Theoretical study of the fibrous capsule tissue growth around a disk-shaped implant.

We analyze the mathematical properties of the fibrous capsule tissue concentration around a disk-shaped implant. We establish stability estimates as well as monotonicity results that illustrate the sensitivity of this growth to the biocompatibility index parameters of the implant. In addition, we prove that the growth of the tissue increases exponentially in time toward an asymptotic regime. We also study the mathematical properties of the solution of the inverse problem consisting in the determination of the values of the biocompatibility index parameters from the knowledge of some fibrous capsule tissue measurements. We prove that this model calibration problem admits a unique solution, and establish a characterization of the index parameters. Furthermore, we demonstrate analytically that such a solution is not continuous with respect to the data, and therefore the considered inverse problem is ill-posed due to the lack of the stability requirement.

Analysis of the foveal microvasculature in sickle cell disease using swept-source optical coherence tomography angiography.

Ischemic microangiopathy was clearly identified in sickle cell disease (SCD) using fluorescein angiography. A prospective observational clinical study was conducted to assess the foveal avascular zone (FAZ) area and explore perifoveal microvasculature changes in the superficial (SCP) and deep (DCP) capillary plexus using optical coherence tomography angiography (OCTA) and compare two genotypes-HbS/HbS (HbSS) and HbS/HbC (HbSC)-to control. All consecutive patients with electrophoretic confirmation of SCD were included. Swept-source OCTA scans (Triton Plus, Topcon, Tokyo, Japan) with a 3 × 3-mm scanning area and ultra-wide field (UWF) retinography (California, Optos, Fife, Scotland) were recorded for all patients. For OCTA analysis, preset parameters were used to segment the SCP and DCP. The FAZ area was manually assessed. The number of vascular branching points was automatically assessed based on the vascular skeletonization using ImageJ software. Eyes were staged based on Goldberg's classification of SCD retinopathy (SCDR) using UWF imaging. Forty-six eyes of 24 patients were included in the HbSS (n = 27) and HbSC (n = 19) groups and 16 eyes of 8 unaffected patients in a control group. In the DCP, the FAZ was significantly larger in the HbSC (p = 0.0001) and HbSS (p = 0.0004) groups compared to controls. The FAZ area in the SCP, CRT and number of superficial vascular branching points did not significantly differ between both genotypes. There were less branching points in the HbSC (p = 0.034) and HbSS (p = 0.0014) groups than in controls. The Goldberg stage was significantly higher in the HbSC group than in the HbSS group (2.21 vs. 1.22, p = 0.0062). OCTA provides useful information on macular microvasculature and structural alterations associated with SCDR. Ischemic abnormalities are more predominant in the DCP in case of SCDR and no difference was found between genotypes of patients visually asymptomatic.

Improved beat-to-beat timing measurements of His-bundle signal.

A simplified bioelectric model of the atrioventricular (AV) junction is proposed to better understand the underlying biophysical generation of intracardiac His-bundle signal and to analyze the effects of electrocatheter displacements on waveform morphology and estimation of AV node conduction time (AVCT). Based on this model, an inverse problem approach has been developed to estimate electrode displacements occurring in real recordings. A measurement correction method is proposed to improve estimation of AVCT. Results illustrate autonomic influences on AVCT, a phenomenon hardly measured with common techniques.

Dynamics of heart rate response to sympathetic nerve stimulation.

Electrical stimulation of the right cardiac sympathetic nerve was used to achieve a step increase of norepinephrine concentration at the sinus node. The heart rate (HR) response to sympathetic stimulation was characterized by a first-order process with a time delay. For moderate to high intensities of stimulation the mean delay and time constant were 0.7 and 2.1 s, respectively, and for low intensities of stimulation they were 0.4 and 1.1 s, respectively. From the analysis of the HR response to different patterns of nerve stimulation, in vivo neurotransmitter kinetics were estimated. The time constant of norepinephrine dissipation averaged approximately 9 s. These results combined with computer simulations revealed two facets of sympathetic neural control of HR: 1) negligible role of the sympathetic system in beat-to-beat regulation of HR under stationary conditions and 2) ability of HR to react relatively quickly (within a few seconds) to sharp increases in sympathetic nerve traffic.

Transfer function analysis of vagal control of heart rate during synchronized vagal stimulation.

Synchronized electrical stimulation was used to study the heart rate (HR) response to fluctuations in parasympathetic input to the sinus node in anesthetized dogs. This was obtained by varying the time interval (interpulse interval) between stimulatory vagal pulses. Spectral methods were used to estimate transfer functions between the excitatory signal and the resulting HR response for different intensities of vagal stimulation. The intensity of vagal stimulation was proportional to the number of pulses delivered in each cardiac cycle. From the estimated transfer functions, and based on a mathematical model of the time course of ACh concentration at the sinus node, filter models were derived by using a system identification approach. HR response was characterized by a combination of two different filter behaviors: a low-pass filter behavior of mean cut-off frequency of 0.065 Hz and an all-pass filter behavior. The magnitude of the low-pass filter gain decreased with increasing intensity of vagal stimulation. The magnitude of the all-pass filter gain increased and then decreased with increasing intensity of vagal stimulation. The all-pass filter characteristics of HR response during synchronized stimulation of the vagus nerves are specific to this mode of stimulation, because they were not observed in nonsynchronized modes of vagal stimulation. We can conclude that, during synchronized vagal stimulation, the HR response exhibits both a slow dynamic component and a fast component related to beat-to-beat variations.

Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a "young" concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create "supermen/women" (doping).