School-Based Telemedicine for Hypertension Management in Urban Adolescents.

PURPOSE: The aim of this study is to determine if hypertensive adolescents from impoverished neighborhoods in Rochester, New York have improved blood pressure (BP) control with the use of school-based telemedicine. METHODS: Adolescents receiving antihypertensive medication had monthly study telemedicine visits at school. BP was measured by a telehealth clinical assistant (CTA) at the school using standard procedures, followed in real time by a teleconferencing visit with the study physician. RESULTS: Six participants were enrolled, and all completed school-based telemedicine visits prior to school closure due to the SARS-CoV-2 pandemic. Mean systolic and diastolic BP at baseline were 139 ± 5 and 75 ± 8 mmHg. All six participants had significant improvement in their blood pressure (final school mean BPs, 127 ± 4 and 67 ± 5 mmHg; systolic, baseline vs. final, p = .003). DISCUSSION: In this pilot study, adolescents with very high levels of neighborhood disadvantage had consistent adherence with school-based telemedicine and significant improvement in hypertension (HTN) control.

Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation.

Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data were fitted simultaneously using the stochastic approximation expectation-maximization algorithm for nonlinear mixed effects. A one-compartment model with linear elimination and first-order absorption after intragastric administration, best described the available pharmacokinetic data. Final parameter estimates indicate that DXC has a high volume of distribution (108 L/kg) as well as high absorption (10.3 h-1) in donkeys. However, results suggest that oral DXC at 10 mg/kg q12 h in donkeys would not result in a therapeutic concentration in serum, urine, synovial fluid or endometrium by comparison to the minimum inhibitory concentration of common equine pathogens. Further studies are recommended to identify appropriate dosage and dosing intervals of oral DXC in donkeys.

Magnetic Resonance Imaging in Childhood Primary Hypertension: Potential in the Study of Cognitive Outcomes.

Primary hypertension in youth and young adulthood is associated with decreased neurocognitive test performance both in midlife and during youth itself, leading to concern of subsequent cognitive decline and dementia in later life. The early vascular effects of hypertension in youth are likely involved in the pathogenesis of hypertensive target organ damage to the brain, but the potential impact of antihypertensive treatment from youth on subsequent cognitive health is not known. This review will highlight the need to answer the question of whether treatment of hypertension from early in life would slow cognitive decline in adulthood, and will then outline, for the nonneurologist, magnetic resonance imaging techniques potentially useful in the study of the pathogenesis of decreased cognition in hypertensive youth and for use as potential biomarkers for early antihypertensive treatment interventions.

Effect of a short pre-anesthetic fast on arterial blood gas values in isoflurane-anesthetized donkeys.

This study compared arterial blood gas parameters in anesthetized adult donkeys after a 5-hour fast (n = 22) or no fast (n = 21). Donkeys were premedicated with xylazine, induced to anesthesia with ketamine and diazepam or midazolam, and maintained with isoflurane in oxygen while breathing spontaneously and positioned in lateral recumbency. Sampling occurred approximately 25 minutes after induction. Arterial pH, bicarbonate concentration, and base excess were higher in fasted donkeys compared to unfasted donkeys. There were no differences in partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, or arterial lactate concentrations. No advantages of a short pre-anesthetic fast were identified.

Effet d'un court jeûne pré-anesthésie sur les valeurs des gaz sanguins artériels chez des ânes anesthésiés à l'isoflurane. La présente étude visait à comparer les paramètres des gaz sanguins artériels chez des ânes adultes anesthésiés après un jeûne de 5 heures (n = 22) ou aucun jeûne (n = 21). Les ânes ont reçu une prémédication de xylazine, l'anesthésie induite avec de la kétamine et du diazépam ou du midazolam, et maintenue avec de l'isoflurane dans de l'oxygène par respiration spontanée et positionnés en décubitus latéral. L'échantillonnage eut lieu environ 25 minutes après l'induction. Le pH artériel, la concentration en bicarbonate, et l'excès de base étaient plus élevés chez les ânes ayant jeûnés comparativement à ceux n'ayant pas jeûnés. Il n'y avait pas de différence dans la pression partielle d'oxygène artériel, la pression partielle de dioxyde de carbone artériel, ou des concentrations de lactate artériel. Aucun avantage à un court jeûne pré-anesthésie ne fut identifié.(Traduit par Dr Serge Messier).

Induction of anesthesia and recovery in donkeys sedated with xylazine: a comparison of midazolam-alfaxalone and midazolam-ketamine.

OBJECTIVE: To compare the induction and recovery characteristics and selected cardiopulmonary variables of midazolam-alfaxalone or midazolam-ketamine in donkeys sedated with xylazine. STUDY DESIGN: Randomized, blinded, crossover experimental trial. ANIMALS: A group of seven adult male castrated donkeys weighing 164 ± 14 kg. METHODS: Donkeys were randomly administered midazolam (0.05 mg kg-1) and alfaxalone (1 mg kg-1) or midazolam (0.05 mg kg-1) and ketamine (2.2 mg kg-1) intravenously following sedation with xylazine, with ≥ 7 days between treatments. Donkeys were not endotracheally intubated and breathed room air. Time to lateral recumbency, first movement, sternal recumbency and standing were recorded. Induction and recovery were assigned scores between 1 (very poor) and 5 (excellent). Heart rate (HR), respiratory rate (fR), invasive arterial blood pressures and arterial blood gases were measured before induction and every 5 minutes following induction until first movement. RESULTS: Time to lateral recumbency (mean ± standard deviation) was shorter after alfaxalone (29 ± 10 seconds) compared with ketamine (51 ± 9 seconds; p = 0.01). Time to first movement was the same between treatments (27 versus 23 minutes). Time to standing was longer with alfaxalone (58 ± 15 minutes) compared with ketamine (33 ± 8 minutes; p = 0.01). Recovery score [median (range)] was of lower quality with alfaxalone [3 (2-5)] compared with ketamine [5 (3-5); p = 0.03]. There were no differences in HR, fR or arterial pressures between treatments. No clinically important differences in blood gases were identified between treatments. Five of seven donkeys administered alfaxalone became hypoxemic (PaO2 <60 mmHg; 8.0 kPa) and all donkeys administered ketamine became hypoxemic (p = 0.13). CONCLUSIONS AND CLINICAL RELEVANCE: Both midazolam-alfaxalone and midazolam-ketamine produced acceptable anesthetic induction and recovery in donkeys after xylazine sedation. Hypoxemia occurred with both treatments.

A Method for Functional Task Alignment Analysis of an Arthrocentesis Simulator.

INTRODUCTION: During simulation-based education, simulators are subjected to procedures composed of a variety of tasks and processes. Simulators should functionally represent a patient in response to the physical action of these tasks. The aim of this work was to describe a method for determining whether a simulator does or does not have sufficient functional task alignment (FTA) to be used in a simulation. METHODS: Potential performance checklist items were gathered from published arthrocentesis guidelines and aggregated into a performance checklist using Lawshe's method. An expert panel used this performance checklist and an FTA analysis questionnaire to evaluate a simulator's ability to respond to the physical actions required by the performance checklist. RESULTS: Thirteen items, from a pool of 39, were included on the performance checklist. Experts had mixed reviews of the simulator's FTA and its suitability for use in simulation. Unexpectedly, some positive FTA was found for several tasks where the simulator lacked functionality. CONCLUSIONS: By developing a detailed list of specific tasks required to complete a clinical procedure, and surveying experts on the simulator's response to those actions, educators can gain insight into the simulator's clinical accuracy and suitability. Unexpected of positive FTA ratings of function deficits suggest that further revision of the survey method is required.

Degree of corneal anesthesia after topical application of 0.4% oxybuprocaine ophthalmic solution in normal equids.

Oxybuprocaine hydrochloride ophthalmic solution has been widely used off-label in horses and donkeys, despite lack of data demonstrating efficacy and safety in these species. The objective of this study was to assess anesthetic efficacy of 0.4% oxybuprocaine hydrochloride ophthalmic solution in horses (n = 5) and donkeys (n = 24) and compare the effects with 0.5% proparacaine hydrochloride ophthalmic solution. The baseline corneal touch threshold (CTT) was measured with a Cochet-Bonnet esthesiometer. Donkeys (n = 12) and horses (n = 5) in group A received sterile ophthalmic solutions 0.4% oxybuprocaine with fluorescein (also termed benoxinate with fluorescein, abbreviated as ben + flu) instilled in one eye and 0.9% sterile sodium chloride solution (NaCl) with fluorescein (Na + flu) in the contralateral eye. Donkeys (n = 12) and horses (n = 5) in group B received sterile ophthalmic solutions (ben + flu) in one eye and 0.5% proparacaine with fluorescein (prop + flu) in the contralateral eye. The CTT was measured at 1 and 5 min post-application and at 5-minute intervals until 75 min after treatment. The CTT changes over time differed significantly between oxybuprocaine-treated and control eyes (P < 0.001). The CTT continued to decrease throughout the duration of the study when compared with baseline values. No statistically significant difference in onset, depth, or duration of corneal anesthesia was found between oxybuprocaine and proparacaine treated eyes during the time of the study. Interestingly, horses were shown to have a significantly more sensitive cornea than donkeys (P = 0.002). Oxybuprocaine and proparacaine reduced corneal sensitivity in donkeys and horses. No local irritation was observed with 0.4% oxybuprocaine.

La solution ophtalmique d'hydrochlorure d'oxybuprocaïne a été utilisée extensivement en dérogation chez les chevaux et les ânes, malgré le manque de données démontrant son efficacité et son innocuité chez ces espèces. L'objectif de la présente étude était d'évaluer l'efficacité anesthétique d'une solution ophtalmique d'hydrochlorure d'oxybuprocaïne 0,4 % chez des chevaux (n = 5) et des ânes (n = 24) et comparer les effets avec une solution ophtalmique d'hydochlorure de proparacaïne 0,5 %. La valeur de base du seuil de contact cornéen (SCT) a été mesurée à l'aide d'un esthésiomètre Cochet-Bonnet. Les ânes (n = 12) et chevaux (n = 5) du groupe A ont reçu une solution ophtalmique stérile d'oxybuprocaïne 0,4 % avec de la fluorescéine (également appelée benoxinate avec fluorescéine, abrévié ben + flu) dans un oeil et une solution stérile de chlorure de sodium 0,9 % (NaCl) avec de la fluorescéine (Na + flu) dans l'oeil contra-latéral. Les ânes (n = 12) et chevaux (n = 5) du groupe B ont reçu les solutions ophtalmiques stériles de (ben + flu) dans un oeil et de la propacaïne 0,5 % avec de la fluorescéine (prop + flu) dans l'oeil contra-latéral. Le SCT a été mesuré à 1 et 5 min post-application et à des intervalles de 5 min jusqu'à 75 min après le traitement. Les changements dans le temps du SCT différaient de manière significative entre les yeux traités à l'oxybuprocaïne et les témoins (P < 0,001). Le SCT continua de diminuer tout au long de la durée de l'étude lorsque comparé aux valeurs de base. Aucune différence significative dans le début, la profondeur, ou la durée de l'anesthésie cornéenne ne fut trouvée entre les yeux traités à l'oxybuprocaïne et la proparacaïne durant la durée de l'étude. De manière intéressante, les chevaux avaient une cornée significativement plus sensible que les ânes (P = 0,002). L'oxybuprocaïne et la proparacaïne ont réduit la sensibilité cornéenne chez les ânes et les chevaux. Aucune irritation locale ne fut observée avec l'oxybuprocaïne 0,4 %.(Traduit par Docteur Serge Messier).

Cardiovascular effects of ozone in healthy subjects with and without deletion of glutathione-S-transferase M1.

CONTEXT: Exposure to ozone has acute respiratory effects, but few human clinical studies have evaluated cardiovascular effects. OBJECTIVE: We hypothesized that ozone exposure alters pulmonary and systemic vascular function, and cardiac function, with more pronounced effects in subjects with impaired antioxidant defense from deletion of the glutathione-S-transferase M1 gene (GSTM1 null). METHODS: Twenty-four young, healthy never-smoker subjects (12 GSTM1 null) inhaled filtered air, 100 ppb ozone and 200 ppb ozone for 3 h, with intermittent exercise, in a double-blind, randomized, crossover fashion. Exposures were separated by at least 2 weeks. Vital signs, spirometry, arterial and venous blood nitrite levels, impedance cardiography, peripheral arterial tonometry, estimation of pulmonary capillary blood volume (Vc), and blood microparticles and platelet activation were measured at baseline and during 4 h after each exposure. RESULTS: Ozone inhalation decreased lung function immediately after exposure (mean ± standard error change in FEV1, air: -0.03 ± 0.04 L; 200 ppb ozone: -0.30 ± 0.07 L; p < 0.001). The immediate post-exposure increase in blood pressure, caused by the final 15-min exercise period, was blunted by 200 ppb ozone exposure (mean ± standard error change for air: 16.7 ± 2.6 mmHg; 100 ppb ozone: 14.5 ± 2.4 mmHg; 200 ppb ozone: 8.5 ± 2.5 mmHg; p = 0.02). We found no consistent effects of ozone on any other measure of cardiac or vascular function. All results were independent of the GSTM1 genotype. CONCLUSIONS: We did not find convincing evidence for early acute adverse cardiovascular consequences of ozone exposure in young healthy adults. The ozone-associated blunting of the blood pressure response to exercise is of unclear clinical significance.

Inhalation of ultrafine carbon particles alters heart rate and heart rate variability in people with type 2 diabetes.

BACKGROUND: Diabetes may confer an increased risk for the cardiovascular health effects of particulate air pollution, but few human clinical studies of air pollution have included people with diabetes. Ultrafine particles (UFP, ≤100 nm in diameter) have been hypothesized to be an important component of particulate air pollution with regard to cardiovascular health effects. METHODS: 17 never-smoker subjects 30-60 years of age, with stable type 2 diabetes but otherwise healthy, inhaled either filtered air (0-10 particles/cm3) or elemental carbon UFP (~107 particles/cm3, ~50 ug/m3, count median diameter 32 nm) by mouthpiece, for 2 hours at rest, in a double-blind, randomized, crossover study design. A digital 12-lead electrocardiogram (ECG) was recorded continuously for 48 hours, beginning 1 hour prior to exposure. RESULTS: Analysis of 5-minute segments of the ECG during quiet rest showed reduced high-frequency heart rate variability with UFP relative to air exposure (p = 0.014), paralleled by non-significant reductions in time-domain heart rate variability parameters. In the analysis of longer durations of the ECG, we found that UFP exposure increased the heart rate relative to air exposure. During the 21- to 45-hour interval after exposure, the average heart rate increased approximately 8 beats per minute with UFP, compared to 5 beats per minute with air (p = 0.045). There were no UFP effects on cardiac rhythm or repolarization. CONCLUSIONS: Inhalation of elemental carbon ultrafine particles alters heart rate and heart rate variability in people with type 2 diabetes. Our findings suggest that effects may occur and persist hours after a single 2-hour exposure.

Effects of outdoor air pollutants on platelet activation in people with type 2 diabetes.

Exposure to air pollution is associated with increased morbidity and mortality from cardiovascular disease. We hypothesized that increases in exposure to ambient air pollution are associated with platelet activation and formation of circulating tissue factor-expressing microparticles. We studied 19 subjects with type 2 diabetes, without clinical evidence of cardiovascular disease, who had previously participated in a human clinical study of exposure to ultrafine particles (UFP). Blood was obtained for measurements of platelet activation following an overnight stay in the Clinical Research Center, prior to each of their two pre-exposure visits. Air pollution and meteorological data, including UFP counts, were analyzed for the 5 days prior to the subjects' arrival at the Clinical Research Center. Contrary to expectations, increases in UFP were associated with decreases in surface expression of platelet activation markers. The number of platelet-leukocyte conjugates decreased by -80 (95% confidence interval (CI) -123 to -37, p = 0.001) on the first lag day (20-44 h prior to the blood draw) and by -85 (CI -139 to -31, p = 0.005) on combined lag days 1 to 5, per interquartile range (IQR) increase in UFP particle number (2482). However, levels of soluble CD40L increased 104 (CI 3 to 205, p = 0.04) pg/ml per IQR increase in UFP on lag day 1, a finding consistent with prior platelet activation. We speculate that, in people with diabetes, exposure to UFP activates circulating platelets within hours of exposure, followed by an increase in soluble CD40L and a rebound reduction in circulating platelet surface markers.

Vascular effects of ultrafine particles in persons with type 2 diabetes.

BACKGROUND: Diabetes confers an increased risk for cardiovascular effects of airborne particles. OBJECTIVE: We hypothesized that inhalation of elemental carbon ultrafine particles (UFP) would activate blood platelets and vascular endothelium in people with type 2 diabetes. METHODS: In a randomized, double-blind, crossover trial, 19 subjects with type 2 diabetes inhaled filtered air or 50 µg/m³ elemental carbon UFP (count median diameter, 32 nm) by mouthpiece for 2 hr at rest. We repeatedly measured markers of vascular activation, coagulation, and systemic inflammation before and after exposure. RESULTS: Compared with air, particle exposure increased platelet expression of CD40 ligand (CD40L) and the number of platelet-leukocyte conjugates 3.5 hr after exposure. Soluble CD40L decreased with UFP exposure. Plasma von Willebrand factor increased immediately after exposure. There were no effects of particles on plasma tissue factor, coagulation factors VII or IX, or D-dimer. CONCLUSIONS: Inhalation of elemental carbon UFP for 2-hr transiently activated platelets, and possibly the vascular endothelium, in people with type 2 diabetes.

DNA and polylysine adsorption and multilayer construction onto cationic lipid-coated microbubbles.

We report on a novel application of the layer-by-layer (LbL) assembly technique to attach multiple layers of DNA and poly-l-lysine (PLL) onto preformed lipid-coated microbubbles to increase the DNA loading capacity. We first measured the effects of the cationic lipid fraction and salt concentration on the microbubble stability. Microbubble production and stability were robust up to a cationic lipid fraction of 40 mol % in 10 mM NaCl. DNA adsorption was heterogeneous over the microbubble shell and occurred primarily on the condensed phase domains. The amount of adsorbed DNA, and subsequently adsorbed PLL, increased linearly with the fraction of cationic lipid in the shell. DNA loading was further enhanced by the LbL assembly method to construct polyelectrolyte multilayers (PEMs) of DNA and PLL. PEM buildup was demonstrated by experimental results from zeta potential analysis, fluorescence microscopy, UV spectroscopy, and flow cytometry. The PEMs exhibited two growth stages and were heterogeneously distributed over the microbubble surface. The DNA loading capacity onto the microbubbles was enhanced by over 10-fold by using five paired layers. However, the PEM shell did not prevent oscillation or destruction during ultrasound insonification. These results suggest that the surface can be compartmentalized to make multifunctional, high-payload ultrasound contrast agents for targeted gene therapy.

Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle.

A new acoustically-active delivery vehicle was developed by conjugating liposomes and microbubbles, using the high affinity interaction between avidin and biotin. Binding between microbubbles and liposomes, each containing 5% DSPE-PEG2kBiotin, was highly dependent on avidin concentration and observed above an avidin concentration of 10 nM. With an optimized avidin and liposome concentration, we measured and calculated as high as 1000 to 10,000 liposomes with average diameters of 200 and 100 nm, respectively, attached to each microbubble. Replacing avidin with neutravidin resulted in 3-fold higher binding, approaching the calculated saturation level. High-speed photography of this new drug delivery vehicle demonstrated that the liposome-bearing microbubbles oscillate in response to an acoustic pulse in a manner similar to microbubble contrast agents. Additionally, microbubbles carrying liposomes could be spatially concentrated on a monolayer of PC-3 cells at the focal point of ultrasound beam. As a result of cell-vehicle contact, the liposomes fused with the cells and internalization of NBD-cholesterol occurred shortly after incubation at 37 degrees C, with internalization of NBD-cholesterol substantially enhanced in the acoustic focus.

Phospholipid vesicles increase the survival of freeze-dried human red blood cells.

In a previous report [Z. Török, G. Satpathy, M. Banerjee, R. Bali, E. Little, R. Novaes, H. Van Ly, D. Dwyre, A. Kheirolomoom, F. Tablin, J.H. Crowe, N.M. Tsvetkova, Preservation of trehalose loaded red blood cells by lyophilization, Cell Preservation Technol. 3 (2005) 96-111.], we presented a method for preserving human red blood cells (RBCs) by loading them with trehalose and then freeze-drying. We have now improved that method, based on the discovery that addition of phospholipid vesicles to the lyophilization buffer substantially reduces hemolysis of freeze-dried RBCs after rehydration. The surviving cells synthesize 2,3-DPG, have low levels of methemoglobin, and have preserved morphology. Among the lipid species we studied, unsaturated PCs were found to be most effective in suppressing hemoglobin leakage. RBC-vesicle interactions depend on vesicle size and structure; unilamellar liposomes with average diameter of less than 300 nm were more effective in reducing the hemolysis than multilamellar vesicles. Trehalose loaded RBCs demonstrated high survival and low levels of methemoglobin during 10 weeks of storage at 4 degrees C in the dry state when lyophilized in the presence of liposomes.

Loading red blood cells with trehalose: a step towards biostabilization.

A method for freeze-drying red blood cells (RBCs) while maintaining a high degree of viability has important implications in blood transfusion and clinical medicine. The disaccharide trehalose, found in animals capable of surviving dehydration can aid in this process. As a first step toward RBC preservation, we present a method for loading RBCs with trehalose. The method is based on the thermal properties of the RBC plasma membranes and provides efficient uptake of the sugar at 37 degrees C in a time span of 7 h. The data show that RBCs can be loaded with trehalose from the extracellular medium through a combination of osmotic imbalance and the phospholipid phase transition, resulting in intracellular trehalose concentrations of about 40 mM. During the loading period, the levels of ATP and 2,3-DPG are maintained close to the levels of fresh RBCs. Increasing the membrane fluidity through the use of a benzyl alcohol results in a higher concentration of intracellular trehalose, suggesting the importance of the membrane physical state for the uptake of the sugar. Osmotic fragility data show that trehalose exerts osmotic protection on RBCs. Flow cytometry data demonstrate that incubation of RBCs in a hypertonic trehalose solution results in a fraction of cells with different complexity and that it can be removed by washing and resuspending the RBCs in an iso-osmotic medium. The data provide an important first step in long-term preservation of RBCs.