Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS

Objective: To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity. Methods: In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 months RESULTS: pRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs (p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged < 51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 μm; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 μm; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R2 0.36, p = 0.001). Conclusions: INL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to disease-modifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choice

Moderate and severe plaque psoriasis: cost-of-illness study in Italy

Psoriasis is a chronic inflammatory, immune-mediated skin disorder that affects 1.5–1.8 million people in Italy. The most common form of the disease is chronic plaque psoriasis, affecting about 90% of psoriasis patients, with about 20%–30% of them suffering from a moderate or severe condition. Little information is available about the economic impact of psoriasis in European countries. The primary objective of this study was to perform a cost-of-illness analysis of patients with moderate and severe plaque psoriasis in Italy. Therefore, direct, indirect costs, and intangible costs (quality of life – QoL) were assessed. In this national, multicenter, prospective, 3-month cost-of-illness study of moderate and severe plaque psoriasis, direct and indirect costs were assessed from the patient, third-party payer (National Health Service, NHS), and societal perspectives. From November 2003 to October 2004 consecutive patients were enrolled over a 1-year period, in order to minimize seasonal fluctuations in disease severity. 150 patients enrolled in 6 investigational sites in Italy, completed the study, and were eligible to be analyzed according to the study protocol. Intangible costs (QoL) were measured using SF36 and DLQI questionnaires. The mean total cost for psoriasis (average Psoriasis Area Severity Index [PASI] score 21.4), including direct and indirect items, was €8,371.61 per patient per year. The mean cost for patients with moderate disease (PASI ≤ 20) was €5,226.04, while the mean cost for patients with more severe disease (PASI > 20) was €11,434.40 per year. Disease heavily affected QoL measured using SF36, and the impairment was greater in patients affected by a more severe form of disease. Moderate and severe plaque psoriasis is associated with extremely high costs, which are related to disease severity. Data from this study show that the more severe plaque psoriasis, the higher the direct and indirect costs for its management. Direct costs are higher than indirect costs; hospitalization represents the most significant item, accounting for 30% of the total expenses. QoL in moderate and severe plaque psoriasis is low compared with the population at large, confirming the high impact of plaque psoriasis on QoL. The relatively high average annual costs per patient point to the need for a more efficient and long-term control of psoriasis

Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property.

The permeability transition pore (PTP) is a mitochondrial channel whose opening causes the mitochondrial membrane potential (deltapsi) collapse that leads to apoptosis. Some ubiquinone analogues have been demonstrated previously to modulate the PTP open-closed transition in isolated mitochondria and thought to act through a common PTP-binding site rather than through oxidation-reduction reactions. We have demonstrated recently both in vitro and in vivo that the ubiquitous free radical scavenger and respiratory chain coenzyme Q10 (CoQ10) prevents keratocyte apoptosis induced by excimer laser irradiation more efficiently than other antioxidants. On this basis, we hypothesized that the antiapoptotic property of CoQ10 could be independent of its free radical scavenging ability and related to direct inhibition of PTP opening. In this study, we have verified this hypothesis by evaluating the antiapoptotic effects of CoQ10 in response to apoptotic stimuli, serum starvation, antimycin A, and ceramide, which do not generate free radicals, in comparison to control, free radical-generating UVC irradiation. As hypothesized, CoQ10 dramatically reduced apoptotic cell death, attenuated ATP decrease, and hindered DNA fragmentation elicited by all apoptotic stimuli. This was accompanied by inhibition of mitochondrial depolarization, cytochrome c release, and caspase 9 activation. Because these events are consequent to mitochondrial PTP opening, we suggest that the antiapoptotic activity of CoQ10 could be related to its ability to prevent this phenomenon

Impact of treatment on cellular immunophenotype in MS: a cross-sectional study

OBJECTIVE: To establish cytometry profiles associated with disease stages and immunotherapy in MS. METHODS: Demographic/clinical data and peripheral blood samples were collected from 227 patients with MS and 82 sex- and age-matched healthy controls (HCs) enrolled in a cross-sectional study at 4 European MS centers (Spain, Italy, Germany, and Norway). Flow cytometry of isolated peripheral blood mononuclear cells was performed in each center using specifically prepared antibody-cocktail Lyotubes; data analysis was centralized at the Genoa center. Differences in immune cell subsets were assessed between groups of untreated patients with relapsing-remitting or progressive MS (RRMS or PMS) and HCs and between groups of patients with RRMS taking 6 commonly used disease-modifying drugs. RESULTS: In untreated patients with MS, significantly higher frequencies of Th17 cells in the RRMS population compared with HC and lower frequencies of B-memory/B-regulatory cells as well as higher percentages of B-mature cells in patients with PMS compared with HCs emerged. Overall, the greatest deviation in immunophenotype in MS was observed by treatment rather than disease course, with the strongest impact found in fingolimod-treated patients. Fingolimod induced a decrease in total CD4(+) T cells and in B-mature and B-memory cells and increases in CD4(+) and CD8(+) T-regulatory and B-regulatory cells. CONCLUSIONS: Our highly standardized, multisite cytomics data provide further understanding of treatment impact on MS immunophenotype and could pave the way toward monitoring immune cells to help clinical management of MS individuals

Quantitative analysis of the thermal distortions in a 100 W CW Nd:YAG ceramic slab laser.

Making use of an interferometric diagnostic system, we analyze the thermo-mechanical distortions taking place in the slab shaped ceramic Nd:YAG active medium of a 100 W class laser. These distortions are collected in different pumping regimes, both in static situations and during transient warm-up, and compared to the results of computer simulations. This procedure enables us to determine the relevance of different stress causes and thus to increase the specific power extraction of the active slab module