Modeling the transport of Saharan dust toward the Mediterranean region: an important issue for its ecological implications

Airborne particulate matter (PM) is presently an environmental problem of primary concern, whose role in air quality, climatic and ecological issues is well recognized, though still a matter of extensive investigations (Intergovernmental Panel on Climate Change, 2007).It is of great scientific interest to detect sources of atmospheric particulate matter and quantify their influence on the global and local scales. Unfortunately, emissions are usually not directly available, while PM concentration time series are experimentally accessible, so that the problem often consists in "inverting" these data to determine the region of influence that caused the measured concentration. In this paper we are concerned with an alternative approach to inverse modeling based on backward trajectory analysis (BTA); this approach has the potential to overcome some limitations associated with traditional BTA.We apply this method to the analysis of PM time series from the Monte Cimone observatory, hereafter MCT, a high altitude station on the top of the Italian Northern Apennines, with the aim of estimate the contribution of Saharan dust transport on PM concentration levels registered in the Mediterranean region

GUCH POPULATION: CARDIOLOGIC AND SURGICAL DEMANDS

To evaluate the cardiologic and surgical demands of the GUCH population followed up in our Department, a retrospective analysis of 709 hospital admissions (HA) of 536 pts (mean age 34?16, range 16-79 years), carried out from 1997 to 2002, has been performed. In 293 pts the basic cardiopathy was simple (SC), in 158 of moderate complexity (MCC) and in 85 of great complexity (GCC). The reason for 169 HA was cardiac surgery and for 537 HA cardiologic issues. The overall HA/pt was 1.3 (1.1 in SC,1.3 in MCC, 2.1 in GCC). In 166 surgical pts, 171 operations were performed. First operations (n=105, 62%) were most commonly for atrial septal defect (n=50, 48%), aortic valve replacement(n=11,10%), ventricular septal defect (n=8, 8%). Reoperations (n=64, 38%) were divided among reintervention after corrective repair (n=45, 70%), further palliation (n=17, 26%), first palliation (n=2, 4%) and the most frequent were: Fontan operation (n=11, 17%), RV-PA conduit replacement (n=8, 12%), aortic valve replacement (n=6, 9%). The mean hospital stay was 19?17 days. Pleuro-pericardial effusion (n=32,18%), bleeding (n=11, 6%) and arrhythmias(n=11, 6%) were the most prevalent complications. Early mortality (n=7/171, 4%) was influenced by cyanosis (6 of 33,18% in cyanotic pts; 1 of 136, 2% in acyanotic, p<0,001) and by complexity of cardiopathy (n=6 of 43 GCC, 14%; n=1 of 72 MCC, 1%; 0 of 54 SC,0%, p<0.001) that was a risk factor also for more serious complications (20% in GCC, with respect of 9% in MCC, p<0,05 and 4% in SC, p<0.001). The principal reasons for 537 cardiologic HA in 432 pts, were: interventional procedures (n=209, 39%), diagnostic catheterisation (n=155, 29%), non invasive evaluation (n=95, 18%), arrhythmias (n=46, 10%). Closure of atrial septal discontinuity (n=167, 80%), patent ductus arteriosus (n=21, 10%), pulmonary valvuloplasty (n=8, 4%) and angioplasty of Coarctation (n=6, 3%), were more prevalent interventional procedures. In pts with GCC, heart failure and cyanosis were more commonly cause of HA than in MGC and SC (p<0.001). Despite the progress of pediatric cardiology and cardiac surgery, medical demands of GUCH remain numerous and complex throughout their lives. Therefore, it is extremely important to provide specialized surgical and cardiologic care for this complicated population

What do central counterparty default funds really cover? A network-based stress test answer

In recent years, an increased effort has been made to further the development of effective stress tests that can be used to quantify the resilience of financial institutions. Here, we propose a stress test methodology for central counterparties (CCPs) based on a network characterization of clearing members (CMs) that takes into account the propagation and amplification of financial distress through the network of bilateral exposures between CMs. We apply the proposed framework to the fixed-income asset class of Cassa di Compensazione e Garanzia (CC&amp;G), the CCP operating in Italy, whose cleared securities are mainly Italian government bonds. We consider two different scenarios where exogenous losses may be incurred: a distributed initial shock and a shock corresponding with the cover 2 regulatory requirement (entailing the simultaneous default of the two most exposed CMs). Network effects turn out to substantially increase the vulnerability of the CMs in both scenarios, though distress propagation is much more rapid in the latter case, where we note a large number of early triggered additional defaults. This shows that setting a default fund to cover insolvencies on a cover 2 basis alone may not be adequate for the taming of systemic events. Overall, our network-based stress test methodology represents a refined tool for calibrating conservative default fund amounts

Drospirenone increases endothelial nitric oxide synthesis via a combined action on progesterone and mineralocorticoid receptors

BACKGROUND: Progestins have actions on the cardiovascular system, which depend on the structure as well as on receptor binding characteristics. Drospirenone (DRSP) is a progestin that uniquely interferes with the signaling of the mineralocorticoid receptor (MR). Hormone therapy containing DRSP results in blood pressure reduction in hypertensive post-menopausal women. METHODS: We describe the effects of DRSP on endothelial nitric oxide (NO) synthesis and compare them with those of progesterone (P) and of medroxyprogesterone acetate (MPA). In addition, we herein tested the relevance of the anti-mineralocorticoid activity of DRSP for NO synthesis. RESULTS: DRSP results in rapid activation of the endothelial NO synthase (eNOS) through mitogen-activated protein kinases and phosphatidylinositol 3-kinase as well as in enhanced eNOS expression. These actions depend on P receptor. When the cells are exposed to aldosterone, a reduction of eNOS expression is found that is antagonized by DRSP. This action is not shared by P or MPA. In addition, DRSP does not interfere with the induction or activation of eNOS induced by estradiol, as opposed to MPA. CONCLUSIONS: DRSP acts on endothelial cells via a combined action through the P and MRs. These results help to interpret the anti-hypertensive effects of hormonal therapies containing DRSP

Gastrostomy and congenital anomalies - a European population-based study

OBJECTIVE: To report and compare the proportion of children with and without congenital anomalies undergoing gastrostomy for tube feeding in their first 5 years. METHODS: A European, population-based data-linkage cohort study (EUROlinkCAT). Children up to 5 years of age registered in nine EUROCAT registries (national and regional) in six countries and children without congenital anomalies (reference children) living in the same geographical areas were included. Data on hospitalisation and surgical procedures for all children were obtained by electronic linkage to hospital databases. RESULTS: The study included 91 504 EUROCAT children and 1 960 272 reference children. Overall, 1200 (1.3%, 95% CI 1.2% to 1.6%) EUROCAT children and 374 (0.016%, 95% CI 0.009% to 0.026%) reference children had a surgical code for gastrostomy within the first 5 years of life. There were geographical variations across Europe with higher rates in Northern Europe compared with Southern Europe. Around one in four children with Cornelia de Lange syndrome and Wolf-Hirschhorn syndrome had a gastrostomy. Among children with structural anomalies, those with oesophageal atresia had the highest proportion of gastrostomy (15.9%). CONCLUSIONS: This study including almost 2 million reference children in Europe found that only 0.016% of these children had a surgery code for gastrostomy before age 5 years. The children with congenital anomalies were on average 80 times more likely to need a gastrostomy before age 5 years than children without congenital anomalies. More than two-thirds of gastrostomy procedures performed within the first 5 years of life were in children with congenital anomalies

Hospital care in the first ten years of life of children with congenital anomalies in six European countries: Data from the EUROlinkCAT Cohort linkage study

Objective To quantify the hospital care for children born with a major congenital anomaly up to 10 years of age compared with children without a congenital anomaly.Design, setting and patients 79 591 children with congenital anomalies and 2 021 772 children without congenital anomalies born 1995–2014 in six European countries in seven regions covered by congenital anomaly registries were linked to inpatient electronic health records up to their 10th birthday.Main outcome measures Number of days in hospital and number of surgeries.Results During the first year of life among the seven regions, a median of 2.4% (IQR: 2.3, 3.2) of children with a congenital anomaly accounted for 18% (14, 24) of days in hospital and 63% (62, 76) of surgeries. Over the first 10 years of life, the percentages were 17% (15, 20) of days in hospital and 20% (19, 22) of surgeries. Children with congenital anomalies spent 8.8 (7.5, 9.9) times longer in hospital during their first year of life than children without anomalies (18 days compared with 2 days) and 5 (4.1–6.1) times longer aged, 5–9 (0.5 vs 0.1 days). In the first year of life, children with gastrointestinal anomalies spent 40 times longer and those with severe heart anomalies 20 times longer in hospital reducing to over 5 times longer when aged 5–9.Conclusions Children with a congenital anomaly consume a significant proportion of hospital care resources. Priority should be given to public health primary prevention measures to reduce the risk of congenital anomalies

Extra-Nuclear Signalling of Estrogen Receptor to Breast Cancer Cytoskeletal Remodelling, Migration and Invasion

BACKGROUND: Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted. METHODOLOGY/PRINCIPAL FINDINGS: In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER alpha with the G protein G alpha(13), which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane. CONCLUSIONS/SIGNIFICANCE: These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G alpha(13)/RhoA/ROCK/moesin signaling cascade as a target of ER alpha in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions

Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion

<p>Abstract</p> <p>Background</p> <p>Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted.</p> <p>Methods</p> <p>We investigated the effects of progesterone (P), medroxyprogesterone acetate (MPA), drospirenone (DRSP) and nestorone (NES) alone or with 17β-estradiol (E2) on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling.</p> <p>Results</p> <p>Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells.</p> <p>Conclusion</p> <p>These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.</p

Differential Signal Transduction of Progesterone and Medroxyprogesterone Acetate in Human Endothelial Cells

AbstractThe conjugated equine estrogens-only arm of the Women's Health Initiative trial, showing a trend toward protection from heart disease as opposed to women receiving also medroxyprogesterone acetate (MPA), strengthens the debate on the cardiovascular effects of progestins. We compared the effects of progesterone (P) or MPA on the synthesis of nitric oxide and on the expression of leukocyte adhesion molecules, characterizing the signaling events recruited by these compounds. Although P significantly increases nitric oxide synthesis via transcriptional and nontranscriptional mechanisms, MPA is devoid of such effects. Moreover, when used together with physiological estradiol (E2) concentrations, P potentiates E2 effects, whereas MPA impairs E2 signaling. These findings are observed both in isolated human endothelial cells as well as in vivo, in ovariectomized rat aortas. A marked difference in the recruitment of MAPK and phosphatidylinositol-3 kinase explains the divergent effects of the two gestagens. In addition, both P and MPA decrease the adhesiveness of endothelial cells for leukocytes when given alone or with estrogen. MPA is more potent than P in inhibiting the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. However, when administered together with physiological amounts of glucocorticoids, MPA (which also binds glucocorticoid receptor) markedly interferes with the hydrocortisone-dependent stabilization of the transcription factor nuclear factor κB and with the expression of adhesion molecules, acting as a partial glucocorticoid receptor antagonist. Our findings show significant differences in the signal transduction pathways recruited by P and MPA in endothelial cells, which may have relevant clinical implications