Observation of Rayleigh-Lamb waves generated by the 2022 Hunga-Tonga volcanic eruption with the POLA detectors at Ny-Ålesund.

The eruption of the Hunga-Tonga volcano in the South Pacific Ocean on January 15, 2022, at about 4:15 UTC, generated a violent explosion, which created atmospheric pressure disturbances in the form of Rayleigh-Lamb waves detected all over the globe. Here we discuss the observation of the Hunga-Tonga shock-wave performed at the Ny-Ålesund Research Station on the Spitsbergen island, by the detectors of the PolarquEEEst experiment and their ancillary sensors. Online pressure data as well as the results of dedicated offline analysis are presented and discussed in details. Results include wave arrival times, wave amplitude measurements and wave velocity calculation. We observed five passages of the shock wave with a significance larger than 3 [Formula: see text] and an amplitude up to 1 hPa. The average propagation velocity resulted to be (308 ± 0.6) m/s. Possible effects of the atmospheric pressure variation associated with the shock-wave multiple passages on the cosmic-ray rate at ground level are also investigated. We did not find any significant evidence of this effect.

Large-Area SiPM Pixels (LASiPs): A cost-effective solution towards compact large SPECT cameras.

Single Photon Emission Computed Tomography (SPECT) scanners based on photomultiplier tubes (PMTs) are still largely employed in the clinical environment. A standard camera for full-body SPECT employs ~50-100 PMTs of 4-8 cm diameter and is shielded by a thick layer of lead, becoming a heavy and bulky system that can weight a few hundred kilograms. The volume, weight and cost of a camera can be significantly reduced if the PMTs are replaced by silicon photomultipliers (SiPMs). The main obstacle to use SiPMs in full-body SPECT is the limited size of their sensitive area. A few thousand channels would be needed to fill a camera if using the largest commercially-available SiPMs of 6 × 6 mm2. As a solution, we propose to use Large-Area SiPM Pixels (LASiPs), built by summing individual currents of several SiPMs into a single output. We developed a LASiP prototype that has a sensitive area 8 times larger than a 6 × 6 mm2 SiPM. We built a proof-of-concept micro-camera consisting of a 40 × 40 × 8 mm3 NaI(Tl) crystal coupled to 4 LASiPs. We evaluated its performance in a central region of 15×15 mm2, where we were able to reconstruct images of a 99mTc capillary with an intrinsic spatial resolution of ~2 mm and an energy resolution of ~11.6% at 140 keV. We used these measurements to validate Geant4 simulations of the system. This can be extended to simulate a larger camera with more and larger pixels, which could be used to optimize the implementation of LASiPs in large SPECT cameras. We provide some guidelines towards this implementation.

Protein kinase Cθ is required for cardiomyocyte survival and cardiac remodeling.

Protein kinase Cs (PKCs) constitute a family of serine/threonine kinases, which has distinguished and specific roles in regulating cardiac responses, including those associated with heart failure. We found that the PKCθ isoform is expressed at considerable levels in the cardiac muscle in mouse, and that it is rapidly activated after pressure overload. To investigate the role of PKCθ in cardiac remodeling, we used PKCθ(-/-) mice. In vivo analyses of PKCθ(-/-) hearts showed that the lack of PKCθ expression leads to left ventricular dilation and reduced function. Histological analyses showed a reduction in the number of cardiomyocytes, combined with hypertrophy of the remaining cardiomyocytes, cardiac fibrosis, myofibroblast hyper-proliferation and matrix deposition. We also observed p38 and JunK activation, known to promote cell death in response to stress, combined with upregulation of the fetal pattern of gene expression, considered to be a feature of the hemodynamically or metabolically stressed heart. In keeping with these observations, cultured PKCθ(-/-) cardiomyocytes were less viable than wild-type cardiomyocytes, and, unlike wild-type cardiomyocytes, underwent programmed cell death upon stimulation with α1-adrenergic agonists and hypoxia. Taken together, these results show that PKCθ maintains the correct structure and function of the heart by preventing cardiomyocyte cell death in response to work demand and to neuro-hormonal signals, to which heart cells are continuously exposed.

Bridging science and health policy in cardiovascular disease: focus on lipid management: A Report from a Session held during the 7th International Symposium on Multiple Risk Factors in Cardiovascular Diseases: Prevention and Intervention--Health Policy, in Venice, Italy, on 25 October, 2008.

In Europe, cardiovascular disease (CVD) represents the main cause of morbidity and mortality, costing countries euro 190 billion yearly (2006). CVD prevention remains unsatisfactory across Europe largely due to poor control of CVD risk factors (RFs), growing incidence of obesity and diabetes, and sedentary lifestyle/poor dietary habits. Hypercholesterolaemia is a proven CVD RF, and LDL-C lowering slows atherosclerotic progression and reduces major coronary events. Lipid-lowering therapy is cost-effective, and intensive treatment of high-risk patients further improves cost effectiveness. In Italy, models indicate that improved cholesterol management translates into potential yearly savings of euro 2.9-4 billion. Identifying and eliminating legislative and administrative barriers is essential to providing optimal lipid care to high-risk patients. Public health and government policy can influence clinical practice rapidly, and guideline endorsement via national health policy may reduce the CVD burden and change physician and patient behaviour. Action to reduce CVD burden should ideally include the integration of strategies to lower the incidence of major CV events, improvement in total CV risk estimation, database monitoring of CVD trends, and development of population educational initiatives on CVD prevention. Failure to bridge the gap between science and health policy, particularly in relation to lipid management, could result in missed opportunities to reverse the burgeoning epidemic of CVD in Europe.

The Lorenzini Foundation in a changing scenario of patient management.

The loss of life, disability, and economic burden attributed to cardiovascular disease (CVD) in Europe has created an urgent need for all stakeholders in CVD prevention to partner together to address the barriers in local health policy and produce effective programs in individual and population risk reduction and rational use of health services. Countries have a legal and moral obligation to achieve the highest standard of CV health care for citizens and to improve national health care systems accordingly. As part of a vision for future potential opportunities in CVD prevention, the Lorenzini Foundation would like to raise awareness of several key areas among the European authorities: Integration of interventions aimed at several risk factors within an individual country's health care system; implementation of a comprehensive approach combining policy development, capacity building, partnership and information support at all levels; promotion of transversal health policies, including coordinated action outside of the health sector to address major determinants of ill health; a combination of health policy and high-risk strategies to link health promotion, public health services, primary care, and hospital care; and, finally, reduction in ethnic, cultural, socioeconomic, and gender inequalities to multiple risk factor management among and within countries through use of cost-effective medications and medical technologies.

Bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, reprograms myogenic cells to acquire a pluripotent, circulating phenotype.

Satellite cells are the main source of myogenic progenitors in postnatal skeletal muscle, but their use in cell therapy for muscle disorders is limited because these cells cannot be delivered through circulation and they are rapidly exhausted in severe myopathies. The search for alternative donor cells is ongoing, but none of the candidates so far show all the features required for successful colonization and repair of diseased muscle. In this study, we show that bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, induces myogenic cells to acquire a gene expression profile and a differentiation potential consistent with the phenotype of a circulating precursors, while maintaining their myogenic potential. These effects are mediated, at least in part, by NF-kappaB activation through the Tyr42-IkappaB-alpha phosphorylation, as shown by the expression of the dominant negative mutant form of the p50 NF-kappaB subunit. Moreover, when bisperoxovanadium-treated cells are injected into the femoral artery of alpha-sarcoglican null dystrophic mice, they are able to circulate and to reach muscle tissue; importantly, they contribute to muscle regeneration, as shown by the expression of alpha-sarcoglican in some fibers. Our observations indicate that bisperoxovanadium, or similar compounds, may prove very valuable to obtain and to expand, from committed cells, multipotent cell populations suitable for gene-cell therapy applications and may help to understand the molecular basis of genome reprogramming and "stem-ness."

Rosuvastatin displays anti-atherothrombotic and anti-inflammatory properties in apoE-deficient mice.

Inflammation contributes importantly to all stages of atherosclerosis, including the onset of acute thrombotic complications. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. Moreover, statins have been shown to possess several pleiotropic properties independent of cholesterol lowering in experimental settings. Based on these premises, we investigated the anti-inflammatory and anti-atherothrombotic properties of rosuvastatin in vivo, testing its effect on cholesterol and monocyte accumulation, and on adhesion molecules and tissue factor (TF) expression. ApoE-deficient female mice were fed a cholesterol-rich diet containing rosuvastatin (0, 1, 2 or 10 mg kg(-1)d(-1)) for 12 weeks. Treatment with rosuvastatin did not significantly affect either body weight gain or plasma total cholesterol (C) and triglyceride levels. However, rosuvastatin treatment dose-dependently reduced ICAM-1 expression in the aortic valves (V) (up to 40% inhibition, p<0.05) and in the proximal segment of the ascending aorta (AA) (-50%, p<0.001). Similarly, rosuvastatin inhibited VCAM-1 expression in the V (-40%) and in the AA (-35%, p<0.05). Moreover, there was a reduced accumulation of macrophages in the V in a dose-dependent and statistically significant manner (-45%, p<0.01). These anti-inflammatory effects were reflected in a reduction of cholesterol deposition in the entire aorta, both in the free and in the esterified form. Finally, the expression of tissue factor, the most potent pro-thrombogenic agent, was consistently reduced in AA by rosuvastatin treatment (-71%, p<0.001). Altogether, these data demonstrate that rosuvastatin has anti-inflammatory and anti-atherothrombotic activities in apoE-deficient mice that could translate in a beneficial effect on atherogenesis.

Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date.

Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines.

Lipid-modified proteins as biomarkers for cardiovascular disease: a review.

Lipid-modified proteins are classified based on the identity of the attached lipid, a post- or co-translational modification required for their biological function. At least five different lipid modifications of cysteines, glycines and other residues on the COOH- and NH(2)-terminal domains have been described. Cysteine residues may be modified by the addition of a 16-carbon saturated fatty acyl group by a labile thioester bond (palmitoylation) or by prenylation processes that catalyze the formation of thioether bond with mevalonate derived isoprenoids, farnesol and geranylgeraniol. The NH(2)-terminal glycine residues may undergo a quite distinct process involving the formation of an amide bond with a 14-carbon saturated acyl group (myristoylation), while glycine residues in the COOH-terminal may be covalently attached with a cholesterol moiety by an ester bond. Finally, cell surface proteins can be anchored to the membrane through the addition of glycosylphosphatidylinositol moiety. Several lines of evidence suggest that lipid-modified proteins are directly involved in different steps of the development of lesions of atherosclerosis, from leukocyte recruitment to plaque rupture, and their expression or lipid modification are likely altered during atherogenesis. This review will briefly summarize the different enzymatic pathways of lipid modification and propose a series of lipid-modified proteins that can be used as biomarkers for cardiovascular disease.

Multiexponential T2-relaxation analysis in cerebrally damaged rats in the absence and presence of a gadolinium contrast agent.

An analysis of the multiexponential relaxation of transverse nuclear magnetization with and without a gadolinium-based paramagnetic contrast agent in spontaneously hypertensive stroke-prone rats (SHR-SP) and in the rat model of ischemia induced by middle cerebral artery occlusion is described. From the multiexponential relaxation, the presence of two T(2) relaxation times in the range of 0.03-0.5 s, T(2A) (shortest) and T(2B) (longest), with very different relative weights (respectively, A and B), is evidenced. In our models of cerebral damage, the changes in A and B were more evident than those in T(2A) and T(2B). The two T(2) values were interpreted as belonging to water molecules in two different compartments; therefore, the difference between the damaged and normal regions revealed by means of standard T(2)-weighted images is suggested to be due to a different water distribution in the two compartments, rather than different T(2)'s. The T(2) relaxation in the SHR-SP stroke model is analyzed for the first time using a multiexponential method. The power of a detailed analysis of MRI relaxation times is confirmed by the correspondence between the revealed changes in T(2A), T(2B), A and B, and the known T(2)W and DWI results about blood-brain barrier functionality.

Lipid and non-lipid effects of statins.

Long- and short-term trials with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have demonstrated significant reductions in cardiovascular events in patients with and without history of coronary heart disease. Statins are well-established low-density lipoprotein (LDL)-lowering agents, but their clinical benefit is believed to result from a number of lipid and non-lipid effects beyond LDL lowering, including a rise in plasma high-density lipoprotein levels. Beyond improving the lipid profile, statins have additional non-lipid effects including benefit on endothelial function, inflammatory mediators, intima-media thickening, prothombotic factors that ultimately result in plaque stabilization. These effects arise through the inhibition of several mevalonate-derived metabolites other than cholesterol itself, which are involved in the control of different cellular functions. Although statins represent the gold standard in the prevention and treatment of coronary heart disease, combination therapy with other lipid-lowering drugs, as well as novel therapeutic indications, may increase their therapeutic potential.

Phytoestrogens: pharmacological and therapeutic perspectives.

Phytoestrogens exert different estrogen receptor-dependent and -independent pharmacological actions. They share with estrogens several structural features and show greater affinity for the newly described estrogen receptor-beta. Many hope that phytoestrogens can exert the cardioprotective, anti-osteoporotic and other beneficial effects of the estrogens used in hormone replacement therapy in postmenopausal women without adversely affecting the risk of thrombosis and the incidence of breast and uterine cancers. Although there are many positive indications that phytoestrogens can fulfil this role, it remains to be proven: controlled interventional studies are lacking, and many questions remain unanswered. This review analyzes, on the basis of available experimental and epidemiological studies, the pros and cons of phytoestrogen use and describes the potential tissue targets and mechanisms of action of phytoestrogens.

[Opinions and attitudes of youngsters about sexually transmitted diseases]. / Cosa pensano i giovani delle malattie sessualmente trasmesse (Indagine conoscitiva su 1.085 studenti valsesiani).

A group of 1.085 students (582 M, 503 F) attending high school (742) and nursing school (343) filled in an anonymous questionnaire on their sexual habits and their knowledge of contraception and sexually transmitted diseases. Overall, 57% of the study population had already a complete sexual intercourse at a mean age of 16,4 (SD +/- 1,8). 74% had 1-3 sexual partners, whereas 28% had more than 3. All students affirmed that it was possible to prevent sexually transmitted diseases and 92,6% indicated correct methods. However 10% of students did not know that AIDS is transmitted sexually as 47% hepatitis B. The responses made by nursing students were more correct that those of high school students.

Safety of HMG-CoA reductase inhibitors: focus on atorvastatin.

Statins effectively lower LDL-cholesterol and some members of this class have been shown to reduce the risk of major cardiovascular events and total mortality in patients with or at risk for coronary heart disease. Statins are in general well tolerated. Withdrawal rates related to adverse events are low (< or =3%). The most common adverse events are mild gastrointestinal symptoms. Elevated serum transaminase levels occur infrequently (< or = 1.5%). These are generally asymptomatic, reversible and rarely require drug withdrawal. Statins do not cause adverse endocrine effects, do not alter glycemic control in diabetic patients, and do not increase cancer risk. Dose-related myopathy and/or rhabdomyolysis also occurs very rarely, although the risk is increased by concomitant administration of cyclosporine, niacin, fibrates, or by CYP3A4 isoenzyme inhibitors (e.g. erythromycin, systemic azole antifungal agents etc.) with statins metabolized by this isoenzyme. The pharmacokinetics of the individual statin should be considered in patients receiving polypharmacological treatments, to minimize the risk of unfavorable drug interactions. Atorvastatin is well tolerated in long-term treatment of dyslipidemia and is characterized by a safety profile similar to the other available statins.

Acute-phase proteins before cerebral ischemia in stroke-prone rats: identification by proteomics.

BACKGROUND AND PURPOSE: A high degree of proteinuria has been reported in stroke-prone spontaneously hypertensive rats (SHRSP). We studied the effect of salt loading on the detailed protein pattern of serum and urine in 3 rat strains: Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbred animal model for a complex form of cerebrovascular disorder resembling the human disease. METHODS: Rats were given a permissive diet and received 1% NaCl in drinking water. The protein pattern in body fluids was assessed over time by 2-dimensional electrophoretic analysis. Brain alterations were monitored by MRI and histology. RESULTS: Several proteins were excreted in urine after weeks of treatment and in advance of stroke: transferrin, hemopexin, albumin, alpha(2)-HS-glycoprotein, kallikrein-binding protein, alpha(1)-antitrypsin, Gc-globulin, and transthyretin. Markers of an inflammatory response, including very high levels of thiostatin, were detected in the serum of SHRSP at least 4 weeks before a stroke occurred. CONCLUSIONS: In SHRSP subjected to salt loading, an atypical inflammatory condition and widespread alterations of vascular permeability developed before the appearance of anomalous features in the brain detected by MRI. Urinary concentrations of each of the excreted serum proteins correlated positively with time before stroke occurred.

Direct effects of estrogen on the vessel wall.

The understanding of the biological effects of estrogen on the vessel wall has improved dramatically since the discovery of estrogen receptors (ERs). Most, but not all estrogen-mediated effects in blood vessels are thought to be mediated by ERs. Two major ER subclasses have been characterized so far: the ERalpha and the more recently described ERbeta. This review will primarily focus on a new perspective that highlights ERs as essential mediators of the vascular effects of estrogen. In view of the rising research interest in this area, it can be also expected that tissue- and ER subclass-selective agonists and antagonists will be developed over the next few years, thus providing invaluable tools for pharmacological and clinical applications.

Lacidipine [correction of Lalsoacidipine] modulates the secretion of matrix metalloproteinase-9 by human macrophages.

Activated macrophages within the arterial wall secrete matrix-degrading metalloproteinases (MMPs) that weaken the atherosclerotic plaque and contribute to its fissuration. Preclinical studies have shown that calcium antagonists may reduce atherogenesis in the arterial wall. In the present study we evaluated the effect of lacidipine on 92-kDa gelatinase B (MMP-9) expression in human macrophages in cultures. Cells were treated for 24 h with lacidipine and the conditioned media were analyzed. Lacidipine (1-20 microM) significantly reduced, in a dose-dependent manner, MMP-9 potential gelatinolytic capacity up to 50%. When MMP-9 expression was stimulated by treatment with phorbol esters or tumor necrosis factor-alpha, lacidipine was able to inhibit this enhanced gelatinolytic capacity up to 50 and 60%, respectively. Western blot analysis and enzyme-linked immunosorbent assay showed a reduction of MMP-9 protein actually released by cells. The addition of lacidipine in the incubation media determined no significant variation in Ca(2+) concentration. The drug did not affect MMP-9 mRNA levels, but it effectively reduced the amount of both active and total free MMP-9 secreted by human macrophages. Lacidipine reduced also the secretion of the tissue inhibitor of metalloproteinase-1 (TIMP-1); however we observed an overall reduction of the gelatinolytic activity of the cells. Finally, peritoneal macrophages, obtained from mice treated with lacidipine, showed a reduced secretion of MMP-9. Together, our data indicate that lacidipine may potentially exert an antiatherosclerotic activity by modulating the secretion of MMP-9 by macrophages. This, in addition to the previously demonstrated inhibition of cholesterol esterification, may contribute to increase plaque stability.