Dim artificial light at night alters gene expression rhythms and growth in a key seagrass species (Posidonia oceanica).

Artificial light at night (ALAN) is a globally spreading anthropogenic stressor, affecting more than 20% of coastal habitats. The alteration of the natural light/darkness cycle is expected to impact the physiology of organisms by acting on the complex circuits termed as circadian rhythms. Our understanding of the impact of ALAN on marine organisms is lagging behind that of terrestrial ones, and effects on marine primary producers are almost unexplored. Here, we investigated the molecular and physiological response of the Mediterranean seagrass, Posidonia oceanica (L.) Delile, as model to evaluate the effect of ALAN on seagrass populations established in shallow waters, by taking advantage of a decreasing gradient of dim nocturnal light intensity (from < 0.01 to 4 lx) along the NW Mediterranean coastline. We first monitored the fluctuations of putative circadian-clock genes over a period of 24 h along the ALAN gradient. We then investigated whether key physiological processes, known to be synchronized with day length by the circadian rhythm, were also affected by ALAN. ALAN influenced the light signalling at dusk/night in P. oceanica, including that of shorter blue wavelengths, through the ELF3-LUX1-ZTL regulatory network, and suggested that the daily perturbation of internal clock orthologs in seagrass might have caused the recruitment of PoSEND33 and PoPSBS genes to mitigate the repercussions of a nocturnal stress on photosynthesis during the day. A long-lasting impairment of gene fluctuations in sites characterised by ALAN could explain the reduced growth of the seagrass leaves when these were transferred into controlled conditions and without lighting during the night. Our results highlight the potential contribution of ALAN to the global loss of seagrass meadows, posing questions about key interactions with a variety of other human-related stressors in urban areas, in order to develop more efficient strategies to globally preserve these coastal foundation species.

Cryoballoon ablation of atrial fibrillation is effectively feasible without previous imaging of pulmonary vein anatomy: insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. METHODS: Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. RESULTS: Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p < 0.001). The procedure, fluoroscopy, and left atrial dwell times were significantly shorter in the no imaging cohort (p < 0.001). The rates of complications were significantly greater in the imaging group compared to the no imaging group (6.9% vs. 2.7%; p = 0.003); this difference was attributed to differences in transient diaphragmatic paralysis. The 12-month freedom from AF was 76.2% in the imaging group and 80.0% in the no imaging group (p = 0.390). CONCLUSIONS: In our analysis, PVI-C was effective regardless of the availability of imaging data on PV anatomy.

Predictors of clinical efficacy of 'Ablate and Pace' therapy in patients with permanent atrial fibrillation.

OBJECTIVE: To evaluate the 2-year clinical improvement after 'Ablate and Pace' therapy and to identify the variables able to influence the efficacy of this therapy in patients with permanent atrial fibrillation (AF). Design Prospective multicentre observational study. Setting Cardiology departments of 19 general hospitals in Italy, Spain and Greece. PATIENTS: 171 patients with drug-refractory severely symptomatic permanent AF considered for AV junction ablation. Interventions Patients underwent AV junction ablation, received a right ventricular (RV) pacing or echo-guided cardiac resynchronisation (CRT) pacing and were followed-up to 24 months. Main outcome measures Non-responders to Ablate and Pace therapy were defined those patients who, during the follow-up period had clinical failure (defined as death or hospitalisation due to heart failure, or worsening heart failure) or showed no improvement in their clinical condition. RESULTS: Responders were 63% of RV-paced patients and 83% of CRT-paced patients. Another 27% showed no clinical improvement (7%) or worsened (20%) (non-responders group). On multivariable Cox regression analysis, CRT mode and echo-optimised CRT were the only independent protective factors against non-response (HR=0.24, 95% CI 0.10-0.58, p=0.001 and HR=0.22, 95% CI 0.07-0.77, p=0.018 respectively). On comparing freedom from non-response, a trend in favour of echo-optimised CRT versus simultaneous biventricular pacing (p=0.077) was seen. CONCLUSIONS: In patients affected by severely symptomatic permanent AF, Ablate and Pace therapy yielded a clinical benefit in 63% of RV-paced patients and 83% of CRT-paced patients. CRT pacing and echo-optimised CRT were the only independent predictor of clinical benefit.

Prognostic significance of endothelial dysfunction in hypertensive patients.

BACKGROUND: Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown. Methods and Results-- Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure. CONCLUSIONS: Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.

Relationship between angiotensin-converting enzyme gene polymorphism and insulin resistance in never-treated hypertensive patients.

The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.

Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C.

Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.

Hypertensive left ventricular remodeling and ACE-gene polymorphism.

OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.

Calcium antagonist isradipine improves abnormal endothelium-dependent vasodilation in never treated hypertensive patients.

OBJECTIVE: To examine whether middle (two months) and long-term (six months) isradipine sustained-release treatment improves endothelium-dependent vasodilation in never treated hypertensive patients. METHODS: The responses of the forearm vasculature to acetylcholine (7.5, 15 and 30 micrograms/min) and sodium nitroprusside (0.8, 1.6, 3.2 micrograms/min) were evaluated in 12 normotensive controls (seven men and five women, aged 25 to 49 years), and in 12 hypertensives (eight men and four women, aged 20 to 47 years) at baseline and after two and six months of isradipine sustained-release treatment. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. RESULTS: At baseline, the response to acetylcholine was significantly lower in hypertensives vs controls: at the highest dose (30 micrograms/min), forearm blood flow was 28.6 +/- 2.4 ml/100 ml of tissue per min in the controls vs 8.9 +/- 1.0 ml/100 ml of tissue per min in hypertensive (p < 0.0001). Similarly, vascular resistance was significantly (p < 0.0001) higher in hypertensives: 4.8 +/- 0.5 units (controls) vs 15.1 +/- 1.7 units (hypertensives). After isradipine treatment, the forearm blood flow in hypertensive patients changed from 8.9 +/- 1.0 ml/100 ml of tissue per min to 16.0 +/- 1.2 ml/100 ml of tissue per min (two months; p < 0.0001) and 15.2 +/- 1.4 ml/100 ml of tissue per min (six months; p < 0.0001). Isradipine treatment did not modify the vasodilating effect of sodium nitroprusside. CONCLUSIONS: Our data demonstrate for the first time that the calcium antagonist isradipine improves acetylcholine-induced vasodilation in hypertensives.