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The Construction of pH- and Temperature-Responsive Drug Delivery Systems Based on Metal Organic Frameworks and Phase Change Materials
No full textIn this study, core-shell microparticles were synthesized using coaxial electrospray techniques, with Zeolitic Imidazolate Framework-8 encapsulating either Rhodamine B or Doxorubicin in the core. ZIF-8 is a material well regarded for its effectiveness in drug delivery systems. Phase change materials are composed of a 4:1 mixture of lauric acid and stearic acid in the shell. The PCM chosen has a melting point close to physiological body temperature. The structural morphology and thermal stability of the microparticles were confirmed using Scanning Electron Microscopy, X-ray Diffraction, Differential Scanning Calorimetry, Thermogravimetric Analysis, and Infrared Spectroscopy. The release of the drug was influenced by both pH and temperature; a dual stimulus-controlled release for the drug was observed, with release rates increasing by 27% at pH 7.4 and 41% at pH 4.0, under the same temperature change. These results demonstrate the capability of the coaxial electrospray system to facilitate targeted and controlled drug release, potentially improving therapeutic outcomes in the treatment of solid tumors by reducing side effects and enhancing patient compliance and effectiveness
Pilot Survey of Attitudes Toward Xenotransplantation Among Nursing Students in London, UK.
No full textBACKGROUND: Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.
METHODS: A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was reviewed and approved by the university research ethics panel.
RESULTS: Fifty-two percent of students viewed xenotransplantation positively when the risks and outcomes were equal to allotransplantation. Students were most positive toward accepting a liver from an animal source and the most negative toward accepting a heart. There was limited concern about the potential psychosocial effects of xenotransplantation. Students believed that xenotransplantation involved several risks, including immunologic, infection, and raising religious, ethical, and philosophical problems.
CONCLUSION: While participants had a moderately positive view toward xenotransplantation when the risks and outcomes were equal to allotransplantation-this dropped significantly if it produced worse outcomes. Their primary concerns about xenotransplantation were its potential infection risks as well as the ethical, philosophical, and religious problems it raises. The fact that the source organs are genetically engineered made students view xenotransplantation more favorably
THE RELATIONSHIP BETWEEN EFFORT COST DECISION MAKING, CONSUMMATORY/ANTICIPATORY PLEASURE, AND HEALTH BEHAVIORS IN SCHIZOTYPY
No full textMotivational and hedonic deficits are not well studied in schizotypy as they relate to health behaviors. Nonclinical undergraduate participants (n= 247) completed self-report measures and a behavioral task (EEfRT) that assessed effort cost decision making. Social anhedonia was positively associated with increased effort but simultaneously reduced responsiveness to increasing rewards, indicating inefficient effort allocation. Consummatory pleasure was the more relevant hedonic predictor of effort, rather than anticipatory pleasure. In exploratory analyses, higher positive schizotypy scores were significantly associated with greater consummatory pleasure, while disorganized schizotypy was unrelated to pleasure indices or effort performance. In secondary hypothesis analyses, all schizotypy traits and consummatory pleasure were significantly associated with poorer sleep. Disorganized schizotypy predicted worse health and exercise. Findings suggest that hedonic and motivational disruptions may emerge early in the psychosis spectrum, but behavioral tasks like the EEfRT may have a limited ability to capture real-world variance in health behaviors
Specific Applications for AI & Education
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The Anti-inflammatory Effects of Perioperative Dexamethasone Administration and the Relationship to Pain: A Systematic Review and Meta-analysis
Get PDFIntroduction: Post-surgical inflammation is a common adverse event that can have detrimental effects on the recovery phase for patients. Commonly associated with pain severity, inflammation can make the management of postoperative pain difficult. Of the multiple inflammatory molecules that can be found in an inflammatory response, interleukin 6 (IL-6) and C-reactive protein (CRP) are two of the most commonly assayed biomarkers of inflammation. Dexamethasone (DEX), with its anti-inflammatory properties, is thought to reduce IL-6 and CRP. It thus may reduce pain when administered perioperatively. In this review, we assessed the anti-inflammatory effects of DEX and the relationship of such effects in the management of postoperative pain.
Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials using the following criteria: patients greater than or equal to eighteen years of age undergoing surgery. The intervention of interest is perioperative DEX administration and the control was normal saline or the absence of DEX administration. Primary outcomes included postoperative IL-6 and CRP levels, with a secondary outcome of postoperative pain scores. Utilizing the RevMan program, a meta-analysis was performed using a random effect model. Studies not able to be analyzed quantitatively were assessed through a narrative approach.
Results: We identified a total of nine studies with 1048 subjects which fulfilled inclusion criteria. Only three of the nine studies were able to be quantitatively analyzed. Our analysis of these studies favored DEX administration for the reduction of postoperative inflammation with regard to IL-6 (SMD = -1.88; 95% CI -2.28 - 1.48; p \u3c 0.01; Figure 3a), and near significant difference with regard to CRP (SMD = -0.93; 95% CI -1.91 - 0.04; p = 0.06; Figure 3b). DEX administration was also shown to significantly reduce postoperative pain (SMD = -1.34; 95% CI -2.12 - -0.56; p \u3c 0.01; Figure 3c). Qualitative analysis for eight of the nine studies favored the administration of DEX for the reduction of inflammation as well as postoperative pain. The total dosage of DEX administered ranged from 6.6 to 40 mg. Regarding complications after DEX administration, all nine studies reported no significant increase in the incidence of serious adverse effects, including hyperglycemia, surgical site infections, or impaired wound healing.
Conclusion: Dexamethasone is a commonly used medication for the management of postoperative nausea and vomiting. Additionally, administration of DEX perioperatively also appears to be efficacious in lowering inflammation and managing postoperative pain from various types of surgical procedures. Complications, including impaired wound healing, hyperglycemia, and surgical site infections, which have been reported in previous studies, have not been observed with significance with the administration of one or two doses of DEX as evidenced by the literature in this review. Further research may justify the utilization of DEX as a means to reduce postoperative inflammation and subsequent pain
Development of Conductive Concrete for Electric Curing Application in Cold Weather
Get PDFThis study aimed to develop conductive concrete suitable for electric curing in cold weather applications. The effect of adding carbon fiber and steel fiber at doses 0.25%, 0.5%, 0.75%, and 1% by volume of concrete in mixes was investigated. Several critical aspects were explored: the fresh and hardened properties of the concrete mixes, their electrical and thermal properties, and the effectiveness of electric curing in maintaining optimal curing temperatures. Fresh properties assessed included slump, air content, and density, while hardened properties were evaluated through test for density, absorption, and voids, and compressive strength and splitting tensile strength tests. The addition of steel fiber to the mix improved the mechanical properties of concrete while carbon fiber slightly reduced the strength. To test the electrical and thermal properties, an electric current was applied to fresh concrete for one hour. Temperature profile and conductivity were obtained, and results showed that carbon fiber improved the conductivity of fresh concrete while steel fiber had an insignificant effect on conductivity. Selected mixes underwent electric curing, and different curing regimes were compared: normal curing at room temperature, traditional curing in cold weather, and electric curing in cold weather. The incorporation of conductive fibers enabled effective electric curing that maintained optimal temperatures and provided strength comparable to concrete cured at ambient temperature
Modeling Differential Expression In scRNA-seq Data With A Difference Of Two Negative Binomial Distributions
Get PDFSingle cell RNA sequencing (scRNA-seq) is a powerful high throughput sequencing technology that quantifies the transcriptome at a single cell resolution. Differential expression (DE) analysis is a key scRNA-seq analysis task that identifies genes with statistically significant expression changes in response to biological stimuli. Existing DE methods inherently attempt to determine whether two sets of negative binomially distributed read counts are significantly different but lack exact testing strategies to do so. This work introduces a novel theoretical distribution, the Difference of Two Negative Binomial Distributions (DOTNB), and implements it within DEGage, an R package for DE analysis. Benchmarking DEGage against DESeq2, DESingle, edgeR, Monocle3, and scDD showed that DEGage offered greater sensitivity and robustness against scRNA-seq specific technical effects. After benchmarking, DEGage successfully identified regulators of long-term memory consolidation in engram neurons, and canonical prostate-cancer markers in a large-scale dataset of heterogeneous prostate cancer tissue. Given their success in the validation studies, DOTNB and DEGage can be further applied to new scRNA-seq projects and other forms of negative binomially distributed count data
Desmoplastic Small Round Cell Tumor: An Update of Current Management Practices
Get PDFBACKGROUND: Desmoplastic small round cell tumor (DSRCT) poses a diagnostic challenge, initiating with imaging techniques like ultrasound, CT, MRI, and PET scans, with CT being the primary choice for abdominal tumor visualization. Despite advances, the absence of a standardized staging system complicates the diagnostic process.
METHODS: A comprehensive literature review and search strategy, encompassing databases like PubMed and Cochrane was performed.
RESULTS: Systemic chemotherapy, notably the P6 regimen, is the cornerstone of DSRCT treatment, while other options, including CDK4/6 inhibitors, antibody-drug conjugates, and anlotinib present varying efficacy. A novel chemotherapeutic agent, ONC-201, exhibits promise, inhibiting tumor growth in preclinical models. Surgical management, encompassing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), reveals improved survival rates, particularly when combined with chemotherapy. Whole abdomen radiotherapy (WART) emerges as a post-chemotherapy treatment option, despite potential complications. A study employing whole abdominopelvic intensity-modulated radiation therapy (WAP-IMRT) suggests reduced radiation toxicity compared to conventional WART. Immunotherapy, targeting receptors such as B7-H3, GD2, EGFR, HER2, tyrosine kinase inhibitors, and androgen receptors is a promising avenue, especially in younger populations, given its favorable long-term effects. Additionally, the inclusion of CCDN1 genomic alterations further informs potential targeted therapies for DSRCT.
DISCUSSION: This comprehensive review provides a current understanding of DSRCT diagnosis and treatment modalities, highlighting the ongoing challenges and promising avenues for future research. The integration of personalized approaches, novel chemotherapeutic agents, and evolving immunotherapy strategies holds the potential to enhance outcomes for individuals with DSRCT
Fixed-Size Ledger of Fungible Tokens
Get PDFHypotheses:
1. Using a fixed number of fixed-size tokens, the storage of transaction history can be outsourced to the owners of the tokens or to the network.
2. With distributed transaction histories, disjunctive (targeted) proof becomes possible
DESIGN AND DEVELOPMENT OF LIPID NANOPARTICLES FOR PLACENTAL GENE THERAPY
No full textThe goal of this dissertation was to design and develop novel lipid nanoparticle (LNP) drug delivery platforms for nucleic acid delivery to the placenta to treat placental dysfunction. Nucleic acids transiently modulate gene expression and have high potential as a therapeutic modality for placental dysfunction-related disorders, such as preeclampsia, which collectively affect 10-15% of pregnancies. First, we employ Design of Experiment approaches to investigate LNP design parameters for LNP-mediated mRNA delivery to placental cells. We utilize an optimized LNP formulation to deliver placental growth factor mRNA, an angiogenic factor downregulated in preeclampsia. Next, we characterize the hypoxic microenvironment of the dysfunctional placenta using 1st and 3rd trimester in vitro models. We investigate how hypoxia impacts LNP delivery to provide insights for LNP design for gene therapy in the hypoxic, diseased placenta. Next, we characterize an in vivo model of placental dysfunction and hypoxia utilizing endothelial nitric oxide synthase knockout (eNOS⁻/⁻) mice. Finally, we exploit the hypoxic microenvironment of the dysfunctional placenta to design a hypoxia-responsive ionizable lipid which, when complexed into LNPs, promotes delivery to hypoxic placental cells. Together, this dissertation provides insights into placental dysfunction that inform the design of novel LNP technologies to treat placental dysfunction-related disorders and improve patient outcomes in maternal-fetal health