Further work is required to decide which scale is most suited to which purpose. Assessment of multiple sclerosis-specific health-related quality of life should be included in future clinical trials to provide a complete picture of patients' health status.

The existing knowledge about the health-related quality of life (HRQoL) and its relationship to cognitive and/or emotional functioning in multiple sclerosis (MS) is scarce. We assessed differences between subgroups of MS outpatients (n = 209) on one HRQoL instrument: a version of the Functional Assessment of Multiple Sclerosis quality of life instrument; on two cognitive functioning tests: the Mini-Mental State Examination and the clock drawing test; and on two emotional functioning tests: the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Three disease-related characteristics were assessed: physical disability, duration of the illness, and clinical course. The results showed that each of these has an effect on at least one dimension of HRQoL and on one mental functioning test. Thus, the more severe, the more progressive, and the longer the illness duration, the lower the HRQoL. Likewise, cognitive mean scores decreased and emotional mean scores increased with greater illness severity and progressive the MS. Furthermore, we also found significant correlations between cognitive and emotional functioning tests and HRQoL dimensions. Thus, the worse cognitive functioning and the higher depressive and anxiety symptoms score the lower the HRQoL.

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in human immunodeficiency virus (HIV) infection therapy. It has been associated with hepatotoxic effects and alterations in lipid and body fat composition. Given the importance of the liver in lipid regulation, we have evaluated the effects of clinically used concentrations of EFV on the mitochondria and lipid metabolism of human hepatic cells in vitro. Mitochondrial function was rapidly undermined by EFV to an extent that varied with the concentration employed; in particular, respiration and intracellular adenosine triphosphate (ATP) levels were reduced whereas reactive oxygen species (ROS) production increased. Results in isolated mitochondria suggest that the mechanism responsible for these actions was a specific inhibition of complex I of the respiratory chain. The reduction in energy production triggered a compensatory mechanism mediated by the enzyme adenosine monophosphate-activated protein kinase (AMPK), the master switch of cellular bioenergetics. Fluorescence and nuclear magnetic resonance demonstrated a rapid intracellular increase of neutral lipids, usually in the form of droplets. This was prevented by the AMPK inhibitor compound C and by removal of fatty acids from the culture medium. These effects were not reproduced by Nevirapine, another NNRTI. EFV is clinically coadministered with two nucleoside reverse transcriptase inhibitors. Evaluation of one of the most common combination, EFV/Lamivudine/Abacavir, revealed that the effects of EFV on ROS production were enhanced. Conclusion: Clinical concentrations of EFV induce bioenergetic stress in hepatic cells by acutely inhibiting mitochondrial function. This new mechanism of mitochondrial interference leads to an accumulation of lipids in the cytoplasm that is mediated by activation of AMPK. (HEPATOLOGY 2010;52:115-125) C ontinuous administration of the drugs included under the term highly active antiretroviral therapy has made acquired immune deficiency syndrome a chronic rather than terminal illness. The initial development of these drugs was particularly rapid and focused on clinical efficacy-reduction of mortality-before all other considerations. However, as the disease has come under control, there has been a growing emphasis on the long-term adverse effects induced by this therapy. Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in initial therapy for human immunodeficiency virus (HIV) infection. It is administered to adults in a single daily dose of 600 mg, which Abbreviations: 3TC, lamivudine; ABC, abacavir; AMPK, adenosine monophosphate-activated protein kinase; ATP, adenosine triphosphate; DCFH-DA, 2 0 ,7 0 -dichlorodihydrofluorescein diacetate; EFV, Efavirenz; HIV, human immunodeficiency virus; HR-MAS, high resolution magic angle spectroscopy; NNRTIs, nonnucleoside reverse transcriptase inhibitors; NRTI, nucleoside reverse transcriptase inhibitors; NVP, nevirapine; P-AMPK, phosphorylated adenosine monophosphate...

Colorectal cancer is the second leading cause of cancer death in developed countries. There is a need for better preventive strategies to improve the outcome of this disease. The increasing availability of high-throughput methodologies opens up new possibilities for screening new markers. The application of NMR metabolic profiling to fecal water extracts has interesting potential as a diagnostic tool for detecting colorectal cancer. We obtained NMR metabolic profiles of fecal water extracts from patients with colorectal cancer and healthy individuals, to characterize possible differences between them and to identify potential diagnostic markers. Our results show that metabolic profiling of fecal water extracts is a cheap, reproducible and effective method for detecting colorectal cancer markers and therefore complements other stool-screening methods. A low concentration of short-chain fatty acids, such as acetate and butyrate, previously associated with the development of colorectal cancer, appears to be the most effective marker. Concentrations of proline and cysteine, which are major components of most colonic epithelium mucus glycoproteins, also display significant changes in samples from colorectal cancer. Differentiation between fecal water extracts from controls and patients with colorectal cancer by NMR spectroscopy combined with chemometric techniques opens up new possibilities for developing new, efficient, high-throughput screening protocols.