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Background: Cystatin C (Cys-C) is recognized as one of the most reliable renal function parameters in the general population, although it might be biased by thyroid status. Herein, we tested Cys-C and conventional renal parameters in a cohort of hypothyroid patients treated with Levothyroxine. Methods: Eighty-four hypothyroid patients were recruited and subgrouped according to their serum thyroid-stimulating hormone (TSH) values as a paradigm for therapeutic targeting (n = 54, optimal TSH range = 0.5–2 µIU/mL; n = 30, TSH > 2µIU/mL). Serum Cys-C, creatinine, measured and estimated glomerular filtration rates (mGFR and eGFR) were assessed. Results—mGFR and eGFR were comparable among the two subgroups, whereas Cys-C was significantly higher in patients with suboptimal TSH values (>2 µIU/mL) (p < 0.0001). TSH significantly correlated with Cys-C in the overall patient group, and in the subgroup with TSH above the target value (>2 µIU/mL). Out of 20 patients with abnormal Cys-C, 19 had suboptimal TSH levels. Receiver operating characteristic (ROC) analysis indicated Cys-C as a moderately accurate diagnostic tool (AUC = 0.871) to assess Levothyroxine replacement efficacy in hypothyroid patients (63% sensitivity, and 98% specificity). Conclusions: The observation of increased serum Cys-C in patients with suboptimal TSH would suggest the importance of a careful interpretation by clinicians of this biomarker in the case of hypothyroid patients.

Recent research on the crossmodal integration of visual and auditory perception suggests that evaluations of emotional information in one sensory modality may tend toward the emotional value generated in another sensory modality. This implies that the emotions elicited by musical stimuli can influence the perception of emotional stimuli presented in other sensory modalities, through a top-down process. The aim of this work was to investigate how crossmodal perceptual processing influences emotional face recognition and how potential modulation of this processing induced by music could be influenced by the subject’s musical competence. We investigated how emotional face recognition processing could be modulated by listening to music and how this modulation varies according to the subjective emotional salience of the music and the listener’s musical competence. The sample consisted of 24 participants: 12 professional musicians and 12 university students (non-musicians). Participants performed an emotional go/no-go task whilst listening to music by Albeniz, Chopin, or Mozart. The target stimuli were emotionally neutral facial expressions. We examined the N170 Event-Related Potential (ERP) and behavioral responses (i.e., motor reaction time to target recognition and musical emotional judgment). A linear mixed-effects model and a decision-tree learning technique were applied to N170 amplitudes and latencies. The main findings of the study were that musicians’ behavioral responses and N170 is more affected by the emotional value of music administered in the emotional go/no-go task and this bias is also apparent in responses to the non-target emotional face. This suggests that emotional information, coming from multiple sensory channels, activates a crossmodal integration process that depends upon the stimuli emotional salience and the listener’s appraisal.

Rationale: The nuclear receptor peroxisome proliferator–activated receptor-γ (PPARγ) is an important regulator of gene transcription in vascular cells and mediates the vascular protection observed with antidiabetic glitazones. Objective: To determine the molecular mechanism of ligand-dependent transrepression in vascular smooth muscle cells and their impact on the vascular protective actions of PPARγ. Methods and Results: Here, we report a molecular pathway in vascular smooth muscle cells by which ligand-activated PPARγ represses transcriptional activation of the matrix-degrading matrix metalloproteinase-9 (MMP-9) gene, a crucial mediator of vascular injury. PPARγ-mediated transrepression of the MMP-9 gene was dependent on the presence of the high-mobility group A1 (HMGA1) protein, a gene highly expressed in vascular smooth muscle cells, newly identified by oligonucleotide array expression analysis. Transrepression of MMP-9 by PPARγ and regulation by HMGA1 required PPARγ SUMOylation at K367. This process was associated with formation of a complex between PPARγ, HMGA1, and the SUMO E2 ligase Ubc9 (ubiquitin-like protein SUMO-1 conjugating enzyme). After PPARγ ligand stimulation, HMGA1 and PPARγ were recruited to the MMP-9 promoter, which facilitated binding of SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), a nuclear corepressor involved in transrepression. The relevance of HMGA1 for vascular PPARγ signaling was underlined by the complete absence of vascular protection through a PPARγ ligand in HMGA1 −/− mice after arterial wire injury. Conclusions: The present data suggest that ligand-dependent formation of HMGA1-Ubc9-PPARγ complexes facilitates PPARγ SUMOylation, which results in the prevention of SMRT corepressor clearance and induction of MMP-9 transrepression. These data provide new information on PPARγ-dependent vascular transcriptional regulation and help us to understand the molecular consequences of therapeutic interventions with PPARγ ligands in the vasculature.