LikeStarter: a Smart-contract based Social DAO for Crowdfunding

Crowdfunding has become a popular form of collective funding, in which small donations or investments, made by groups of people, support the development of new projects in exchange of free products or different types of recognition. Social network sites, on the other hand, promote user cooperation and currently are at the basis of any individuals cyber-interactions. In this paper, we present LikeStarter, a blockchain-based decentralized platform that combines social interactions with crowdfunding mechanisms, allowing any user to raise funds while becoming popular in the social network. Being built over the Ethereum blockchain, LikeStarter is structured as a Decentralized Autonomous Organization (DAO), that fosters crowdfunding without the intervention of any central authority, and recognizes the active role of donors, enabling them to support artists or projects, while making profits.Comment: Proceedings of the 2st Workshop on Cryptocurrencies and Blockchains for Distributed Systems (CryBlock'19). Paris, France, 29 April, 201

Are We What We Eat? Impact of Diet on the Gut-Brain Axis in Parkinson's Disease

Parkinson’s disease is characterized by motor and non-motor symptoms, such as defects in the gut function, which may occur before the motor symptoms. To date, there are therapies that can improve these symptoms, but there is no cure to avoid the development or exacerbation of this disorder. Dysbiosis of gut microbiota could have a crucial role in the gut–brain axis, which is a bidirectional communication between the central nervous system and the enteric nervous system. Diet can affect the microbiota composition, impacting gut–brain axis functionality. Gut microbiome restoration through probiotics, prebiotics, synbiotics or other dietary means could have the potential to slow PD progression. In this review, we will discuss the influence of diet on the bidirectional communication between gut and brain, thus supporting the hypothesis that this disorder could begin in the gut. We also focus on how food-based therapies might then have an influence on PD and could ameliorate non-motor as well as motor symptoms

Microbiological and 16S rRNA analysis of sulphite-reducing clostridia from river sediments in central Italy

<p>Abstract</p> <p>Background</p> <p>Microbiological indicators are commonly used in the assessment of public health risks associated with fecal contamination of freshwater ecosystems. Sediments are a reservoir of microorganisms, and can thus provide information on past pollution events, not obtainable through the testing of surface water. Moreover, pathogens present in sediment may represent future threats to human health. <it>Clostridium perfringens</it>, a typical colonizer of sediments, has been suggested as an alternative indicator of fecal pollution. In order to be suitable for such purpose, the microorganism should be widely distributed in contaminated environments. The objective of this study was thus to determine the composition of the anaerobic community in sediment samples of the lower Tiber basin, in central Italy, through a combined approach involving granulometric analysis of sediment samples, as well as a microbiological and molecular (16S rRNA) analysis of strains.</p> <p>Results</p> <p>Granulometry showed a similar, clayey sediment composition, in most sampling sites. The microbiological method, employing, an adaptation of the standard method, proved to be effective in isolating anaerobic bacteria from the environmental matrix for the purpose of genetic analysis. Eighty-three strains of bacteria were isolated and the partial 16S rRNA gene sequenced. While biochemical analysis detected only <it>C. perfringens </it>strains, phylogenetic analysis indicated the presence of three clusters: <it>C. perfringens, C. bifermentans </it>and <it>B. cereus</it>, comprising eight taxa. <it>C. perfringens</it>, the commonest in almost all sediment sampling sites, was present in all sites, and in both seasons (seasonal sampling was carried out only along the Tiber and Aniene rivers). None of the described genetic profiles showed complete similarity with GenBank sequences.</p> <p>Conclusion</p> <p>The study underlines the value of <it>C. perfringens </it>as an alternative microbial indicator of fecal contamination in river sediments. This is supported by the bacterium's presence in all sampling sites, and in both seasons, coupled with its detectability using commercial diagnostic kits.</p> <p>The study also illustrates the presence of an anaerobic community of considerable biodiversity in the lower Tiber basin, with <it>C. perfringens </it>as its main component. The 16S rRNA analysis, while confirming the phylogenetic relationships among isolated species, also showed haplotype patterns different from those present in the NCBI database.</p

Physiology and Pathophysiology of PPARs in the Eye

Peroxisome proliferator-activated receptor (PPARs) are ligand-activated transcription factors that exert significant roles in the control of multiple physiological processes. The last decade has shown an increasing interest in the role played by the agonists of PPARs in anti-inflammatory, anti-angiogenic, anti-fibrotic effects and in modulating oxidative stress response in different organs. Since the pathologic mechanisms of the majority of the blinding diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma and optic neuropathy (ON), often involve neo-angiogenesis, inflammation and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPAR modulation to prevent or ameliorate eye pathologies. In this review, we focused on the description of what is known about the role of PPARs in the ocular pathophysiological processes and on PPARs agonists as innovative adjuvants in the treatment of ocular diseases

Effects of Chronic Oral Probiotic Treatment in Paclitaxel-Induced Neuropathic Pain

Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for the therapeutic effect of chemotherapeutic drugs for inhibiting tumor growth and contributed to the pathogenesis of the CIPN. The use of nutraceuticals has receiving growing attention from the research community due to their phytochemical, biological, and pharmacological properties. It has been demonstrated that probiotic formulations may both reduce inflammation and modulate the expression of pain receptors. Our studies tested the efficacy of a probiotic formulation, SLAB51, in preventing paclitaxel-induced neuropathy. Interestingly, our probiotic formulation was able to keep the gut integrity, preserving its functionality, in CIPN-mice, moreover, it prevented the mechanical and cold hypersensitivity induced in paclitaxel-mice. Additionally, ex-vivo analysis showed that in CIPN-mice the pro-biotic treatment increased the expression of opioid and cannabinoid receptors in spinal cord, it prevented in the reduction in nerve fiber damage in the paws and modulated the serum proinflammatory cytokines concentration. On basis of these data, the use of this specific probiotic formulation may represent a valid adjuvant agent to paclitaxel, useful and not toxic for long-lasting therapies

A realistic morpho-anatomical connection strategy for modelling full-scale point-neuron microcircuits

The modeling of extended microcircuits is emerging as an effective tool to simulate the neurophysiological correlates of brain activity and to investigate brain dysfunctions. However, for specific networks, a realistic modeling approach based on the combination of available physiological, morphological and anatomical data is still an open issue. One of the main problems in the generation of realistic networks lies in the strategy adopted to build network connectivity. Here we propose a method to implement a neuronal network at single cell resolution by using the geometrical probability volumes associated with pre- and postsynaptic neurites. This allows us to build a network with plausible connectivity properties without the explicit use of computationally intensive touch detection algorithms using full 3D neuron reconstructions. The method has been benchmarked for the mouse hippocampus CA1 area, and the results show that this approach is able to generate full-scale brain networks at single cell resolution that are in good agreement with experimental findings. This geometric reconstruction of axonal and dendritic occupancy, by effectively reflecting morphological and anatomical constraints, could be integrated into structured simulators generating entire circuits of different brain areas facilitating the simulation of different brain regions with realistic models

Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer

Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant of the receptor constitutively activated and does not require the presence of androgens for the activation AR down-stream pathways. Since high AR-V7 expression is one of the most common features of CRPC, targeting this receptor variant is considered as one of the most promising strategies for treating this disease. Therefore anti-AR-V7 molecules could lead to a potential shift in paradigm in the treatment of CRPC. Niclosamide, an already FDA-approved anti-helminthic drug, was identified as a potent AR-V7 inhibitor in prostate cancer cells. Due to the recent positive preclinical results, niclosamide may be an interesting and novel type of targeted treatments for CRPC. This mini-review outlines the most recent pre- and clinical- data on the current status of niclosamide in the treatment of ARV7-positive CRPC patients

Association between neutropenia and response to ramucirumab and paclitaxel in patients with metastatic gastric cancer

PURPOSE: The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer.METHODS: This is a retrospective study of patients treated with ramucirumab plus paclitaxel.RESULTS: Fifty-three patients were evaluated. Among these, 10 patients (26.5%) developed grade ≥3 neutropenia. Patients with grade ≥3 neutropenia reported a progression-free survival of 6.6 months (95% confidence interval 3.3-8.4) and overall survival of 11 months (95% confidence interval 5.9-13.1) vs. 4.4 months (95% confidence interval 3.9-5.2) and 8.7 months (95% confidence interval 7.8-10.1) respectively in patients' group with lower grade events.CONCLUSION: Our analysis seems to suggest that the occurrence of neutropenia predicts response to treatment with ramucirumab and paclitaxel.</p

Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression

"Stockpile" of slight transcriptomic changes determines the indirect genotoxicity of low-dose BPA in thyroid cells

Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity