Determinants of fibrinogen in an Italian population suffering from claudication. Lower fibrinogen in the south compared to middle and north of Italy. The ADEP Group.

Prospective studies have shown that high plasma levels of fibrinogen are independently associated with the risk of cardiovascular complications. In patients suffering from peripheral vascular disease (PVD) fibrinogen has been shown to be an independent predictor of cardiovascular disease but its determinants have never been examined in this clinical setting. DESIGN AND METHODS: Fibrinogen levels were related to clinical and laboratory variables in 2,111 patients suffering from PVD. We also analyzed whether there was a regional distribution of risk factors. RESULTS: The median values of fibrinogen was 312 mg/dL. The clinical variables examined did not differentiate patients with elevated or normal fibrinogen levels. In particular, patients with ankle/arm pressure ratio < 0.8 did not show a higher prevalence of fibrinogen > 312 mg/dL. Conversely, white blood cell (WBC) count and serum cholesterol levels were significantly associated with high fibrinogen levels (p < 0.0001). Multiple logistic regression analysis demonstrated that areas of Italy were differently associated with high plasma fibrinogen levels (p < 0.03): subjects in the north and middle of Italy having significantly higher values of fibrinogen than subjects in the south of Italy (p < 0.01). A similar regional distribution was observed for WBC count and serum cholesterol levels. INTERPRETATION AND CONCLUSIONS: The regional distribution of risk factors raises the question as to whether the already reported large variability of cardiovascular events so in PVD may be attributed to a non homogeneous distribution of risk factors

Market dynamics associated with credit ratings: a literature review.

Credit ratings produced by the major credit rating agencies (CRAs) aim to measure the creditworthiness, or more specifically the relative creditworthiness of companies, i.e. their ability to meet their debt servicing obligations. In principle, the rating process focuses on the fundamental long-term credit strength of a company. It is typically based on both public and private information, except for unsolicited ratings, which focus only on public information. The basic rationale for using ratings is to achieve information economies of scale and solve principal-agent problems. Partly for the same reasons, the role of credit ratings has expanded significantly over time. Regulators, banks and bondholders, pension fund trustees and other fiduciary agents have increasingly used ratings-based criteria to constrain behaviour. As a result, the influence of the opinions of CRAs on markets appears to have grown considerably in recent years. One aspect of this development is its potential impact on market dynamics (i.e. the timing and path of asset price adjustments, credit spreads, etc.), either directly, as a consequence of the information content of ratings themselves, or indirectly, as a consequence of the “hardwiring” of ratings into regulatory rules, fund management mandates, bond covenants, etc. When considering the impact of ratings and rating changes, two conclusions are worth highlighting. – First, ratings correlate moderately well with observed credit spreads, and rating changes with changes in spreads. However, other factors, such as liquidity, taxation and historical volatility clearly also enter into the determination of spreads. Recent research suggests that reactions to rating changes may also extend beyond the immediately-affected company to its peers, and from bond to equity prices. Furthermore, this price reaction to rating changes seems to be asymmetrical, i.e. more pronounced for downgrades than for upgrades, and may be more significant for equity prices than for bond prices. – Second, the hardwiring of regulatory and market rules, bond covenants, investment guidelines, etc., to ratings may influence market dynamics, and potentially lead to or magnify threshold effects. The more that different market participants adopt identical ratings-linked rules, or are subject to similar ratings-linked regulations, the more “spiky” the reaction to a credit event is likely to be. This reaction may include, in some cases, the emergence of severe liquidity pressures. Efforts have recently been made, notably with support from the rating agencies themselves, to encourage a more systematic disclosure of rating triggers and to renegotiate and smooth the possibly more destabilising forms of rating triggers. However, the lack of a clear disclosure regime makes it difficult to assess how far this process has evolved. Questions also remain as to the extent to which ratings-based criteria introduce a fundamentally new element into market behaviour, or, conversely, the extent to which they are simply a va riant of more traditional contractual covenants. Rating agencies strive to provide credit assessments that remain broadly stable through the course of the business cycle (rating “through the cycle”). Agencies and other analysts frequently contrast the fundamental credit analysis on which ratings are based with market sentiment — measured for example by bond spreads — which is arguably subject to more short-term influences. Agencies are adamant that they do not directly incorporate market sentiment into ratings (although they may use market prices as a diagnostic tool). On the contrary, they make every effort to exclude transient market sentiment. However, as reliance on ratings grows, CRAs are being increasingly expected to satisfy a widening range of constituencies, with different, and even sometimes conflicting, interests: issuers and “traditional” asset managers will look for more than a simple statement of near-term probability of loss, and will stress the need for ratings to exhibit some degree of stability over time. On the other hand, mark-to-market traders, active investors and risk managers may seek more frequent indications of credit changes. Hence, in the wake of major bankruptcies with heightened credit stress, rating agencies have been under considerable pressure to provide higher-frequency readings of credit status, without loss of quality. So far, they have responded to this challenge largely by adding more products to their traditional range, but also through modifications in the rating process. The rating process and the range of products offered by rating agencies have thus evolved over time, with, for instance, an increasing emphasis on the analysis of liquidity risks, a new focus on the hidden liabilities of companies and an increased use of market-based tools. It is too early, however, to judge whether these changes should simply be regarded as a refinement of the agencies’ traditional methodology or whether they suggest a more fundamental shift in the approach to credit risk measurement. For the same reason, it is not possible to draw any firm conclusions about changes in the effects of credit ratings on market dynamics.

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Aplysina aerophoba (Nardo, 1833) (Porifera, Demospongiae): an unexpected miniaturised growth form from the tidal zone of Mediterranean caves: morphology and DNA barcoding

In the Mediterranean Sea, the two sponges of the genus Aplysina (A. aerophoba and A. cavernicola) are identified on the basis of their external morphology and the environment in which they live. During a research program on the sponge fauna in semi-submerged caves of the Italian coasts, we have sampled an abundant very small yellow sponge, often living in the tidal zone, which were attributed to the genus Aplysina. Failing to assign the samples to a species through classical taxonomic methodologies (growth form and skeleton arrangement) and for the particular environment where this sponge lives, we have decided to use the COI analysis to solve the taxonomic problem offered by these miniaturized specimens. The analysis indicated that, in spite of the morphological differences, they belong to A. aerophoba. During old detailed surveys, conducted in the '60 years in some of the studied caves, this species was not recorded. It is possible that its abundant presence is related to the modifications occurred in the Mediterranean sponge communities occurred in the last decades in relation to global warming

Spaces of Memory

In the last decade, museums, memorials and monuments have become the battlefield for competing and conflicting visions of the past and the hegemonic or counter memories of the so-called “difficult heritage” or “traumatic heritage”. Far from being mere spaces of musealization that freeze and fix dominant narratives of the past, spaces of memory are increasingly turning into sites of negotiations and reconfigurations of meaning in which social and political identities are debated, strengthened, or weakened in reference to the traumatic experiences of the past which they “represent”. Yet, what does it mean to spatially represent a (traumatic) memory, and what is a space of memory? In expanding and, simultaneously, problematizing Pierre Nora’s (Nora 1996) category of lieu de mémoire, the way we think of spaces of memory aims at an in-depth examination of the peculiar yet specific ways of re-thinking the nexus between space and memory: how do we elaborate, activate, and make visible spaces for memory? This question points to the dynamic construction that underlines the production and connection of spatiality and memory, as well as to the coexistence of a plurality of meanings and experiences that characterize spaces of memory

Local Amplification of Platelet Function by 8-Epi Prostaglandin F2α Is Not Mediated by Thromboxane Receptor Isoforms

8-epi-Prostaglandin (PG) F2alpha may be formed by cyclooxygenases 1 and 2 or by a free radical catalyzed process as an isoprostane. Concentrations of 8-epi-PGF2alpha in the range 1 nM to 1 microM induce a dose-dependent increase in platelet shape change, in calcium release from intracellular stores [Ca2+]iand in inositol phosphates; it also causes irreversible platelet aggregation, dependent on thromboxane generation, when incubated with subthreshold concentrations of ADP, thrombin, collagen, and arachidonic acid. Much higher concentrations of 8-epi-PGF2alpha (10-20 microM) alone induce weak, reversible aggregation. Although these effects are prevented by pharmacological thromboxane receptor antagonists, they are unlikely to be mediated by thromboxane receptors. Thus, 8-epi-PGF2alpha does not compete for binding at the stably expressed placental or endothelial isoforms of the thromboxane receptor or for binding of thromboxane ligands to human platelets. Furthermore, the response to 8-epi PGF2alpha exhibits structural specificity versus 8-epi PGF3alpha and PGF2alpha. Concentrations in the range that evoke its effects on platelets do not desensitize the aggregation response stimulated by thromboxane or PGH2 analogs. Unlike primary prostaglandins, which are rapidly metabolized to inactive products, 8-epi PGF2alpha circulates in plasma. However, the systemic concentrations found in healthy volunteers (median 48 pmol/liter) and in patients with hepatic cirrhosis (median 147 pmol/liter), a syndrome of oxidant stress in vivo, fall well below those which modulate platelet function. 8-Epi PGF2alpha may amplify the response to platelet agonists in syndromes where oxidant stress and platelet activation coincide. Despite blockade by thromboxane antagonists, 8-epi PGF2alpha does not activate either of the thromboxane receptor isoforms described in platelets. Activation of a distinct receptor would be consistent with the enzymatic formation of 8-epi PGF2alpha by cyclooxygenases. However, incidental activation of such a receptor by systemic concentrations of 8-epi PGF2alpha is unlikely to occur, even in syndromes of excessive free radical generation in vivo

Sildenafil as a therapeutic option for digital ischemic ulceration: case report.

We report the case of a 37-year-old woman who developed critical upper limb ischemia caused by a cervical rib. Because the malformation was initially undiagnosed, a vascular bypass was performed, and failure occurred. Following a 6-month therapy with sildenafil, revascularization of the arm was successful and amputation was avoided. A 6-year follow-up shows a rich collateral network at the compression site and normal values of digital plethysmography. Because hand surgeons often see patients with digital ulcerations and other manifestations of peripheral vascular pathology, therapy of ischemia with sildenafil could be an effective treatment option in patients not responding to classic drugs

Dietary intake of calcium, phosphorus and magnesium in a Northern Italian community.

Minerals are essential micronutrients for growth, development, and maintenance of healthy tissues, the long term insufficient intake of minerals may lead to bone demineralization and often requires the use of food supplements. The ratios of certain minerals intake like calcium and phosphorus are also proved to can affect the bioavailability of calcium and even lead to adverse health consequence. This study was designed to explore the dietary sources of calcium (Ca), phosphorus (P), and magnesium (Mg) and the ratios between different minerals (Ca/P). We measured the content of these elements in foods composing typical Italian diet using inductively coupled plasma-mass spectrometry and we estimated their daily dietary intakes assessing through a semi-quantitative food frequency questionnaire specifically developed within the European Prospective Investigation into Cancer and Nutrition (EPIC) study in a Northern Italian Community. In 890 analyzed food samples the main contributors to calcium are milk and dietary products, dry fruits, legumes and sweet products. Important sources of phosphorus are represented by dry fruits, legumes, milk and dairy products and meat. While dry fruits, legumes, cereals and fish symbolized the most important sources for magnesium. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 786.3 (592.2-1062.7) μg/day for calcium; 1291.7 (1017.2-1591.4) mg/day for phosphorus and 323.2 (260.3-396.6) mg/day for magnesium. The calcium-phosphorus (Ca/P) ratio in this study was 0.63 (0.52-0.73). These values are in agreement with those suggested by European and International recommended intake for adult population, with the exception of calcium which is slightly lower than recommended values and suggest that this population does not present nutritional deficiencies requiring any supplementation

Assessment of food contamination and dietary intake of lead and thallium in a Northern Italy population.

Lead and thallium are heavy metals released in the environment after natural and anthropogenic activities. Food and water intake are the major sources of human exposure to these elements. In this study, we aimed at characterizing lead and thallium content in foods consumed in Northern Italy population, in order to estimate the dietary intake of these metals. To do that we bought food samples in markets and groceries collected during the period from October 2016 to February 2017 in the Emilia Romagna region, and we measured their element content using inductively coupled plasma-mass spectrometry. Finally, after assessing dietary habits of an Emilia-Romagna community by using a validated food frequency questionnaire, we eventually estimated dietary intake of these metals in that community. In the 890 analyzed food samples, the highest lead contamination levels were found in seafood, vegetables, sweets and beverages. The estimated dietary intake of lead was 5.758 (interquartile range-IQR: 4.547-7.427) µg/day, corresponding to 0.089 (IQR: 0.069-0.113) µg/kg of body weight per day, with cereals, beverages and vegetables as major contributors. About thallium, one third of specimens showed very low levels below the limit of detection, with the highest contamination levels in vegetables, dry fruits and sweets. The dietary intake of thallium was 0.236 (IQR: 0.183-0.312) µg/day, mainly from vegetables, beverages, cereals and sweets. In conclusion, our study provides an estimation of lead and thallium intake in a Northern Italian community and shows a generally low exposure levels from dietary sources