Lipotoxicity in Obesity and Coronary Artery Disease. Studies by PET, CT and MR

Lipotoxicity is a condition in which fatty acids (FAs) are not efficiently stored in adipose tissue and overflow to non-adipose tissue, causing organ damages. A defect of adipose tissue FA storage capability can be the primary culprit in the insulin resistance condition that characterizes many of the severe metabolic diseases that affect people nowadays. Obesity, in this regard, constitutes the gateway and risk factor of the major killers of modern society, such as cardiovascular disease and cancer. A deep understanding of the pathogenetic mechanisms that underlie obesity and the insulin resistance syndrome is a challenge for modern medicine. In the last twenty years of scientific research, FA metabolism and dysregulations have been the object of numerous studies. Development of more targeted and quantitative methodologies is required on one hand, to investigate and dissect organ metabolism, on the other hand to test the efficacy and mechanisms of action of novel drugs. The combination of functional and anatomical imaging is an answer to this need, since it provides more understanding and more information than we have ever had. The first purpose of this study was to investigate abnormalities of substrate organ metabolism, with special reference to the FA metabolism in obese drug-naïve subjects at an early stage of disease. Secondly, trimetazidine (TMZ), a metabolic drug supposed to inhibit FA oxidation (FAO), has been for the first time evaluated in obese subjects to test a whole body and organ metabolism improvement based on the hypothesis that FAO is increased at an early stage of the disease. A third objective was to investigate the relationship between ectopic fat accumulation surrounding heart and coronaries, and impaired myocardial perfusion in patients with risk of coronary artery disease (CAD). In the current study a new methodology has been developed with PET imaging with 11C-palmitate and compartmental modelling for the non-invasive in vivo study of liver FA metabolism, and a similar approach has been used to study FA metabolism in the skeletal muscle, the adipose tissue and the heart. The results of the different substudies point in the same direction. Obesity, at the an early stage, is associated with an impairment in the esterification of FAs in adipose tissue and skeletal muscle, which is accompanied by the upregulation in skeletal muscle, liver and heart FAO. The inability to store fat may initiate a cascade of events leading to FA oversupply to lean tissue, overload of the oxidative pathway, and accumulation of toxic lipid species and triglycerides, and it was paralleled by a proportional growth in insulin resistance. In subjects with CAD, the accumulation of ectopic fat inside the pericardium is associated with impaired myocardial perfusion, presumably via a paracrine/vasocrine effect. At the beginning of the disease, TMZ is not detrimental to health; on the contrary at the single organ level (heart, skeletal muscle and liver) it seems beneficial, while no relevant effects were found on adipose tissue function. Taken altogether these findings suggest that adipose tissue storage capability should be preserved, if it is not possible to prevent excessive fat intake in the first place.Siirretty Doriast

A Reliable Low-area Low-power PUF-based Key Generator

This paper reports the implementation of a lowarea low-power 128-bit PUF-based key generation module which exploits a novel Two-Stage IDentification (TSID) cell showing a higher noise immunity then a standard SRAM cell. In addition, the pre-selection technique introduced in [1] is applied. This results in a stable PUF response in spite of process and environmental variations thus requiring a low cost error correction algorithm in order to generate a reliable key. The adopted PUF cell array includes 1056 cells and shows a power consumption per bit of 4:2 W at 100MHz with an area per bit of 2:4 m2. In order to evaluate reliability and unpredictability of the generated key, extensive tests have been performed both on the raw PUF data and on the final key. The raw PUF data after pre-selection show a worst case intra-chip Hamming distance below 0:7%. After a total of more than 5 109 key reconstructions, no single fail has been detected

SKIN, INFLAMMATION AND SULFUROUS WATERS: WHAT IS KNOWN, WHAT IS BELIEVED

One could argue that balneotherapy and mud therapy would have not lasted 2,000 years or so If they were not effective. No doubt a long history cannot be taken per se as scientific proof of efficacy. Some empiricism is still present in the field: the concept of spa itself is quite confounding, whereas spring waters are used for leisure purposes but also for non-acute patient therapy and late phases of clinical recovery. These confounding elements ultimately feed the opinion of those who aprioristically reject any potential beneficial effect of balneotherapy: instead, it should at least generate questions that deserve scientific answers. Clinical practices sequentially integrating pharmacological therapy with those natural principles for which a sufficient scientific demonstration is available, would probably cut the costs of public health, generating widespread advantages for the community. Recently, it has become evident that mineral waters may have intrinsic pharmacological properties. Of the numerous salts dissolved in thermal waters that might show pharmacological properties, for certain hydrogen sulfide (H2S) contained in sulfurous waters is the one that has obtained greater scientific attention, to which should be added the extensive scientific effort recently dedicated to H2S as a cellular gasotransmitter, independently from its natural sources. Dermatology and cosmetics are among the most studied applications of sulfurous waters, around which, however, some empiricism still confounds opinions: we therefore considered that a state-of-the-art focus on this topic might be timely and useful for future studies

FDG uptake and walking ability

Includes bibliographical references.Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS). While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (4 men) and 8 sex matched healthy controls performed 15 minutes of treadmill walking at a self-selected pace, during which ≈ 322 MBq of the positron emission tomography glucose analogue [18F]-Fluorodeoxyglucose was injected. Immediately after the cessation of walking, participants underwent positron emission tomography imaging. Patients with MS had lower FDG uptake in ≈ 40% of the brain compared to the healthy controls (pFWE-corr > 0.001, qFDR-corr -0.75, P < 0.032). Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036), hippocampus (r = -0.72, P = 0.045), and calcarine sulcus (r = -0.77, P = 0.026). This data suggests that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.Published with support from the Colorado State University Libraries Open Access Research and Scholarship Fund

Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in OlderWomen Born from Normal Weight Mothers

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR) and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (p = 0.015). DHA/FA associated significantly with skeletal muscle glucose uptake (GU) (p = 0.031) and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value) in the OLM group only (p = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.Peer reviewe

Traumatic brain injury presenting with bilateral basal ganglia hemorrhage

Context Traumatic basal ganglia hemorrhage (TBGH) is a rare presentation of traumatic brain injury. Bilateral lesions are even rarer. Only twelve similar cases were previously published. Case report We report the case of a patient with bilateral TBGH. He was managed conservatively. Long-term follow-up disclosed a cognitive dysfunctions attributed to associated diffuse axonal injury. Acceleration and deceleration forces may have torn pallidum arterial branches determining hemorrhage. Conclusion Bilateral TBGH is an uncommon presentation of traumatic brain injury. Associated diffuse axonal injury worsens the outcome

The Challenge of Fostering Healthy Organizations: An Empirical Study on the Role of Workplace Relational Civility in Acceptance of Change and Well-Being

The world of work in the twenty-first century is characterized by globalization, instability, and unavoidable change. Organizations need to develop a positive relational environment in the workplace thereby enabling workers to enhance their personal resources in order to face with on-going changes in the sphere of work for promoting their well-being. Against this background, the aim of this research was to examine the relationship between workplace relational civility and both acceptance of change and well-being (hedonic well-being as well as eudaimonic well-being) beyond the effect of personality traits. The following instruments were administered to 261 Italian workers: the Ten Item Personality Inventory (TIPI), the Acceptance of Change Scale (ACS), the Satisfaction With Life Scale (SWLS), and the Meaningful Life Measure (MLM). The results of hierarchical regression analyses revealed that workplace relational civility explained a percentage of incremental variance beyond personality traits in relation to acceptance of change, life satisfaction, and meaning in life. These results underscore the positive relationship between workplace relational civility and acceptance of change, hedonic well-being, and eudaimonic well-being, offering new research and intervention opportunities to meet the challenge of fostering healthy organizations

False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam

At the bone marrow transplantation center of the San Martino Hospital ( Genoa), we observed an increase in the rate of patients with positive Platelia Aspergillus (PA; Bio-Rad) test results, from 10% ( 38 of 386 patients) in the period from January 1999 through January 2003 to 36% ( 21 of 59 patients) in the period from February 2003 through May 2003. Positivity was significantly (P < .001) associated with the administration of piperacillin-tazobactam (PT) (17 [74%] of 23 patients who received PT had positive results vs. 4 [11%] of 36 who did not receive PT). Multivariate analysis found administration of PT (&chi;2 = 34.7; P < .001) and underlying disease (chi(2) = 21.14; P < .001) to be associated with PA positivity. of 15 PT batches tested, 12 had positive PA test results.Natl Inst Canc Res, Infect Dis Unit, I-16132 Genoa, ItalyUniv Genoa, Genoa, ItalyNatl Inst Canc Res, Epidemiol Unit, I-16132 Genoa, ItalyOsped San Martino Genova, Dept Hematol, Genoa, ItalyUniversidade Federal de São Paulo, Infect Dis Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Infect Dis Unit, São Paulo, BrazilWeb of Scienc

Vertical distribution of aerosol optical properties in the Po Valley during the 2012 summer campaigns

Studying the vertical distribution of aerosol particle physical and chemical properties in the troposphere is essential to understand the relative importance of local emission processes vs. long-range transport for column-integrated aerosol properties (e.g. the aerosol optical depth, AOD, affecting regional climate) as well as for the aerosol burden and its impacts on air quality at the ground. The main objective of this paper is to investigate the transport of desert dust in the middle troposphere and its intrusion into the planetary boundary layer (PBL) over the Po Valley (Italy), a region considered one of the greatest European pollution hotspots for the frequency that particulate matter (PM) limit values are exceeded. Events of mineral aerosol uplift from local (soil) sources and phenomena of hygroscopic growth at the ground are also investigated, possibly affecting the PM concentration in the region as well. During the PEGASOS 2012 field campaign, an integrated observing–modelling system was set up based on near-surface measurements (particle concentration and chemistry), vertical profiling (backscatter coefficient profiles from lidar and radiosoundings) and Lagrangian air mass transport simulations by FLEXPART model. Measurements were taken at the San Pietro Capofiume supersite (44°39′ N, 11°37′ E; 11 m a.s.l.), located in a rural area relatively close to some major urban and industrial emissive areas in the Po Valley. Mt. Cimone (44°12′ N, 10°42′ E; 2165 m a.s.l.) WMO/GAW station observations are also included in the study to characterize regional-scale variability. Results show that, in the Po Valley, aerosol is detected mainly below 2000 m a.s.l. with a prevalent occurrence of non-depolarizing particles ( > 50 % throughout the campaign) and a vertical distribution modulated by the PBL daily evolution. Two intense events of mineral dust transport from northern Africa (19–21 and 29 June to 2 July) are observed, with layers advected mainly above 2000 m, but subsequently sinking and mixing in the PBL. As a consequence, a non-negligible occurrence of mineral dust is observed close to the ground (  ~7 % of occurrence during a 1-month campaign). The observations unambiguously show Saharan dust layers intruding the Po Valley mixing layer and directly affecting the aerosol concentrations near the surface. Finally, lidar observations also indicate strong variability in aerosol on shorter timescales (hourly). Firstly, these highlight events of hygroscopic growth of anthropogenic aerosol, visible as shallow layers of low depolarization near the ground. Such events are identified during early morning hours at high relative humidity (RH) conditions (RH  > 80 %). The process is observed concurrently with high PM1 nitrate concentration (up to 15 µg cm−3) and hence mainly explicable by deliquescence of fine anthropogenic particles, and during mineral dust intrusion episodes, when water condensation on dust particles could instead represent the dominant contribution. Secondly, lidar images show frequent events (mean daily occurrence of  ~ 22 % during the whole campaign) of rapid uplift of mineral depolarizing particles in afternoon–evening hours up to 2000 m a.s.l. height. The origin of such particles cannot be directly related to long-range transport events, being instead likely linked to processes of soil particle resuspension from agricultural lands