S-adenosylmethionine and superoxide dismutase 1 synergistically counteract Alzheimer's disease features progression in tgCRND8 mice

Recent evidence emphasizes the role of dysregulated one-carbon metabolism in Alzheimer's Disease (AD). Exploiting a nutritional B-vitamin deficiency paradigm, we have previously shown that PSEN1 and BACE1 activity is modulated by one-carbon metabolism, leading to increased amyloid production. We have also demonstrated that S-adenosylmethionine (SAM) supplementation contrasted the AD-like features, induced by B-vitamin deficiency. In the present study, we expanded these observations by investigating the effects of SAM and SOD (Superoxide dismutase) association. TgCRND8 AD mice were fed either with a control or B-vitamin deficient diet, with or without oral supplementation of SAM + SOD. We measured oxidative stress by lipid peroxidation assay, PSEN1 and BACE1 expression by Real-Time Polymerase Chain Reaction (PCR), amyloid deposition by ELISA assays and immunohistochemistry. We found that SAM + SOD supplementation prevents the exacerbation of AD-like features induced by B vitamin deficiency, showing synergistic effects compared to either SAM or SOD alone. SAM + SOD supplementation also contrasts the amyloid deposition typically observed in TgCRND8 mice. Although the mechanisms underlying the beneficial effect of exogenous SOD remain to be elucidated, our findings identify that the combination of SAM + SOD could be carefully considered as co-adjuvant of current AD therapies

Conventional and organic foods: A comparison focused on animal products

AbstractThe term "organic" denotes a product of a food production system that is socially, ecologically, and economically sustainable. The organic food market is growing in response to an ever increasing demand for organic products. They are often considered more nutritious, healthier, and free from pesticides than conventional foods. However, the results of scientific studies do not show that organic products are more nutritious and safer than conventional foods. In this work a comparison between conventional and organic foods is made, the focus is on animal products. The data available in the existing literature is often conflicting, even if the differences are often associated with breeds suited to organic vs. conventional production systems. In order to have a clear understanding of the role that "organic effect" plays on animal foods, further research is necessary

The mutant p53-driven secretome has oncogenic functions in pancreatic ductal adenocarcinoma cells

The cancer secretome is a rich repository of useful information for both cancer biology and clinical oncology. A better understanding of cancer secretome is particularly relevant for pancreatic ductal adenocarcinoma (PDAC), whose extremely high mortality rate is mainly due to early metastasis, resistance to conventional treatments, lack of recognizable symptoms, and assays for early detection. TP53 gene is a master transcriptional regulator controlling several key cellular pathways and it is mutated in ~75% of PDACs. We report the functional effect of the hot-spot p53 mutant isoforms R175H and R273H on cancer cell secretome, showing their influence on proliferation, chemoresistance, apoptosis, and autophagy, as well as cell migration and epithelial-mesenchymal transition. We compared the secretome of p53-null AsPC-1 PDAC cells after ectopic over-expression of R175H-mutp53 or R273H-mutp53 to identify the differentially secreted proteins by mutant p53. By using high-resolution SWATH-MS technology, we found a great number of differentially secreted proteins by the two p53 mutants, 15 of which are common to both mutants. Most of these secreted proteins are reported to promote cancer progression and epithelial-mesenchymal transition and might constitute a biomarker secreted signature that is driven by the hot-spot p53 mutants in PDAC

electrolysed water in the food industry as supporting of environmental sustainability

Food safety is a priority for the food industry and to achieve this result a correct plant sanitation programme is of the utmost importance. Among various disinfection techniques, an emerging one is represented by the use of electrolysed water (EW) as the disinfecting agent. The use of EW is compliant with the desire to find alternatives to chlorination and heat treatments, representing a green cleaning alternative to toxic disinfectants. EW is an activated liquid, obtained by passing a diluted saline solution (NaCl, KCl or MgCl2) through an electrolytic cell, thus causing the production from the anode side of electrolysed oxidising water, containing high dissolved oxygen, free chlorine and characterised by a low pH (2.3–2.7) and a high oxidation–reduction potential (ORP > 1,000 mV). At the same time from the cathode side electrolysed reduced water is produced, with high pH (10.0–11.5), high dissolved hydrogen and low ORP (−800 to −900 mV). Unlike other chemical disinfectants, EW is not harmful for skin and mucous membranes and is quite easy to handle. Furthermore, the use of EW is relatively inexpensive and, above all, is a sustainable technique. Currently used sanitisers (e.g. glutaraldehyde, formaldehyde, etc.) are effective, but their adverse effects on the environment are well known. Differently from these chemicals, the use of EW has a reduced impact on the environment and because of its properties, it may find several applications in the food industry. In this work, the characteristics and some EW applications as sustainable sanitation technique applied in the food industry are reported and discussed

Health conditions of inmates in Italy

Abstract Background Several studies have shown that prison is characterized by a higher prevalence of chronic diseases than unconfined settings. The aim of this study was to describe the characteristics and health of inmates, focusing on internal diseases. Methods We designed a specific clinical record using the Python programming language. We considered all of the diagnoses according to the ICD-9-CM. Results Of a total of 17,086 inmates, 15,751 were enrolled in our study (M = 14,835; F = 869), corresponding to 92.2% of the entire inmate population (mean age of 39.6 years). The project involved a total of 57 detention facilities in six Italian regions (for a total of 28% of all detainees in Italy), as counted in a census taken on February 3, 2014. From the entire study sample, 32.5% of prisoners did not present any disorders, while 67.5% suffered from at least one disease. The most frequent pathologies were psychiatric (41.3%), digestive (14.5%), infectious (11.5%), cardiovascular (11.4%), endocrine, metabolic, and immune (8.6%), and respiratory (5.4%). Conclusion The findings showed that a large number of detainees were affected by several chronic conditions such as hypertension, dyslipidemia and type 2 diabetes mellitus, with an unusually high prevalence for such a young population. Therefore, a series of preventive measures is recommended to strengthen the entire care process and improve the health and living conditions of prisoners

IDH-wild type glioblastomas featuring at least 30% giant cells are characterized by frequent RB1 and NF1 alterations and hypermutation

: Giant cell glioblastoma (GC-GBM) is a rare variant of IDH-wt GBM histologically characterized by the presence of numerous multinucleated giant cells and molecularly considered a hybrid between IDH-wt and IDH-mutant GBM. The lack of an objective definition, specifying the percentage of giant cells required for this diagnosis, may account for the absence of a definite molecular profile of this variant. This study aimed to clarify the molecular landscape of GC-GBM, exploring the mutations and copy number variations of 458 cancer-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI) in 39 GBMs dichotomized into having 30-49% (15 cases) or\u2009 65\u200950% (24 cases) GCs. The type and prevalence of the genetic alterations in this series was not associated with the GCs content (<\u200950% or 65\u200950%). Most cases (82% and 51.2%) had impairment in TP53/MDM2 and PTEN/PI3K pathways, but a high proportion also featured TERT promoter mutations (61.5%) and RB1 (25.6%) or NF1 (25.6%) alterations. EGFR amplification was detected in 18% cases in association with a shorter overall survival (P\u2009=\u20090.004). Sixteen (41%) cases had a TMB\u2009>\u200910 mut/Mb, including two (5%) that harbored MSI and one with a POLE mutation. The frequency of RB1 and NF1 alterations and TMB counts were significantly higher compared to 567 IDH wild type (P\u2009<\u20090.0001; P\u2009=\u20090.0003; P\u2009<\u20090.0001) and 26 IDH-mutant (P\u2009<\u20090.0001; P\u2009=\u20090.0227; P\u2009<\u20090.0001) GBMs in the TCGA PanCancer Atlas cohort. These findings demonstrate that the molecular landscape of GBMs with at least 30% giant cells is dominated by the impairment of TP53/MDM2 and PTEN/PI3K pathways, and additionally characterized by frequent RB1 alterations and hypermutation and by EGFR amplification in more aggressive cases. The high frequency of hypermutated cases suggests that GC-GBMs might be candidates for immune check-point inhibitors clinical trials

Mucuna pruriens for Parkinson's disease: Low-cost preparation method, laboratory measures and pharmacokinetics profile

Abstract Background Parkinson's disease (PD) is a progressive neurological condition. Levodopa (LD) is the gold standard therapy for PD patients. Most PD patients in low-income areas cannot afford long-term daily Levodopa therapy. The aim of our study was to investigate if Mucuna pruriens (MP), a legume with high LD content that grows in tropical regions worldwide, might be potential alternative for poor PD patients. Methods We analyzed 25 samples of MP from Africa, Latin America and Asia. We measured the content in LD in various MP preparations (dried, roasted, boiled). LD pharmacokinetics and motor response were recorded in four PD patients, comparing MP vs. LD+Dopa-Decarboxylase Inhibitor (DDCI) formulations. Results Median LD concentration in dried MP seeds was 5.29%; similar results were obtained in roasted powder samples (5.3%), while boiling reduced LD content up to 70%. Compared to LD+DDCI, MP extract at similar LD dose provided less clinical benefit, with a 3.5-fold lower median AUC. Conclusion Considering the lack of a DDCI, MP therapy may provide clinical benefit only when content of LD is at least 3.5-fold the standard LD+DDCI. If long-term MP proves to be safe and effective in controlled clinical trials, it may be a sustainable alternative therapy for PD in low-income countries

Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi‑directionally convert into cancer stem cells

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed when metastatic events have occurred. Cancer stem cells (CSCs) play an important role in tumor initiation, metastasis, chemoresistance and relapse. A growing number of studies have suggested that CSCs exist in a dynamic equilibrium with more differentiated cancer cells via a bi‑directional regeneration that is dependent on the environmental stimuli. In this investigation, we obtain, by using a selective medium, PDAC CSCs from five out of nine PDAC cell lines, endowed with different tumorsphere‑forming ability. PDAC CSCs were generally more resistant to the action of five anticancer drugs than parental cell lines and were characterized by an increased expression of EpCAM and CD44v6, typical stem cell surface markers, and a decreased expression of E‑cadherin, the main marker of the epithelial state. PDAC CSCs were able to re‑differentiate into parental cells once cultured in parental growth condition, as demonstrated by re‑acquisition of the epithelial morphology, the decreased expression levels of EpCAM and CD44v6 and the increased sensitivity to anticancer drugs. Finally, PDAC CSCs injected into nude mice developed a larger subcutaneous tumor mass and showed a higher metastatic activity compared to parental cells. The present study demonstrates the ability to obtain CSCs from several PDAC cell lines and that these cells are differentially resistant to various anticancer agents. This variability renders them a model of great importance to deeply understand pancreatic adenocarcinoma biology, to discover new biomarkers and to screen new therapeutic compounds

Auras in temporal lobe epilepsy with hippocampal sclerosis: Relation to seizure focus laterality and post surgical outcome

We examined the relationship between presence and frequency of different types of auras and side of lesion and post surgical outcomes in 205 patients with medically intractable mesial temporal lobe epilepsy (MTLE) with unilateral hippocampal sclerosis (HS). With respect to the number of auras, multiple auras were not associated with side of lesion (p=0.551). the side of HS was not associated with the type of auras reported. One hundred fifty-seven patients were operated. the occurrence of multiple auras was not associated with post-surgical outcome (p=0.740). the presence of extratemporal auras was significantly higher in patients with poor outcome. in conclusion, this study suggests that the presence of extratemporal auras in patients with MTLE-HS possibly reflects extratemporal epileptogenicity in these patients, who otherwise showed features suggestive of TLE. Therefore, TLE-HS patients undergoing pre-surgical evaluation and presenting clinical symptoms suggestive of extratemporal involvement should bemore extensively evaluated to avoid incomplete resection of the epileptogenic zone. (C) 2012 Elsevier Inc. All rights reserved.Universidade Federal de São Paulo, Dept Neurol & Neurocirurgia, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imagem, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol & Neurocirurgia, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imagem, BR-04024002 São Paulo, BrazilWeb of Scienc

Incentivizing the Dynamic Workforce: Learning Contracts in the Gig-Economy

In principal-agent models, a principal offers a contract to an agent to perform a certain task. The agent exerts a level of effort that maximizes her utility. The principal is oblivious to the agent's chosen level of effort, and conditions her wage only on possible outcomes. In this work, we consider a model in which the principal is unaware of the agent's utility and action space. She sequentially offers contracts to identical agents, and observes the resulting outcomes. We present an algorithm for learning the optimal contract under mild assumptions. We bound the number of samples needed for the principal obtain a contract that is within $\epsilon$ of her optimal net profit for every $\epsilon>0$