Modelling 3D Tumour Microenvironment In Vivo: A Tool to Predict Cancer Fate.

Recently, many studies demonstrated the fundamental role of the tumour microenvironment (TME) in cancer progression. Here, we describe a method to visualize in 3D the behaviour of tumours in zebrafish embryos. We highlight two major actors of the TME, macrophages and vessels. This valuable tool is transposable to Patient-Derived Xenograft imaging in order to predict the fate of malignant tumours according to the dynamics of their TME.

Assessing Relationships between Physically Demanding Work and Late-Life Disability in Italian Nonagenarian Women Living in a Rural Area.

As more and more persons live into their 90s and beyond, investigating causes of disability in the oldest-old population is relevant for public health implications to plan preventive strategies and rehabilitation interventions. A negative association between physically demanding work and midlife physical function has been shown, but there is a paucity of longitudinal studies investigating possible work-related long-term effects in the oldest old. This study investigates the relationship between physically demanding work exposure and late-life physical performances, disability, general health status, and quality of life in a sample of women aged 90 years and over inside the Mugello Study. Sociodemographic data, cognitive and functional status, lifestyle, medical history, drug use, and work history were collected from 236 participants. Farmers had a lower percentage of individuals with preserved independence in basic activities of daily living compared to other occupations. However, in the multivariate analysis, only a higher cognitive function remained associated with functional independence. While confirming the well-known association between cognitive and functional decline in very old age, our results do not support the hypothesis that the negative effects of physical work exposure observed in midlife are relevant to predict disability in nonagenarian women.

A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome.

Metabolic syndrome is a pathological condition characterized by obesity, hyperglycemia, hypertension, elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol that increase cardiovascular disease risk and type 2 diabetes. Although numerous predisposing genetic risk factors have been identified, the biological mechanisms underlying this complex phenotype are not fully elucidated. Here we introduce a systems biology approach based on network analysis to investigate deregulated biological processes and subsequently identify drug repurposing candidates. A proximity score describing the interaction between drugs and pathways is defined by combining topological and functional similarities. The results of this computational framework highlight a prominent role of the immune system in metabolic syndrome and suggest a potential use of the BTK inhibitor ibrutinib as a novel pharmacological treatment. An experimental validation using a high fat diet-induced obesity model in zebrafish larvae shows the effectiveness of ibrutinib in lowering the inflammatory load due to macrophage accumulation.

DTI-derived indexes of brain WM correlate with cognitive performance in vascular MCI and small-vessel disease. A TBSS study.

Indexes derived from diffusion tensor imaging (DTI) are sensitive to changes of both T2-hyperintense and normal-appearing brain white matter (WM) in elderly subjects with variable cognitive status. We investigated correlations between global cognitive performance and DTI-derived indexes along the WM tracts in the brain of patients with vascular mild cognitive impairment (MCI) and small vessel disease (SVD). Seventy-six patients with vascular MCI and SVD were assessed through Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) test and underwent DTI examination on a 1.5 T MR scanner. We used Tract Based Spatial Statistics (TBSS) to assess voxel-wise in the entire brain the spatial distribution of the correlation between values of fractional anisotropy, mean, axial/radial diffusivity and global cognitive performance as assessed with MoCA and MMSE tests. All correlations were statistically tested with a significant p-value <0.05 using a family-wise error correction for multiple comparisons. The MoCA score significantly correlated with fractional anisotropy (positive correlation) and mean, axial and radial diffusivity (negative correlations) in WM tracts of cerebral hemispheres and corpus callosum, as well as in the intra-thalamic WM tracts and the superior cerebellar peduncle decussation in the midbrain. No significant correlations were observed for MMSE score. Global cognitive performance, as measured by the MoCA score, in patients with vascular MCI and SVD is associated with microstructural changes in WM tracts underlying intra- and inter-hemispheric cerebral, thalamo-cortical and cerebello-thalamic connections.

Anatomical variations of the posterior circulation: case reports and a review of literature.

INTRODUCTION: The intracranial vascular anatomical variations, although rare, represent a interesting field of research, since many anomalous variants are possible and in most cases they remain asymptomatic. The capability of the cerebral circulation to adapt to several flow changes is confirmed by the fact that in several cases these anatomical variation compensate for an eventual unsuccessful development of the normal circulation, expecially in the posterior section of cerebral circulation. MATERIALS AND METHODS: A comprehensive review of PubMed literature was performed and three clinical cases have been analyzed. RESULTS: Several angiographic and MR-angiography reports have been evaluated, regarding general and specific anatomical variants of the posterior circulation. DISCUSSION: Although rare, the anatomical variations of the posterior intracranial circulation represent an interesting field of investigation in order to achieve a better comprehension of the embryological development of the circulatory system.

Comparing and combining gamma-hydroxybutyric acid (GHB) and naltrexone in maintaining abstinence from alcohol: an open randomised comparative study.

Maintaining abstinence from alcohol is the main goal in treating alcohol dependence. Our aim was to evaluate the efficacy of gamma-hydroxybutyric acid (GHB) and naltrexone (NTX), and their combination in maintaining abstinence. Fifty-five alcoholics were randomly enrolled in three groups and treated for 3 months with GHB, GHB plus NTX, and NTX, respectively. At the end of treatments, abstinence was maintained by 13 patients (72.2%) in combination group, 8 patients (40%; P=0.03) in GHB group, and one patient (5.9%; P=0.0001) in NTX group. Relapses in heavy drinking tended to occur more frequently in GHB group (15%) than in either combination group (no cases) or NTX group (5.9%), but such differences were not statistically significant. The GHB/NTX combination was more effective than either drug given alone; this suggests that the two drugs combine their different actions synergistically without suppressing the favourable effects of each other.

Suppression of craving for gamma-hydroxybutyric acid by naltrexone administration: three case reports.

Gamma-hydroxybutyric acid (GHB) is currently used to induce and maintain abstinence from alcohol. Cases of craving and desire to increase doses of GHB have been reported in both clinical trials and nonclinical self-administration. The enhancement of dopamine activity induced by GHB receptor activation might play a role in the euphoric effect and potential craving and the consequent abuse of this drug. Naltrexone (NTX), a mu-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol-dependent outpatients. Taking into account the alcohol antireward property of NTX, we tested its activity in reducing craving for GHB in 3 consecutive cases of alcoholics who manifested craving for this drug. In all patients the combination with NTX suppressed the craving for GHB. The antireward effect of NTX likely results from its interference with the GHB-induced dopamine release, leading to a partial blockade of the GHB reinforcing effect responsible of the craving for the drug. A combined therapy with GHB and NTX seems to be able to suppress craving for the former, thus improving the manageability and safety of treatment.