2D High-Temperature Superconductor Integration in Contact Printed Circuit Boards.

Inherent properties of superconducting Bi2Sr2CaCu2O8+x films, such as the high superconducting transition temperature Tc, efficient Josephson coupling between neighboring CuO layers, and fast quasiparticle relaxation dynamics, make them a promising platform for advances in quantum computing and communication technologies. However, preserving two-dimensional superconductivity during device fabrication is an outstanding experimental challenge because of the fast degradation of the superconducting properties of two-dimensional flakes when they are exposed to moisture, organic solvents, and heat. Herein, to realize superconducting devices utilizing two-dimensional (2D) superconducting films, we develop a novel fabrication technique relying on the cryogenic dry transfer of printable circuits embedded into a silicon nitride membrane. This approach separates the circuit fabrication stage requiring chemically reactive substances and ionizing physical processes from the creation of the thin superconducting structures. Apart from providing electrical contacts in a single transfer step, the membrane encapsulates the surface of the crystal, shielding it from the environment. The fabricated atomically thin Bi2Sr2CaCu2O8+x-based devices show a high superconducting transition temperature of Tc ≃ 91 K close to that of the bulk crystal and demonstrate stable superconducting properties.

Encapsulating High-Temperature Superconducting Twisted van der Waals Heterostructures Blocks Detrimental Effects of Disorder.

High-temperature cuprate superconductors based van der Waals (vdW) heterostructures hold high technological promise. One of the obstacles hindering their progress is the detrimental effect of disorder on the properties of the vdW-devices-based Josephson junctions (JJs). Here, a new method of fabricating twisted vdW heterostructures made of Bi2 Sr2 CuCa2 O8+δ , crucially improving the JJ characteristics and pushing them up to those of the intrinsic JJs in bulk samples, is reported. The method combines cryogenic stacking using a solvent-free stencil mask technique and covering the interface by insulating hexagonal boron nitride crystals. Despite the high-vacuum condition down to 10-6 mbar in the evaporation chamber, the interface appears to be protected from water molecules during the in situ metal deposition only when fully encapsulated. Comparing the current-voltage curves of encapsulated and unencapsulated interfaces, it is revealed that the encapsulated interfaces' characteristics are crucially improved, so that the corresponding JJs demonstrate high critical currents and sharpness of the superconducting transition comparable to those of the intrinsic JJs. Finally, it is shown that the encapsulated heterostructures are more stable over time.

High-Quality Ferromagnetic Josephson Junctions Based on Aluminum Electrodes.

Aluminum Josephson junctions are the building blocks for the realization of superconducting quantum bits. Attention has been also paid to hybrid ferromagnetic Josephson junctions, which allow switching between different magnetic states, making them interesting for applications such as cryogenic memories, single-photon detectors, and spintronics. In this paper, we report on the fabrication and characterization of high-quality ferromagnetic Josephson junctions based on aluminum technology. We employed an innovative fabrication process inspired by niobium-based technology, allowing us to obtain very high-quality hybrid aluminum Josephson junctions; thus, supporting the use of ferromagnetic Josephson junctions in advanced quantum circuits. The fabrication process is described in detail and the main DC transport properties at low temperatures (current-voltage characteristic, critical current as a function of the temperature, and the external magnetic field) are reported. Here, we illustrate in detail the fabrication process, as well as the main DC transport properties at low temperatures (current-voltage characteristic, critical current as a function of the temperature, and the external magnetic field).

The impact of the SARS-CoV-2 epidemic outbreak on the vascular access team operations after conversion to COVID-19 dedicated hospital.

BACKGROUND: On February 21 2020, in Schiavonia Hospital occurred the first death by COVID-19 in Italy and since this date SARS-CoV-2 caused more than 100,000 deaths in our country. Our hospital was immediately closed and re-opened after 15 days as a reference Covid Hospital. Among services involved in a process of destruction and rebirth there was also the Vascular Access Team. METHODS: We analyzed our Vascular Access Team activity comparing data from the first month (March) in which basically it did not work and data from the following month (April) in which we began to re-build the Team adapting it to the new reality. RESULTS: In all patients admitted to Intensive Care Unit a Centrally Inserted Central Catheter multilumen was placed, but in March only 5.5% of patients admitted to Medicine-Sub-intensive Unit had a catheter different from the short peripheral cannula while in April it was possible to guarantee a more suitable catheter 31.7% of patients admitted to Medicine-Sub-intensive Unit (p < 0.000). In April, compared to March, a significant higher number of Midline were implanted in Medicine-Sub-intensive Unit (36/139 vs 12/238 p < 0.000) where also a higher number of Centrally Inserted Central Catheter and Femoral Inserted Central Catheter were implanted (8/139 vs 1/238 p = 0.003). This change allowed us to implant more vascular accesses in Medicine-Sub-intensive Unit favoring Midline with a longer average duration. Only one patient with Midline developed a catheter vein thrombosis, and in only one patient the device was removed for suspected infection. CONCLUSIONS: The experience we gained will allow us to be more prepared in the future and our experience has highlighted that a structured Vascular Access Team is necessary to respond adequately to COVID-19 patients' needs, to ensure the effectiveness of the maneuver, to reduce complications and to avoid the waste of resources, always working in safe condition.

Rebirth in a COVID hospital: a point of view.

BACKGROUND: Since COVID-19 was declared a pandemic, governments have taken actions to limit the transmission of the virus such as lockdown measures and reorganization of the local Health System. Quarantine measures have influenced pregnant women's daily lives. The aim of this study was to understand the impact of the changes imposed by COVID-19 emergency on the well-being of pregnant women and how the transformation of Schiavonia Hospital into a dedicated COVID hospital affected their pregnancy experience. METHODS: A cross-sectional survey was conducted. Pregnant women who gave birth in Schiavonia Hospital during the period May-September 2020 have been included. The assessment examined clinical characteristics, attitudes in relation to the pandemic and how it affected birth plans, perception of information received, and attitudes regards giving birth in a COVID hospital. RESULTS: One hundred four women responded to the survey, with an enrolment rate of 58%. About the influence of COVID-19 pandemic, 51% of respondents reported changing some aspect of their lifestyle. The identification of Schiavonia Hospital as COVID hospital did not modify the trust in the facility and in the obstetrics ward for the 90% of women, in fact for the 85.6% it was the planned Birth Center since the beginning of pregnancy. The communication was complete and exhaustive for 82.7% of the respondents. CONCLUSIONS: Despite the COVID hospital transformation, the women who came to give birth at Schiavonia Birth Center rated the healthcare assistance received at high level, evidencing high affection for the structure and the healthcare workers.

Schiavonia Hospital response to COVID-19 outbreak: a first single-center experience.

INTRODUCTION: On 21 February 2020, Schiavonia Hospital (SH) detected the first 2 cases of COVID-19 in Veneto Region. As a result of the underlying concomitant spread of infection, SH had to rearrange the clinical services in terms of structural changes to the building, management of spaces, human resources and supplies, in order to continue providing optimal care to the patients and staff safety. The aim of this article is to describe how SH was able to adjust its services coping with the epidemiological stages of the pandemic. MATERIAL AND METHODS: Three periods can be identified; in each one the most important organizational modifications are analyzed (hospital activities, logistical changes, communication, surveillance on HCW). RESULTS: The first period, after initial cases' identification, was characterized by the hospital isolation. In the second period the hospital reopened and it was divided into two completely separated areas, named COVID-19 and COVID-free, to prevent intra-hospital contamination. The last period was characterized by the re-organization of the facility as the largest COVID Hospital in Veneto, catching exclusively COVID-19 patients from the surrounding areas. CONCLUSIONS: SH changed its organization three times in less than two months. From the point of view of the Medical Direction of the Hospital the challenges had been many but it allowed to consolidate an organizational model which could answer to health needs during the emergency situation.

Uniform doping of graphene close to the Dirac point by polymer-assisted assembly of molecular dopants.

Tuning the charge carrier density of two-dimensional (2D) materials by incorporating dopants into the crystal lattice is a challenging task. An attractive alternative is the surface transfer doping by adsorption of molecules on 2D crystals, which can lead to ordered molecular arrays. However, such systems, demonstrated in ultra-high vacuum conditions (UHV), are often unstable in ambient conditions. Here we show that air-stable doping of epitaxial graphene on SiC-achieved by spin-coating deposition of 2,3,5,6-tetrafluoro-tetracyano-quino-dimethane (F4TCNQ) incorporated in poly(methyl-methacrylate)-proceeds via the spontaneous accumulation of dopants at the graphene-polymer interface and by the formation of a charge-transfer complex that yields low-disorder, charge-neutral, large-area graphene with carrier mobilities ~70 000 cm2 V-1 s-1 at cryogenic temperatures. The assembly of dopants on 2D materials assisted by a polymer matrix, demonstrated by spin-coating wafer-scale substrates in ambient conditions, opens up a scalable technological route toward expanding the functionality of 2D materials.

Hyperhomocysteinemia is an independent predictor of sub-clinical carotid vascular damage in subjects with grade-1 hypertension.

Although the role of homocysteinemia (Hcy) as a coronary risk factor (RF) has been scaled down, hyper-Hcy and carotid vascular damage (CVD) are still considered as RFs for cerebrovascular events. In 276 grade-1 hypertensives (160 men and 116 women aged 59.6 ± 15.0 years) without known cardiovascular disease and having hyper-Hcy (≥15 µM/L), subclinical CVD was evaluated by ultrasonographic carotid-wall intima media thickness (IMT). Hcy was divided into quartiles and C667→T polymorphism codifying for methylenetetrahydrofolate reductase (MTHFR) was determined. According to the genotype, subjects were divided into CC (wild), CT (heterozygote) and TT (homozygous mutation). Differences between continuous variables were evaluated by analysis of variance, while gender specific odds ratio (OR) and 95 % confidence intervals (CI) of CVD (IMT >0.9 mm or plaque) were calculated by multivariate logistic regression analysis. Blood pressure (BP) values were not different across the quartiles of Hcy. In 46.4 % of cases, sub-clinical CVD was found, with a prevalence increasingly distributed in the quartiles of Hcy (31.9, 42, 52.2, 59.4 %, p < 0.001). Prevalence of TT allele of the MTHFR genotype was also significantly distributed in the quartiles of Hcy (13.6, 12.3, 23.5 and 50.6 %, p < 0.0001), whereas no relationship was found between genotype and CVD. The last quartile of Hcy predicted CVD (OR 1.32, CI 1.12-2.2, p = 0.02) independent of age (OR 1.23, CI 1.002-1.56, p = 0.0001), systolic BP (OR 1.52, CI 1.24-2.10), diabetes (OR 2.11, CI 1:32-2.88, p = 0.01) and smoking (OR 1.45, CI 1.14-1.98, p = 0.04). Adding gender did not modify the model. In hypertensives, Hcy values >36.5 µM/L independently predict CVD and in those who are also diabetic and smokers, Hcy assessment without MTHFR genotype should be recommended to obtain a better stratification of global cerebrovascular risk.

Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features.

Pheochromocytoma (PH) and paraganglioma (PG) are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and the sympathetic ganglia, respectively. Although are unusual cause of hypertension (HT) accounting for at most 0.1-0.2 % of cases, they may lead to severe and potentially lethal hypertensive crisis due to the effects of the released catecholamines. However, both PH and PG may be asymptomatic as ~30 % of subjects are normotensive or have orthostatic hypotension and in these cases the 24 h ambulatory blood pressure (BP) monitoring is an important toll to diagnose and treat HT. HT treatment may be difficult when PH or PG occurs in pregnancy or in the elderly subjects and in these cases a multidisciplinary team is required. When surgical excision is mandatory the perioperative management requires the administration of selective α1-adrenergic blocking agents (i.e., doxazosin, prazosin or terazosin) followed by a ß-adrenergic blockade (i.e., propranolol, atenolol). This latter should never be started first because blockade of vasodilatory peripheral ß-adrenergic receptors with unopposed α-adrenergic receptor stimulation can lead to a further elevation of BP. Although labetalol is traditionally considered the ideal agent due to its α- and ß-adrenergic antagonism, experimental studies do not support its use in this clinical setting. As second regimen, the administration of vasodilators as calcium channel blockers (i.e., nicardipine, nifedipine) may be required to control BP. Oral and sublingual short-acting nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. The latest evidences into the diagnosis and treatment of hypertensive crisis due to PH and PG are reviewed here.

Medical professional values and education: a survey on italian students of the medical doctor school in medicine and surgery.

BACKGROUND: The values such as participation/empathy, communication/sharing, self-awareness, moral integrity, sensitivity/trustfulness, commitment to ongoing professional development, and sense of duty linked to the practice of the medical professionalism were defined by various professional oaths. AIMS: The aim of this study was to evaluate how these values are considered by the students of the degree course of medicine. MATERIALS AND METHODS: Four hundred twenty three students (254 females, 169 males) taking part of the first, fourth, and fifth years of the degree course in medicine were asked to answer seven questions. Pearson's Chi-square, Wilcoxon rank sum test, and Kruskal-Wallis test were used for the statistical analysis. RESULTS: The survey showed a high level of knowledge and self-awareness about the values and skills of medical profession. In particular, the respect, accountability, and the professional skills of competence were considered fundamental in clinical practice. However, the students considered that these values not sufficiently present in their educational experience. CONCLUSIONS: Teaching methods should be harmonized with the contents and with the educational needs to ensure a more complex patient-based approach and the classical lectures of teachers should be more integrated with learning through experience methods.

Recurrent syncope in a hypertensive subject with vascular cognitive impairment and permanent pacemaker.

Syncope following permanent pacemaker (PM) implantation is a nightmare for electrophysiologists. We describe a case of daily recurrent syncope in an 84-year-old man having a dual-chamber pacemaker implanted for complete atrio-ventricular block occurred 4 years before the admission to our department. He had a history of arterial hypertension, parossistic atrial fibrillation, chronic obstructive pulmonary disease, stage-III chronic renal failure, mild vascular cognitive impairment and glaucoma. The initial work-up including electrocardiogram (ECG), repeated PM interrogations, Holter electrocardiogram, blood pressure measurement in orthostatic position, complete blood count, serum glycaemia, electrolytes and thyroid function tests showed normal findings. Syncope occurred in lying position and during 90° left clockwise neck rotation and was associated to pallor, sweating, tonic-clonic seizures and transient self-limited loss of consciousness lasting a few seconds. Electroencephalogram was normal. During continuous ECG monitoring, the right rotation of the head determined a ventricular asystolic pause lasting 9 seconds associated with loss of consciousness. Restoration of sinus rhythm was observed after bringing back the head in axis. The PM interrogation, performed during pacing failure, recorded low impedance of bipolar ventricular lead, suggesting a damage in lead insulation. It is likely that lead movements during clockwise neck rotation produced an intermittent short circuit that prevented sufficient energy delivery to the myocardium with a consequence of sudden loss of capture.

Intermittent Broca's aphasia management in an emergency unit: from theory to practice.

Although Broca's aphasia (BA) may mimic different neurological illness, its sudden onset often requires an emergency approach. In this paper, the management of a case of intermittent BA occurred in a young woman without history of neurological, cardiovascular and arrhythmic diseases is discussed. Diffusion-weighted magnetic resonance imaging showed two areas of hypoperfusion in the terminal branches of the left medial cerebral artery not previously diagnosed by computed tomography. Although there were no eligibility criteria for thrombolysis, patient received intravenous treatment with recombinant tissue-type plasminogen activator (rt-PA) over 1 h and at the end of rt-PA infusion aphasia completely disappeared without neurological sequelae. Transesophageal echocardiography revealed a thrombus in the left atrial appendage not previously detected by transthoracic echocardiography. In the month following the cardioembolic stroke, heart rhythm was monitored for 30 days by an external loop recorder and during this test two episodes of silent lone atrial fibrillation were collected.

Renal scintigraphy predicts global cardiovascular risk in hypertensive subjects with normal serum creatinine levels.

BACKGROUND. This cross-sectional study investigates the role of renal scintigraphy on cardiovascular (CV) risk stratification in normoalbuminuric, non-diabetic hypertensive subjects (HTs) free from CV disease and renal dysfunction. METHODS. In 200 HTs aged 55-75 years, glomerular filtration rate (GFR) was measured by technetium-99m-diethylene triamine pentacetic acid clearance during renal scintigraphy. Stage III chronic kidney disease (CKD) was defined as GFR < 60 ml/min/1.73 m(2). For comparing the impact of different methods for CKD diagnosis on CV risk stratification, CKD was also considered as GFR estimated by the Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault's formula. Target organ damage (TOD) was assessed by echocardiography and carotid ultrasonography. Gender-specific odds ratio (OR) with 95% confidence intervals for CKD were derived from a multiple stepwise logistic regression analysis. Global CV risk was stratified according to routine examinations, TOD and CKD. RESULTS. In 38% of cases, an unknown stage III CKD was found. Independent of age, CKD was predicted by history of hypertension (OR = 1.69, p = 0.0001), albuminuria (OR = 1.25, p = 0.0001), smoking (OR = 1.85, p = 0.028) and pulse pressure (OR = 1.21, p = 0.019) in men only. Men had an increased risk of CKD (OR = 2.62, p = 0.002) in comparison with women. Prevalence of TOD was significantly higher only in HTs having CKD diagnosed by renal scintigraphy; TOD and CKD assessment added to classic risk factors modified the CV risk stratification from low-moderate to high and very high. CONCLUSIONS. Renal scintigraphy is an important aid in risk stratification and should be performed in HTs aged >55 years. Pulse pressure was the main blood pressure component that predicted the risk of stage III CKD.

Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up study.

OBJECTIVES: Potential causes of cryptogenic cerebrovascular (CV) events are patent foramen ovale (PFO) and hyper homocysteinemia (H-Hcys), this latter a well-established risk factor for thrombosis particularly in the presence of mutation for the methylenetetrahydrofolate reductase (MTHFR) gene. This study investigated if in uncomplicated hypertensive subjects (HTs) with isolated PFO and H-Hcys, a different MTHFR polymorphism pattern for C667→T gene mutation could influence PFO management and to reduce the CV risk. METHODS: In thirty-two HTs aged 55.6±14.4years, PFO was diagnosed by echocardiography. MTHFR genotype was evaluated by a multiplex polymerase chain reaction with reverse line blot hybridization assay. In relation to the T allele distribution, HTs were divided in normal (CC), heterozygote (CT) and homozygote (TT) for the MTHFR genotype. All subjects received a supplementation of oral folate (5mg daily) and were evaluated yearly for 2years. Analysis of variance for repeated measures (ANOVA) was used to compare changes of Hcys at baseline and at the end of follow-up and differences between continuous variables were evaluated in the three MTHFR groups with the Tukey's post hoc test after adjustment for confounders. RESULTS: At the follow-up, Hcys levels significantly normalized from baseline both in TT (38.1±6.7 vs. 15±3.6, p<0.01) and CT (26.6±2.3 vs. 9.2±1.6, p<0.01) but not in CC subjects (18.2±1.8 vs. 16.0±1.6, NS). Independently of age, BMI, vitamin treatment both systolic and diastolic blood pressure (BP) significantly decrease at the follow-up in all the MTHFR genotypes. No CV events were observed during the follow-up. CONCLUSIONS: In HTs with isolated PFO and H-Hcys, oral folate supplementation reduces Hcys levels both in TT and CT subjects with C667→T mutation of MTHFR. In addition the BP normalization probably contributed to reduce CV risk in these genotypes.

Comparison of methods for determination of glomerular filtration rate in hypertensive subjects with normal serum creatinine.

BACKGROUND: Glomerular filtration rate (GFR) measured through technetium-99m diethyl triamine penta-acetic acid (Tc(99m)DTPA) renal scintigraphy (rsGFR) was compared with that estimated (eGFR) from 24-h creatinine clearance (CrCl) and, using both the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas, in a population of hypertensive subjects (HTs) with normal serum creatinine (SCr) levels. PATIENTS AND METHODS: In 200 normoalbuminuric (<30 mg/24 h) HTs 55-75 years old, without diabetes and history of coronary and cerebrovascular diseases, Pearson's correlation assess the relationship between rsGFR and eGFR. The Bland-Altman method was used to assess the agreement between rsGFR and eGFR, separately in subjects with low (<60 ml/min/1.73 m(2)) and normal (≥60 ml/min/1.73 m(2)) rsGFR. The span between -1.96 and +1.96 standard deviations of mean difference (bias) was calculated and used for this purpose. RESULTS: In 76 subjects, an unknown low renal function was found by Tc(99m)DTPA renal scintigraphy. In subjects with normal rsGFR the Bland-Altman analysis showed that the smallest span between rsGFR and eGFR was evident for ClCr values (26.0 ml/min/1.73 m(2)), whereas higher values were detected with the CG and MDRD formulas (41.0 and 40.4 ml/min/1.73 m(2), respectively). The same results were observed for low rsGFR, where a smaller span was found for ClCr (21.2 ml/min/1.73 m(2)), whereas CG and MDRD methods gave greater results (30.4 and 31.8 ml/min/1.73 m(2) respectively); no differences were found between genders. The degree of agreement for eGFR estimated with the CG and MDRD formulas was wider than that derived from ClCr, reflecting a greater between-methods variability and a considerable discrepancy of rsGFR values in the former than in the latter. CONCLUSIONS: In HTs with normal SCr values, Tc(99m)DTPA renal scintigraphy discovered un known renal organ damage in 38% of cases. If this methodology is not available, ClCr measurement should be preferred to estimate GFR whereas CG and MDRD formulas are of limited efficacy.

Green tea attenuates angiotensin II-induced cardiac hypertrophy in rats by modulating reactive oxygen species production and the Src/epidermal growth factor receptor/Akt signaling pathway.

We previously documented a clear-cut antihypertensive effect of green teat extract (GTE), which was associated with correction of endothelial dysfunction and prevention of left ventricular hypertrophy in an angiotensin II (Ang II)-dependent model of hypertension, but the molecular mechanisms remain to be defined. As several effects of Ang II involve production of reactive oxygen species (ROS) and activation of 2nd messengers, such as mitogen-activated protein kinase (MAPK) and Akt, we investigated the effect of GTE on these signal transduction pathways in Ang II-treated rats. Rats were treated for 2 wk with Ang II infusion (700 mug.kg(-1).d(-1); n = 6, via osmotic minipumps), Ang II plus GTE (6 g/L) dissolved in the drinking water; n = 6), or vehicle (n = 6) to serve as controls. Blood pressure was monitored by telemetry throughout the study. The activation and expression of NAD(P)H oxidase subunits, protein kinase C isoforms, Src, epidermal growth factor receptor (EGFR), Akt, and MAPK were determined in the heart in vitro through immunoprecipitation and western blot analysis with specific antibodies. NAD(P)H oxidase enzymatic activity was measured by cytochrome c reduction assay. GTE blunted Ang II-induced blood pressure increase and cardiac hypertrophy. In Ang II-treated rats, GTE decreased the expression of the NAD(P)H oxidase subunit gp91(phox) and the translocation of Rac-1, as well as NAD(P)H oxidase enzymatic activity. Furthermore, it specifically reduced Ang II-induced Src, EGFR, and Akt phosphorylation. These results show that GTE blunts Ang II-induced cardiac hypertrophy specifically by regulating ROS production and the Src/EGFR/Akt signaling pathway activated by Ang II.

Prevention of hypertension, cardiovascular damage and endothelial dysfunction with green tea extracts.

BACKGROUND: We investigated the effect of green tea extract (GTE) in arterial hypertension with high oxidative stress. Angiotensin (Ang) II induces endothelial dysfunction (ED) that is crucial for the development of atherosclerosis and hypertension. METHODS: Male Sprague-Dawley rats, 13 weeks old, randomly assigned to drinking water with or without GTE (6 mg/mL) received a vehicle, a high (700 microg/kg/d) or a low (350 microg/kg/d) Ang II dose for 13 days, by osmotic mini-pumps. Blood pressure (BP) was measured with telemetry. After sacrifice, left ventricular (LV) mass index, small mesenteric artery media-to-lumen ratio, and concentration-response curves of phenylephrine-precontracted arteries to acetylcholine were evaluated. The effect of the superoxide dismutase (SOD-1) analog tempol on artery responses to acetylcholine was assessed. Oxidative stress was measured by plasma hydroperoxides and nitrotyrosine levels. The mRNA of heme oxygenase 1 (HO-1), NADPH oxidase endothelial p22(phox) subunit, and SOD-1 was also measured in the aorta. RESULTS: Compared with vehicle high Ang II increased BP, LV mass index, media-to-lumen ratio, and hydroperoxide radicals. The GTE blunted these increases, prevented the increase in HO-1, p22(phox), and SOD-1 mRNA in aorta caused by Ang II, and reduced them below baseline levels. Low Ang II dose increased BP values and plasma hydroperoxides only during the first week. Both Ang II doses shifted rightward the curves to acetylcholine; this was prevented in vivo by GTE and abolished in vitro by tempol. CONCLUSIONS: The GTE prevented hypertension and target organ damage induced by a high Ang II dose, likely by prevention or scavenging of superoxide anion generation.

Prospective evaluation of the saline infusion test for excluding primary aldosteronism due to aldosterone-producing adenoma.

BACKGROUND: Data on the performance of the tests used to confirm the diagnosis of primary aldosteronism (PA) are limited. OBJECTIVE: To prospectively investigate the accuracy of the saline infusion test (SIT). METHODS: Three hundred and seventeen (26.9%) out of 1125 patients screened in the PAPY study underwent measurement of plasma aldosterone, cortisol and renin activity after infusion of 2 l of isotonic saline intravenously over 4 h. They comprised patients with a baseline aldosterone/renin ratio (ARR) > 40 and one every four patients not fulfilling such criterion. The area under the receiver-operator characteristic curves (AUC) of aldosterone values after SIT was used as a measure of accuracy for diagnosing PA, aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). RESULTS: One hundred and twenty (37.9%) patients had PA that was due to an APA in 46 (38.3%) and to IHA in 74 (61.7%). No untoward effect occurred with the SIT. The AUC (0.811 +/- 0.026, 0.878 +/- 0.040 and 0.784 +/- 0.034 for identification of PA, APA and IHA, respectively) was higher (P < 0.0001) than that under the diagonal. By sensitivity/specificity versus criterion values plot, the best aldosterone cut-off values for identifying APA and IHA were 6.75 and 6.91 ng/dl, respectively. However, even at these optimal cut-offs, sensitivity and specificity were moderate because of values overlapping between patients with and without the disease. Moreover, there were no differences of AUC and aldosterone cut-offs between APA and IHA. CONCLUSION: In a multicenter study the SIT was safe and specific for excluding PA, but had no place for discriminating between an APA and IHA.

The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients.

OBJECTIVES: This study sought to investigate the impact of a common T(-786)C single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective cohort study. BACKGROUND: The T(-786)C SNP eNOS gene implies a blunted endothelium-dependent vasodilation in hypertensive patients and was associated with multivessel coronary artery disease in cross-sectional studies, but it remained unsettled whether it carried prognostic information. METHODS: In consecutive white patients of the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study, who underwent coronary angiography between 1999 and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C and the exon 7 G(894)T SNPs were determined by melting curve analysis of amplicons from allele-specific fluorescence resonance energy transfer probes. Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also measured. The Kaplan-Meier and Cox regression analyses were used to assess the impact of SNPs on event-free survival. RESULTS: Complete follow-up data were obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4 to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no differences in CV death rates across G(894)T genotypes. The TT individuals, who showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and lower levels of nitrotyrosine (p < 0.0001) than CC patients. CONCLUSIONS: The T(-786)C SNP in the promoter of eNOS bears independent prognostic information and is associated with changes in markers of oxidant stress in high-risk white patients referred for coronary angiography.