Deeply Implanted Conformal Antenna for Real-Time Bio-Telemetry Applications.

The design and experimental verification of a deeply implanted conformal printed antenna is presented. The hip implant acts as the ground plane for a coaxial-cable-fed trapezoidal radiator designed to transmit biological signals collected within the body by proper biosensors. The arrangement, consisting of a metallic (or equivalent) hip implant, bio-compatible gypsum-based dielectric, and conformal radiator, was tested when the hosting 3D-printed plastic bone was immersed in tissue-like liquid contained in a plastic bucket. The dimensions of the set-up are similar to a human leg. Matching and radiation characteristics are presented in the industrial, scientific, and medical (ISM) frequency band (2.4-2.5 GHz), showing the feasibility of the proposed arrangement.

A Single Image Deep Learning Approach to Restoration of Corrupted Landsat-7 Satellite Images.

Remote sensing is increasingly recognized as a convenient tool with a wide variety of uses in agriculture. Landsat-7 has supplied multi-spectral imagery of the Earth's surface for more than 4 years and has become an important data source for a large number of research and policy-making initiatives. Unfortunately, a scan line corrector (SLC) on Landsat-7 broke down in May 2003, which caused the loss of up to 22 percent of any given scene. We present a single-image approach based on leveraging the abilities of the deep image prior method to fill in gaps using only the corrupt image. We test the ability of deep image prior to reconstruct remote sensing scenes with different levels of corruption in them. Additionally, we compare the performance of our approach with the performance of classical single-image gap-filling methods. We demonstrate a quantitative advantage of the proposed approach compared with classical gap-filling methods. The lowest-performing restoration made by the deep image prior approach reaches 0.812 in r2, while the best value for the classical approaches is 0.685. We also present the robustness of deep image prior in comparing the influence of the number of corrupted pixels on the restoration results. The usage of this approach could expand the possibilities for a wide variety of agricultural studies and applications.

Electrogenetics: Bridging synthetic biology and electronics to remotely control the behavior of mammalian designer cells.

Electrogenetics, the combination of electronics and genetics, is an emerging field of mammalian synthetic biology in which electrostimulation is used to remotely program user-designed genetic elements within designer cells to generate desired outputs. Here, we describe recent advances in electro-induced therapeutic gene expression and therapeutic protein secretion in engineered mammalian cells. We also review available tools and strategies to engineer electro-sensitive therapeutic designer cells that are able to sense electrical pulses and produce appropriate clinically relevant outputs in response. We highlight current limitations facing mammalian electrogenetics and suggest potential future directions for research.

Investigational New Drug Enabling Nonclinical Safety Pharmacology Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent.

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a broad-spectrum antiviral drug candidate with demonstrated activity in vitro and in vivo against multiple, diverse viruses. Nonclinical safety pharmacology studies were conducted to support the filing of an Investigational New Drug (IND) application. Preliminary in vitro pharmacology testing evaluating potential for binding to "off-target" receptors and enzymes indicated no significant liability for advanced development of UV-4. The safety pharmacology of UV-4 was evaluated in the in vitro human ether-à-go-go-related gene (hERG) assay, in a central nervous system (CNS) study in the mouse (modified Irwin test), in a respiratory safety study in conscious mice using whole body plethysmography, and in a cardiovascular safety study in conscious, radiotelemetry-instrumented beagle dogs. There were no observed adverse treatment-related effects following administration of UV-4 as the hydrochloride salt in the hERG potassium channel assay, on respiratory function, in the CNS study, or in the cardiovascular assessment. Treatment-related cardiovascular effect of decreased arterial pulse pressure after 50 or 200 mg of UV-4/kg was the only change outside the normal range, and all hemodynamic parameters returned to control levels by the end of the telemetry recording period. These nonclinical safety pharmacology assessments support the evaluation of this host-targeted broad-spectrum antiviral drug candidate in clinical studies.

Experiences and outcomes on the use of telemetry to monitor the fetal heart during labour: findings from a mixed methods study.

BACKGROUND: Wireless continuous electronic fetal monitoring (CEFM) using telemetry offers potential for increased mobility during labour. United Kingdom national recommendations are that telemetry should be offered to all women having CEFM during labour. There is limited contemporary evidence on experiences of telemetry use or impacts it may have. AIM: To gather in-depth knowledge about the experiences of women and midwives using telemetry, and to assess any impact that its use may have on clinical outcomes, mobility in labour, control or satisfaction. METHODS: A convergent parallel mixed-methods study was employed. Grounded theory was adopted for interviews and analysis of 13 midwives, 10 women and 2 partners. Satisfaction, positions during labour and clinical outcome data was analysed from a cohort comparing telemetry (n = 64) with wired CEFM (n = 64). Qualitative and quantitative data were synthesised to give deeper understanding. FINDINGS: Women using telemetry were more mobile and adopted more upright positions during labour. The core category A Sense of Normality encompassed themes of 'Being Free, Being in Control', 'Enabling and Facilitating' and 'Maternity Unit Culture'. Greater mobility resulted in increased feelings of internal and external control and increased perceptions of autonomy, normality and dignity. There was no difference in control or satisfaction between cohort groups. CONCLUSIONS: When CEFM is used during labour, telemetry provides an opportunity to improve experience and support physiological capability. The use of telemetry during labour contributes to humanising birth for women who have CEFM and its use places them at the centre and in control of their birth experience.

Music to reduce stress in hospitalized patients.

PURPOSE: To determine the impact of music on the physiologic and psychological stress experienced by hospital inpatients. METHODS: This pilot study monitored vital signs; utilized pain, anxiety, and agitation rating scales; and gathered verbal feedback from 50 participating inpatients at the authors' healthcare facility as they listened to music via an audiovisual interactive patient engagement technology system. RESULTS: After listening to music for 30 minutes, patients reported significantly lower pain and anxiety. CONCLUSION: Music offered a helpful tool to reduce pain and anxiety for patients in the ICU and telemetry units at the authors' healthcare facility. Future research may be geared toward incremental expansion and monitoring of this music intervention in other units.

Quarter-Wave Plates to Improve Rotational Misalignment Robustness in Medical Telemetry.

A major challenge in developing robust wireless links to implanted/ingestible antennas is the potential for rotational misalignment. In this paper, we present an artificially anisotropic quarter-wave plate (QWP) capable of developing a circularly polarized wave from a linearly polarized wave. Without loss of generality, our QWP is composed of plastic and hydrogel, while the linearly polarized wave is developed by a bio-matched antenna-a high gain, broadband antenna with a dielectric engineered to match to biological tissues. Using a basic implanted patch antenna, we demonstrate a 1.00 dB (1.26) variance in transmission coefficient over a 90° variance, with a remarkable average measured transmission coefficient of -34.4 dB (3.63 × 10-4 ) at 2.4 GHz. Without the QWP, the rotational variance is 12.52 dB (17.9). Notably, the QWP increases the maximum input power to comply with specific absorption rate limitations. In our case, this allows for -15.0 dBm (31.6 µW) of power to be received by the implant, which is comparable to the -15.7 dBm (26.9 µW) received without the QWP. Additionally, we demonstrate that with the QWP, the standard deviation from the mean transmission for rotational misalignments remains below 3 dB (2.00) from 2 to 3.62 GHz, resulting in a simulated 57.7% fractional bandwidth. © 2021 Bioelectromagnetics Society.

Noninvasive Neuroprosthesis Promotes Cardiovascular Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) leads to severe impairment in cardiovascular control, commonly manifested as a rapid, uncontrolled rise in blood pressure triggered by peripheral stimuli-a condition called autonomic dysreflexia. The objective was to demonstrate the translational potential of noninvasive transcutaneous stimulation (TCS) in mitigating autonomic dysreflexia following SCI, using pre-clinical evidence and a clinical case report. In rats with SCI, we show that TCS not only prevents the instigation of autonomic dysreflexia, but also mitigates its severity when delivered during an already-triggered episode. Furthermore, when TCS was delivered as a multisession therapy for 6 weeks post-SCI, the severity of autonomic dysreflexia was significantly reduced when tested in the absence of concurrent TCS. This treatment effect persisted for at least 1 week after the end of therapy. More importantly, we demonstrate the clinical applicability of TCS in treatment of autonomic dysreflexia in an individual with cervical, motor-complete, chronic SCI. We anticipate that TCS will offer significant therapeutic advantages, such as obviating the need for surgery resulting in reduced risk and medical expenses. Furthermore, this study provides a framework for testing the potential of TCS in improving recovery of other autonomic functions such lower urinary tract, bowel, and sexual dysfunction following SCI.

Core battery safety pharmacology testing - An assessment of its utility in early drug development.

Requirements for safety pharmacology testing have been in place since the issue of initial regulatory guidance over 20 years ago. An evaluation of such testing, supporting first clinical entry of 105 small molecule drug candidates over the last decade, showed that a "core battery" of in vitro electrophysiological (hERG), conscious non-rodent telemetry cardiovascular, rodent central nervous system (CNS) (modified Irwin's or functional observational battery [FOB] test) and respiratory function (plethysmography) studies was performed. Routine use of the latter 2 studies appears to have limited utility, with only 21% and 28% of studies, respectively, giving findings of which none were identified as of obvious concern to moving the affected drugs into the clinic. The use of a stand-alone hERG assay does not appear to be particular sensitive in predicting proarrythmic risk as a tool by itself. Telemetry study testing had utility especially for identifying effects on QTc interval (about 10% of studies), resulting on some occasions in a lower clinical starting dose and/or increased awareness for potential effects on the cardiovascular system in the Phase I study. Overall, this investigation provides information supporting an overhaul of the current "box ticking" core battery approach used for safety pharmacology testing. However, in order to achieve a more focused examination to investigate potential undesirable pharmacodynamic effects of a new candidate drug and also support 3Rs (Replacement, Reduction and Refinement) thinking in performing unnecessary studies, there will not only need to be a sea change by drug developers but also a change in current regulatory guidance.

Cariogenic potential of oral nutritional supplements measured by intraoral plaque pH telemetry.

BACKGROUND & AIMS: Oral nutritional supplements (ONS) administered to malnourished elders and other patients contain high-levels of carbohydrates that could be a potential risk factor for dental caries. This study aimed to evaluate the cariogenic potentials of ONS using intraoral plaque telemetry. METHODS: Ten ONS were tested on five healthy volunteers (mean age: 76.8 ± 9.15 years). Participants were requested to refrain from performing oral hygiene 3-7 days prior to testing. The pH-value below the dental plaque on the tooth was measured while the ONS was being consumed. After neutralizing the participant's saliva, a control solution (10% sucrose) was administered and telemetry measurements were repeated. Mean relative cariogenicity (RC) was calculated for each ONS. ANOVA and post hoc tests were used for statistical analyses (p < 0.05). RESULTS: All ten ONS were potentially cariogenic on enamel with an overall RC of 0.519 ± 0.35 (Range: Min = 0.31 ± 0.16; Max = 1.00 ± 0.34). RC differed significantly between the ONS (p = 0.002). RC was lower in ONS that contained high-protein (p = 0.018). RC was not influenced by other factors such as readily consumable (p = 0.102), flavor (p = 0.869), consistency (p = 0.126), fiber containing (p = 0.134), style (p = 0.112), and age of plaque (p = 0.339). CONCLUSIONS: The ONS administered to elders and malnourished patients are potentially cariogenic. It is imperative that the administration of ONS must be based on individual needs to potentiate a maximum benefit. Wherever possible, an attempt to limit the use of high-carbohydrate containing ONS must be practiced along with the adoption of suitable preventive measures to arrest the development and progression of caries.

Effects of Anisodine Hydrobromide on the Cardiovascular and Respiratory Functions in Conscious Dogs.

PURPOSE: Anisodine hydrobromide (Ani) is isolated from the medicinal plant Anisodus tanguticus (Maxim.) Pascher for clinical use. Although considerable research regarding Ani has been reported, the safety profiles of Ani are currently unknown. This study investigated the cardiorespiratory effects of Ani in conscious dogs to provide clinicians a detailed safety profile of Ani on the cardiorespiratory system. MATERIALS AND METHODS: Using the Latin square design, the study was divided into six phases, where in each phase, six telemetered beagle dogs received one dose of normal saline or sotalol hydrochloride or Ani (0.1, 0.4, 1.6, or 6.4 mg/kg). Electrocardiogram, blood pressure (BP) and respiratory parameters were collected before and after administration for 24 hours. Statistical comparisons were performed at scheduled time-points. RESULTS: The heart rate was significantly increased, PR and QTCV intervals were significantly shortened in Ani 0.4, 1.6, 6.4 mg/kg treatment group after drug administration. Compared with the saline group, a significant increase in heart rate and shortening of PR, QTCV intervals were observed in the Ani 1.6, 6.4 mg/kg treatment groups from 5 min to 4 h time-points. Diastolic and mean BP were significantly increased in Ani 1.6, 6.4 mg/kg from 1 h to 2 h time-points compared to those of the saline control. Accelerated breathing was observed in the first 20 min after Ani 0.4, 1.6, and 6.4 mg/kg treatment, although not statistically significant. Furthermore, no significant differences were observed in any of the corresponding indexes of Ani 0.1 mg/kg treatment group at different time-points compared to those of the saline group. CONCLUSION: Ani may have adverse effects on the cardio-respiratory systems of dogs at doses above 0.4 mg/kg, whereas Ani 0.1 mg/kg was devoid of potentially deleterious effects on cardiorespiratory function.

Applications of a novel radiotelemetry method for the measurement of intrathoracic pressures and physiological rhythms in freely behaving mice.

Techniques to comprehensively evaluate pulmonary function carry a variety of limitations, including the ability to continuously record intrathoracic pressures (ITP), acutely and chronically, in a natural state of freely behaving animals. Measurement of ITP can be used to derive other respiratory parameters, which provide insight to lung health. Our aim was to develop a surgical approach for the placement of a telemetry pressure sensor to measure ITP, providing the ability to chronically measure peak pressure, breath frequency, and timing of the respiratory cycle to facilitate circadian analyses related to breathing patterns. Applications of this technique are shown using a moderate hypoxic challenge. Male C57Bl/6 mice were implanted with radiotelemetry devices to record heart rate, temperature, activity, and ITP during 24-h normoxia, 24-h hypoxia ([Formula: see text] = 0.15), and return to 48-h normoxia. Radiotelemetry of ITP permitted the detection of hypoxia-induced increases in "the ITP equivalent" of ventilation, which were driven by increases in breathing frequency and ITP on a short-term time scale. Respiratory frequency, derived from pressure waveforms, was increased by a decrease in expiratory time without changes in inspiratory time. Chronically, telemetric recording allowed for circadian analyses of respiratory drive, as assessed by inspiratory pressure divided by inspiratory time, which was increased by hypoxia and remained elevated for 48 h of recovery. Furthermore, respiratory frequency demonstrated a circadian rhythm, which was disrupted through the recovery period. In conclusion, radiotelemetry of ITP is a viable, long-term, chronic methodology that extends traditional methods to evaluate respiratory function in mice.NEW & NOTEWORTHY We have demonstrated for the first time in mice that radiotelemetry is an effective tool for the continuous and chronic recording of intrathoracic pressure (ITP) to facilitate circadian rhythm analyses. We show that continuous 24-h hypoxic stress alters the circadian rhythms of heart rate, body temperature, activity, and respiratory parameters, acutely and perpetually, through normoxic recovery. Radiotelemetry of ITP can complement traditional methods for evaluating respiratory function and better our understanding of respiratory pathophysiology.

Improving Quiet at Night on a Telemetry Unit: Introducing a Holistic Sleep Menu Intervention.

In a patient's recovery process, restful sleep is crucial. Although the essential role of sleep in healing has long been recognized, excessive noise in hospital environments remains a persistent and pervasive problem. For hospitalized patients, environmental noise can result in sleep deprivation and adverse health outcomes; not surprisingly, hospital noise ranks as a major patient complaint. At a small suburban community hospital, patients responding to a quiet-at-night question in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey gave the hospital's telemetry unit the lowest possible score: 1 out of 5 points. In response, the unit's quality improvement team, coordinated by a clinical nurse leader, introduced a holistic "sleep menu" intervention. The multicomponent intervention subsequently improved patients' care experience and staff engagement. The percentage of patients who self-reported five or more hours of uninterrupted sleep rose from 31% at baseline to 80% during the intervention. This improvement was sustained over the three-month intervention period and led to a quiet-at-night HCAHPS score of 4. The sleep menu initiative resulted in substantial benefits that optimized both patient and organizational outcomes.

Device profile of the MED-EL cochlear implant system for hearing loss: overview of its safety and efficacy.

INTRODUCTION: Patients suffering from severe to profound hearing loss or even deafness can achieve a hearing improvement with a cochlear implant (CI) treatment that is significantly higher than the results achieved with conventional hearing aids. The CI system consists of an implantable stimulator, which is inserted retro-auricularly into the mastoid, and an externally worn processor unit, which provides the pickup of sound and processing of acoustic information as well as the power supply for the stimulator and internal current sources. The stimulator has an electrode array that is inserted into the cochlea. AREAS COVERED: This is a descriptive overview of MED-EL's multichannel CI system (MED-EL, Innsbruck, Austria), which was introduced to the European market in 1994. The continuing development of the implant as well as the external components is outlined and various other aspects (stimulation strategy, adaptation, results, reliability) are discussed. EXPERT COMMENTARY: The strength of the company is the continuous pursuit of innovative ideas. This is evidenced by numerous innovations. The reliability of the implants has been continuously improved. The current SYNCHRONY models of the manufacturer show no indication of technically caused failures over an observation period of 5 years.

Loop Recorder Implantation on a Telemetry Ward.

The implantable loop recorder (ILR) is a valuable tool used in the evaluation of syncope, arrhythmia, and cryptogenic stroke. In the inpatient setting, ILRs are routinely implanted in the electrophysiology (EP) lab despite the low complication rate. The purpose of this study was to evaluate the safety, feasibility, and cost of implanting ILRs at the patient's bedside by both electrophysiologists and advanced practice providers (APPs). This was a single center, retrospective study of consecutive ILR implantations performed from February 2018 to May 2019. We examined 3 groups: implantations in the EP lab by electrophysiologists (EP Lab/MD), implantations at the bedside by electrophysiologists (Floor/MD), and implantations at the bedside by APPs (Floor/APP). Over 15 months, 152 patients underwent ILR implantation: 48 in the EP Lab/MD group, 57 in the Floor/MD group, and 47 in the Floor/APP group. The procedure duration was longer in the Floor/APP group (14.2 ± 5.9 minutes) compared with the EP Lab/MD and Floor/MD groups (6.8 ± 4.3 minutes, 9.1 ± 4.9 minutes, p <0.001). The overall complication rate was low (2.6%) with no differences between the groups (p = 0.83). The calculated costs per implant for the EP Lab/MD group, Floor/MD group, and Floor/APP group were $482.05, $162.82, and $73.08, respectively.

Evaluating Associations Between Nonclinical Cardiovascular Functional Endpoints and Repeat-dose Cardiovascular Toxicity in the Beagle Dog: A Cross-company Initiative.

Integrating nonclinical in vitro, in silico, and in vivo datasets holistically can improve hazard characterization and risk assessment. In pharmaceutical development, cardiovascular liabilities are a leading cause of compound attrition. Prior to clinical studies, functional cardiovascular data are generated in single-dose safety pharmacology telemetry studies, with structural pathology data obtained from repeat-dose toxicology studies with limited concurrent functional endpoints, eg, electrocardiogram via jacketed telemetry. Relationships between datasets remain largely undetermined. To address this gap, a cross-pharma collaboration collated functional and structural data from 135 compounds. Retrospective functional data were collected from good laboratory practice conscious dog safety pharmacology studies: effects defined as hemodynamic blood pressure or heart rate changes. Morphologic pathology findings (mainly degeneration, vacuolation, inflammation) from related toxicology studies in the dog (3-91 days repeat-dosing) were reviewed, harmonized, and location categorized: cardiac muscle (myocardium, epicardium, endocardium, unspecified), atrioventricular/aortic valves, blood vessels. The prevalence of cardiovascular histopathology changes was 11.1% of compounds, with 53% recording a functional blood pressure or heart rate change. Correlations were assessed using the Mantel-Haenszel Chi-square trend test, identifying statistically significant associations between cardiac muscle pathology and (1) decreased blood pressure, (2) increased heart rate, and between cardiovascular vessel pathology and increased heart rate. Negative predictive values were high, suggesting few compounds cause repeat-dose cardiovascular structural change in the absence of functional effects in single-dose safety pharmacology studies. Therefore, observed functional changes could prompt moving (sub)chronic toxicology studies forward, to identify cardiovascular liabilities earlier in development, and reduce late-stage attrition.

Electrogram morphology discriminators in implantable cardioverter defibrillators: A comparative evaluation.

BACKGROUND: Morphology algorithms are currently recommended as a standalone discriminator in single-chamber implantable cardioverter defibrillators (ICDs). However, these proprietary algorithms differ in both design and nominal programming. OBJECTIVE: To compare three different algorithms with nominal versus advanced programming in their ability to discriminate between ventricular (VT) and supraventricular tachycardia (SVT). METHODS: In nine European centers, VT and SVTs were collected from Abbott, Boston Scientific, and Medtronic dual- and triple-chamber ICDs via their respective remote monitoring portals. Percentage morphology matches were recorded for selected episodes which were classified as VT or SVT by means of atrioventricular comparison. The sensitivity and related specificity of each manufacturer discriminator was determined at various values of template match percentage from receiving operating characteristics (ROC) curve analysis. RESULTS: A total of 534 episodes were retained for the analysis. In ROC analyses, Abbott Far Field MD (area under the curve [AUC]: 0.91; P < .001) and Boston Scientific RhythmID (AUC: 0.95; P < .001) show higher AUC than Medtronic Wavelet (AUC: 0.81; P < .001) when tested for their ability to discriminate VT from SVT. At nominal % match threshold all devices provided high sensitivity in VT identification, (91%, 100%, and 90%, respectively, for Abbott, Boston Scientific, and Medtronic) but contrasted specificities in SVT discrimination (85%, 41%, and 62%, respectively). Abbott and Medtronic's nominal thresholds were similar to the optimal thresholds. Optimization of the % match threshold improved the Boston Scientific specificity to 79% without compromising the sensitivity. CONCLUSION: Proprietary morphology discriminators show important differences in their ability to discriminate SVT. How much this impact the overall discrimination process remains to be investigated.

Value of provocative electrophysiology testing in the management of pediatric patients after congenital heart surgery.

OBJECTIVE: To determine the impact of provocative electrophysiology testing in postoperative congenital heart disease (CHD) patients on the management of supraventricular tachycardia (SVT) and clinical outcomes. METHODS: This is a retrospective study including patients <18 years of age with surgery for CHD who had postoperative SVT between 2006 and 2017. Postoperative outcomes were compared between patients with and without postoperative electrophysiology testing using the Wilcoxon rank sum test, Fisher's exact test, Kaplan-Meier method with the log-rank test, and Cox proportional hazard model. RESULTS: From 341 patients who had SVT after surgery for CHD, 65 (19%) had postoperative electrophysiology testing. There was no significant difference in baseline patient characteristics or surgical complexity between patients with and without electrophysiology testing. Patients with inducible SVT on electrophysiology testing were more likely to have recurrence of SVT prior to hospital discharge with an odds ratio 4.0 (95% confidence interval 1.3, 12.0). Patients who underwent postoperative electrophysiology testing had shorter intensive care unit (12 [6, 20] vs 16 [9, 32] days, HR 2.1 [95% CI 1.6, 2.8], P < .001) and hospital (25 [13, 38] vs 31 [18, 54] days, HR 1.8 [95% CI 1.4, 2.4], P < .001) length of stay. CONCLUSION: Postoperative electrophysiology testing was associated with improved postoperative outcomes, likely related to the ability to predict recurrence of arrhythmia and tailored antiarrhythmic management.