Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure > or = 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B). In the 12 Group A patients, 60+/-10 years old, with symptomatic heart failure for 6.3+/-4.3 years, vasodilator therapy was intensified in the 2.0+/-0.5 years of follow-up, achieving final doses of enalapril 78+/-19 mg and isosorbide dinitrate 293 +/-106 mg per day. New York Heart Association classification improved from 2.9+/-0.8 to 1.3+/-0.5 (P < or = .0001), with a reduction in heart-failure-related hospitalizations. Left ventricular ejection fraction increased from 17+/-6% to 40+/-10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116+/-14 to 154+/-13 mm Hg (P = .0001) and from 71+/-9 to 85+/-14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A. Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.     

Inhaled nanomaterials and the respiratory microbiome: clinical,immunological and toxicological perspectives

Our development and usage of engineered nanomaterials has grown exponentially despite concerns about their unfavourable cardiorespiratory consequence, one that parallels ambient ultrafine particle exposure from vehicle emissions. Most research in the field has so far focused on airway inflammation in response to nanoparticle inhalation, however, little is known about nanoparticle-microbiome interaction in the human airway and the environment. Emerging evidence illustrates that the airway, even in its healthy state, is not sterile. The resident human airway microbiome is further altered in chronic inflammatory respiratory disease however little is known about the impact of nanoparticle inhalation on this airway microbiome. The composition of the airway microbiome, which is involved in the development and progression of respiratory disease is dynamic, adding further complexity to understanding microbiota-host interaction in the lung, particularly in the context of nanoparticle exposure. This article reviews the size-dependent properties of nanomaterials, their body deposition after inhalation and factors that influence their fate. We evaluate what is currently known about nanoparticle-microbiome interactions in the human airway and summarise the known clinical, immunological and toxicological consequences of this relationship. While associations between inhaled ambient ultrafine particles and host immune-inflammatory response are known, the airway and environmental microbiomes likely act as intermediaries and facilitate individual susceptibility to inhaled nanoparticles and toxicants. Characterising the precise interaction between the environment and airway microbiomes, inhaled nanoparticles and the host immune system is therefore critical and will provide insight into mechanisms promoting nanoparticle induced airway damage.     

BioMOCA: A Transport Monte Carlo Model for Ion Channels

Ion channels are proteins that form natural water-filled nanotubes in the membranes of all biological cells. They regulate ion transport in and out of the cell thereby maintaining the correct internal ion composition that is crucial to cell survival and function. Every channel carries a strong permanent charge, which plays a critical role in the conduction mechanisms of the open channel. Many channels can selectively transmit or block a particular ion species and most have switching properties similar to electronic devices. These device-like features are appealing to the electronics community for their possible application in the design of novel bio-devices. Here we describe a three-dimensional (3-D) transport Monte Carlo ion channel simulation, BioMOCA, based on the approach taken in semiconductor device simulations. Since ion diameters are comparable with channel dimensions a physical model of the volume of the ions must also be included.     

Comparison of Double-Gate MOSFETs and FinFETs with Monte Carlo Simulation

A full-band Monte Carlo simulator has been used to analyze and compare the performance of n-channel double-gate MOSFETs and FinFETs. Size quantization effects were accounted for by using a quantum correction based on Schrödinger equation. FinFETs are a variation of typical double-gate devices with the gate surrounding the channel on three sides. From our simulations, we observed that the quantization effects in double-gate devices are less significant as compared to bulk MOSFETs. The total sheet charge density drops only slightly as the depletion of charge at the interface is counterbalanced by the increased volume inversion effect. We also observed an appreciable drop in average velocity distribution when quantum corrections were applied. For FinFETs, the fin extension lengths on either side of the gate affect the device performance significantly. These underlap regions have low carrier concentration and behave as large resistors. The current drops non-linearly with increasing fin extension lengths.     

Simulation of Ion Conduction in the ompF Porin Channel Using BioMOCA

In this paper, we present a full three-dimensional simulation of the ompF porin channel using BioMOCA, a self-consistent particle-based ion channel simulation tool, based on the Boltzmann Transport Monte Carlo methodology widely used to simulate conduction in the solid-state device. Significant computational speed-up over atomistic Molecular Dynamics simulations is achieved by treating protein, membrane and water as continuum dielectric background media and computing only the trajectories of mobile ions in solution. A realistic channel structure with permanent fixed charges is mapped onto a finite mesh using the Cloud-in-Cell scheme. Electrostatic forces, computed by solving Poisson equation at regular intervals, are added to a pair-wise ion-ion interaction, which is necessary to prevent the unphysical coalescence of finite-sized ions. The interaction between ions and water is modeled as a random scattering process that thermalizes the ion. Using this tool we computed the complete current-voltage characteristic of the porin channel in approximately one week using ten IBM p690 processors. We also present steady-state ion channel occupancies and compare them with results obtained from recent drift-diffusion based simulations.     

Monte Carlo simulations of double-gate MOSFETs

A fullband Monte Carlo simulator has been used to analyze the performance of scaled n-channel double-gate (DG) MOSFETs. Size quantization in the channel is accounted for by using a quantum correction based on Schrodinger equation. Scattering induced by the oxide interface is included with a model calibrated with measurements for bulk devices. The detailed self-consistent treatment of quantum effects leads to several interesting observations. We observe that the sheet charge in DG devices does not decrease as much as expected in bulk devices when quantum-mechanical effects are included. The average carrier velocity in the channel is also somewhat reduced by quantum effects, as a second-order effect. In the test cases studied here, application of quantum effects causes a reduction in simulated current not exceeding 15%. In a DG structure, quantum effects tend to concentrate the charge density in the center of the channel, where transverse fields are lower. Because of this, interface scattering appears to be less pronounced when quantum effects are included.