Chromo-Fluorogenic Rhodamine-Based Amphiphilic Probe as a Selective and Sensitive Sensor for Intracellular Cu(I) in Living Cells.

Fluorescent probes are widely studied for metal ion detection because of their multiple favorable properties such as high sensitivity and selectivity, quick response, naked eye detection, and in situ monitoring. However, optical probes that can effectively detect the Cu(I) level in cell interiors are rare due to the difficulty associated with selectively and sensitively detecting this metal ion in a cell environment. Therefore, we designed and synthesized three water-soluble probes (1-3) with a 1,3,5-triazine core decorated by three substituents: a hydrophobic alkyl chain, a hydrophilic maltose, and a rhodamine B hydrazine fluorophore. Among the probes, probe 1, which has an octyl chain and a branched maltose group, was the most effective at sensing Cu+ in aqueous solution. Upon addition of Cu+, this probe showed a dramatic color change from colorless to pink in daylight and displayed an intense yellow fluorescence emission under 365 nm light. The limit of detection and dissociation constant (Kd) of this probe were 20 nM and 1.1 × 10-12 M, respectively, which are the lowest values reported to date. The two metal ion-binding sites and the aggregation-induced emission enhancement effect, endowed by the branched maltose group and the octyl chain, respectively, are responsible for the high sensitivity and selectivity of this probe for Cu+ detection, as demonstrated by 1H NMR, dynamic light scattering, and transmission electron microscopy studies. Furthermore, the probe successfully differentiated the Cu(I) level of cancer cells from that of the normal cells. Thus, the probe holds potential for real-time monitoring of Cu(I) level in biological samples and bioimaging of cancer cells.

Fluorescence-based ratiometric sensors as emerging tools for CN- detection: Chemical structures, sensing mechanisms and applications.

Hazardous cyanide anions (CN-) are increasingly threatening the environment and human health due to their widespread use in industry and many other fields. Over the past three decades, a large number of probes have been reported to sensitively and selectively detect this toxic anion, while a rather limited number of ratiometric fluorescent probes have been developed. The ratiometric probes have significant potential in bio-imaging and biomedical applications because of the ability to detect CN- in a quick, convenient and affordable way. In this review, we introduce 42 ratiometric fluorescent probes reported in the past 6 years (2018-2023) for CN- detection. Our description includes the chemical structures, photo-physical properties, CN- sensing mechanisms, solution color changes, limits of detection (LODs) and/or various applications of these chemical probes. This review provides guidelines for design and development of a new ratiometric probe for effective CN- detection.

Nurses' Subjectivity in Patient-Centered Communication for End-of-Life Patients.

Effective patient-centered communication is essential in providing quality care for patients at the end of life. This study aimed to explore the subjectivity of nurses' communication approaches using Q methodology. In this study, 33 Q-samples were constructed based on in-depth interviews with 12 hospice nurses. The Q classification was performed by a total of 38 hospice nurses who had more than 3 years of experience in hospice settings. The collected data were analyzed through the principal component analysis method and the varimax rotation process using the PQ method program. As a result, a total of 4 distinct types emerged: "sincere listener," "family-centered caregiver," "resource utilization facilitator," and "sufficient time devoter." The factors accounted for 64% of the variance: 19%, 15%, 16%, and 14% respectively. By identifying distinct viewpoints, valuable insights into the diverse perspectives held by nurses in patient-centered communication were gained. Understanding these viewpoints will contribute to the development of tailored communication strategies and training programs. In addition, the study underscores the need for training, resources, and organizational support to enhance nurses' communication skills.

Can multifaceted educational intervention improve clinical practice and patient outcomes regarding delirium in nursing homes?

AIM: We aimed to develop and evaluate a multifaceted and evidence-based delirium educational program for practitioners in nursing home settings. METHODS: A pre- and posttest comparison group design was employed. The recruited practitioners included nurses and care workers from two nursing homes. The intervention group (n = 51) received the developed delirium educational program for 3 weeks, whereas the control group (n = 23) received a delirium handbook. We examined pre- and posttest differences in the scores for delirium knowledge and confidence in providing delirium care. We also examined the nurses' ability to clinically detect delirium in patients and delirium incidence for 8-week periods both before and after the intervention. RESULTS: There were significant improvements in the participants' aptitudes (delirium knowledge and confidence in providing delirium care) and clinical practice (ability to clinically detect delirium in the patients) only in the intervention group; however, there were no significant differences in patient outcomes (incidence of delirium) between either group. Additionally, it was observed that the nurses' improved understanding of distinct clinical features of delirium, such as acute change or fluctuation, was the key factor that directly affected the success of delirium screening. CONCLUSIONS: This study revealed that implementation of a multifaceted and evidence-based delirium educational program for practitioners in nursing home settings was effective in promoting the knowledge, confidence, and ability to detect delirium. The developed program can also be implemented in settings where most patients are older individuals, such as geriatric care units, or long-term care hospitals.

The Delirium Observation Screening Scale: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy.

Delirium is a reversible impairment of metabolism in the human brain. Early detection is important, and an effective screening tool for nurses is crucial. The Delirium Observation Screening (DOS) scale is one such screening tool; however, its diagnostic test accuracy has not yet been thoroughly examined. This study, therefore, aimed to evaluate the accuracy of the scale through a systematic review and meta-analysis. In July 2019, a search was conducted in the MEDLINE, CINAHL, Embase, and PsycARTICLES databases, and following a review against pre-defined eligibility criteria, eight studies were finally included. The quality assessment tool of diagnostic accuracy studies was applied to each study and a hierarchical regression model was used to calculate the pooled estimates of sensitivity (90%; 76%-97%, CI 95%) and specificity (92%; 88%-94%, CI 95%). The findings indicated a high diagnostic test accuracy for the DOS scale.

Development and Evaluation of Clinical Practice Guideline for Delirium in Long-Term Care.

Delirium is highly prevalent and leads to several bad outcomes for older long-term care (LTC) residents. For a more successful translation of delirium knowledge, Clinical Practice Guidelines (CPGs) tailored to LTC should be developed and applied based on the understanding of the barriers to implementation. This study was conducted to develop a CPG for delirium in LTC and to determine the barriers perceived by healthcare professionals related to the implementation of the CPG. We followed a structured, evidence- and theory-based procedure during the development process. After a systematic search, quality appraisal, and selection for eligible up-to-date CPGs for delirium, the recommendations applicable to the LTC were drafted, evaluated, and confirmed by an external group of experts. To evaluate the barriers to guideline uptake from the users' perspectives, semi-structured interviews were conducted which resulted in four major themes: (1) a lack of resources, (2) a tendency to follow mindlines rather than guidelines, (3) passive attitudes, and (4) misunderstanding delirium care in LTC. To minimize adverse prognoses through prompt delirium care, the implementation of a CPG with an approach that comprehensively considers various barriers at the system, practice, healthcare professional, and patients/family levels is necessary.

Diagnostic Test Accuracy of the 4AT for Delirium Detection: A Systematic Review and Meta-Analysis.

Under-recognition of delirium is an international problem. For the early detection of delirium, a feasible and valid screening tool for healthcare professionals is needed. This study aimed to present a scientific reason for using the 4 'A's Test (4AT) through a systematic review and meta-analysis of studies on the diagnostic test accuracy. We systematically searched articles in the EMBASE, MEDLINE, CINAHL, and PsycINFO databases and selected relevant articles on the basis of the predefined inclusion criteria. The quality of the included articles was evaluated using the Quality Assessment of the Diagnostic Accuracy Studies-2 tool. We estimated the pooled values of diagnostic test accuracy by employing the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model in data synthesis. A total of 3729 patients of 13 studies were included in the analysis. The pooled estimates of sensitivity and specificity of the 4AT were 81.5% (95% confidence interval: 70.7%, 89.0%) and 87.5% (79.5%, 92.7%), respectively. Given the 4AT's evidence of accuracy and practicality, we suggest healthcare professionals to utilize this tool for routine screening of delirium. However, for detecting delirium in the dementia population, further work is required to evaluate the 4AT with other cut-off points or scoring methods in order for it to be more sensitive and specific.

Diagnostic test accuracy of the Nursing Delirium Screening Scale: A systematic review and meta-analysis.

AIMS: To evaluate the diagnostic test accuracy of the Nursing Delirium Screening Scale through a systematic review and meta-analysis. DESIGN: A systematic review with meta-analysis. DATA SOURCES: Articles were searched systematically in the MEDLINE, EMBASE, PsycINFO, and CINAHL databases up to April 2019. REVIEW METHODS: Data extraction and quality assessment were conducted using the Quality Assessment of the Diagnostic Accuracy Studies-2 tool. Pooled sensitivities, specificities, likelihood ratio, and diagnostic odds ratio for the tool were estimated and its hierarchical summary receiver-operating characteristic curve was derived through a bivariate model meta-analysis. RESULTS: Eleven studies with a total of 2,245 patients were included in this review. The pooled estimates of sensitivity and specificity of the Nursing Delirium Screening Scale were 68.6% (95% confidence interval; 55.3%, 79.5%) and 89.4% (83.3%, 93.5%), respectively. The pooled estimate of the area under the hierarchical summary receiver-operating characteristic curve was 0.88. CONCLUSION: Use of the Nursing Delirium Screening Scale provides moderate to high sensitivity and high specificity. This review supports the Nursing Delirium Screening Scale as a validate tool of screening for delirium. IMPACT: With the best evidence of the accuracy of the Nursing Delirium Screening Scale, we recommend nursing leaders to use this easy-to-use and validated tool for daily screening of delirium in any hospital setting, which possibly contribute to an early detection of delirium and, ultimately, assist to obtain an accurate estimation of prevalence of delirium.

Extremely Low-Frequency Magnetic Fields Exposure Measurement during Lessons in Elementary Schools.

Schools are an important place for children's exposure to electromagnetic fields, which may cause adverse health effects. To better understand environmental extremely low-frequency magnetic fields (ELF-MFs) exposure among elementary school students, we measured numeric values of ELF-MFs in five classrooms at four schools during digital learning class hours. The measurement of ELF-MFs was taken with an EMDEX II field analyzer. Specifically, we examined the level of exposure to ELF-MFs for each student's seating position in the classroom. The results showed that ELF-MFs exposure levels were lower than those in the International Commission on Non-Ionizing Radiation Protection guidelines; however, there were significant differences in the level of magnetic field exposure at each school and at each student's seat. The exposure to ELF-MFs at students' seat positions was mostly caused by electrical appliances, electronic wiring, and distribution boxes, but the exposure level decreased as the distance increased. Therefore, it is important to design safe and appropriate environments for digital learning in schools, such as proper seating arrangements, to avoid ELF-MFs exposure to students as much as possible. Future studies should measure ELF-MFs levels in other areas and investigate the effects of exposure to ELF-MFs during school hours on children's health.

Human Norovirus Replication in Temperature-Optimized MDCK Cells by Forkhead Box O1 Inhibition.

Human noroviruses (HuNoVs) are a leading cause of gastroenteritis outbreaks worldwide. However, the paucity of appropriate cell culture model for HuNoV replication has prevented developing effective anti-HuNoV therapy. In this study, first, the replication of the virus at various temperatures in different cells was compared, which showed that lowering the culture temperature from 37°C significantly increased virus replication in Madin-Darby canine kidney (MDCK) cells. Second, the expression levels of autophagy-, immune-, and apoptosis-related genes at 30°C and 37°C were compared to explore factors affecting HuNoV replication. HuNoV cultured at 37°C showed significantly increased autophagy- (ATG5 and ATG7) and immune- (IFNA, IFNB, ISG15, and NFKB) related genes compared to mock. However, the virus cultured at 30°C showed significantly decreased expression of autophagy- (ATG5 and ATG7) and not significantly different in major immune- (IFNA, ISG15, and NFKB) related genes compared to mock. Importantly, expression of the transcription factor FOXO1, which controls autophagy- and immune-related gene expression, was significantly lower at 30°C. Moreover, FOXO1 inhibition in temperature-optimized MDCK cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized MDCK cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1, providing adaptability to different genotypes.

Toward a conceptual framework for the interdisciplinary function-focused care in nursing homes.

AIM: To develop a conceptual framework to structure the shared roles and tasks of interdisciplinary teams for efficient function-focused care of nursing home (NH) residents. METHODS: A qualitative study using focus groups. Two focus group interviews were conducted on NH practitioners and professors. Focus group 1 consisted of six practitioners with more than 5 years of practical experience in NHs. Focus group 2 consisted of six professors with more than 5 years of educational experience in geriatrics or gerontology and who are capable of adopting theoretical approaches to older adults' functions. RESULTS: The post-acute care-rehabilitation quality framework furnished the underlying structure for the focus group interview questionnaire to develop the shared interdisciplinary function-focused care framework. The focus of the framework is how resident care processes should be based on individuality of the residents and include holistic continuous assessments, integration of care, and professional interventions by each discipline. An interdisciplinary process involves setting shared goals, communicating and coordinating roles and tasks of interdisciplinary teams, and providing complementary care. Shared final outcomes are defined as improving residents' independence and quality of life and reducing hospital transfer and admission rates. CONCLUSION: In this study, we have developed the first conceptual framework of interdisciplinary function-focused care in NHs, which will provide an evidence-based foundation for integrated and continuous function-focused care for NH residents. The results of this study will contribute to efficient communication among the interdisciplinary teams and improvement of the outcomes of function-focused care subjects.

The Shared Subjective Frames of Interdisciplinary Practitioners Involved in Function-Focused Care in a Nursing Home: Q-Methodology.

BACKGROUND: An interdisciplinary team-based approach in nursing homes has been suggested in the literature as a strategy for delaying functional decline in residents. Function-focused care is a philosophy-based approach in which interdisciplinary practitioners assess functional capacity and help older adults to optimize and maintain their remaining abilities. PURPOSE: This study explored and described the shared subjective frames of interdisciplinary practitioners as regards function-focused care for nursing home residents. METHODS: Q-methodology was used to analyze the subjectivity of each factor of function-focused care for nursing home residents. Data were collected from August to September 2016. Thirty-four Q-statements were selected and scored by the 30 interdisciplinary practitioners on a 9-point scale with a normal distribution. Data were analyzed using the PQ Method 2.33 program. RESULTS: The results revealed four factors of function-focused care, including (a) using a wait-and-see approach to encourage self-care, (b) maintaining interactive communications to identify and respond to changes, (c) reinforcing residents' inner and outer strengths for homeostasis, and (d) using a tailored approach based on comparisons between the past and the present. Shared subjectivity may provide an important collaborative framework to identify and solve complex problems related to the functional needs of nursing home residents. CONCLUSIONS: The results of this study elucidate the subjectivities of interdisciplinary practitioners and better enable their provision of effective care in support of the remaining functional abilities of older adults living in nursing homes. The findings may be used as a reference to establish communication methods and shared documentation for interdisciplinary practitioners in nursing homes and construct interdisciplinary function-focused care practice guidelines.

Sequential Two-Stage Network and Thematic Analysis for Exploring an Interdisciplinary Care Approach in Nursing Homes.

Since various groups of older adults with different conditions and levels of function coexist in nursing homes, it is necessary to develop integrated care strategies through collaboration among experts across related fields. The purposes of this study are to identify the regularity of information sharing in managing daily function for older adults, with a special focus on interdisciplinary cooperation, and to explore a practical care strategy for nursing home residents. The collaborative methods of network and thematic analysis were done by conducting in-depth interviews with 33 interdisciplinary experts working at seven nursing homes. This study proposed three relationships and three themes as interrelated key factors for providing interdisciplinary care to the elderly at various levels of function based on the experiences accumulated by the practitioners. First, independent sharing is required to make professional judgments about how daily function in older adults changes from reported baselines. Second, practitioners accurately judge clinical situations and supplement experts' judgments through partial sharing. Finally, all interdisciplinary consensus through complete sharing achieves the ultimate goal of maintaining remaining function in older adults. These findings can be the first step in developing practical care guidelines for interdisciplinary use, and the results can be used to develop integrated assessment and intervention strategies.

The clock drawing test: A systematic review and meta-analysis of diagnostic accuracy.

AIM: The aim of this study was to evaluate the accuracy of the clock drawing test and to compare its scoring methods. BACKGROUND: Dementia refers to a symptom where an adult demonstrates memory disorder and cognitive impairment. Early diagnosis of dementia is very important for medication management and prognosis. The clock drawing test is one of the most used cognitive screening tools for dementia. However, due to its scoring system, the accuracy of the clock drawing test remains a topic of debate. DESIGN: A systematic review with meta-analysis following Cochrane's methods and the guidelines of the Agency for Healthcare Research and Quality. DATA SOURCES: A literature search was carried out in the OVID-MEDLINE, OVID-EMBASE and OVID-PsycINFO databases (27 October 2015). REVIEW METHOD: The quality assessment of diagnostic accuracy studies (QUADAS-2) tool was employed for this review. We used hierarchical regression models to pool the values of diagnostic accuracy in a random effects model. RESULTS: A total of 18 studies with 5,531 participants were identified for this review. Fifteen of these studies were included for meta-analysis according to each scoring system. The pooled sensitivity and specificity of the clock drawing test using the Shulman system were 82% and 75.7% respectively. In the Sunderland system, these were 72.6% and 87.9% respectively. CONCLUSIONS: The findings indicate that the accuracy of the clock drawing test using the Shulman system was the most studied and highly sensitive. After gaining a better understanding of the clock drawing test through this study, we recommend it for widespread use in the diagnosis of dementia.

Preoperative biomarkers in patients with idiopathic normal pressure hydrocephalus showing a favorable shunt surgery outcome.

INTRODUCTION: Idiopathic normal pressure hydrocephalus (INPH) is known to be a potentially treatable neurologic condition. The neurocognitive outcomes after surgery, however, have been variable. It is important to define preoperative characteristics of patients that predicts the shunting outcome. We aimed to compare baseline differences between shunt-responsive and unresponsive patients after 1year from surgery in order to identify preoperative predictors showing favorable clinical outcomes. METHODS: Among 69 candidates, 31 patients with probable INPH completed the study. Patients were divided into two groups, responsive group (n=17) and unresponsive group (n=14), according to the clinical outcomes on INPH grading scale and modified Rankin score (MRS). Preoperative cerebrospinal (CSF) Aß, tau levels, MRI findings, and clinical characteristics were compared between the groups. Correlations between shunt responsiveness and preoperative characteristics were also assessed. RESULTS: After 1year from shunt, gait problem was the most likely to improve. Shunt-responsive group showed lower CSF p-tau/Aß, fewer lacunes, and higher incidence of disproportionately enlarged subarachnoid space (DESH) signs on MRIs compared to those in unresponsive group. Favorable outcome was related with positive DESH sign and fewer lacunes. CONCLUSIONS: Our results suggest that biomarkers representing non-INPH related pathology including Alzheimer's disease and small vessel disease might show less favorable clinical outcomes after 1year from surgery.

Exploring nurses' recognition of delirium in the elderly by using Q-methodology.

AIM: Despite its high prevalence and seriousness, delirium has been underrecognized by nurses. One reason is that the original characteristics of delirium are relatively unspecific and phenomenologically diverse, which makes a nurse's subjective decision more important in delirium detection. This study aims to identify the experiences, practices, and viewpoints of nurses in recognizing delirium in the elderly. METHODS: In this study, Q-methodology, which is a method for analyzing subjectivity, was used. Following the steps of Q-methodology, 32 nurses with experiences in caring for the delirious elderly sorted 34 Q-statements into the shape of a normal distribution. A centroid factor analysis and varimax rotation using the PQMethod program were conducted. RESULTS: This study revealed four factors regarding nurses toward delirium recognition in the elderly. They were: Factor I, prediction from the integrated signs; Factor II, visible symptom-centered detection; Factor III, the detection of abnormal changes based on concentrated observation; and Factor IV, identification by relying on the diagnostic data. CONCLUSION: The result of the study can help to understand elderly delirium detection more practically from a nurse's point of view. It is expected to be used as a basis for a practical and accessible delirium education for nurses that reflects nurses' subjective viewpoints.

Effectiveness of Periodic Treatment of Quercetin against Influenza A Virus H1N1 through Modulation of Protein Expression.

Kimchi, a traditional fermented food regularly consumed in Korea, contains various types of antimicrobial compounds. Among the tested compounds present in common spices used in Kimchi, quercetin showed the highest selectivity index against influenza A virus (IAV) H1N1. In this study, the effect of pretreatment and periodic treatment with quercetin against IAV in Madin-Darby canine kidney cells was observed. Compared to pretreatment, periodic treatment resulted in significantly higher cell viability but lower relative expression of the IAV PA gene and total apoptosis and cell death. To explain the mechanisms underlying the antiviral effects of quercetin treatment, a comparative proteomic analysis was performed in four samples (mock, quercetin-treated, IAV-infected, and quercetin-treated IAV-infected). Among the 220 proteins, 56 proteins were classified nonhierarchically into three clusters and were differentially modulated by quercetin treatment in IAV-infected cells. Post-translational modifications were identified in 68 proteins. In conclusion, periodic treatment with quercetin is effective in reducing IAV infection, and differentially regulates the expression of key proteins, including heat shock proteins, fibronectin 1, and prohibitin to reduce IAV replication.

Identification of regulators of the early stage of viral hemorrhagic septicemia virus infection during curcumin treatment.

The effect of curcumin pretreatment (15-240 µM) in fathead minnow cells infected with viral hemorrhagic septicemia virus (VHSV) was evaluated. Cell viability, apoptosis and viral copy number were analyzed using Cell Counting Kit-8 assay, Annexin V staining, and reverse transcription-PCR, respectively. Pretreatment with 120 µM curcumin showed an increase in viability (>90% of mock) of VHSV-infected cells and reduction in the copy number (0.2-log reduction in VHSV N gene expression), reactive oxygen species and apoptosis in the cells without cytotoxic effects. To understand the mechanisms underlaying the antiviral effects of curcumin pretreatment, a comparative proteomic analysis was performed in four samples (M, mock; C, curcumin-treated; V, VHSV-infected; and CV, curcumin-treated VHSV-infected) in triplicate. In total, 185 proteins were detected. The analysis showed that three proteins, including heat shock cognate 71 (HSC71), actin, alpha cardiac muscle (ACTC1) and elongation factor 1 (EEF1) were differentially expressed between V and CV samples. Network analysis performed by Ingenuity Pathways Analysis (IPA) showed that HSC71 was the primary protein interacting with fibronectin (FN) 1, actins (ACTB, ACTG, F-actin) and gelsolin (GSN) in both V and CV samples and thus is a strong target candidate for the protection from VHSV infection at the viral entry stage. Our proteomics data suggest that curcumin pretreatment inhibits entry of VHSV in cells by downregulating FN1 or upregulating F-actin. For both proteins, HSC71 acts as a binding protein that modulates their functions. Furthermore, consistent with the effect of a heat shock protein inhibitor (KNK437), curcumin downregulated HSC71 expression with increasing viability of VHSV-infected cells and inhibited VHSV replication, suggesting that the downregulation of HSC71 could be responsible for the antiviral activity of curcumin. In conclusion, this study indicates that the suppression of viral entry by rearrangement of the F-actin/G-actin ratio via downregulating HSC71 is a plausible mechanism by which curcumin pretreatment controls the early stages of VHSV infection.

Modulation of proteome expression by F-type lectin during viral hemorrhagic septicemia virus infection in fathead minnow cells.

Lectins found in fish tissues play an important role in the innate immune response against viral infection. A fucose-binding type lectin, RbFTL-3, from rock bream (Oplegnathus fasciatus) was identified using expressed sequence tag (EST) analysis. The expression of RbFTL-3 mRNA was higher in intestine than other tissues of rock bream. To determine the function of RbFTL-3, VHSV-susceptible fathead minnow (FHM) cells were transfected with pcDNA3.1(+) or pcDNA3.1(+)-RbFTL-3 and further infected with VHSV. The results show that the viability of FHM cells transfected with pcDNA3.1(+)-RbFTL-3 is higher than that of cells transfected with pcDNA3.1(+) (relative cell viability: 28.9% vs 56.2%). A comparative proteomic analysis, performed to explore the proteins related to the protective effect of RbFTL-3 in the cells during VHSV infection, identified 90 proteins differentially expressed in VHSV-infected FHM cells transfected with pcDNA3.1(+) or pcDNA3.1(+)-RbFTL-3. The expression of RbFTL-3 inhibits a vascular-sorting protein (SNF8) and diminishes the loss of prothrombin, which are closely associated with controlling viral budding and hemorrhage in fish cells, respectively. Subsequent Ingenuity Pathways Analysis enabled prediction of their biofunctional groupings and interaction networks. The results suggest RbFTL-3 modulates the expression of proteins related to viral budding (SNF8, CCT5 and TUBB) and thrombin signaling (F2) to increase the viability of VHSV infected cells.

Transdermal delivery of molecules is limited by full epidermis, not just stratum corneum.

PURPOSE: Most methods to increase transdermal drug delivery focus on increasing stratum corneum permeability, without addressing the need to increase permeability of viable epidermis. Here, we assess the hypothesis that viable epidermis offers a significant permeability barrier that becomes rate limiting upon sufficient permeabilization of stratum corneum. METHODS: We tested this hypothesis by using calibrated microdermabrasion to selectively remove stratum corneum or full epidermis in pig and human skin, and then measuring skin permeability to a small molecule (sulforhodamine) and macromolecules (bovine serum albumin, insulin, inactivated influenza vaccine) in vitro. RESULTS: We found that removal of stratum corneum dramatically increased skin permeability to all compounds tested. However, removal of full epidermis increased skin permeability by another 1-2 orders of magnitude. We also studied the effects of removing skin tissue only from localized spots on the skin surface by covering skin with a mask containing 125-µm holes during tissue removal. Skin permeabilized in this less-invasive way showed similar results. This suggests that microdermabrasion of skin using a mask may provide an effective way to increase skin permeability. CONCLUSIONS: We conclude that viable epidermis offers a significant permeability barrier that becomes rate limiting upon removal of stratum corneum.