Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa environment interaction

Influence of dietary vitamin E supplementation on cholesterol oxidation and fresh colour in beef aged for 3 and 14 days

The effects of dietary vitamin E supplementation on the susceptibility to lipid oxidation and colour of the Longissimus thoracis (LT) muscle aged in vacuum packaged conditions for 3 or 14 days were studied. For this purpose, Charolais cattle were fed on a diet providing daily 60 mg (control) or 5500 mg of vitamin E per animal (supplemented) for 30 and 60 days before slaughter. Dietary vitamin E supplementation increased the liver vitamin E content, but not in the LT muscle of treated animals. The vitamin supplementation for 30 and 60 days has shown non-consistent effects in reducing cholesterol oxidation products of vacuum-packed aged meat. However, the vitamin E supplementation for 60 days was effective on Lightness stability in LT muscle during vacuum-packed ageing. Overall, from the practical standpoint, this study suggests that supranutritional supplementation up to 60 days may not increase the vitamin E content of Charolais LT muscle giving little, if any, benefits on meat colour and cholesterol oxidation. However, the present study suggests that it would be interesting to determine in which extent specific oxysterols are related to the meat colour and whether colour parameters can be useful for predicting the formation of cholesterol oxidation products along the industrial meat production chain.The effects of dietary vitamin E supplementation on the susceptibility to lipid oxidation and colour of the Longissimus thoracis (LT) muscle aged in vacuum packaged conditions for 3 or 14 days were studied. For this purpose, Charolais cattle were fed on a diet providing daily 60mg (control) or 5500mg of vitamin E per animal (supplemented) for 30 and 60 days before slaughter. Dietary vitamin E supplementation increased the liver vitamin E content, but not in the LT muscle of treated animals. The vitamin supplementation for 30 and 60 days has shown non-consistent effects in reducing cholesterol oxidation products of vacuum-packed aged meat. However, the vitamin E supplementation for 60 days was effective on Lightness stability in LT muscle during vacuum-packed ageing. Overall, from the practical standpoint, this study suggests that supranutritional supplementation up to 60 days may not increase the vitamin E content of Charolais LT muscle giving little, if any, benefits on meat colour and cholesterol oxidation. However, the present study suggests that it would be interesting to determine in which extent specific oxysterols are related to the meat colour and whether colour parameters can be useful for predicting the formation of cholesterol oxidation products along the industrial meat production chain

Ageing and creeping management in major accident plants according to seveso III directive

The focus of this paper is the management of critical equipment ageing within the context of lower and upper tier Seveso process plants, with a peculiar insight into the effectiveness of safety management systems in setting-up reliable procedure for critical element identification. Recent research studies in fact evidenced that in Europe nearly 50% of major 'loss of containment' events, arising from technical plant failures, were primarily due to ageing plant mechanisms such as erosion, corrosion and fatigue. The critical ageing elements should be included in maintenance, inspection and periodic monitoring programs in relation to their reliability, as assumed in the risk assessment and their lifetime or frequency ranges, based on their operational experience. This paper will accurately discuss how the issue of ageing is currently handled in the process industry. The methodology builds on the critical results of actual findings from the inspections on the safety management systems of major accident plants, which were performed by a working group. The primary objective is to stimulate the introduction of effective ageing management changes into the safety management of companies, by taking advantages of findings of the previous assessment and establishing proper and effective audits

Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration

Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3g/kg), which caused the death of >70% of Brn-3a+ RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration

Design Tools

This book aims at encompassing the panorama of design tools being developed, tested and adopted by researchers and professors at the Department of Design of Politecnico di Milano. The tools are organized in a taxonomy that reflects the path of choice of a possible user in need for the right tool for a task to be performed. The taxonomy is based on a formalization of the design process proposed by the authors, which characterizes the Design System at Politecnico di Milano. The book essentially offers two main contributions: an original taxonomy that guides towards the organization of design tools and their usage with different actors; a representative collection of design tools developed within the Department of Design of Politecnico di Milano with specific instructions on how to use them. Design Tools is addressed both to practitioners and academics in the field of design that are interested in getting to know more about the discourse around design tools in general and in particular how this discourse takes a shape within Politecnico di Milano and resolves in usable and shareable tools

Assessing the eco-hydraulic effects of a hydropeaking mitigation measure with increased energy production in the Noce River (Italian Alps)

We investigated the ecohydraulic effects of a recently implemented hydropeaking mitigation measure in the Upper Noce Stream (NE Italy, Italian Alps), which also allows for additional hydropower production. The Upper Noce, a 3rd order gravel-bed stream, was affected since the mid-1920s by storage hydropower production and associated hydropeaking. The mitigation measure consisted in the diversion of most of the released hydropeaks into a sequence of three newly-installed, cascading run-of-the-river power plants, fed by a penstock running almost parallel to the former hydropeaking reach. The hydropeaking-diversion mitigation measure markedly reduced hydropeaking on a 10-km stream reach, and hydropeaking is now released immediately upstream the confluence with a major free-flowing tributary, which increases the hydropeaking baseflow. The flow regime in the mitigated reach shifted from hydropeaking-dominated to baseflow-dominated regime in winter, with flow variability represented only by snowmelt and rainfall in late spring and summer. We applied two sets of indicators (the Hydropeaking Indicators HP1, HP2 and the COSH method) and conducted a simplified hydraulic analysis of the hydropeaking wave propagation. We assessed the ecological effects of the mitigation measure using three complementary data sources: the analysis of (a) the benthic and (b) hyporheic invertebrate communities, based on datasets collected before and after the implementation of the diversion measure, and (c) ancillary data monitored by the diversion plant manager for required environmental monitoring, which included the suspended sediment regime and the Extended Biotic Index, measured yearly from the year before to the four subsequent years after the implementation of the mitigation measure. Three main changes in eco-hydraulic processes associated with hydropeaking mitigation were detected. i) The flow regime in the mitigated reach changed to a residual flow type, with much less frequent residual hydropeaks, with an average two-fold increase in downramping rates that were recorded downstream the junction with a major tributary. ii) The functional composition of the macrobenthic communities shifted slightly in response to flow mitigation, but the taxonomic composition did not recover to conditions typical of more natural flow regimes. This was likely due to the reduced dilution of pollutants and resulting slight worsening in water quality. iii) The hyporheic communities conversely showed an increase in diversity and abundance of interstitial taxa, especially in the sites most affected by hydropeaking, and this effect was likely due to changes in the interstitial space availability, brought by an alteration of the previous time-space pattern of fine sediment transport, which eventually resulted in reduction of fine sediments clogging of the gravel bed interstices. Besides illustrating a feasible hydropeaking mitigation option for Alpine streams, this work suggests the importance of monitoring both benthic and hyporheic communities, together with the flow and sediment supply regimes, and physico-chemical water quality parameters, for carefully detecting changes in eco-hydraulic processes associated with hydropeaking mitigation that may not be fully expected in the design phase

Moving waters to mitigate hydropeaking: a case study from the Italian Alps

We assessed the effect of a hydropeaking diversion mitigation measure that allows for additional hydropower production, which markedly reduced hydropeaking on a 10-km stream reach in the north-eastern Italian Alps. Hydropeaking, caused by a storage hydropower plant, affected the study reach from the 1920s to 2015, when a cascade of three small run-of-the-river plants was installed to divert the hydropeaks from the plant outlet directly into the intake of the RoRs plants, and hydropeaking was released downstream the confluence with a major free-flowing tributary. The flow regime in the mitigated reach shifted from a hydropeaking-dominated to a baseflow-dominated regime in winter, with flow variability represented only by snowmelt and rainfall in late spring and summer. The application of two recently proposed sets of hydropeaking indicators, the hydraulic analysis of the hydropeaking wave, together with the assessment of biotic changes, allowed quantifying the changes in ecohydraulic processes associated with hydropeaking mitigation. The flow regime in the mitigated reach changed to a residual flow type, with much less frequent residual hydropeaks; although an average two-fold increase in downramping rates were recorded downstream the junction with the tributary, these changes did not represent an ecological concern. The functional composition of the macrobenthic communities shifted slightly in response to flow mitigation, but the taxonomic composition did not recover to conditions typical of more natural flow regimes. This was likely due to the reduced dilution of pollutants and resulting slight worsening in water quality. Conversely, the hyporheic communities showed an increase in diversity and abundance of interstitial taxa, especially in the sites most affected by hydropeaking. This effect was likely due to changes in the interstitial space availability, brought by a reduction of fine sediments clogging. Besides illustrating a feasible hydropeaking mitigation option for Alpine streams, our work suggests the importance of monitoring both benthic and hyporheic communities, together with the flow and sediment supply regimes, and physico-chemical water quality parameters

Compensatory growth following long term multi-phase cyclic feeding in rainbow trout (Oncorhynchus mykiss)

Compensatory growth (CG) during recovery from feed deprivation is a well-known phenomenon in fish, making the practice of cyclic feed restriction-refeeding a possible tool for aquaculturists to optimize growth performance. While earlier studies in this direction focused on relatively short single feed restriction-refeeding protocols, the present trial was designed to evaluate the impact of different repeated cyclic feeding schemes on the zootechnical response of rainbow trout (O. mykiss) over a complete growing phase up to the commercial size. Three hundred trout (body weight 72\ub16 g) were randomly distributed among 12 tanks, each of 0.5 m3 capacity and supplied with 8 L min-1 of well water at a temperature of 12.7\ub10.8\ub0C. Triplicated groups of fish were subjected over 27 weeks to one of the following treatments: C, control, continuous feeding to visual satiety 6 days a week; T1, cyclic feeding regularly alternating 1 week starvation (S) and 3 weeks refeeding (F) (1S+3F); T2, cyclic feeding consisting in 3 consecutive phases: 1S+3F, 2S+6F, and 3S+12F; T3, where a feed restriction (70% of the satiety level observed in the previous week) was applied instead of starvation with the same schedule as T2. The same trout feed (45% crude protein, 28% crude lipid) was used throughout the trial. At the end of the trial the different cyclic feeding protocols resulted in the same zootechnical outcome (P>0.05). A nearly complete convergence of body mass was evident as no significant differences were found among treatments in individual weight (543\ub128g), specific growth rate (1.06\ub10.03%), feed conversion ratio (0.84\ub10.03) and protein efficiency ratio (2.64\ub10.12) despite a lower feed consumption in treatments T1, T2 and T3 relative to controls (357 vs. 390 g fish-1, P<0.05). All protocols imposing fasting or feed restriction resulted in CG at the end of each re-feeding phase. Hyperphagia was a major cause of CG. Both phenomena were emphasized with treatment T3 after recovering from the last 3-week fasting period, when they were associated to a marked improvement of feed conversion ratio relative to controls (0.75 vs. 0.85, P<0.05). The results obtained so far suggest repeated cyclic feeding as a reliable practice in trout farming, provided fasting or feed restriction periods are followed by refeeding phases of suitable length to allow recovery of body mass. This could result in improved profitability and environmental sustainability