OLIMPIC : a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization

Purpose: To evaluate criteria driving retreatment with ranibizumab in Italian patients with myopic choroidal neovascularization (mCNV). Methods: OLIMPIC was a 12-month, phase IIIb, open-label study. Patients with active mCNV were treated with ranibizumab 0.5 mg according to the European label. The study assessed local criteria in Italy driving retreatment decisions with ranibizumab; and the efficacy, safety, and tolerability of ranibizumab. Results: The mean (standard deviation [SD]) age of treated patients (N = 200) was 61.8 (12.7) years; range 22\u201385 years. The multivariate regression model indicated that presence of active leakage (odds ratio [OR] 95% confidence interval [CI]: 11.30 [1.03\u2013124.14]), presence of intraretinal fluid (OR [95%CI]: 28.21 [1.55\u2013513.73]), and an improvement in best-corrected visual acuity (BCVA) from baseline < 10 letters (OR [95%CI]: 17.60 [1.39\u2013222.75]) were the factors with the greatest effect on retreatment with ranibizumab. The mean (SD) BCVA gain from baseline to month 12 was 8.4 (12.8) letters (P < 0.0001). The mean (SD) number of injections was 2.41 (1.53); range 1\u20139. Ocular and non-ocular adverse events were reported in 41 (20.5%) and 30 (15.0%) patients, respectively. Conclusions: Individualized treatment with ranibizumab was effective in improving BCVA in patients with mCNV over 12 months. Both anatomical and functional variables had significant effects on causing retreatment. There were no new safety findings. Trial registration: www.ClinicalTrials.Gov (NCT No: NCT02034006)

A method for the assessment of time-varying brain shift during navigated epilepsy surgery

Image guidance is widely used in neurosurgery. Tracking systems (neuronavigators) allow registering the preoperative image space to the surgical space. The localization accuracy is influenced by technical and clinical factors, such as brain shift. This paper aims at providing quantitative measure of the time-varying brain shift during open epilepsy surgery, and at measuring the pattern of brain deformation with respect to three potentially meaningful parameters: craniotomy area, craniotomy orientation and gravity vector direction in the images reference frame

Theranostic nanocages for imaging and photothermal therapy of prostate cancer cells by active targeting of neuropeptide-Y receptor

Gold nanocages (AuNCs) have been shown to be a useful tool for imaging and hyperthermia therapy of cancer, thanks to their unique optical properties, low toxicity and facile surface functionalization. Herein, we use AuNCs for selective targeting of prostate cancer cells (PC3) via specific interaction between neuropeptide Y (NPY) receptor and three different NPY analogs conjugated to AuNCs (Figure 1). Localized surface plasmon band of the nanoconjugates was set around 800 nm, which is particularly promising for in vivo applications. Long-term stability of nanoconjugates in different media was confirmed by UV-vis and DLS studies. Active NPY receptor targeting was observed by confocal microscopy showing time-dependent AuNCs cellular uptake. Activation of ERK1/2 pathway was evaluated by Western blot to confirm the receptor-mediated specific interaction with PC3. Cellular uptake kinetics were compared as a function of peptide structure. Cytotoxicity of nanoconjugates was evaluated by MTS and Annexin V assays, confirming their safety within the concentration range explored. Hyperthermia studies were carried out irradiating the cells, previously incubated with AuNCs, with a pulsed laser at 808 nm wavelength, showing a heating enhancement from 6 to 35 \ub0C above the culture temperature dependent on the irradiation power (between 1.6 and 12.7 W/cm2). Only cells treated with AuNCs underwent morphological alterations in the cytoskeleton structure upon laser irradiation, leading to membrane blebbing and loss of microvilli associated to cell migration. This effect is particularly promising in view of possible inhibition of proliferation and invasion of cancer cells. In summary, our Au-peptide NCs proved to be an efficient theranostic nanosystem for targeted detection and activatable killing of prostate cancer cells

Developmental learning impairments in a rodent model of nodular heterotopia

Developmental malformations of neocortex—including microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans