Injury to the heart results in cardiomyocyte cell death and can lead to pathological remodeling of remaining cells, contributing to heart failure. Despite the therapeutic potential of new drugs and ...small molecules, there remains a gap in the ability to efficiently deliver cardioprotective agents in a cell specific manner while minimizing nonspecific delivery to other organs. Exosomes derived from cardiosphere-derived cells (CDCs) have been shown to stimulate angiogenesis, induce endogenous cardiomyocyte proliferation and modulate cardiomyocyte apoptosis and hypertrophy. While innately cardioprotective at high doses, unmodified CDC-exosomes demonstrate limited cardiac tropism. To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered CDCs to express Lamp2b, an exosomal membrane protein, fused to a cardiomyocyte specific peptide (CMP), WLSEAGPVVTVRALRGTGSW. Exosomes isolated from engineered CDCs expressed CMP on their surface and retained their native physical properties. Targeted exosomes resulted in increased uptake by cardiomyocytes, decreased cardiomyocyte apoptosis, and higher cardiac retention following intramyocardial injection when compared with non-targeted exosomes. Importantly, we established a novel targeting system to improve exosomal uptake by cardiomyocytes and laid the foundation for cell-specific exosomal delivery of drug and gene therapies to improve the functional capacity of the heart following both ischemic and non-ischemic injury.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To analyze quality and frequency of OCTA artifacts and to evaluate their impact on the interpretability of OCTA images.
75 patients with diabetic retinopathy (DR), retinal artery occlusion (RAO), ...retinal vein occlusion (RVO), or neovascular age-related macular degeneration (nAMD) and healthy controls were enrolled in this cross-sectional study in the outpatient department of a tertiary eye care center.
All participants underwent an OCTA examination (spectral domain OCT Cirrus 5000 equipped with the AngioPlex module). OCTA scans were analyzed independently by two experienced ophthalmologists. Frequency of various artifacts for the entire OCTA scan and for different segmentation layers and the grading of OCTA interpretability were investigated.
The analysis of 75 eyes of 38 women and 37 men between 24 and 94 years were included. Six eyes had no retinal disease, 19 eyes had nAMD, 16 had DR, 19 eyes had RVO, and 15 eyes showed RAO. A macular edema (ME) was present in 40 of the diseased eyes. Projection artifacts occurred in all eyes in any structure below the superficial retinal vessel layer, segmentation and motion artifacts were found in 55% (41/75) and 49% (37/75) of eyes, respectively. Other artifacts occurred less frequently. Segmentation artifacts were significantly more frequent in diseased than in healthy eyes (p<0.01). Qualitative assessment of OCTA images was graded as excellent in 65% and sufficient in 25% of cases, adding up to 91% images deemed acceptable for examination. Presence of ME was associated with a significantly poorer interpretability (p<0.01).
Various artifacts appear at different frequencies in OCTA images. Nevertheless, a qualitative assessment of the OCTA images is almost always possible. Good knowledge of possible artifacts and critical analysis of the complete OCTA dataset are essential for correct clinical interpretation and determining a precise clinical diagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An environmentally friendly magnesium fuel cell system using seawater electrolyte and atmospheric oxygen was tested under practical considerations for use as maritime power supply. The hydrogen rate ...and therefore the power density of the system were increased by a factor of two by using hydrogen evolution cathodes with a gas separation membrane instead of submerged cathodes without gas separation. Commercial magnesium AZ31 rolled sheet anodes can be dissolved in seawater for hydrogen production, down to a thickness below 100 μm thickness, resulting in hydrogen generation efficiency of the anode of over 80%. A practical specific energy/energy density of the alloy of more than 1200 Wh/kg/3000 Wh/l was achieved when coupled to a fuel cell with atmospheric air breathing cathode. The performance of several AZ31 alloy anodes was tested as well as the influence of temperature, electrolyte concentration and anode – cathode separation. The excess hydrogen produced by the magnesium hydrogen evolving cell, due to the negative difference effect, is proportional to the cell current in case of the AZ31 alloys, which simplifies system control considerably. Stable long-term operation of the system was demonstrated at low pressures which can be maintained in an open-seawater-submerged hydrogen generator.
•Hydrogen is produced reproducibly in galvanic sea water cell by anodic dissolution of magnesium.•Use of hydrogen evolving Raney nickel cathodes with gas separation membrane.•Complete hydrogen generation fuel cell power supply demonstrated.•Advantages of magnesium AZ31 alloys demonstrated.•1200 Wh/kg, 3000 Wh/l electricity achieved from magnesium alloy sheets as the fuel.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although Josephson junction qubits show great promise for quantum computing, the origin of dominant decoherence mechanisms remains unknown. Improving the operation of a Josephson junction based phase ...qubit has revealed microscopic two-level systems or resonators within the tunnel barrier that cause decoherence. We report spectroscopic data that show a level splitting characteristic of coupling between a two-state qubit and a two-level system. Furthermore, we show Rabi oscillations whose "coherence amplitude" is significantly degraded by the presence of these spurious microwave resonators. The discovery of these resonators impacts the future of Josephson qubits as well as existing Josephson technologies.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Describe the significant changes that have occurred to elevate radiation therapy as a significant modality in treating cancer.
Peer-reviewed and lay publications.
Radiation has been used in medicine ...since its discovery in the 19th century. Since the start of the 20th century, radiation has been increasingly used to diagnose and treat cancer. Although, radiation therapy was often known to destroy healthy tissue in its attempt to kill cancer cells, technological advancements have allowed for precise and accurate therapy, providing a viable option as a cure for individuals diagnosed with cancer.
As radiation therapy is increasingly utilized as a treatment option for patients with cancer, it is critical for oncology nurses to be cognizant of this treatment modality and to understand how it impacts our patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This is a qualitative study of written reflection projects by medical learners who completed a clinical rotation in Palliative Care (PC) at an academic tertiary care center.
Upon completing their ...rotation in PC, medical learners were asked to complete an open-ended reflection project that captured their overall impressions of this training and experience. Fourteen reflections were coded and analyzed.
Upon analyzing the reflections, 5 main themes emerged. The first theme is that this rotation helped the learners become more empathetic and compassionate towards patients and their families. Second, the learners were able to recognize the humanity in their patients, regardless of their medical condition. Third, each of the learners in this study had meaningful interactions with numerous patients and really felt that they played a supportive and important role in the death of patients with whom they were working. Fourth, this experience challenged the learners to think and act in ways that they have not been taught in medical school. Lastly, the learners experienced a sense of transformation and a new-found appreciation for all of the emotions involved with working with dying patients.
Rotating through PC and reflecting upon that experience can be very meaningful for medical learners who have not worked much with dying patients and their families.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:To evaluate the methodological quality and thematic completeness of existing clinical practice guidelines, addressing early mobilization of adults in the ICU.
DATA SOURCES:Systematic ...review of Medline, Embase, CINAHL, Cochrane, and grey literature from January 2008 to February 2020.
STUDY SELECTION:Two reviewers independently screened titles and abstracts and then full texts for eligibility. Ten publications were included.
DATA EXTRACTION:A single reviewer extracted data from the included publications and a second reviewer completed cross-checking. Qualitative data were extracted in five categories relating to the key factors influencing delivery of early mobilization to critically ill patients.
DATA SYNTHESIS:Methodological quality was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Appraisal of Guidelines for Research and Evaluation II scores for applicability were low. Median quality scores for editorial independence, rigor of development, and stakeholder engagement were also poor. Narrative synthesis of publication content was undertaken. All publications supported implementation of early mobilization. Most documents agreed upon seven topics1) early mobilization is safe and may reduce healthcare costs, 2) safety criteria should be provided, 3) a protocolized or structured approach should be used, 4) collaborative teamwork is required, 5) staff require specific skills or experience, 6) patient and family engagement is important, and 7) program evaluation and outcome measurement are a key component of implementation. There was no consensus on dosage and patient selection. The areas of team culture and leadership were poorly addressed.
CONCLUSIONS:Despite significant variation in the methodological quality of clinical practice guidelines for early mobilization, there were important consistencies in recommendations internationally. Future research should address gaps related to patient selection, dosage, team culture, and expertise. Future clinical practice guidelines in this area should focus on engagement of patients and families in the development process and provision of resources to support implementation based on the consideration of known barriers and facilitators.
The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will ...open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.
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