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A COMPASS for Navigating Relationships in Co-Production Processes Involving Vulnerable Populations

INTERNATIONAL JOURNAL OF PUBLIC ADMINISTRATION 2021年第9期44卷 790-802页

作者： Mulvale, Gillian Miatello, Ashleigh Green, Jenn Tran, Maxwell Roussakis, Christina Mulvale, Alison McMaster Univ DeGroote Sch Business Burlington ON Canada McMaster Univ Hlth Policy PhD Program Hamilton ON Canada Univ Toronto Fac Med MD Program Toronto ON Canada Univ Toronto Fac Law Toronto ON Canada Canadian Mental Hlth Assoc Toronto Branch Toronto ON Canada

When it comes to engaging vulnerable populations in co-production, power imbalances across stakeholder groups can create methodological challenges. A thoughtful, planned, and responsive approach is needed to prepare vulnerable participants to fully engage in co-production processes. Data from key informant interviews (n = 16) and author reflections on three Experience-based co-design (EBCD) studies involving youth (16-25 years) with mental health issues in Ontario Canada, were analyzed. Four overarching themes and 12 subthemes were identified, and heuristic tools (a relational COMPASS and MAPS directions) were developed to assist researchers in navigating vulnerability, power and relational issues in co-production processes involving vulnerable populations.

关键词： Co-production experience-based co-design child and youth mental health vulnerable populations relational safety power

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Minimally-invasive dentistry via dual-function novel bioactive low-shrinkage-stress flowable nanocomposites

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DENTAL MATERIALS 2022年第2期38卷 409-420页

作者： Albeshir, Ebtehal G. Balhaddad, Abdulrahman A. Mitwalli, Heba Wang, Xiaohong Sun, Jirun Melo, Mary Ann S. Weir, Michael D. Xu, Hockin H. K. Univ Maryland PhD Program Dent Biomed Sci Sch Dent Baltimore MD 21201 USA King Abdul Aziz Med City Dept Restorat Dent Riyadh 11426 Saudi Arabia Imam Abdulrahman Bin Faisal Univ Coll Dent Dept Restorat Dent Sci Dammam 31441 Saudi Arabia King Saud Univ Coll Dent Dept Restorat Dent Sci Riyadh 11451 Saudi Arabia Amer Dent Assoc Fdn Volpe Res Ctr Frederick MD 21704 USA Forsyth Inst 245 First St Cambridge MA 02142 USA Univ Maryland Sch Dent Dept Adv Oral Sci & Therapeut Baltimore MD 21201 USA Univ Maryland Dept Gen Dent Div Operat Dent Sch Dent Baltimore MD 21201 USA Univ Maryland Ctr Stem Cell Biol & Regenerat Med Sch Med Baltimore MD 21201 USA Univ Maryland Marlene & Stewart Greenebaum Canc Ctr Sch Med Baltimore MD 21201 USA

The objectives of this in vitro study were to develop a novel low-shrinkage-stress flowable nanocomposite with antibacterial properties through the incorporation of dimethylami- nohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phos- phate (NACP), and investigate the mechanical and oral biofilm properties, to be used in minimally-invasive techniques. Methods: The light-cured low-shrinkage-stress flowable resin was formulated by mixing urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE) at a 1:1 mass ratio. Different mass fractions of glass, and either 5% DMAHDM or 20%NACP or both were incorporated. Paste flowability, ultimate micro tensile strength and surface roughness were evaluated. The antibacterial response of DMAHDM resin was assessed by using biofilms of human saliva-derived microcosm model. Virtuoso flowable composite was used as a control. Results: (45% resin+5% DMAHDM+20% NACP+30% glass) formula yielded the needed out-comes. It had flow rate within the range of ISO requirement. The micro tensile strength was (39.1 +/- 4.3) MPa, similar to (40.1 +/- 4.0) MPa for commercial control (p > 0.05). The surface roughness values of the novel composite (0.079 +/- 0.01) mu m similar to commercial composite (0.09 +/- 0.02) mu m (p > 0.05). Salivary microcosm biofilm colony forming unit values were reduced by 5-6 logs (p < 0.05). Biofilm metabolic activity was also sub-stantially reduced, compared to control composite (p < 0.05). Significance: The novel bioactive flowable nanocomposite achieved strong antibacterial activities without compromising the mechanical properties. It is promising to be used as pit and fissure sealants, and as fillings in conservative cavities to inhibit recurrent caries and increase restoration longevity. (c) 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

关键词： Minimally-invasive dentistry Bioactive nanocomposite Flowable composite Sealant Antibacterial monomer Low polymerization stress Oral biofilm Secondary caries Dental material

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Clinical Applications of Aromatherapy

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Hu li za zhi The journal of nursing 2023年第6期70卷 6-11页

作者： Chen, Shuo-Fei Hu, Tsung-Ming PhD RN Associate Professor Bachelor's Program of Sports and Health Promotion College of Management Fo Guang University Taiwan ROC Attending Physician Department of Psychiatry Superintendent Taipei Veterans General Hospital Yuli Branch ROC MD Taiwan

TITLE: 芳香療法在臨床上的應用. 芳香療法是以精油為媒介，經皮、經鼻或經口進入身體，達到促進健康的自然療法。臨床芳香療法是指在醫療場域中採用精油作為輔助療法，由於過程涉及醫療安全、道德與法律規定，因此，醫療人員需要充分... 详细信息

TITLE: 芳香療法在臨床上的應用. 芳香療法是以精油為媒介，經皮、經鼻或經口進入身體，達到促進健康的自然療法。臨床芳香療法是指在醫療場域中採用精油作為輔助療法，由於過程涉及醫療安全、道德與法律規定，因此，醫療人員需要充分了解臨床芳香療法管理，並且精進芳香療法的知識。本篇提供臨床芳香療法管理程序並參考統合分析文獻，整理芳香療法在焦慮、憂鬱、睡眠障礙及疼痛的應用，期將芳香療法適切的考量到照護系統中，以提升照護品質並增進醫病福祉。.;Aromatherapy is a natural therapy that utilizes essential oils that enter the body through the skin, inhalation, or ingestion to promote health. Clinical aromatherapy refers to the incorporation of essential oils as a complementary therapy within the medical field and is conducted in accordance with medical safety, ethical, and regulatory requirements. Healthcare professionals must have a comprehensive understanding of clinical aromatherapy management and enhance their knowledge of aromatherapy. Based on a meta-analysis of the related literature, clinical aromatherapy management procedures and the various applications of aromatherapy for anxiety, depression, sleep disorders, and pain are introduced. The goal is to help appropriately integrate aromatherapy into the healthcare system to enhance quality of care and improve well-being in patients and healthcare providers.

关键词： anxiety clinical aromatherapy depression pain sleep disorders

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Mesenchymal stromal cells in wound healing applications: role of the secretome, targeted delivery and impact on recessive dystrophic epidermolysis bullosa treatment

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CYTOTHERAPY 2021年第11期23卷 961-973页

作者： Riedl, Julia Popp, Courtney Eide, Cindy Ebens, Christen Tolar, Jakub Univ Minnesota Med Sci Training Program MD PhD Minneapolis MN USA Univ Minnesota Dept Pediat Div Blood & Marrow Transplantat 420 Delaware St SEMMC 293 Minneapolis MN 55455 USA Univ Minnesota Stem Cell Inst Minneapolis MN USA

Mesenchymal stromal cells (MSCs) are multi-potent stromal-derived cells capable of self-renewal that possess several advantageous properties for wound healing, making them of interest to the field of dermatology. Research has focused on characterizing the unique properties of MSCs, which broadly revolve around their regenerative and more recently discovered immunomodulatory capacities. Because of ease of harvesting and expansion, differentiation potential and low immunogenicity, MSCs have been leading candidates for tissue engineering and regenerative medicine applications for wound healing, yet results from clinical studies have been variable, and promising pre-clinical work has been difficult to reproduce. Therefore, the specific mechanisms of how MSCs influence the local microenvironment in distinct wound etiologies warrant further research. Of specific interest in MSC-mediated healing is harnessing the secretome, which is composed of components known to positively influence wound healing. Molecules released by the MSC secretome can promote re-epithelialization and angiogenesis while inhibiting fibrosis and microbial invasion. This review focuses on the therapeutic interest in MSCs with regard to wound healing applications, including burns and diabetic ulcers, with specific attention to the genetic skin disease recessive dystrophic epidermolysis bullosa. This review also compares various delivery methods to support skin regeneration in the hopes of combating the poor engraftment of MSCs after delivery, which is one of the major pitfalls in clinical studies utilizing MSCs. (c) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

关键词： epidermolysis bullosa immunomodulation MSCs regenerative medicine skin wound healing

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Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics

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TRANSFUSION 2022年第3期62卷 681-684页

作者： Hartmann, Jan Bloch, Evan M. Burnouf, Thierry Haemonetics Corp Dept Med Affairs Boston MA USA Johns Hopkins Univ Sch Med Dept Pathol Baltimore MD 21205 USA Taipei Med Univ Grad Inst Biomed Mat & Tissue Engn Coll Biomed Engn Taipei Taiwan Taipei Med Univ Int PhD Program Biomed Engn Coll Biomed Engn Taipei Taiwan

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Multimodal identification of the mouse brain using simultaneous Ca²⁺ imaging and fMRI

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COMMUNICATIONS BIOLOGY 2025年第1期8卷 1-14页

作者： Mandino, Francesca Horien, Corey Shen, Xilin Desrosiers-Gregoire, Gabriel Luo, Wendy Markicevic, Marija Constable, R. Todd Papademetris, Xenophon Chakravarty, Mallar M. Betzel, Richard F. Lake, Evelyn M. R. Yale Univ Dept Radiol & Biomed Imaging Sch Med New Haven CT 06520 USA Yale Univ Sch Med Interdept Neurosci Program New Haven CT USA Yale Univ MD PhD Program Sch Med New Haven CT USA Douglas Mental Hlth Univ Inst Computat Brain Anat Lab Montreal PQ Canada McGill Univ Integrated Program Neurosci Montreal PQ Canada Yale Univ Sch Med Dept Biomed Engn New Haven CT 06511 USA Yale Univ Sch Med Dept Neurosurg New Haven CT USA Yale Univ Deparment Biomed Informat & Data Sci New Haven CT USA Indiana Univ Dept Psychol & Brain Sci Bloomington IN USA Yale Univ Wu Tsai Inst New Haven CT 06510 USA

Individual differences in neuroimaging are of interest to clinical and cognitive neuroscientists based on their potential for guiding the personalized treatment of various heterogeneous neurological conditions and diseases. Despite many advantages, the prevailing modality in this field-blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI)-suffers from low spatiotemporal resolution and specificity as well as a propensity for noise and spurious signal corruption. To better understand individual differences in BOLD-fMRI data, we can use animal models where fMRI, alongside complementary but more invasive contrasts, can be accessed. Here, we apply simultaneous wide-field fluorescence calcium imaging and BOLD-fMRI in mice to interrogate individual differences using a connectome-based identification framework adopted from the human fMRI literature. This approach yields high spatiotemporal resolution cell-type specific signals (here, from glia, excitatory, as well as inhibitory interneurons) from the whole cortex. We found mouse multimodal connectome-based identification to be successful and explored various features of these data.

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A combinatorial system to examine the enzymatic repair of multiply damaged DNA substrates

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NUCLEIC ACIDS RESEARCH 2022年第13期50卷 7406-7419页

作者： Hsu, Chia Wei Conrad, James W. Sowers, Mark L. Baljinnyam, Tuvshintugs Herring, Jason L. Hackfeld, Linda C. Hatch, Sandra S. Sowers, Lawrence C. Univ Texas Med Branch Dept Pharmacol & Toxicol 301 Univ Blvd Galveston TX 77555 USA Univ Texas Med Branch MD PhD Combined Degree Program 301 Univ Blvd Galveston TX 77555 USA Univ Texas Med Branch Dept Radiat Oncol 301 Univ Blvd Galveston TX 77555 USA Univ Texas MD Anderson Canc Ctr Dept Radiat Oncol Houston TX 77030 USA Univ Texas Med Branch Dept Internal Med 301 Univ Blvd Galveston TX 77555 USA

DNA damage drives genetic mutations that underlie the development of cancer in humans. Multiple pathways have been described in mammalian cells which can repair this damage. However, most work to date has focused upon single lesions in DNA. We present here a combinatorial system which allows assembly of duplexes containing single or multiple types of damage by ligating together six oligonucleotides containing damaged or modified bases. The combinatorial system has dual fluorescent labels allowing examination of both strands simultaneously, in order to study interactions or competition between different DNA repair pathways. Using this system, we demonstrate how repair of oxidative damage in one DNA strand can convert a mispaired T:G deamination intermediate into a T:A mutation. We also demonstrate that slow repair of a T:G mispair, relative to a U:G mispair, by the human methyl-binding domain 4 DNA glycosylase provides a competitive advantage to competing repair pathways, and could explain why CpG dinucleotides are hotspots for C to T mutations in human tumors. Data is also presented that suggests repair of closely spaced lesions in opposing strands can be repaired by a combination of short and long-patch base excision repair and simultaneous repair of multiply damage sites can potentially lead to lethal double strand breaks.

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Why is everyone talking about brain state?

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TRENDS IN NEUROSCIENCES 2023年第7期46卷 508-524页

作者： Greene, Abigail S. Horien, Corey Barson, Daniel Scheinost, Dustin Constable, R. Todd Yale Sch Med Interdept Neurosci Program New Haven CT 06520 USA Yale Sch Med MD PhD Program New Haven CT 06520 USA Yale Sch Med Dept Neurosci New Haven CT 06520 USA Yale Sch Med Dept Radiol & Biomed Imaging New Haven CT 06520 USA Yale Sch Engn & Appl Sci Dept Biomed Engn New Haven CT 06520 USA Yale Univ Dept Stat & Data Sci New Haven CT 06511 USA Yale Sch Med Child Study Ctr New Haven CT 06520 USA Yale Sch Med Dept Neurosurg New Haven CT 06520 USA

The rapid and coordinated propagation of neural activity across the brain provides the foundation for complex behavior and cognition. Technical advances across neuroscience subfields have advanced understanding of these dynamics, but points of convergence are often obscured by semantic differences, creating silos of subfield-specific findings. In this review we describe how a parsimonious conceptualization of brain state as the fundamental building block of whole-brain activity offers a common framework to relate findings across scales and species. We present examples of the diverse techniques commonly used to study brain states associated with physiology and higher-order cognitive processes, and discuss how integration across them will enable a more comprehensive and mechanistic characterization of the neural dynamics that are crucial to survival but are disrupted in disease.

关键词： neural dynamics integrative neuroscience multiscale analysis spontaneous activity arousal

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Perturb-tracing enables high-content screening of multi-scale 3D genome regulators

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NATURE METHODS 2025年第5期22卷 1-12页

作者： Cheng, Yubao Hu, Mengwei Yang, Bing Jensen, Tyler B. Zhang, Yuan Yang, Tianqi Yu, Ruihuan Ma, Zhaoxia Radda, Jonathan S. D. Jin, Shengyan Zang, Chongzhi Wang, Siyuan Yale Univ Yale Sch Med Dept Genet New Haven CT 06520 USA Yale Univ MD PhD Program New Haven CT 06520 USA Univ Virginia Dept Genome Sci Charlottesville VA USA Univ Virginia Dept Biochem & Mol Genet Charlottesville VA USA Univ Virginia Dept Biomed Engn Charlottesville VA USA Univ Virginia UVA Comprehens Canc Ctr Charlottesville VA USA Yale Univ Yale Sch Med Dept Cell Biol New Haven CT 06520 USA Yale Univ Yale Combined Program Biol & Biomed Sci New Haven CT 06520 USA Yale Univ Mol Cell Biol Genet & Dev Program New Haven CT 06520 USA Yale Univ Biochem Quantitat Biol Biophys & Struct Biol Progr New Haven CT 06520 USA Yale Univ Sch Med Yale Ctr RNA Sci & Med New Haven CT 06520 USA Yale Univ Sch Med Yale Liver Ctr New Haven CT 06520 USA

Three-dimensional (3D) genome organization becomes altered during development, aging and disease, but the factors regulating chromatin topology are incompletely understood and currently no technology can efficiently screen for new regulators of multi-scale chromatin organization. Here, we developed an image-based high-content screening platform (Perturb-tracing) that combines pooled CRISPR screens, a cellular barcode readout method (BARC-FISH) and chromatin tracing. We performed a loss-of-function screen in human cells, and visualized alterations to their 3D chromatin folding conformations, alongside perturbation-paired barcode readout in the same single cells. We discovered tens of new regulators of chromatin folding at different length scales, ranging from chromatin domains and compartments to chromosome territory. A subset of the regulators exhibited 3D genome effects associated with loop extrusion and A-B compartmentalization mechanisms, while others were largely unrelated to these known 3D genome mechanisms. Finally, we identified new regulators of nuclear architectures and found a functional link between chromatin compaction and nuclear shape. Altogether, our method enables scalable, high-content identification of chromatin and nuclear topology regulators that will stimulate new insights into the 3D genome.

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Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands

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NUCLEIC ACIDS RESEARCH 2021年第22期49卷 13179-13193页

作者： Swain, Monalisa Ageeli, Abeer A. Kasprzak, Wojciech K. Li, Mi Miller, Jennifer T. Sztuba-Solinska, Joanna Schneekloth, John S. Koirala, Deepak Piccirili, Joseph Fraboni, Americo J. Murelli, Ryan P. Wlodawer, Alexander Shapiro, Bruce A. Baird, Nathan Le Grice, Stuart F. J. NCI Basic Res Lab Frederick MD 21702 USA Frederick Natl Lab Canc Res Basic Sci Program Frederick MD 21702 USA Univ Sci Dept Chem & Biochem Philadelphia PA 19104 USA Jazan Univ Fac Sci Chem Dept Female Sect Jazan 82621 Saudi Arabia NCI Ctr Struct Biol Frederick MD 21702 USA Auburn Univ Dept Biol Sci Auburn AL 36849 USA NCI Chem Biol Lab Frederick MD 21702 USA Univ Chicago Dept Biochem & Mol Biol Chicago IL 60637 USA Univ Chicago Dept Chem Chicago IL 60637 USA CUNY Dept Chem Brooklyn Coll Brooklyn NY 11210 USA CUNY Grad Ctr PhD Program Chem New York NY 10016 USA CUNY Grad Ctr PhD Program Biochem New York NY 10016 USA NCI RNA Biol Lab Frederick MD 21702 USA Univ Maryland Baltimore Cty Dept Chem & Biochem Baltimore MD 21250 USA

Cellular and virus-coded long non-coding (Inc) RNAs support multiple roles related to biological and pathological processes. Several lncRNAs sequester their 3' termini to evade cellular degradation machinery, thereby supporting disease progression. An intramolecular triplex involving the lncRNA 3' terminus, the element for nuclear expression (ENE), stabilizes RNA transcripts and promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi's sarcoma-associated herpesvirus (KSHV) polyadenylated nuclear (PAN) lncRNA, represent targets for therapeutic development. Towards identifying novel ligands targeting the PAN ENE triplex, we screened a library of immobilized small molecules and identified several triplex-binding chemotypes, the tightest of which exhibits micromolar binding affinity. Combined biophysical, biochemical, and computational strategies localized ligand binding to a platform created near a dinucleotide bulge at the base of the triplex. Crystal structures of apo (3.3 angstrom) and ligand-soaked (2.5 angstrom) ENE triplexes, which include a stabilizing basal duplex, indicate significant local structural rearrangements within this dinucleotide bulge. md simulations and a modified nucleoside analog interference technique corroborate the role of the bulge and the base of the triplex in ligand binding. Together with recently discovered small molecules that reduce nuclear MALAT1 lncRNA levels by engaging its ENE triplex, our data supports the potential of targeting RNA triplexes with small molecules.

关键词： dinucleoside phosphates helix (snails) human herpesvirus 8 ligands nucleotides rna affinity small molecule catabolism crystal structure molecule

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