The Palermo Capuchin Catacombs Project: a multidisciplinary approach to the study of a modern Mummy Collection (ca 1600-1900)

In this paper we present a multidisciplinary project for the study of the present conditions, history, bioanthropological features and conservation status of a large collection of modern human mummies, kept in the Capuchin Catacombs of Palermo (Sicily, Italy). Due to the large amount of spontaneously and anthropogenically mummified human bodies, and to an abundant presence of associated artefacts, this collection provides a unique opportunity to carry out a large multidisciplinary survey useful for a thorough biocultural understanding of these remains, a conservation plan, and testing of new restoration protocols

Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing–remitting multiple sclerosis patients, aged 18–50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 mg (three times weekly) for 12 months, were randomized to combination therapy (interferon+atorvastatin 20mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n 1⁄4 21) or B (n 1⁄4 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p 1⁄4 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p 1⁄4 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone

ADC Benchmark Range for Correct Diagnosis of Primary and Recurrent Middle Ear Cholesteatoma

Objectives. Magnetic resonance imaging (MRI) and in particular diffusion-weighted imaging (DWI) have been broadly proven to be the reference imaging method to discriminate between cholesteatoma and noncholesteatomatous middle ear lesions, especially when high tissue specificity is required. The aim of this study is to define a range of apparent diffusion coefficient (ADC) values within which the diagnosis of cholesteatoma is almost certain. Methods. The study was retrospectively conducted on a cohort of 124 patients. All patients underwent first- or second-look surgery because primary or secondary acquired cholesteatoma was clinically suspected; they all had preoperative MRI examination 15 days before surgery, including DWI from which the ADC maps were calculated. Results. Average ADC value for cholesteatomas was 859,4 × 10−6 mm2/s (range 1545 × 10−6 mm2/s; IQR = 362 × 10−6 mm2/s; σ = 276,3 × 10−6 mm2/s), while for noncholesteatomatous inflammatory lesions, it was 2216,3 × 10−6 mm2/s (range 1015 × 10−6 mm2/s; IQR = 372,75 × 10−6 mm2/s; σ = 225,6 × 10−6 mm2/s). Interobserver agreement with Fleiss’ Kappa statistics was 0,96. No overlap between two groups’ range of values was found and the difference was statistically significant for p<0.0001. Conclusions. We propose an interval of ADC values that should represent an appropriate benchmark range for a correct differentiation between cholesteatoma and granulation tissue or fibrosis of noncholesteatomatous inflammatory lesions

Effect of Aqueous Extract of Maca Addition to an Extender for Chilled Canine Semen

Antioxidant supplementation has been proposed as a new strategy to improve the long-term preservation of semen. The aim of this study was to evaluate the effect of Maca supplementation of semen extender on quality-related canine semen parameters during cooling. Ejaculates from nine dogs were cooled for 7 days in the absence (control group) or in the presence of 10, 20 and 50 μL/mL of an aqueous extract of Maca. Sperm were evaluated for sperm viability, motility, DNA fragmentation and lipid peroxidation after 3 h, 24 h, 4 days and 7 days of storage. The addition of 10 μL/mL of Maca preserved sperm DNA and plasma membrane integrity at 3 h and increased sperm curvilinear velocity after 24 h. Treatment with 20 and 50 μL/mL of Maca increased the percentage of hyperactivated sperm after 3 h. Moreover, semen treated with 20 μL/mL of Maca decreased lipid peroxidation at 24 h. A significant reduction of sperm DNA and plasma membrane integrity as well as of kinetics parameters between 3 and 24 h of refrigerated storage with the higher concentration tested was observed. Although Maca was not able to protect canine semen with extended refrigeration storage time, it increased hyperactivation and preserved DNA integrity in short-term storage

Identification of a Novel p53 Modulator Endowed with Antitumoural and Antibacterial Activity through a Scaffold Repurposing Approach

Intracellular pathogens, such as Chlamydia trachomatis, have been recently shown to induce degradation of p53 during infection, thus impairing the protective response of the host cells. Therefore, p53 reactivation by disruption of the p53-MDM2 complex could reduce infection and restore pro-apoptotic effect of p53. Here, we report the identification of a novel MDM2 inhibitor with potential antitumoural and antibacterial activity able to reactivate p53. A virtual screening was performed on an in-house chemical library, previously synthesised for other targets, and led to the identification of a hit compound with a benzo[a]dihydrocarbazole structure, RM37. This compound induced p53 up-regulation in U343MG glioblastoma cells by blocking MDM2-p53 interaction and reduced tumour cell growth. NMR studies confirmed its ability to dissociate the MDM2-p53 complex. Notably, RM37 reduced Chlamydia infection in HeLa cells in a concentration-dependent manner and ameliorated the inflammatory status associated with infection

Apoptosis Therapy in Cancer: The First Single-molecule Co-activating p53 and the Translocator Protein in Glioblastoma

In the complex scenario of cancer, treatment with compounds targeting multiple cell pathways has been emerging. In Glioblastoma Multiforme (GBM), p53 and Translocator Protein (TSPO), both acting as apoptosis inducers, represent two attractive intracellular targets. On this basis, novel indolylglyoxylyldipeptides, rationally designed to activate TSPO and p53, were synthesized and biologically characterized. The new compounds were able to bind TSPO and to reactivate p53 functionality, through the dissociation from its physiological inhibitor, murine double minute 2 (MDM2). In GBM cells, the new molecules caused Δψm dissipation and inhibition of cell viability. These effects resulted significantly higher with respect to those elicited by the single target reference standards applied alone, and coherent with the synergism resulting from the simultaneous activation of TSPO and p53. Taken together, these results suggest that TSPO/MDM2 dual-target ligands could represent a new attractive multi-modal opportunity for anti-cancer strategy in GBM

D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans

The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene

A preliminary investigation on kinetics of zeolite A crystallisation using optical diagnostic.

Preliminary data concerning the monitoring in situ of the zeolite A crystallisation from clear solutions are reported. Experiments were performed at 60 and 70 °C with fresh and aged solutions having the following composition: 8.6Na 2O·0.18SiO 2·Al 2O 3·150H 2O. The formation of early phases in the crystallization process were followed using diagnostics such as dynamic light scattering (DLS), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The comparison of the available data seems to indicate the formation of a precursor phase (like gel) in the case of not aged solution. Conversely, crystallization in aged solution seems to proceed without intermediate phases. At the same time, an investigation on the kinetics aspects of the zeolite A crystallisation was carded out. As far as the reproducibility test is concerned, the chemical system selected showed good results on a large number of tests