Switching Multiple Sclerosis Patients with Breakthrough Disease to Second-Line Therapy

BACKGROUND: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. METHODS: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. RESULTS: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). CONCLUSIONS: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies

Influenza del gloss sulla visione e misurazione del colore

L’insieme delle caratteristiche ottiche percepite visivamente di un oggetto in funzione delle condizioni di illuminazione e di osservazione e che ne consento il riconoscimento e la distinzione è definito dalla CIE come “appearance” [1]. L’“appearance” della superficie di un oggetto è uno dei parametri più critici da misurare perché dipende da molteplici fattori, i più rilevanti e normalmente considerati sono:  le caratteristiche ottiche dei materiali, tra cui le più importanti sono il gloss, la texture, il fattore spettrale di riflessione (o trasmissione) e la sua ripartizione spaziale (in termini fotometrici BRDF/BTDF o per tenere conto di fenomeni più complessi BSSRDF)  l’osservatore e le condizioni di adattamento  la sorgente di luce  le condizioni geometriche di illuminazione e osservazione Ma in realtà l’“appearance” complessiva (total appearance secondo la CIE [1].) di un oggetto è il risultato della percezione e interpretazione soggettiva di diversi attributi visivi della superficie dell’oggetto, percepiti dall’osservatore a seguito dell’interazione dell’oggetto con la luce incidente su di esso [2] tenendo conto anche del contesto (tra cui gli altri sensi) e delle esperienze pregresse

Antibiofilm activity on Candida albicans and mechanism of action on biomembrane models of the antimicrobial peptide Ctn[15-34]

Ctn[15-34], the C-terminal fragment of crotalicidin, an antimicrobial peptide from the South American rattlesnake Crotalus durissus terrificus venom, displays remarkable anti-infective and anti-proliferative activities. Herein, its activity on Candida albicans biofilms and its interaction with the cytoplasmic membrane of the fungal cell and with a biomembrane model in vitro was investigated. A standard C. albicans strain and a fluconazole-resistant clinical isolate were exposed to the peptide at its minimum inhibitory concentration (MIC) (10 µM) and up to 100 × MIC to inhibit biofilm formation and its eradication. A viability test using XTT and fluorescent dyes, confocal laser scanning microscopy, and atomic force microscopy (AFM) were used to observe the antibiofilm effect. To evaluate the importance of membrane composition on Ctn[15-34] activity, C. albicans protoplasts were also tested. Fluorescence assays using di-8-ANEPPS, dynamic light scattering, and zeta potential measurements using liposomes, protoplasts, and C. albicans cells indicated a direct mechanism of action that was dependent on membrane interaction and disruption. Overall, Ctn[15-34] showed to be an effective antifungal peptide, displaying antibiofilm activity and, importantly, interacting with and disrupting fungal plasma membrane