Patterns of neuropsychological impairment in MCI patients with small subcortical infarcts or hippocampal atrophy

We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease. (JINS, 2008, 14, 611–619.

Numerical and experimental analysis of the leaning Tower of Pisa under earthquake

Twenty years have passed from the most recent studies about the dynamic behavior of the leaning Tower of Pisa. Significant changes have occurred in the meantime, the most important ones concerning the soil-structure interaction. From 1999 to 2001, the foundation of the monument was consolidated through under-excavation, and the "Catino" at the basement was rigidly connected to the foundation. Moreover, in light of the recent advances in the field of earthquake engineering, past studies about the Tower must be revised. Therefore, the present research aims at providing new data and results about the structural response of the Tower under earthquake. As regards the experimental assessment of the Tower, the dynamic response of the structure recorded during some earthquakes has been analyzed in the time- and frequency-domain. An Array 2D test has been performed in the Square of Miracles to identify a soil profile suitable for site response analyses, thus allowing the definition of the free-field seismic inputs at the base of the Tower. On the other hand, a synthetic evaluation of the seismic input in terms of response spectra has been done by means of a hybrid approach that combines Probabilistic and Deterministic Seismic Hazard Assessment methods. Furthermore, natural accelerograms have been selected and scaled properly. A finite element model that takes into account the inclination of the structure has been elaborated, and it has been updated taking into account the available experimental results. Finally, current numerical and experimental efforts for enhancing the seismic characterization of the Tower have been illustrated

Faecal Microbiota Characterisation of Potamochoerus porcus Living in a Controlled Environment

Intestinal bacteria establish a specific relationship with the host animal, which causes the acquisition of gut microbiota with a unique composition classified as the enterotype. As the name suggests, the Red River Hog is a wild member of the pig family living in Africa, in particular through the West and Central African rainforest. To date, very few studies have analysed the gut microbiota of Red River Hogs (RRHs) both housed under controlled conditions and in wild habitats. This study analysed the intestinal microbiota and the distribution of Bifidobacterium species in five Red River Hog (RRH) individuals (four adults and one juvenile), hosted in two different modern zoological gardens (Parco Natura Viva, Verona, and Bioparco, Rome) with the aim of disentangling the possible effects of captive different lifestyle and host genetics. Faecal samples were collected and studied both for bifidobacterial counts and isolation by means of culture-dependent method and for total microbiota analysis through the high-quality sequences of the V3-V4 region of bacterial 16S rRNA. Results showed a host-specific bifidobacterial species distribution. Indeed, B. boum and B. thermoacidophilum were found only in Verona RRHs, whereas B. porcinum species were isolated only in Rome RRHs. These bifidobacterial species are also typical of pigs. Bifidobacterial counts were about 106 CFU/g in faecal samples of all the individuals, with the only exception for the juvenile subject, showing 107 CFU/g. As in human beings, in RRHs a higher count of bifidobacteria was also found in the young subject compared with adults. Furthermore, the microbiota of RRHs showed qualitative differences. Indeed, Firmicutes was found to be the dominant phylum in Verona RRHs whereas Bacteroidetes was the most represented in Roma RRHs. At order level, Oscillospirales and Spirochaetales were the most represented in Verona RRHs compared with Rome RRHs, where Bacteroidales dominated over the other taxa. Finally, at the family level, RRHs from the two sites showed the presence of the same families, but with different levels of abundance. Our results highlight that the intestinal microbiota seems to reflect the lifestyle (i.e., the diet), whereas age and host genetics are the driving factors for the bifidobacterial population

Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials

Improved GMP compliant approach to manipulate lipoaspirates, to cryopreserve stromal vascular fraction, and to expand adipose stem cells in xeno-free media

Abstract Background The stromal vascular fraction (SVF) derived from adipose tissue contains adipose-derived stromal/stem cells (ASC) and can be used for regenerative applications. Thus, a validated protocol for SVF isolation, freezing, and thawing is required to manage product administration. To comply with Good Manufacturing Practice (GMP), fetal bovine serum (FBS), used to expand ASC in vitro, could be replaced by growth factors from platelet concentrates. Methods Throughout each protocol, GMP-compliant reagents and devices were used. SVF cells were isolated from lipoaspirates by a standardized enzymatic protocol. Cells were cryopreserved in solutions containing different albumin or serum and dimethylsulfoxide (DMSO) concentrations. Before and after cryopreservation, we analyzed: cell viability (by Trypan blue); immunophenotype (by flow cytometry); colony-forming unit-fibroblast (CFU-F) formation; and differentiation potential. ASC, seeded at different densities, were expanded in presence of 10% FBS or 5% supernatant rich in growth factors (SRGF) from platelets. The differentiation potential and cell transformation grade were tested in expanded ASC. Results We demonstrated that SVF can be obtained with a consistent yield (about 185 × 103 cells/ml lipoaspirate) and viability (about 82%). Lipoaspirate manipulation after overnight storage at +4 °C reduced cell viability (−11.6%). The relative abundance of ASC (CD34+CD45−CD31–) and endothelial precursors (CD34+CD45−CD31+) in the SVF product was about 59% and 42%, respectively. A period of 2 months cryostorage in autologous serum with added DMSO minimally affected post-thaw SVF cell viability as well as clonogenic and differentiation potentials. Viability was negatively affected when SVF was frozen at a cell concentration below 1.3 × 106 cells/ml. Cell viability was not significantly affected after a freezing period of 1 year. Independent of seeding density, ASC cultured in 5% SRGF exhibited higher growth rates when compared with 10% FBS. ASC expanded in both media showed unaltered identity (by flow cytometry) and were exempt from genetic lesions. Both 5% SRGF- and 10% FBS-expanded ASC efficiently differentiated to adipocytes, osteocytes, and chondrocytes. Conclusions This paper reports a GMP-compliant approach for freezing SVF cells isolated from adipose tissue by a standardized protocol. Moreover, an ASC expansion method in controlled culture conditions and without involvement of animal-derived additives was reported

Disentangling the Possible Drivers of Indri indri Microbiome: A Threatened Lemur Species of Madagascar

Research on the gut microbiome may help with increasing our understanding of primate health with species’ ecology, evolution, and behavior. In particular, microbiome-related information has the potential to clarify ecology issues, providing knowledge in support of wild primates conservation and their associated habitats. Indri (Indri indri) is the largest extant living lemur of Madagascar. This species is classified as “critically endangered” by the IUCN Red List of Threatened Species, representing one of the world’s 25 most endangered primates. Indris diet is mainly folivorous, but these primates frequently and voluntarily engage in geophagy. Indris have never been successfully bred under human care, suggesting that some behavioral and/or ecological factors are still not considered from the ex situ conservation protocols. Here, we explored gut microbiome composition of 18 indris belonging to 5 different family groups. The most represented phyla were Proteobacteria 40.1 ± 9.5%, Bacteroidetes 28.7 ± 2.8%, Synergistetes 16.7 ± 4.5%, and Firmicutes 11.1 ± 1.9%. Further, our results revealed that bacterial alpha and beta diversity were influenced by indri family group and sex. In addition, we investigated the chemical composition of geophagic soil to explore the possible ecological value of soil as a nutrient supply. The quite acidic pH and high levels of secondary oxide-hydroxides of the soils could play a role in the folivorous diet’s gut detoxification activity. In addition, the high contents of iron and manganese found the soils could act as micronutrients in the indris’ diet. Nevertheless, the concentration of a few elements (i.e., calcium, sulfur, boron, nickel, sodium, and chromium) was higher in non-geophagic than in geophagic soils. In conclusion, the data presented herein provide a baseline for outlining some possible drivers responsible for the gut microbiome diversity in indris, thus laying the foundations for developing further strategies involved in indris’ conservation

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible