Statin therapy, fitness, and mortality risk in middle-aged hypertensive male veterans

BACKGROUND Hypertension often coexists with dyslipidemia, accentuating cardiovascular risk. Statins are often prescribed in hypertensive individuals to lower cardiovascular risk. Higher fitness is associated with lower mortality, but exercise capacity may be attenuated in hypertension. The combined effects of fitness and statin therapy in hypertensive individuals have not been assessed. Thus, we assessed the combined health benefits of fitness and statin therapy in hypertensive male subjects. METHODS Peak exercise capacity was assessed in 10,202 hypertensive male subjects (mean age = 60.4±10.6 years) in 2 Veterans Affairs Medical Centers. We established 4 fitness categories based on peak metabolic equivalents (METs) achieved and 8 categories based on fitness status and statin therapy. RESULTS During the follow-up period (median = 10.2 years), there were 2,991 deaths. Mortality risk was 34% lower (hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.59–0.74; P \u3c 0.001) among individuals treated with statins compared with those not on statins. The fitness-related mortality risk association was inverse and graded regardless of statin therapy status. Risk reduction associated with exercise capacity of 5.1–8.4 METs was similar to that observed with statin therapy. However, those achieving ≥8.5 METs had 52% lower risk (HR = 0.48; 95% CI = 0.37–0.63) when compared with the least-fit subjects (≤5 METs) on statin therapy. CONCLUSIONS The combination of statin therapy and higher fitness lowered mortality risk in hypertensive individuals more effectively than either alone. The risk reduction associated with moderate increases in fitness was similar to that achieved by statin therapy. Higher fitness was associated with 52% lower mortality risk when compared with the least fit subjects on statin therapy

ESONET LIDO Demonstration Mission: the East Sicily node

Off East Sicily (at 2100 m depth, 25 km off the harbour of Catania) a prototype of a cabled deep-sea observatory (NEMO-SN1) was set up and has been operational in real-time since 2005 (the cabled deep-sea multi-parameter station SN1, equipped with geophysical and environmental sensors and the cabled NEMO-OνDE, equipped with 4 broadband hydrophones). The Western Ionian Sea is one of the node sites for the upcoming European permanent underwater network (EMSO). Within the activities of the EC project ESONET-NoE some demonstration missions have been funded. The LIDO-DM (Listening to the Deep Ocean-Demonstration Mission) is one of these and is re- lated to two sites, East Sicily and Iberian Margin (Gulf of Cadiz), the main aims being geo-hazards monitoring and warning (seismic, tsunami, and volcanic) and bio-acoustics. The LIDO-DM East Sicily installation represents a fur- ther major step within ESONET-NoE, resulting in a fully integrated system for multidisciplinary deep-sea science, capable to transmit and distribute data in real time to the scientific community and to the general public. LIDO-DM East Sicily hosts a large number of sensors aimed at monitoring and studying oceanographic and environmental parameters (by means of CTD, ADCP, 3-C single point current meter, turbidity meter), geophysical phenomena (low frequency hydrophones, accelerometer, gravity meter, vector and scalar magnetometers, seismometer, abso- lute and differential pressure gauges), ocean noise monitoring and identification and tracking of biological acoustic sources in deep sea. The latter will be performed using two tetrahedral arrays of 4 hydrophones, located at a relative distance of about 5 km, and at about 25 km from the shore. The whole system will be connected and powered from shore, by means of the electro-optical cable net installed at the East Sicily Site Infrastructure, and synchronised with GPS. Sensors data sampling is performed underwater and transmitted via optical fibre link, with optimal S/N ratio for all signals. This will also permit real-time data acquisition, analysis and distribution on-shore. Innova- tive electronics for the off-shore data acquisition and transmission systems has been designed, built and tested. A dedicated computing and networking infrastructure for data acquisition, storage and distribution through the internet has been also created. The deployment and connection of the deep sea structures will be performed using the dedicated ROV and Deep Sea Shuttle handling facilities (PEGASO, owned by INGV and INFN). LIDO-DM constitutes the enhancement of the Western Ionian site in view of the EMSO Research Infrastructure.PublishedVienna1.8. Osservazioni di geofisica ambientaleope

ESONET LIDO Demonstration Mission: the Iberian Margin node.

The Gulf of Cadiz is one of two the test sites chosen for the demonstration of the ESONET - LIDO Demonstration Mission (DM) [1], which will establish a first nucleus of regional network of multidisciplinary sea floor observatories. The Gulf of Cadiz is a highly populated area, characterized by tsunamigenic sources, which caused the devastating earthquake and tsunamis that struck Lisbon in 1755. The seismic activity is concentrated along a belt going from this region to the Azores and the main tsunamigenic tectonic sources are located near the coastline. In the framework of the EU - NEAREST project [2] the GEOSTAR deep ocean bottom multi-parametric observatory was deployed for a one year mission off cape Saint Vincent at about 3200 m depth. GEOSTAR was equipped with a set of oceanographic, seismic and geophysical sensors and with a new tsunami detector prototype. In November 2009 the GEOSTAR abyssal station equipped with the tsunami prototype was redeployed at the same site on behalf of NEAREST and ESONET - LIDO DM. The system is able to communicate from the ocean bottom to the land station via an acoustic and satellite link. The abyssal station is designed both for long term geophysical and oceanographic observation and for tsunami early warning purpose. The tsunami detection is performed by two different algorithms: a new real time dedicated tsunami detection algorithm which analyses the water pressure data, and a seismic algorithm which triggers on strong events. Examples of geophysical and oceanographic data acquired by the abyssal station during the one year mission will be shown. The development of a new acoustic antenna equipped with a stand alone and autonomous acquisition system will allow the recording of marine mammals and the evaluation of environmental noise. ReferencesEGUPublishedVienna1.8. Osservazioni di geofisica ambientaleope

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation

Sympatho-renal axis in chronic disease

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney’s somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics—insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders

Towards neuro-inspired symbolic models of cognition: linking neural dynamics to behaviors through asynchronous communications

A computational architecture modeling the relation between perception and action is proposed. Basic brain processes representing synaptic plasticity are first abstracted through asynchronous communication protocols and implemented as virtual microcircuits. These are used in turn to build mesoscale circuits embodying parallel cognitive processes. Encoding these circuits into symbolic expressions gives finally rise to neuro-inspired programs that are compiled into pseudo-code to be interpreted by a virtual machine. Quantitative evaluation measures are given by the modification of synapse weights over time. This approach is illustrated by models of simple forms of behaviors exhibiting cognition up to the third level of animal awareness. As a potential benefit, symbolic models of emergent psychological mechanisms could lead to the discovery of the learning processes involved in the development of cognition. The executable specifications of an experimental platform allowing for the reproduction of simulated experiments are given in “Appendix”

ESONET LIDO Demonstration Mission: the East Sicily node

Off East Sicily (at 2100 m depth, 25 km off the harbour of Catania) a prototype of a cabled deep-sea observatory (NEMO-SN1) was set up and has been operational in real-time since 2005 (the cabled deep-sea multi-parameter station SN1, equipped with geophysical and environmental sensors and the cabled NEMO-OνDE, equipped with 4 broadband hydrophones). The Western Ionian Sea is one of the node sites for the upcoming European permanent underwater network (EMSO). Within the activities of the EC project ESONET-NoE some demonstration missions have been funded. The LIDO-DM (Listening to the Deep Ocean-Demonstration Mission) is one of these and is re- lated to two sites, East Sicily and Iberian Margin (Gulf of Cadiz), the main aims being geo-hazards monitoring and warning (seismic, tsunami, and volcanic) and bio-acoustics. The LIDO-DM East Sicily installation represents a fur- ther major step within ESONET-NoE, resulting in a fully integrated system for multidisciplinary deep-sea science, capable to transmit and distribute data in real time to the scientific community and to the general public. LIDO-DM East Sicily hosts a large number of sensors aimed at monitoring and studying oceanographic and environmental parameters (by means of CTD, ADCP, 3-C single point current meter, turbidity meter), geophysical phenomena (low frequency hydrophones, accelerometer, gravity meter, vector and scalar magnetometers, seismometer, abso- lute and differential pressure gauges), ocean noise monitoring and identification and tracking of biological acoustic sources in deep sea. The latter will be performed using two tetrahedral arrays of 4 hydrophones, located at a relative distance of about 5 km, and at about 25 km from the shore. The whole system will be connected and powered from shore, by means of the electro-optical cable net installed at the East Sicily Site Infrastructure, and synchronised with GPS. Sensors data sampling is performed underwater and transmitted via optical fibre link, with optimal S/N ratio for all signals. This will also permit real-time data acquisition, analysis and distribution on-shore. Innova- tive electronics for the off-shore data acquisition and transmission systems has been designed, built and tested. A dedicated computing and networking infrastructure for data acquisition, storage and distribution through the internet has been also created. The deployment and connection of the deep sea structures will be performed using the dedicated ROV and Deep Sea Shuttle handling facilities (PEGASO, owned by INGV and INFN). LIDO-DM constitutes the enhancement of the Western Ionian site in view of the EMSO Research Infrastructure