Toward a comprehensive care of HIV patients: Finding a strategy to detect depression in a Spanish HIV cohort

Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.

Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.