The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. ...This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single‐dose i.v. infusion of 150‐mg fosaprepitant and single‐dose oral administration of 165‐mg aprepitant, using serial 18FMK‐0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (Tmax; ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41–75%, respectively. After aprepitant, NK1R occupancy rates at these time points (Tmax ~4 h) were ≥99, ≥99, ≥97, and 37–76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.
Clinical Pharmacology & Therapeutics (2012); 92 2, 243–250. doi:10.1038/clpt.2012.62
Walking on a split-belt treadmill is often compared to walking on tied belts at the average speed, but the relationship between the metabolic energy costs of split- and tied-belt walking remains ...largely unexplored. Recent simulation work has suggested that people could take advantage of a belt speed difference and lower their energy costs, but this effect has not yet been observed experimentally. To relate metabolic energy costs across a range of belt speed combinations, we had 10 participants each complete 14 tied-belt and 39 split-belt walking trials, with early split-belt trials incorporating additional time for training. The average speeds ranged from 0.6 to 1.8 m/s with belt speed differences up to 1.4 m/s. We used ANOVA to determine differences in energy cost due to average speed and belt speed difference. We fit a linear model to estimate the tied-belt speed with the same energy cost as a given pair of split belt speeds. The cost of split-belt walking was on average just 0.13 ± 0.32 W/kg more expensive than the cost of tied-belt walking at the average speed. Contrary to predictions from simple dynamical models, increased belt speed difference resulted in increased energy cost, and the energetically equivalent tied-belt speed could be estimated as veq=vavg+0.065⋅Δv. Clinicians designing rehabilitation protocols can balance the therapeutic benefits of higher belt speed difference with increased energetic demands. Open questions remain about why people cannot fully take advantage of mechanical work performed by a split-belt treadmill.
Asset-based community development (ABCD) is a promising practice for communities to engage in self-determination through the efforts residents invest in identifying community assets, framing and ...documenting the issues communities face, and taking action to advance quality of life. The ABCD literature does not report on the application of ABCD methods specifically involving children as leaders of community development efforts. This article begins to rectify this limitation by presenting and analyzing the use of ABCD methods by primary school children in Addis Ababa, Ethiopia. The three-year project engaged 100 primary-school-age children who undertook experiential subprojects to advance their own education involving language development, the performing arts, and community service. Social work educators, students, and practitioners can learn from the involvement of children in this kind of community partnership taking place in Africa. As such, the project is important in informing community development practice with children.
Pancreatic Islets and Gestalt Principles Dybala, Michael P; Butterfield, John K; Hendren-Santiago, Bryce K ...
Diabetes (New York, N.Y.),
09/2020, Letnik:
69, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The human brain has inherent methodology to efficiently interpret complex environmental stimuli into understanding. This visual perception is governed by the law of simplicity, which is fundamental ...to Gestalt theory. First introduced in a seminal article by Wertheimer in 1923, the theory explains how the mind groups similar images and fills in gaps in order to perceive an amenable version of reality. The world we see consists of complex visual scenes, but rarely is the entire picture visible to us. Since it is inefficient for all visual data to be analyzed at once, certain patterns are given higher importance and made to stand out from the rest of the field in our brain. Here we propose that Gestalt theory may explain why rodent islet architecture has historically been seen as having a core-mantle arrangement. By filling in apparent gaps in the non-β-cell lining, the mind interprets it as a "whole" mantle, which may have further led to widely accepted notions regarding islet microcirculation, intra-islet signaling, and islet development. They are largely based on the prevailing stereotypic islet architecture in which an enclosed structure is presumed. Three-dimensional analysis provides more integrated views of islet and pancreatic microcirculation.
Organic nanoparticles are used in nanomedicine, including for cancer treatment and some types of COVID-19 vaccines. Here, we demonstrate the scalable, rapid, reproducible, and cost-effective ...synthesis of three model organic nanoparticle formulations relevant to nanomedicine applications. We employed a custom-made, low-cost fluid mixer device constructed from a commercially available three-dimensional printer. We investigated how systematically changing aqueous and organic volumetric flow rate ratios determined liposome, polymer nanoparticle, and solid lipid nanoparticle sizes, size distributions, and payload encapsulation efficiencies. By manipulating inlet volumes, we synthesized organic nanoparticles with encapsulation efficiencies approaching 100% for RNA-based payloads. The synthesized organic nanoparticles were safe and effective at the cell culture level, as demonstrated by various assays. Such cost-effective synthesis approaches could potentially increase the accessibility to clinically relevant organic nanoparticle formulations for personalized nanomedicine applications at the point of care, especially in nonhospital and low-resource settings.
The split-belt rimless wheel Butterfield, Julia K; Simha, Surabhi N; Donelan, J Maxwell ...
The International journal of robotics research,
09/2022, Letnik:
41, Številka:
11-12
Journal Article
Recenzirano
Odprti dostop
Split-belt treadmill walking, in which the two belts move at different speeds, reveals a mechanism through which energy can be extracted from the environment. When a person walks with positive step ...length asymmetry on a split-belt treadmill, the treadmill can perform net positive work on the person. Here we use a split-belt rimless wheel model to explore how people could take advantage of the treadmill. We show that a split-belt rimless wheel can passively walk steadily by capturing energy from the treadmill to overcome collision losses, whereas it loses energy on each step with no way to recover the losses when walking on tied belts. Our simulated split-belt rimless wheel can walk steadily for a variety of leg angle and belt speed combinations, tolerating both speed disturbances and ground height variability. The wheel can even capture enough energy to walk uphill. We also built a physical split-belt rimless wheel robot and demonstrated that it can walk continuously without additional energy input. In comparing the wheel solutions to human split-belt gait, we found that humans do not maximize positive work performed by the treadmill. Other aspects of walking, such as costs associated with swing, balance, and free vertical moments, likely limit people’s ability to benefit from the treadmill. This study uses a simple walking model to characterize the mechanics and energetics of split-belt walking, demonstrating that energy capture through intermittent contact with two belts is possible and providing a simple model framework for understanding human adaptation during split-belt walking.
The editors offer Six Promising Principles to guide successful practice by social work educators in international settings, including research, travel and study programs, technical assistance and ...training, and interdisciplinary efforts. These principles inform the content, which illuminates the specific role of U.S. social work educators in international efforts that stem, in part, from their academic positions. In addition to successes, the book also shares some of the difficulties and lessons learned by the authors during their international work.
Individuals' awarenessof moral issues is an important first step in the ethicaldecision-making process. Relying on research in social cognition andbusiness ethics, we hypothesized that moral ...awareness is influenced byissue-related factors (magnitude of consequences of the moral issueand issue framing in moral terms) and social contextrelated factors(competitive context and perceived social consensus that the issue isethically problematic). The hypotheses were tested in a fieldexperiment involving 291competitive intelligence practitioners.Results generally supported the hypotheses. Qualitative analysisyielded additional insights into the content of respondents' moralawareness.
To evaluate the effect of platelet-rich plasma (PRP) on autogenous bone graft remodeling during sinus augmentation in a rabbit model.
Twelve New Zealand White rabbits were divided randomly into 3 ...groups based on their time of sacrifice (2, 4, and 8 weeks). All animals underwent a general anesthetic and harvesting of an autogenous bone graft from the right iliac crest with subsequent bilateral maxillary sinus augmentation. PRP was prepared via standard approved technique by acquiring 21 cc of autogenous blood and performing differential centrifugation to obtain PRP. One cc of PRP was produced that was mixed with bovine topical thrombin and calcium chloride. The left maxillary sinus received only autogenous bone, while the right maxillary sinus received a mixture of PRP mixed with autogenous bone, thus each animal acted as its own control. Equal volumes of bone were inserted in each maxillary sinus. Animals were sacrificed at 2, 4, and 8 weeks and all specimens were harvested for peripheral quantitative computed tomography (pQ-CT), static, and dynamic and histomorphometric analysis.
Student t tests were performed comparing bone density via pQ-CT analysis, histomorphometric parameters of total bone area, and bone apposition rate. PRP had no statistically significant effect on bone graft healing in maxillary sinus augmentation when compared using standard pQ-CT, static, and dynamic histologic criteria.
This study fails to find a direct stimulatory effect of PRP on healing of autogenous bone grafts using pQ-CT, static, and dynamic histomorphometric analyses.
We used heparosan (HEP) polysaccharides for controlling nanoparticle delivery to innate immune cells. Our results show that HEP-coated nanoparticles were endocytosed in a time-dependent manner by ...innate immune cells via both clathrin-mediated and macropinocytosis pathways. Upon endocytosis, we observed HEP-coated nanoparticles in intracellular vesicles and the cytoplasm, demonstrating the potential for nanoparticle escape from intracellular vesicles. Competition with other glycosaminoglycan types inhibited the endocytosis of HEP-coated nanoparticles only partially. We further found that nanoparticle uptake into innate immune cells can be controlled by more than 3 orders of magnitude via systematically varying the HEP surface density. Our results suggest a substantial potential for HEP-coated nanoparticles to target innate immune cells for efficient intracellular delivery, including into the cytoplasm. This HEP nanoparticle surface engineering technology may be broadly used to develop efficient nanoscale devices for drug and gene delivery as well as possibly for gene editing and immuno-engineering applications.
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