Studies In Human Subjects Research Articles

A Simple-Units Complex-Structure Neural Network model of the Basal Ganglia to simulate reinforcement learning tasks

In the computation psychiatry field, the reinforcement learning tasks aim at measuring a subject’s sensitivity to rewards and punishments. We aim at providing a mechanistic account of behavioral data of participants undergoing reinforcement learning tasks in Wroclaw Medical University by quantitatively reproduce the observed tendencies through computer simulations of the developed Simple-Units Complex-Structure Neural Network. The network mimics the core properties of the Basal Ganglia which is a group of subcortical nuclei present in the brain responsible for motor control and learning from rewards and punishments. We demonstrate the performance of the proposed network on three reinforcement learning tasks: probabilistic selection task, probabilistic reversal task, and instructed version of the probabilistic learning task. Our simulations show that the network can express the behavior observed in studies of human subjects performing reinforcement learning tasks.

Autonomous, Real-Time Monitoring Electrochemical Aptasensor for Circadian Tracking of Cortisol Hormone in Sub-microliter Volumes of Passively Eluted Human Sweat.

The proposed work involves the development of an autonomous, label-free electrochemical sensor for real-time monitoring of cortisol levels expressed naturally in sub-microliter sweat volumes, for prolonged sensing periods of ∼8 h. Highly specific single-stranded DNA (ssDNA) aptamer is used for affinity capture of cortisol hormone eluted in sweat dynamically. The cortisol present in sweat binds to the aptamer capture probe that changes conformation and modulates electrochemical properties at the electrode-buffer interface, which was studied using dynamic light scattering studies for the entire physiological sweat pH. Attenuated total reflectance-Fourier transform infrared spectroscopy and UV-vis spectroscopy were used to optimize the binding chemistry of the elements of the sensor stack. Nonfaradaic electrochemical impedance spectroscopy was used to calibrate the sensor for a dynamic range of 1-256 ng/mL. An R2 of 0.97 with an output signal range of 20-50% was obtained. Dynamic cortisol level variation tracking was studied using continuous dosing experiments to calibrate the sensor for temporal variation. The sensor did not show significant susceptibility to noise due to cross-reactive interferents and nonspecific buffer constituents. The performance of the developed aptasensor was compared with the previously established cortisol immunosensor in terms of surface charge behavior and nonfaradaic biosensing. The aptamer sensor shows a higher signal-to-noise ratio, better resolution, and has a larger output range for the same input range as the cortisol immunosensor. The feasibility of deploying the developed aptasensing scheme as continuous lifestyle and performance monitors was validated through human subject studies.

How a Network Came Together to Manage a Large Research Program During the Pandemic

Hackensack Meridian Health, a large New Jersey network comprised of 17 hospitals, a medical school, and 200 ambulatory care centers, executes a large research program with approximately 1000 active human subjects studies. With the arrival of the coronavirus disease-2019 (COVID-19) pandemic, the Office of Research Administration was confronted with a series of challenges. These included minimizing face-to-face contact among research participants and staff, allocating limited resources to handle the influx of COVID-19 related proposals, providing human subjects protection training to the physicians and staff who were needed to run the clinical trials, adjusting bio-repository activities to meet the increased demand for samples, and disseminating all of the new regulatory and operational information to the thousands of researchers in the network. The network’s success in modifying its research program quickly and effectively to adapt to the changing landscape can be attributed, in large part, to the centralized nature of the research administration.

Effects of the BDNF Val66Met polymorphism on functional status and disability in young stroke patients.

Background and purposeThe preponderance of evidence from recent studies in human subjects supports a negative effect of the BDNF Val66Met polymorphism on motor outcomes and motor recovery. However prior studies have generally reported the effect of the Met allele in older stroke patients, while potential effects in younger stroke patients have remained essentially unexamined. The lack of research in younger patients is significant since aging effects on CNS repair and functional recovery after stroke are known to interact with the effects of genetic polymorphisms. Here we present a study of first-ever ischemic stroke patients aged 15–49 years that examines the effect of Met carrier status on functional disability.Methods829 patients with a first ischemic stroke (Average age = 41.4 years, SD = 6.9) were recruited from the Baltimore-Washington region. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington. Our sample contained 165 Met carriers and 664 non-Met carriers. Modified Rankin scores as recorded at discharge were obtained from the hospital records by study personnel blinded to genotype, and binarized into “Good” versus “Poor” outcomes (mRS 0–2 vs. 3+), with mRS scores 3+ reflecting a degree of disability that causes loss of independence.ResultsOur analysis showed that the Met allele conveyed a proportionally greater risk for poor outcomes and disability-related loss of independence with mRS scores 3+ (adjusted OR 1.73, 95% CI 1.13–2.64, p = 0.01).ConclusionsThe BDNF Val66Met polymorphism was negatively associated with functional outcomes at discharge in our sample of 829 young stroke patients. This finding stands in contrast to what would be predicted under the tenets of the resource modulation hypothesis (i.e. that younger patients would be spared from the negative effect of the Met allele on recovery since it is posited to arise as a manifestation of age-related decline in physiologic resources).

Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice.

Mouse line BTBR T+ Iptr3tf/J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and in situ hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. The transcriptome profiling identified 1,280 differentially expressed genes (DEGs; 974 downregulated and 306 upregulated genes, including 498 non-coding RNAs [ncRNAs]) in BTBR/R mice compared to B6 mice. Among these DEGs, 53 genes were consistent with ASD-related genes already established. Gene Ontology (GO) enrichment analysis highlighted 78 annotations (GO terms) including DNA/chromatin regulation, transcriptional/translational regulation, intercellular signaling, metabolism, immune signaling, and neurotransmitter/synaptic transmission-related terms. RNA interaction analysis revealed novel RNA–RNA networks, including 227 ASD-related genes. Weighted correlation network analysis highlighted 10 enriched modules including DNA/chromatin regulation, neurotransmitter/synaptic transmission, and transcriptional/translational regulation. Finally, the behavioral analyses showed that, compared to B6 mice, BTBR/R mice have mild but significant deficits in social novelty recognition and repetitive behavior. In addition, the BTBR/R data were comprehensively compared with those reported in the previous studies of human subjects with ASD as well as ASD animal models, including BTBR/J mice. Our results allow us to propose potentially important genes, ncRNAs, and RNA interactions. Analysis of the altered brain transcriptome data of the BTBR/R and BTBR/J sublines can contribute to the understanding of the genetic underpinnings of autism susceptibility.

Systematic Review and Meta-Analysis on Hysterectomy by Vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) Compared to Laparoscopic Hysterectomy for Benign Indications.

(1) Objective: We aimed to report an update of the systematic review and meta-analysis by Baekelandt et al. (2016). (2) Method: We followed PRISMA guidelines to perform this systematic review. We searched MEDLINE, EMBASE, CENTRAL and additional sources and aimed to retrieve randomised controlled trials (RCTs), controlled clinical trials (CCTs) and prospective/retrospective cohort studies in human subjects that allowed direct comparison of vNOTES to laparoscopy. (3) Results: Our search yielded one RCT and five retrospective cohort trials. Pooled analysis of two subgroups showed that, compared to conventional laparoscopy, vNOTES is equally effective to successfully remove the uterus in individuals meeting the inclusion criteria. vNOTES had significantly lower values for operation time, length of stay and estimated blood loss. There was no significant difference in intra- and postoperative complications, readmission, pain scores at 24 h postoperative and change in hemoglobin (Hb) on day 1 postoperative.

11C‐PBR28 brain PET imaging with lipopolysaccharide challenge for the study of microglia function in Alzheimer’s disease

AbstractBackgroundThe study of neuroimmune function in Alzheimer’s disease (AD) has been challenging, partly because the underlying mechanisms are still incompletely understood. Here we present the results of a novel imaging study in human subjects to assess microglial activity in cognitively normal (CN) participants compared to participants with mild cognitive impairment (MCI) or mild dementia (MD) due to AD.MethodThis pilot study used positron emission tomography (PET) imaging with the radioligand 11C‐PBR28, which is specific for the 18 kDa‐translocator protein (TSPO), a marker sensitive to acute immune effects of lipopolysaccharide (LPS). The 11C‐PBR28 volume of distribution (VT) was measured from two scans, one at baseline and a second at 180 minutes after intravascular administration of lipopolysaccharide (LPS‐ 0.4 ng/Kg). We calculated microglia activation reserve index (MARI) as the proportional increase in binding of 11C‐PBR28, 180 minutes after the administration of the LPS: MARI = [(VT,LPS‐VT,Baseline)/ VT,Baseline] x 100.ResultsCN participants had a significantly higher global cerebral MARI of 35% (SD 13%, n=5) compared to the AD group (MARI=15%, SD 15%, n=5, p=0.030). We found no significant differences between global 11C‐PBR‐28 VT at baseline in CN participants compared to the AD group. MARI values correlated with clinical dementia rating (CDR) ‐ sum of boxes (CDR‐SB) score (R2=0.55, p=0.013), but not with MOCA scores. Conversely baseline 11C‐PBR‐28 VT correlated with MOCA scores (R2=0.44, p=0.025) but not CDR‐SB. TSPO gene polymorphism (high vs. medium affinity binding) did not make a difference in the response pattern. Measurements of serum cytokines indicated that the response differences between the two groups were central and not related to the peripheral immune response.ConclusionOur experiment presents preliminary human data on reduced brain microglial activity in AD.. Our novel method provides a unique opportunity to test the dynamic response of microglia in vivo. However, further investigations with larger sample sizes are required for better understanding of the role of microglia in AD.

Do Programmers Prefer Predictable Expressions in Code?

Source code is a form of human communication, albeit one where the information shared between the programmers reading and writing the code is constrained by the requirement that the code executes correctly. Programming languages are more syntactically constrained than natural languages, but they are also very expressive, allowing a great many different ways to express even very simple computations. Still, code written by developers is highly predictable, and many programming tools have taken advantage of this phenomenon, relying on language model surprisal as a guiding mechanism. While surprisal has been validated as a measure of cognitive load in natural language, its relation to human cognitive processes in code is still poorly understood. In this paper, we explore the relationship between surprisal and programmer preference at a small granularity-do programmers prefer more predictable expressions in code? Using meaning-preserving transformations, we produce equivalent alternatives to developer-written code expressions and run a corpus study on Java and Python projects. In general, language models rate the code expressions developers choose to write as more predictable than these transformed alternatives. Then, we perform two human subject studies asking participants to choose between two equivalent snippets of Java code with different surprisal scores (one original and transformed). We find that programmers do prefer more predictable variants, and that stronger language models like the transformer align more often and more consistently with these preferences.

Dimensionality Reduction and Motion Clustering During Activities of Daily Living: Three-, Four-, and Seven-Degree-of-Freedom Arm Movements.

This paper is the first in a two-part series analyzing human arm and hand motion during a wide range of unstructured tasks. The wide variety of motions performed by the human arm during daily tasks makes it desirable to find representative subsets to reduce the dimensionality of these movements for a variety of applications, including the design and control of robotic and prosthetic devices. This paper presents a novel method and the results of an extensive human subjects study to obtain representative arm joint angle trajectories that span naturalistic motions during Activities of Daily Living (ADLs). In particular, we seek to identify sets of useful motion trajectories of the upper limb that are functions of a single variable, allowing, for instance, an entire prosthetic or robotic arm to be controlled with a single input from a user, along with a means to select between motions for different tasks. Data driven approaches are used to discover clusters and representative motion averages for the wrist 3 degree of freedom (DOF), elbow-wrist 4 DOF, and full-arm 7 DOF motions. The proposed method makes use of well-known techniques such as dynamic time warping (DTW) to obtain a divergence measure between motion segments, Ward's distance criterion to build hierarchical trees, and functional principal component analysis (fPCA) to evaluate cluster variability. The emerging clusters associate various recorded motions into primarily hand start and end location for the full-arm system, motion direction for the wrist-only system, and an intermediate between the two qualities for the elbow-wrist system.

Personal Metabolic Fuel Sensor

The advent of miniature low power sensors for gas concentration, temperature, humidity, and volumetric flow rate measurement has enabled the development of a metabolic fuel and energy sensor which is sufficiently small in size, easy to use, and low cost to support personal ownership for on-demand metabolic measurement and tracking. The sensor is ~100× smaller than conventional metabolic carts and utilizes a novel passive proportional valveless breath sampling architecture to support on-demand measurement of fuel substrate utilization and energy expenditure over the full range of activity from rest to intense exercise. The sensor functions over the full range of humidity and temperatures above freezing, and does not require consumables. The accuracy and measurement range are demonstrated by means of a controlled mechanical breathing simulator and independently validated in a human subject study which compared the sensor measurements to a gold-standard clinical metabolic cart.

Acute effects of dry extract of ginger on energy expenditure in eutrophic women: A randomized clinical trial.

The thermic effect of food (TEF) is one of the components of total energy expenditure (TEE). Some bioactive compounds present in food could be useful to increase TEE. In this context, ginger has been extensively used as a thermogenic food despite no clear effect has been demonstrated yet. Herein, we evaluated the acute thermogenic effect of gingerol, a bioactive compound present in ginger, in healthy women. We carried out a randomized double-masked, cross-over and placebo-controlled clinical trial with 20 healthy eutrophic women. Anthropometric, body composition, indirect calorimetry and clinical variables were collected at baseline and throughout the intervention phase. A standardized breakfast was offered together with two dry extract of ginger capsules (5% gingerol) or a placebo (cellulose). Indirect calorimetry, blood pressure, heart rate, axillary temperature and blood collection were assessed at baseline and thereafter, at 30, 60, 120, 180 and 240min postprandial. The analyses were repeated with a minimum of seven days' washout period. Ginger intake did not increase the TEF of a standardized breakfast compared to the placebo. Oxygen consumption, respiratory quotient, blood pressure, heart rate, axillary temperature and metabolic profile were not different as well. Our data show that gingerol did not modify the acute TEF in healthy women. More studies in human subjects, using different concentrations of gingerol, administration methods and intervention type (chronic effect) are necessary to clarify the putative thermogenic effect of ginger. Registered at ClinicalTrials.gov (Thermogenic Effect of Ginger - NCT03089593).

Longitudinal changes in DTI parameters of specific spinal white matter tracts correlate with behavior following spinal cord injury in monkeys

This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.

Effect of backward walking training on knee osteoarthritis: protocol of a systematic review and meta-analysis

IntroductionBackward walking (BW) is otherwise known as retrowalking. As opposed to forward walking, BW is a countersequential exercise and is a common method of rehabilitation training and disease-assisted treatment. Studies...

SAFETY AND PHARMACOKINETICS OF VARDENAFIL INHALATION POWDER (RT234) FOLLOWING ORAL INHALATION IN HEALTHY ADULT VOLUNTEERS

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Vardenafil Inhalation Powder (RT234) is being developed for use as an as-needed treatment of episodic symptoms of Pulmonary Arterial Hypertension (PAH), to acutely improve exercise capacity, performance, and disease-associated symptom impacts. To evaluate the pharmacokinetics (PK) and safety of RT234, a Phase 1 single-center, open label, randomized clinical study in healthy human adult subjects was performed in two parts, a crossover single ascending dose (SAD), followed by a multiple ascending dose (MAD) study. METHODS: SAD: Single ascending doses of 0.2, 0.6, 1.2, and 2.4 mg of vardenafil hydrochloride were administered via oral inhalation with the RS01 monodose dry powder inhaler (Plastiape, Osnago, Italy) (N=6/group). The 0.6 mg dose group was compared to a 20 mg oral tablet of Levitra in a crossover design. Safety, tolerability and pharmacokinetics were assessed. MAD: The 2.4 mg dose was then administered for up to four times daily over a period of 9 days (N=8). SAD: Single ascending doses of 0.2, 0.6, 1.2, and 2.4 mg of vardenafil hydrochloride were administered via oral inhalation with the RS01 monodose dry powder inhaler (Plastiape, Osnago, Italy) (N=6/group). The 0.6 mg dose group was compared to a 20 mg oral tablet of Levitra in a crossover design. Safety, tolerability and pharmacokinetics were assessed. MAD: The 2.4 mg dose was then administered for up to four times daily over a period of 9 days (N=8). RESULTS: SAD: RT234 was well tolerated with all treatment emergent adverse events (TEAEs) mild to moderate in intensity. Headache and dizziness the most commonly reported TEAEs. Brief, asymptomatic decreases in systolic, diastolic, and mean arterial pressure were noted. These changes were not associated with reflex tachycardia or AEs of dizziness, and were not considered clinically significant. Vardenafil was rapidly absorbed in a dose proportional manner, with a Tmax at the first timepoint, 5 minutes post-administration. After Cmax, the plasma concentration declined rapidly in an exponential fashion. MAD: Treatment-related TEAEs were similar in the SAD and MAD cohorts. No clinically significant accumulation was observed in the MAD study. Mean half-life values were comparable to that measured in the SAD portion of the study. CONCLUSIONS: Vardenafil Inhalation Powder (RT234), was found to be safe and well tolerated when orally inhaled in normal human volunteers. This study indicates that vardenafil, administered via oral inhalation, is rapidly absorbed into the bloodstream, and when combined with vardenafil’s known long binding time at the catalytic receptor on the phosphodiesterase-5 enzyme, is well-suited for further clinical development as an as-needed therapeutic in PAH. CLINICAL IMPLICATIONS: Safety and Pharmacokinetics of Vardenafil Inhalation Powder (RT234) are ideal for further development as an as-needed therapy for PAH. A Phase 2a clinical study is underway. DISCLOSURES: No relevant relationships by Michael Eldon, source=Web Response Employee relationship with Respira Therapeutics, Inc. Please note: >$100000 Added 03/23/2020 by Mari Maurer, source=Web Response, value=Salary Consultant relationship with Respira Therapeutics Please note: $20001 - $100000 Added 03/26/2020 by Ed Parsley, source=Web Response, value=Consulting fee Employee relationship with Respira Therapeutics Please note: >$100000 Added 03/22/2020 by Jeffry Weers, source=Web Response, value=Salary

Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.

Recent studies suggest that both sex-specific genetic risk factors and those shared between dementia and stroke are involved in dementia pathogenesis. We performed both single-variant and gene-based genome-wide association studies of>11,000 whole genome sequences from the Women's Health Initiative cohort to discover loci associated with dementia, with adjustment for age, ethnicity, stroke, and venous thromboembolism status. Evidence for prior evidence of association and differential gene expression in dementia-related tissues and samples was gathered for each locus. Our multiethnic studies identified significant associations between variants within APOE, MYH11, FZD3, SORCS3, and GOLGA8B and risk of dementia. Ten genes implicated by these loci, including MYH11, FZD3, SORCS3, and GOLGA8B, were differentially expressed in the context of Alzheimer's disease. Our association of MYH11, FZD3, SORCS3, and GOLGA8B with dementia is supported by independent functional studies in human subjects, model systems, and associations with shared risk factors for stroke and dementia.

Atorvastatin prevents hearing impairment in the presence of hyperlipidemia

It is known that hyperlipidemia is a risk factor for sensorineural hearing loss. However, the biological mechanisms underlying hyperlipidemia and hearing impairment have not been completely elucidated in the cochlea. Based on our previous study of human subjects, elderly people taking drugs for hyperlipidemia showed better hearing than those not taking any medications. We hypothesized that drugs for hyperlipidemia, such as statins, may have the potential to prevent hearing impairment. The aim of this study was to investigate the correlation between hyperlipidemia and hearing impairment and the hearing preservation effect of atorvastatin using a hyperlipidemic mouse model with diet-induced obesity (DIO). Here, we demonstrate that DIO mice had a significant hearing impairment as well as increased levels of reactive oxygen species (ROS) and hair cell death due to reduced levels of pAKT and superoxide dismutase 2 (SOD2). However, these changes were significantly prevented by atorvastatin. Oxidative stress-induced intrinsic apoptosis was decreased by the high expression of Nrf2 and antioxidant genes, which improved mitochondrial function and ROS via activation of the PI3K-pAKT pathway by atorvastatin. Therefore, atorvastatin has the potential to prevent hearing impairment via redox balance in the presence of hyperlipidemia.

Leptin, Obesity, and Hypertension: A Review of Pathogenetic Mechanisms.

The adipokine leptin is expressed at higher concentrations in obese subjects, who also incidentally have a higher prevalence of hypertension. The pathogenesis of this obesity-related hypertension is controversial and is believed to be related to many factors including increased sympathetic activity, abnormalities of the renin-angiotensin system, sodium retention, and an endotheliopathy acting independently or in concert with increased circulating leptin. This review discusses the potential mechanisms through which changes in leptin signal transduction pathways in tissues with the leptin receptor, especially the hypothalamus, mediate the pathogenetic relationships between obesity and hypertension. The hypothesis is explored that leptin effects on blood pressure (BP) are meditated by the downstream effects of hypothalamic leptin signaling and ultimately result in activation of specific melanocortin receptors located on sympathetic neurons in the spinal cord. The physiological consequences of this sympathetic activation of the heart and kidney are activation of the renin-angiotensin system, sodium retention and circulatory expansion and finally, elevated BP. This sequence of events has been elegantly demonstrated with leptin infusion and gene knockout studies in animal models but has not been convincingly reproducibly confirmed in humans. Further studies in human subjects on the specific roles of hypothalamic leptin in essential hypertension are indicated as elucidation of the signaling pathways should provide better understanding of the role of weight loss in BP control and afford an additional mechanism for pharmacologic control of BP in adults and children at risk of cardiovascular disease.

Abstract IA06: Wearable sweat sensor for personalized health monitoring

Abstract The rising research interest in personalized and precision medicine promises to revolutionize traditional medical practices. This presents a tremendous opportunity for developing wearable devices toward predictive analytics and treatment. In this talk, I will introduce fully integrated flexible biosensors for multiplexed in situ perspiration analysis, which can selectively and accurately measure a wide spectrum of sweat analytes (e.g., metabolites, electrolytes, heavy metals, drugs, and other small molecules). This platform allows us to gain real-time insight into the sweat secretion and gland physiology. I will also demonstrate an integrated wearable sweat extraction and sensing system that can be programmed to induce sweat on demand with various secretion profiles. To demonstrate the clinical value of our wearable sweat-sensing platform, human subject studies were performed toward fitness monitoring, physiologic monitoring, disease diagnosis, and drug monitoring. These wearable and flexible devices open the door to a wide range of personalized monitoring and diagnostic applications. Citation Format: Wei Gao. Wearable sweat sensor for personalized health monitoring [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr IA06.

Mobilization of a peritoneal dialysis catheter using an extra-corporeal magnet: preliminary experimental phase study.

To evaluate in an experimental model, the mobility of a novel peritoneal dialysis catheter with a metallic tip (Mag-Cath) using an extra-corporeal magnet. The Mag-Cath was installed in a porcine model under general anesthesia using laparoscopic access. A senior urologist, a urology resident, and a 3rd-year medical student were assigned to complete 2 tasks guided by fluoroscopy: (1) Move the catheter tip from the right flank to the pelvis and (2) move the catheter tip from the pelvis to the left flank. Accomplishment and time to complete the tasks were recorded. Participants were asked independently to grade the difficulty of the tasks using an analog scale from 1 (extremely easy) to 10 (extremely difficult). All participants completed the tasks. The difficulty of the tasks was graded equal to 1 by the senior urologist and urology resident and equal to 3 by the medical student. The time to move the Mag-Cath from the right flank to the target was 14, 10, and 55s for the senior urologist, urology resident, and medical student, respectively. The time to move the Mag-Cath from the target to the left flank was 17, 18, and 43s for the senior urologist, urology resident, and medical student, respectively. In this preliminary analysis, the use of an extra-corporeal magnet to move the Mag-Cath was feasible, with a low grade of difficulty, and individuals with different levels of expertise could perform it. Further studies in human subjects are needed to evaluate the clinical applicability of the Mag-Cath properly.

Enhancing the oral bioavailability of natural astaxanthin using plant-based micro- and nano-encapsulation materials: Results of an In vitro evaluation and a cross-over study in humans

<img src=“https://s3.amazonaws.com/production.scholastica/article/16781/large/prnano_492020_ga.jpg?1598886381”> Astaxanthin (AX) is a red xanthophyll carotenoid found mainly in algae (notably Haematococcus pluvialis microalga) and marine animals. AX is a stronger antioxidant than vitamin E and β–carotene, but has very low oral bioavailability. The purpose of this study was to develop a potato protein (PP)-based delivery system for increasing oral bioavailability of lipophilic bioactives (nutraceuticals and drugs), using AX as a model, and to evaluate the system in vitro and in vivo in a cross-over clinical study in human volunteers. Three different formulations were prepared, encapsulating AX oleoresin (AXO) with: (1) PP only, (2) PP+lecithin (LEC), (3) PP+olive oil (OO). The average particle diameters after preparation were 0.29, 0.29 and 1.76 µm, and after freeze-drying and reconstitution 0.17, 0.07 and 6.93 µm, respectively. In vitro bioaccessibilities were 33, 47 and 69%, respectively, vs. 16% only for the raw AXO. In a randomized, double-blind, cross-over study in human subjects, the PP-OO-AX formulation had a 4.8-fold higher median plasma AX area under the concentration-over time curve (AUC; P<0.001) compared to the raw AXO formulation. In conclusion, a non-allergenic, vegan, PP-based delivery system made of “all natural ingredients” offers a great promise for increasing oral bioavailability of lipophilic bioactives such as AX, for the enrichment of food and for dietary supplements, or for oral delivery of lipophilic drugs.