Flexible gastrointestinal motility pressure sensors based on aluminum thin-film strain-gauge arrays

This paper reports on an innovative approach to measuring intraluminal pressure in the upper gastrointestinal (GI) tract, especially monitoring GI motility and peristaltic movements. The proposed approach relies on thin-film aluminum strain gauges deposited on top of a Kapton membrane, which in turn lies on top of an SU-8 diaphragm-like structure. This structure enables the Kapton membrane to bend when pressure is applied, thereby affecting the strain gauges and effectively changing their electrical resistance. The sensor, with an area of 3.4 mm2, is fabricated using photolithography and standard microfabrication techniques (wet etching). It features a linear response (R2 = 0.9987) and an overall sensitivity of 2.6 mV mmHg−1. Additionally, its topology allows a high integration capability. The strain gauges’ responses to pressure were studied and the fabrication process optimized to achieve high sensitivity, linearity, and reproducibility. The sequential acquisition of the different signals is carried out by a microcontroller, with a 10-bit ADC and a sample rate of 250 Hz. The pressure signals are then presented in a user-friendly interface, developed using the Integrated Development Environment software, QtCreator IDE, for better visualization by physicians.

Studies on survival, biological activities and behavior of Biomphalaria glabrata, the host snail of Schistosomiasis, submitted to increased hydrostatic pressure: a technique

To study changes in survival, in biological activities and behavior of planorbids submitted to increased hydrostatic pressure, we developed a technique using two transparent chambers and a hydraulic piston. The apparatus permitted renewal of the liquid medium without substantial variations in pressure, thus eliminating excretion products and maintaining the desired O2 level and thereby permitting us to evaluate the effects of pressure independently of the occurrence of anoxia. Pressure was maintained without any contact of the liquid medium with compressed air, a situation which reproduced with relative fidelity what occurs in nature and assured the presence of the same amounts of gases in the two observation chambers (Control and Experimental). Biomphalaria glabrata was found to be able to survive at least 48 hours when submitted to 49.02 x 10**4 Pa (equivalent to a water depth of 48.8 m), continuing to day egg masses and showing few behavioral changes when compared with the control group.

Online estimation of respiratory mechanics in non-invasive pressure support ventilation: a bench model study.

An online algorithm for determining respiratory mechanics in patients using non-invasive ventilation (NIV) in pressure support mode was developed and embedded in a ventilator system. Based on multiple linear regression (MLR) of respiratory data, the algorithm was tested on a patient bench model under conditions with and without leak and simulating a variety of mechanics. Bland-Altman analysis indicates reliable measures of compliance across the clinical range of interest (± 11-18% limits of agreement). Resistance measures showed large quantitative errors (30-50%), however, it was still possible to qualitatively distinguish between normal and obstructive resistances. This outcome provides clinically significant information for ventilator titration and patient management.

Triatominae as a model of morphological plasticity under ecological pressure

The use of biochemical and genetic characters to explore species or population relationships has been applied to taxonomic questions since the 60s. In responding to the central question of the evolutionary history of Triatominae, i.e. their monophyletic or polyphyletic origin, two important questions arise (i) to what extent is the morphologically-based classification valid for assessing phylogenetic relationships? and (ii) what are the main mechanisms underlying speciation in Triatominae? Phenetic and genetic studies so far developed suggest that speciation in Triatominae may be a rapid process mainly driven by ecological factors.

Cardiac dysfunction and impaired compensatory response to pressure overload in mice deficient in stem cell antigen-1.

Stem cell antigen-1 (Sca-1) has been used to identify cardiac stem cells in the mouse heart. To investigate the function of Sca-1 in aging and during the cardiac adaptation to stress, we used Sca-1-deficient mice. These mice developed dilated cardiomyopathy [end-diastolic left ventricular diameter at 18 wk of age: wild-type (WT) mice, 4.2 mm ± 0.3; Sca-1-knockout (Sca-1-KO) mice, 4.6 mm ± 0.1; ejection fraction: WT mice, 51.1 ± 2.7%; Sca-1-KO mice, 42.9 ± 2.7%]. Furthermore, the hearts of mice lacking Sca-1 demonstrated exacerbated susceptibility to pressure overload [ejection fraction after transaortic constriction (TAC): WT mice, 43.5 ± 3.2%; Sca-1-KO mice, 30.8% ± 4.0] and increased apoptosis, as shown by the 2.5-fold increase in TUNEL(+) cells in Sca-1-deficient hearts under stress. Sca-1 deficiency affected primarily the nonmyocyte cell fraction. Indeed, the number of Nkx2.5(+) nonmyocyte cells, which represent a population of cardiac precursor cells (CPCs), was 2-fold smaller in Sca-1 deficient neonatal hearts. In vitro, the ability of CPCs to differentiate into cardiomyocytes was not affected by Sca-1 deletion. In contrast, these cells demonstrated unrestricted differentiation into cardiomyocytes. Interestingly, proliferation of cardiac nonmyocyte cells in response to stress, as judged by BrdU incorporation, was higher in mice lacking Sca-1 (percentages of BrdU(+) cells in the heart after TAC: WT mice, 4.4 ± 2.1%; Sca-1-KO mice, 19.3 ± 4.2%). These data demonstrate the crucial role of Sca-1 in the maintenance of cardiac integrity and suggest that Sca-1 restrains spontaneous differentiation in the precursor population. The absence of Sca-1 results in uncontrolled precursor recruitment, exhaustion of the precursor pool, and cardiac dysfunction.

Pulmonary artery pressure and cardiac function in children and adolescents after rapid ascent to 3,450 m.

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine.

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Surgical menopause increases salt sensitivity of blood pressure

Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2+/-3.5), undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

Modelling the cardiovascular system for automatic interpretation of the blood pressure curve

A four compartment model of the cardiovascular system is developed. To allow for easy interpretation and to minimise the number of parameters, an effort was made to keep the model as simple as possible. A sensitivity analysis is first carried out to determine which are the most important model parameters to characterise the blood pressure signal. A four stage process is then described which accurately determines all parameter values. This process is applied to data from three patients and good agreement is shown in all cases.

Pressure Ulcers In Palliative home Care Patients: Prevalence And Characteristics

Persons in palliative care develop pressure ulcers (PU) as death approaches, but the extent of the problem is still unknown. The objectives were to identify the prevalence of pressure ulcers in people with cancer in palliative home care, compare the socio-demographic and clinical profile of patients with and without pressure ulcers, and analyze the characteristics of the ulcers. This descriptive, cross-sectional study included 64 people with advanced cancer in palliative home care. Twelve of them (18.8%) had PU, of whom 75.0% were men. The participants had one to three PU, amounting to 19 lesions, 89.4% of those developed at home and 47.4% at stage 3. The presence of PU was higher among those who had a history of previous wound. PU consisted of a significant event occurring in the studied population, indicating that preventive measures should be included in the home palliative care health team.


Development of Implantable Flow-Through Left Ventricular Pressure Telemetric Transmitter for small Rodent Animals

Objective: Although 24-hour arterial blood pressure can be monitored in a free-moving animal using pressure telemetric transmitter mostly from Data Science International (DSI), accurate monitoring of 24-hour mouse left ventricular pressure (LVP) is not available because of its insufficient frequency response to a high frequency signal such as the maximum derivative of mouse LVP (LVdP/dtmax and LVdP/dtmin). The aim of the study was to develop a tiny implantable flow-through LVP telemetric transmitter for small rodent animals, which can be potentially adapted for human 24 hour BP and LVP accurate monitoring. Design and Method: The mouse LVP telemetric transmitter (Diameter: _12 mm, _0.4 g) was assembled by a pressure sensor, a passive RF telemetry chip, and to a 1.2F Polyurethane (PU) catheter tip. The device was developed in two configurations and compared with existing DSI system: (a) prototype-I: a new flow-through pressure sensor with wire link and (b) prototype-II: prototype-I plus a telemetry chip and its receiver. All the devices were applied in C57BL/6J mice. Data are mean_SEM. Results: A high frequency response (>100 Hz) PU heparin saline-filled catheter was inserted into mouse left ventricle via right carotid artery and implanted, LV systolic pressure (LVSP), LVdP/dtmax, and LVdP/dtmin were recorded on day2, 3, 4, 5, and 7 in conscious mice. The hemodynamic values were consistent and comparable (139_4 mmHg, 16634_319, - 12283_184 mmHg/s, n¼5) to one recorded by a validated Pebax03 catheter (138_2mmHg, 16045_443 and -12112_357 mmHg/s, n¼9). Similar LV hemodynamic values were obtained with Prototype-I. The same LVP waveforms were synchronically recorded by Notocord wire and Senimed wireless software through prototype-II in anesthetized mice. Conclusion: An implantable flow-through LVP transmitter (prototype-I) is generated for LVP accurate assessment in conscious mice. The prototype-II needs a further improvement on data transmission bandwidth and signal coupling distance to its receiver for accurate monitoring of LVP in a freemoving mouse.

Quantification of glucuronidated and sulfated steroids in human urine by ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry.

The urinary steroid profile is constituted by anabolic androgenic steroids, including testosterone and its relatives, that are extensively metabolized into phase II sulfated or glucuronidated steroids. The use of liquid chromatography coupled to mass spectrometry (LC-MS) is an issue for the direct analysis of conjugated steroids, which can be used as urinary markers of exogenous steroid administration in doping analysis, without hydrolysis of the conjugated moiety. In this study, a sensitive and selective ultra high-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) method was developed to quantify major urinary metabolites simultaneously after testosterone intake. The sample preparation of the urine (1 mL) was performed by solid-phase extraction on Oasis HLB sorbent using a 96-well plate format. The conjugated steroids were analyzed by UHPLC-QTOF-MS(E) with a single-gradient elution of 36 min (including re-equilibration time) in the negative electrospray ionization mode. MS(E) analysis involved parallel alternating acquisitions of both low- and high-collision energy functions. The method was validated and applied to samples collected from a clinical study performed with a group of healthy human volunteers who had taken testosterone, which were compared with samples from a placebo group. Quantitative results were also compared to GC-MS and LC-MS/MS measurements, and the correlations between data were found appropriate. The acquisition of full mass spectra over the entire mass range with QTOF mass analyzers gives promise of the opportunity to extend the steroid profile to a higher number of conjugated steroids.

Target blood pressure attainment with antihypertensive therapy in Swiss primary care.

Introduction: The control of high blood pressure (BP) remains insufficient in developed as well as in developing countries. We conducted a cross-sectional survey to investigate the management of hypertension and the achievement of target BPs in a large population of hypertensive patients treated by Swiss primary care physicians. Methods. Data from 4594 hypertensive patients were collected and assessed for demographic data, mode of treatment and BP achievements for the overall population and for high-risk patients such as diabetics and patients with impaired renal function (CKD patients). Furthermore, we analysed the achieved BP in patients receiving single pill combinations or dual free combinations for the three most commonly prescribed substances. Results. In this large patient population, 84% of patients were receiving an antihypertensive treatment of which 54% showed BP control (< 140/90 mmHg or < 130/80 mmHg for diabetics and patients with CKD). Considering the higher BP target in the elderly, 60.6% of treated patients were on target. In contrast, 28.8% of treated diabetics and 29.7% of patients with impaired renal function met BP goals. Diuretics and blockers of the renin-angiotensin system were the most commonly prescribed substances. High-risk patients and patients at advanced age (≥ 80 years) received dual free combination more frequently than younger patients. The use of diuretics was particularly high because of the prescription of single pill formulations. Differences in the pattern of drug prescription were found according to the linguistic areas. Conclusion. The control of hypertension in the Swiss hypertensive population is relatively high but still insufficient particularly among high cardiovascular risk patients such as diabetics and patients with impaired renal function. A further improvement of BP control could perhaps be achieved with a greater use of single pill combinations particularly in patients with complicated hypertension.

Evaluation of arterial compliance-pressure curves. Effect of antihypertensive drugs.

A new high-precision ultrasonic device was developed to determine noninvasively arterial compliance as a function of blood pressure. Because of the nonlinear elastic properties of arterial walls, measurements of compliance can be appropriately compared only if obtained over a range of pressures. This apparatus was used to evaluate in a double-blind, parallel fashion the effect of three different antihypertensive drugs and of a placebo on radial artery compliance. Thirty-two normotensive volunteers were randomly allocated to an 8-day, once-a-day oral treatment with either a placebo, 100 mg atenolol, 20 mg nitrendipine, or 20 mg lisinopril. Blood pressure, heart rate, radial artery diameter, and arterial compliance were measured immediately before as well as 6 hours after dosing on the first and last days of the study. On the eighth day of administration, within 6 hours after dosing, lisinopril induced an acute increase in radial artery diameter, from 2.99 +/- 0.06 to 3.28 +/- 0.09 mm (mean +/- SEM, p less than 0.01). The compliance-pressure curve was shifted upward on day 1 (p less than 0.01) as well as on day 8 (p less than 0.05). None of the other drugs induced any significant modification of these parameters. Arterial compliance has a strong nonlinear dependency on intra-arterial pressure and therefore has to be defined as a function of pressure. Antihypertensive drugs acting by different mechanisms may have different effects on the mechanical properties of large arteries.