207 research outputs found
Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of tuberous sclerosis complex
No full textTuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism, anxiety and depressive behaviour. Rapamycin is a potent inhibitor of mTOR and its efficacy in treating epilepsy and neurological symptoms remains elusive. In a mouse model in which Tsc1 has been deleted in embryonic telencephalic neural stem cells, we analyzed anxiety- and depression-like behaviour by elevated-plus maze (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension test (TST), after chronic administration of rapamycin. In addition, spectral analysis of background EEG was performed. Rapamycin-treated mutant mice displayed a reduction in anxiety- and depression-like phenotype, as shown by the EPM/OFT and FST, respectively. These results were inline with EEG power spectra outcomes. The same effects of rapamycin were observed in wild-type mice. Notably, in heterozygous animals we did not observe any EEG and/or behavioural variation after rapamycin treatment. Together these results suggest that both TSC1 deletion and chronic rapamycin treatment might have a role in modulating behaviour and brain activity, and point out to the potential usefulness of background EEG analysis in tracking brain dysfunction in parallel with behavioural testing. (c) 2012 Elsevier Ltd. All rights reserved
Visual evoked potentials can be reliably recorded using noninvasive epidermal electrodes in the anesthetized rat
No full textPurpose: Visual evoked potentials (VEPs) are a powerful tool to evaluate nervous conduction along the visual pathways, both in humans and in animal models. Traditionally, epidural screw electrodes are used to record VEPs in preclinical research. Here we tested the feasibility in the preclinical setting of the same noninvasive technique used for clinical VEP acquisition, by using epidermal cup electrodes with no surgical procedures. Methods: Monocular flash VEPs were recorded bilaterally under sevoflurane anesthesia once a week for 6 weeks in 14 dark Agouti rats, 7 with implanted epidural screws and 7 with epidermal 6 mm Ø Ag/AgCl cups. Results: VEP traces obtained with the two techniques were morphologically comparable. There were no significant differences in latency of the main visual component between screw-recorded VEPs (sVEPs) and cup-recorded VEPs (cVEPs). Amplitude values with epidermal cups were significantly lower than those with epidural screws. Both techniques provided latencies and amplitudes which were stable over time. Furthermore, with regard to latency both methods ensured highly repeatable measurements over time, with epidermal cups even providing slightly better results. On the other hand, considering amplitudes, cVEPs and sVEPs provided fairly acceptable repeatability. Conclusions: Epidermal cup electrodes can provide comparable results to those obtained with the “gold standard” epidural screws, while representing a simpler and less invasive technique to test nervous conduction along the visual pathways in the preclinical setting
Ritratti e travisamenti
No full textPartendo da un’analisi dei ritratti di Valerio Adami e dalle loro premesse letterarie, il saggio ordisce una sorta di decostruzione della categoria estetica del “ritratto”, dimostrando come i cosiddetti “ritratti” dipinti dall’artista italiano siano una ripetuta riflessione sull’impossibilità di ritrarre veramente un volto. Sicché tali ritratti si rivelano consapevoli travisamenti del visibile, icone discontinue che, nelle loro fratture, rivelano tuttavia il volto sempre nascosto e irrapresentabile del personaggio ritratto
Una maestra in casa editrice: Ornella (Oronzina Tanzarella) tra Bemporad e Mondadori
No full textThe article aims at retracing the relationship between a teacher-author and her publishers through correspondence preserved in two different publishers' archives (1919-1940). Besides the author's ability in getting special consideration from her publishers, the correspondence proposes an example of both the reception of fascist guidelines by authors and publishers and their efforts in bypassing unfavourable regulations such as "Libro di Stato"
Ritratti e travisamenti
No full textPartendo da un’analisi dei ritratti di Valerio Adami e dalle loro premesse letterarie, il saggio ordisce una sorta di decostruzione della categoria estetica del “ritratto”, dimostrando come i cosiddetti “ritratti” dipinti dall’artista italiano siano una ripetuta riflessione sull’impossibilità di ritrarre veramente un volto. Sicché tali ritratti si rivelano consapevoli travisamenti del visibile, icone discontinue che, nelle loro fratture, rivelano tuttavia il volto sempre nascosto e irrapresentabile del personaggio ritratto
Sperimentazione e validazione di una nuova prova di esame di abilitazione nel corso di laurea in infermieristica
No full textLongitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix‐Saguenay Ataxia
No full textObjective: In autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease, severity and age of onset vary greatly, hindering to objectively measure and predict clinical progression. Thickening of the retinal nerve fiber layer is distinctive of ARSACS patients, as assessed by optical coherence tomography, whereas conventional brain magnetic resonance imaging findings include both supratentorial and infratentorial changes. Because longitudinal imaging studies in ARSACS patients are not available to define these changes as biomarkers of disease progression, we aimed to address this issue in the ARSACS mouse model. Methods: We performed longitudinal retinal OCT and brain MRI in the Sacs−/− ARSACS mouse model, alongside motor and coordination assessment in the beam walking test. We also investigated visual function and the molecular mechanisms underlying RNFL increased thickness by histology and immunofluorescence. Results: We demonstrated that RNFL thickening by OCT gradually increases in the early stages of pathology in the Sacs−/− mouse model, reflecting the progression of motor impairment, and later reaches a plateau when thinning of the posterior corpus callosum becomes detectable by MRI. Mechanistically, we unveiled that RNFL thickening is associated with aberrant accumulation of non-phosphorylated neurofilament H and glial fibrillary acidic protein. We also uncovered mild signs of myelin pathology coherent with increased latency of visual evoked potentials, and altered retinal activation by photopic electroretinography. Interpretation: We show that both RNFL thickening and MRI changes may represent biomarkers of disease progression in the Sacs−/− mouse model. Our data gathers knowledge instrumental to clinical studies, holding potential as readout for treatment efficacy. ANN NEUROL 2024
Cas9/sgRNA selective targeting of the P23H Rhodopsin mutant allele for treating retinitis pigmentosa by intravitreal AAV9.PHP.B-based delivery
No full textP23H is the most common mutation in the RHODOPSIN (RHO) gene leading to a dominant form of retinitis pigmentosa (RP), a rod photoreceptor degeneration that invariably causes vision loss. Specific disruption of the disease P23H RHO mutant while preserving the wild-type (WT) functional allele would be an invaluable therapy for this disease. However, various technologies tested in the past failed to achieve effective changes and consequently therapeutic benefits. We validated a CRISPR/Cas9 strategy to specifically inactivate the P23H RHO mutant, while preserving the WT allele in vitro. We, then, translated this approach in vivo by delivering the CRISPR/Cas9 components in murine Rho+/P23H mutant retinae. Targeted retinae presented a high rate of cleavage in the P23H but not WT Rho allele. This gene manipulation was sufficient to slow photoreceptor degeneration and improve retinal functions. To improve the translational potential of our approach, we tested intravitreal delivery of this system by means of adeno-associated viruses (AAVs). To this purpose, the employment of the AAV9-PHP.B resulted the most effective in disrupting the P23H Rho mutant. Finally, this approach was translated successfully in human cells engineered with the homozygous P23H RHO gene mutation. Overall, this is a significant proof-of-concept that gene allele specific targeting by CRISPR/Cas9 technology is specific and efficient and represents an unprecedented tool for treating RP and more broadly dominant genetic human disorders affecting the eye, as well as other tissues
Can Clinical and Surgical Parameters Be Combined to Predict How Long It Will Take a Tibia Fracture to Heal? A Prospective Multicentre Observational Study: The FRACTING Study
No full textHealing of tibia fractures occurs over a wide time range of months, with a number of risk factors contributing to prolonged healing. In this prospective, multicentre, observational study, we investigated the capability of FRACTING (tibia FRACTure prediction healING days) score, calculated soon after tibia fracture treatment, to predict healing time.
Methods:
The study included 363 patients. Information on patient health, fracture morphology, and surgical treatment adopted were combined to calculate the FRACTING score. Fractures were considered healed when the patient was able to fully weight-bear without pain.
Results:
319 fractures (88%) healed within 12 months from treatment. Forty-four fractures healed after 12 months or underwent a second surgery. FRACTING score positively correlated with days to healing: r = 0.63 (p < 0.0001). Average score value was 7.3 ± 2.5; ROC analysis showed strong reliability of the score in separating patients healing before versus after 6 months: AUC = 0.823.
Conclusions:
This study shows that the FRACTING score can be employed both to predict months needed for fracture healing and to identify immediately after treatment patients at risk of prolonged healing. In patients with high score values, new pharmacological and nonpharmacological treatments to enhance osteogenesis could be tested selectively, which may finally result in reduced disability time and health cost savings
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