittin enhanced the long-range collective and local undulation motions of BµEs. Considered together, our results indicate that incorporation of melittin modulates the dynamics differently depending on the spatial and temporal regimes, in which the dynamics are being probed. The addition of melittin at low concentrations increased the magnitude of the zeta potential, but further increase of the melittin concentration decreased it. This suggests that addition of melittin at low concentrations led to increase in the surfactant concentration, but did not affect the negative charge per surfactant molecule, while further addition of melittin led to ion pairing of melittin with the oppositely charged surfactant. This study therefore demonstrates how the addition of melittin hinders the lateral motion of surfactants as a result of the strong association between melittin and SDS, suggesting that the release of AMPs from BµE-based delivery vehicles may be hindered.

Contrasting Behaviors of FA and MA Cations in APbBr3.

It is known that the organic units in hybrid halide perovskites are free to rotate, but it is not clear if this freedom is of any relevance to the structure-property relationship of these compounds. We have employed quasi-elastic neutron scattering using two different spectrometers, thus providing a wide dynamic range to investigate the cation dynamics in methylammonium lead bromide (MAPbBr3) and formamidinium lead bromide (FAPbBr3) over a large temperature range covering all known crystallographic phases of these two compounds. Our results establish a plastic crystal-like phase forming above 30 K within the orthorhombic phase of MAPbBr3 related to 3-fold rotations of MA units around the C-N axis with an activation energy, Ea, of ∼27 meV, which has no counterpart in the FA compound. MA exhibits an additional 4-fold orientational motion of the whole molecule via rotation of the C-N axis itself with an Ea of ∼68 meV common for the high-temperature tetragonal and cubic phases. In contrast, the FA compound exhibits only an isotropic orientational motion of the whole FA unit with Ea ≈ 106 meV within the orthorhombic phase and a substantially reduced common Ea of ∼62 meV for the high-temperature tetragonal and cubic phases. Our results suggest that the rotational dynamics of the organic units, crystallographic phases, and physical properties of these compounds are intimately connected.

Effects of NSAIDs on the nanoscopic dynamics of lipid membrane.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for their antipyretic, anti-inflammatory, and painkiller actions despite a wide spectrum of side effects. The mechanisms involved in their therapeutic actions and side-effects have not been clearly understood yet. The assertion that effects of NSAIDs are related to their action at cellular membrane level has stimulated the investigation of interaction between NSAIDs and membranes. Here, we report effects of two different NSAIDs, ibuprofen and indomethacin, on the thermotropic phase behaviour and the dynamics of DMPC membrane as studied using neutron scattering techniques. Elastic intensity scan measurements showed that both drugs substantially alter the phase behaviour of the membrane. However, the effects of these drugs are found to differ quantitatively, which is correlated with their respective interactions with phospholipid membrane. Quasielastic neutron scattering measurements showed that in the ordered phase, both drugs enhance the dynamics of the membrane, but the drugs' effects on the membrane dynamics differ in the fluid phase. Indomethacin suppresses the dynamics of the membrane, whereas ibuprofen does not show significant effect at the same molar concentration. We have also investigated the effect of concentration of ibuprofen on the dynamics of the membrane. Our measurements provide clear evidence that interaction of NSAID with the membrane depends on both the physical state of the membrane and the nature and concentration of NSAID. Hence, one must investigate each NSAID independently while analysing its action mechanism. Better understanding of NSAID-membrane interaction can pave the way for designing more effective NSAID with reduced side effects.

Analytical and computational studies of the nonlinear vibrations of SWCNTs embedded in viscous elastic matrix using KBM method.

The forced vibration analysis of single wall carbon nanotubes (SWCNTs) embedded in the viscous elastic matrix subjected to axial parametric excitation has been investigated. The Euler Bernoulli beam model of the non-local continuum theory is used. The resonant and non-resonant solutions are analytically studied using the Krylov Bogoliubov and Mitropolsky method. It has been seen that the amplitude remains constant up to the second order of approximation. The resonant solutions are also found to analyze the possibility of chaos in the neighborhood of resonance. The computational techniques are used, and plots of time series, phase plot, and Poincaré surface of section are also drawn to confirm the chaotic behavior for certain values of parameters of SWCNTs, which may lead the aging process in the SWCNTs after a long time.

Validation of the Gel & Wax Boluses and Comparison of their Dosimetric Performance with Virtual Bolus.

BACKGROUND: In general, radiotherapy treatment planning is performed using the virtual bolus. It is necessary to investigate physical bolus in comparison to virtual one. OBJECTIVES: In the present study, first, radiological properties of superflab Gel bolus and Paraffin wax bolus was investigated in terms of their relative electron density. Then, dosimetric performance of both the bolus (i.e. Gel and Parafin wax) was compared with Virtual bolus. MATERIAL AND METHODS: In This experimental study, the radiological property of Wax and Gel boluses was investigated using two methods. In one, the relative electron density of both the Gel and Wax boluses was calculated by measuring their linear attenuation coefficient where in another method relative electron density was calculated by recording their CT No directly from their CT scan. Later CT scan of solid water slab phantom (dimension 30x30x15 cm3), with physical boluses (i.e. Gel and Wax bolus) of appropriate thicknesses required to deliver a dose of 200 cGy at Dmax using 4 MV, 6 MV and 15 MV photon beams, was taken. These CT data sets were retrieved to TPS. A plan was done to deliver a dose of 200 cGy at Dmax using Single 4 MV, 6 MV and 15 MV photon beams. Dose at depths Dmax, 1 cm, 2 cm, 3 cm, 4 cm and 5 cm was recorded. Using this similar method, doses at depths viz Dmax, 1 cm, 2 cm, 3 cm, 4 cm and 5 cm was recorded for the Gel and Wax boluses. The differences in dose of gel and wax bolus from virtual bolus were recorded for comparison of their dosimetric performance. RESULTS: The measured (calculated) relative electron density of wax and Gel bolus was found to be 0.958 (0.926) and 0.923 (0.907), respectively. Variation in dosimetric performance of Gel and Wax with reference to Virtual bolus was studied. However, on average, Gel bolus was more consistent with virtual bolus. CONCLUSION: To avoid any dose difference between, delivered (using physical bolus) and planned (using virtual bolus), the physical boluses should be investigated for their dosimetric performance in comparison to virtual bolus. The results obtained and methodology used in this study can be applied in routine radiotherapy practices.

Nanoscopic dynamics of bicontinous microemulsions: effect of membrane associated protein.

Bicontinous microemulsions (BµE) generally consist of nanodomains formed by surfactant in a mixture of water and oil at nearly equal proportions and are potential candidates for the solubilization and purification of membrane proteins. Here we present the first time report of nanoscopic dynamics of surfactant monolayers within BµEs formed by the anionic surfactant sodium dodecyl sulfate (SDS) measured on the nanosecond to picosecond time scale using quasielastic neutron scattering (QENS). BµEs investigated herein consisted of middle phases isolated from Winsor-III microemulsion systems that were formed by mixing aqueous and oil solutions under optimal conditions. QENS data indicates that surfactants undergo two distinct motions, namely (i) lateral motion along the surface of the oil nanodomains and (ii) localized internal motion. Lateral motion can be described using a continuous diffusion model, from which the lateral diffusion coefficient is obtained. Internal motion of surfactant is described using a model which assumes that a fraction of the surfactants' hydrogens undergoes localized translational diffusion that could be considered confined within a spherical volume. The effect of cytochrome c, an archetypal membrane-associated protein known to strongly partition near the surfactant head groups in BµEs (a trend supported by small-angle X-ray scattering [SAXS] analysis), on the dynamics of BµE has also been investigated. QENS results demonstrated that cytochrome c significantly hindered both the lateral and the internal motions of surfactant. The lateral motion was more strongly affected: a reduction of the lateral diffusion coefficient by 33% was measured. This change is mainly attributable to the strong association of cytochrome c with oppositely charged SDS. In contrast, analysis of SAXS data suggested that thermal fluctuations (for a longer length and slower time scale compared to QENS) were increased upon incorporation of cytochrome c. This study demonstrates the utility of QENS for evaluating dynamics of BµEs in nanoscopic region, and that proteins directly affect the microscopic dynamics, which is of relevance for evaluating release kinetics of encapsulated drugs from BµE delivery systems and the use of BµEs as biomembrane mimetic systems for investigating membrane protein-biomembrane interactions.

On the structure and dynamics of water associated with single-supported zwitterionic and anionic membranes.

We have used high-resolution quasielastic neutron scattering (QENS) to investigate the dynamics of water molecules (time scale of motion ∼10-11-10-9 s) in proximity to single-supported bilayers of the zwitterioniclipid DMPC (1,2-dimyristoyl-sn-glycero-3-phosphorylcholine) and the anionic lipid DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) in the temperature range 160-295 K. For both membranes, the temperature dependence of the intensity of neutronsscattered elastically and incoherently from these samples indicates a series of freezing/melting transitions of the membrane-associated water, which have not been observed in previous studies of multilayer membranes. We interpret these successive phase transitions as evidence of different types of water that are common to the two membranes and which are defined by their local environment: bulk-like water located furthest from the membrane and two types of confined water in closer proximity to the lipids. Specifically, we propose a water type termed "confined 2" located within and just above the lipid head groups of the membrane and confined 1 water that lies between the bulk-like and confined 2 water. Confined 1 water is only present at temperatures below the freezing point of bulk-like water. We then go on to determine the temperature dependence of the translational diffusion coefficient of the water associated with single-supported DMPG membranes containing two different amounts of water as we have previously done for DMPC. To our knowledge, there have been no previous studies comparing the dynamics of water in proximity to zwitterionic and anionic membranes. Our analysis of the water dynamics of the DMPG and DMPC membranes supports the classification of water types that we have inferred from their freezing/melting behavior. However, just as we observe large differences in the freezing/melting behavior between these model membranes for the same water type, our measurements demonstrate variation between these membranes in the dynamics of their associated water over a wide temperature range. In particular, there are differences in the diffusive motion of water closest to the lipid head groups. Previously, QENS spectra of the DMPC membranes have revealed the motion of water bound to the lipid head groups. For the DMPG membrane, we have found some evidence of such bound water molecules; but the signal is too weak for a quantitative analysis. However, we observe confined 2 water in the DMPG membrane to undergo slow translational diffusion in the head group region, which was unobserved for DMPC. The weak temperature dependence of its translational diffusion coefficient allows extrapolation to physiological temperatures for comparison with molecular dynamics simulations.

Incorporation of aspirin modulates the dynamical and phase behavior of the phospholipid membrane.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used medications in the world for their analgesic, antipyretic, and anti-inflammatory actions, despite a well-known incidence of a wide spectrum of their adverse effects. To a great extent, beneficial action and side effects of NSAIDs are associated with the interaction of these drugs at the cell membrane level. Here, we use neutron scattering to combine elastic intensity scans, quasielastic and neutron spin echo (NSE) measurements to understand the effect of aspirin, a commonly used NSAID, on the dynamical and phase behavior of the membrane of dimyristoylphosphatidylcholine (DMPC), a prominent representative of phospholipids residing in the outer leaflet of the human erythrocyte membrane. Elastic intensity scans reveal that addition of aspirin not only eliminates the pre-transition (solid gel to ripple phase), but also broadens the main phase transition (ripple to fluid phase) in the membrane. Moreover, the main phase transition becomes shifted toward a lower temperature. These results are found to be consistent with our differential scanning calorimetry measurements. Elastic intensity scans further suggest that aspirin inhibits the membrane from going into the ordered phase and overall induces disorder in the membrane, thus indicating enhancement in the fluidity of the membrane. Quasielastic neutron scattering (QENS) data show that aspirin affects both lateral lipid motion within the leaflet and the localized internal motion of the lipid. Aspirin accelerates both lateral and internal motions, with the more pronounced effect observed for the ordered phase of the neat membrane. Intermediate scattering function as observed by NSE has been analyzed using the Zilman Granek model, which indicates that addition of aspirin alters the bending modulus of the membrane to make the membrane softer. Our study provides a quantitative description of the effect of an archetypal NSAID, aspirin, on the various physical properties of the model biological membrane, which is essential for understanding the complex drug-membrane interaction.

Water dynamics in rigid ionomer networks.

The dynamics of water within ionic polymer networks formed by sulfonated poly(phenylene) (SPP), as revealed by quasi-elastic neutron scattering (QENS), is presented. These polymers are distinguished from other ionic macromolecules by their rigidity and therefore in their network structure. QENS measurements as a function of temperature as the fraction of ionic groups and humidity were varied have shown that the polymer molecules are immobile while absorbed water molecules remain dynamic. The water molecules occupy multiple sites, either bound or loosely constrained, and bounce between the two. With increasing temperature and hydration levels, the system becomes more dynamic. Water molecules remain mobile even at subzero temperatures, illustrating the applicability of the SPP membrane for selective transport over a broad temperature range.

Dynamical and Phase Behavior of a Phospholipid Membrane Altered by an Antimicrobial Peptide at Low Concentration.

The mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.

Protein-Style Dynamical Transition in a Non-Biological Polymer and a Non-Aqueous Solvent.

Temperature-dependent onset of apparent anharmonicity in the microscopic dynamics of hydrated proteins and other biomolecules has been known as protein dynamical transition for the last quarter of a century. Using neutron scattering and molecular dynamics simulation, techniques most often associated with protein dynamical transition studies, we have investigated the microscopic dynamics of one of the most common polymers, polystyrene, which was exposed to toluene vapor, mimicking the process of protein hydration from water vapor. Polystyrene with adsorbed toluene is an example of a solvent-solute system, which, unlike biopolymers, is anhydrous and lacks hydrogen bonding. Nevertheless, it exhibits the essential traits of the dynamical transition in biomolecules, such as a specific dependence of the microscopic dynamics of both solvent and host on the temperature and the amount of solvent adsorbed. We conclude that the protein dynamical transition is a manifestation of a universal solvent-solute dynamical relationship, which is not specific to either biomolecules as solute, or aqueous media as solvent, or even a particular type of interactions between solvent and solute.

Effect of α-Tocopherol on the Microscopic Dynamics of Dimyristoylphosphatidylcholine Membrane.

Vitamin E behaves as an antioxidant and is well known for its protective properties of the lipid membrane. The most biologically active form of vitamin E in the human organism is α-tocopherol (aToc). Very recently (Marquardt, D.; et al. J. Am. Chem. Soc. 2014, 136, 203-210) it has been shown that aToc resides near the center of dimyristoylphosphatidylcholine (DMPC) bilayer, which is in stark contrast with other PC membranes, where aToc is located near the lipid-water interface. Here we report an unusual effect of this exceptional location of aToc on the dynamical behavior of DMPC membrane probed by incoherent elastic and quasielastic neutron scattering. For pure DMPC vesicles, elastic scan data show two step-like drops in the elastic intensity at 288 and 297 K, which correspond to the pre- and main phase transitions, respectively. However, inclusion of aToc into DMPC membrane inhibits the step-like elastic intensity drops, indicating a significant impact of aToc on the phase behavior of the membrane. This observation is supported by our differential scanning calorimetry data, which shows that inclusion of aToc leads to a significant broadening of the main phase transition peak, whereas the peak corresponding to the pretransition disappears. We have performed quasielastic neutron scattering (QENS) measurements on DMPC vesicles with various concentrations of aToc at 280, 293, and 310 K. We have found that aToc affects both the lateral diffusion and the internal motions of the lipid molecules. Below the main phase transition temperature inclusion of aToc accelerates both the lateral and the internal lipid motions. On the other hand, above the main phase transition temperature the addition of aToc restricts only the internal motion, without a significant influence on the lateral motion. Our results support the finding that the location of aToc in DMPC membrane is deep within the bilayer.

Fluorescein angiography and optical coherence tomography in myopic choroidal neovascularization.

PURPOSE: To assess intra/inter-observer agreement, and diagnostic capabilities of a color fundus photograph, fundus fluorescein angiography (FFA), and spectral domain optical coherence tomography (SD-OCT) in making a diagnosis of myopic choroidal neovascularization (CNV). PATIENTS AND METHODS: Two masked observers evaluated FFA and SD-OCT images to identify the presence of myopic CNV in 80 high-myopic eyes of 57 patients. A third masked observer identified CNV on a color fundus photo. Presence of myopic CNV on a fundus photo was defined as presence of subretinal hemorrhage, thickening of the retina and/or visible membrane at the macula. Presence of myopic CNV on FFA was defined as hyperfluorescence in the early phase with increase in intensity and size in the late phase; presence of a large irregular lesion; and hypofluorsescence due to subretinal hemorrhage. Myopic CNV on SD-OCT was defined as the hyper-reflective lesion with or without intraretinal fluid or subretinal fluid with retinal thickening. RESULTS: Intraobserver repeatability on FFA and SD-OCT was 0.54 and 0.44, respectively. Agreement (kappa) between FFA and SD-OCT was 0.38 and 0.3, respectively. Among 34 eyes, which had the presence of CNV on a color fundus photo, CNV was diagnosed in 18 (53%) eyes on FFA and in 20 (58.8%) eyes on SD-OCT. Sensitivity and specificity of FFA was 47 and 80.4%, respectively, and that of SD-OCT was 58.8 and 86.9%, respectively. CONCLUSION: Repeatability and reproducibility for diagnosis of myopic CNV was better with FFA compared with SD-OCT; however, agreement is very poor between FFA and SD-OCT. SD-OCT is comparatively a better tool to rule out presence of myopic CNV.

Mechanism of the malabaricone C-induced toxicity to the MCF-7 cell line.

In this study, we studied the mechanism of the cytotoxicity of malabaricone C (mal C) against human breast cancer MCF-7 cell line. Mal C dose-dependently increased the sub G1 cell population, associated with cytoplasmic oligonucleosome formation and chromatin condensation. The mal C-induced apoptosis led to mitochondrial damage as revealed by fluorescence microscopy and flow cytometry of the JC-1-stained cells as well as from the release of mitochondrion-specific nuclease proteins AIF and endo G. Mal C also released intracellular Ca(2+) from the MCF-7 cells, but the Ca(2+)-modulators BAPTA-AM and Ru360 only partially abrogated the apoptosis. The calpain activation by mal C did not have any effect on its cytotoxicity. On the other hand, after mal C treatment significant lysosomal membrane permeabilization (LMP), along with release of cathepsin B, as well as Bid-cleavage and its translocation to mitochondria were observed much earlier than the mitochondrial damage. This suggested that cytotoxicity of mal C against human MCF-7 human breast cancer cell line may proceed through LMP as the initial event that triggered a caspase-independent, but cathepsin B and t-Bid-dependent intrinsic mitochondrial apoptotic pathway. A significant accumulation of cells in the S or G2-M phases along with upregulation of the cyclins E and A due to mal C exposure promises it to be a potential anti-cancer agent.

Effect of binding to carbon black on the dynamics of 1,4-polybutadiene.

The nature of the interactions of polymers at the surface of nanoparticles is crucial to understanding the dynamics and their relation to mechanical properties. The effect of binding (both chemical attachment and physical adsorption) on the local and global dynamics of chain molecules remains a controversial subject. Using neutron scattering and dynamic mechanical spectroscopies, we measured the slow conformational and terminal relaxations, as well as the fast local dynamics, of 1,4-polybutadiene (PBD) containing carbon black (CB) particles. We observed a substantial decrease in the flexibility of bound segments at temperatures through the glass transition temperature, T(g). The longer range motions of the PBD become more suppressed and cooperative as temperature decreases, while the relaxation time of the fast local dynamics is little affected by the CB particles. The mobile fraction of PBD is less sensitive to temperature when bound. Mechanical spectroscopy indicates that both the local segmental dynamics and the global chain modes are slowed by the filler. These results are consistent with transient structural arrest of the slow dynamics of atoms adjacent to the particles.

Low-temperature water dynamics in an aqueous methanol solution.

An aqueous methanol solution (x(MeOH) = 0.30) has been studied by quasielastic neutron scattering. The single-particle water dynamics were effectively isolated by employing deuterated methanol. A smooth dynamic transition to a sub-Arrhenius temperature dependence has been observed in the relaxation times. We associate this behavior with the formation of small crystallites in the system. These findings are compared with molecular dynamics simulations and previous nuclear magnetic resonance measurements. We discuss possible dynamic signatures of structuring in the mixture.

What do we know about self-reported fatigue in systemic lupus erythematosus?

Fatigue is one of the most complex and ill understood symptoms of chronic illness often reported as the number one complaint by patients with systemic lupus erythematosus (SLE). This paper aims to provide a comprehensive review of the literature on fatigue in SLE. A pool of 55 relevant articles was retrieved via electronic searches of six databases including MEDLINE, EMBASE, CINAHL, AMED, PsychINFO and PubMed. Fatigue in the studies reviewed was assessed by a range of self-report instruments, the content of which is varied. The results displayed a consensus on the high prevalence of fatigue in SLE, which is significantly higher when compared with controls. The aetiology of fatigue appears to be multifactorial. Disease activity is not always significantly associated with fatigue, in comparison with other secondary features of SLE and psychological variables. The literature is limited by the cross-sectional nature of most of the studies, which does not permit for any firm conclusion regarding the direction of causal relationships to be made. The high prevalence of fatigue in SLE emphasizes the need for further detailed prospective research to inform the understanding of its aetiology, course and management.