Numerical Investigation of Layered Homogeneous Skull Model for Simulations of Transcranial Focused Ultrasound.

BACKGROUND AND OBJECTIVES: The influence of the intracranial pressure field must be discussed with the development of a single-element transducer for low-intensity transcranial focused ultrasound because the skull plays a significant role in blocking and dispersing ultrasound wave propagation. Ultrasound propagation is mainly affected by the structure and acoustic properties of the skull; thus, we aimed to investigate the impact of simplifying the acoustic properties of the skull on the simulation of the transcranial pressure field to present guidance for efficient skull modeling in full-wave simulations. MATERIALS AND METHODS: We constructed a three-dimensional computational model for ultrasound transmission with the same structure but varying acoustic properties of the skull. The structural information and heterogeneous acoustic properties of the skull were acquired from computed tomography images, and we segmented the skull into three layers (3 L), including spongy and compact bones. We then assigned homogeneous acoustic properties to a single layer (1 L) or 3 L of the skull. In addition, we investigated the influence of different types of transducers and different ultrasound frequencies (1.1 MHz, 0.5 MHz, and 0.25 MHz) on the intracranial pressure field to provide a comparison of the heterogenous and homogeneous models. RESULTS: We indicated the importance of numerical simulations in estimating the intracranial pressure field of the skull owing to beam distortions. When we simplified the skull model, both the 1 L and 3 L models showed contours of the acoustic focus comparable to those of the heterogeneous model. When we evaluated the peak pressure and volume of the acoustic focus, the 1 L model produced a better estimation of peak pressure with a difference <10%, and the 3 L model is suitable to obtain smaller errors in the volume of the acoustic focus. CONCLUSIONS: In conclusion, we examined the possibility of simplification of skull models using 1 L and 3 L homogeneous properties in the numerical simulation for focused ultrasound. The results show that the layered homogeneous model can provide characteristics comparable to those of the acoustic focus in heterogeneous models.

Empowering powdered activated carbon (PAC) with 3D printing: Achieving highly efficient and reusable cationic dye removal.

Powdered activated carbon (PAC) has been extensively used as an effective adsorbent. Despite its excellent adsorption ability, PAC has drawbacks, including difficulty in filtration and reactivation after use, limitations of mass transfer in deeper areas because of its aggregated powder form, and limited applicability in high-flow systems. To overcome these limitations, we used a three-dimensional (3D) printing system to fabricate PAC into a 3D structure. Spectral and microscopic analyses indicated that PAC was embedded into 3D monolith and exhibited high porosity suitable for facile mass transfer. The designed 3D PAC filter effectively removed 200 ppm-methylene blue (MB) within 8 h and showed an adsorption efficiency of 93.4 ± 0.9%. The adsorption of MB onto the 3D PAC filter was described by the pseudo-first-order kinetic and Freundlich isotherm models. The negatively charged 3D PAC filter might attract the positively charged MB, thus favoring the physical adsorption of MB onto the 3D PAC filter. The adsorption performance of the 3D PAC filter was tested at various pH levels of 4-10 and against MB spiked in seawaters and freshwaters to evaluate its feasibility for use in real environments. Finally, the reproducibility and reusability of the 3D PAC filter were demonstrated through repeated adsorption and desorption processes against MB.

Distribution and ecological risk assessment of priority water pollutants in surface river sediments with emphasis on industrially affected areas.

Priority water pollutants comprising six plasticizers, 18 volatile organic compounds (VOCs), total petroleum hydrocarbon (TPH), 1,4-dioxane, epichlorohydrin, formaldehyde, acrylamide, and cyanides were determined in surface river sediments to assess their distribution patterns and ecological risks. Among these, di (2-ethylhexyl) phthalate (DEHP), toluene, TPH, and acrylamide were frequently found in sediments. The industrial sites had higher concentrations of ∑plasticizers (median 628 ng/g dry weight (dw)), ∑VOCs (median 3.35 ng/g dw), acrylamide (median 0.966 ng/g dw), and TPH (median 152 µg/g dw) in sediments than the mixed and non-industrial areas. The other pollutants did not show the significant differences in levels according to site types because of their relatively low detection frequencies. Volatile and soluble substances as well as hydrophobic pollutants were predominantly detected in surface sediments from industrial areas. Sediment contamination patterns were affected by the size and composition of the industrial zones around the sampling sites. The ecological risks determined using the sediment quality guidelines (DEHP, VOCs, and TPH) and the mean probable effect level quotients (DEHP) were mostly acceptable. However, the two most representative industrial regions (the largest industrial area and the first industrial city) showed risks of concern for DEHP and TPH.

The effects of heavy rain on the fate of urban and agricultural pollutants in the riverside area around weirs using multi-isotope, microbial data and numerical simulation.

The increase in extreme heavy rain due to climate change is a critical factor in the fate of urban and agricultural pollutants in aquatic system. Nutrients, including NO3- and PO43-, are transported with surface and seepage waters into rivers, lakes and aquifers and can eventually lead to algal blooms. δ15N-NO3-, δ18O-NO3-, and δ11B combined with hydrogeochemical and microbial data for groundwater and surface water samples were interpreted to evaluate the fate of nutrients in a riverside area around weirs in Daegu, South Korea. Most of the ions showed similar concentrations in the groundwater samples before and after heavy rain while concentrations of major ions in surface water samples were diluted after heavy rain. However, Si, PO43-, Zn, Ce, La, Pb, Cu and a number of waterborne pathogens increased in surface water after heavy rain. The interpretation of δ11B, δ15N-NO3-, and δ18O-NO3- values using a Bayesian mixing model revealed that sewage and synthetic fertilizers were the main sources of contaminants in the groundwater and surface water samples. δ18O and SiO2 interpreted using the Bayesian mixing model indicated that the groundwater component in the surface water increased from 4.4 % to 17.9 % during the wet season. This is consistent with numerical simulation results indicating that the direct surface runoff and the groundwater baseflow contributions to the river system had also increased 6.4 times during the wet season. The increase in proteobacteria and decrease of actinobacteria in the surface water samples after heavy rain were also consistent with an increase of surface runoff and an increased groundwater component in the surface water. This study suggests that source apportionment based on chemical and multi-isotope data combined with numerical modeling approaches can be useful for identifying main hydrological and geochemical processes in riverside areas around weirs and can inform suggestions of effective methods for water quality management.

Maternal exposure to polystyrene microplastics impairs social behavior in mouse offspring with a potential neurotoxicity.

As plastic production has been increasing steadily, environmental pollution resulting from microplastics (MPs) continues to draw considerable attention of the researchers. Several studies have reported that MPs are risk factors for various cellular and systemic dysfunctions. However, the effects of chronic MP exposure from the embryonic stage to adulthood on mouse brain remain unclear. Accordingly, determining the impacts of maternal exposure to MPs on mouse offspring was the main goal of this study. To this end, single cells of primary cortical neurons were isolated from mouse embryos. Subsequently, the cells were exposed to 2 µm polystyrene microplastics (PS-MPs), which resulted in a notable reduction in dendritic length, and PS-MPs cannot pass through the cellular membrane of neurons. Moreover, exposure to PS-MPs caused the proliferation increase and apoptosis in primary cortical neuronal cells. We then evaluated the neurotoxicity associated with chronic PS-MP exposure from the embryonic stage to adulthood in C57BL/6 J mouse offspring. PS-MPs were found to accumulate in the digestive and excretory organs of the offspring but not in the brain tissue. However, offspring exposed to PS-MPs exhibited no differences in the levels of expression of genes related to brain cell markers or synaptic organization. Nevertheless, PS-MP-exposed mice exhibited impaired social novelty preferences; however, no changes were observed in the emotional, compulsive, or cognitive behaviors. Taken together, these results demonstrate the potential neurotoxic effects of chronic exposure to PS-MPs in mouse offspring.

Asymmetric anti-CLL-1×CD3 bispecific antibody, ABL602 2+1, with attenuated CD3 affinity endows potent antitumor activity but limited cytokine release.

BACKGROUND: Acute myeloid leukemia (AML) is a type of leukemia in adults with a high mortality rate and poor prognosis. Although targeted therapeutics, chemotherapy, and hematopoietic stem cell transplantation can improve the prognosis, the recurrence rate is still high, with a 5-year survival rate of approximately 40%. This study aimed to develop an IgG-based asymmetric bispecific antibody that targets CLL-1 and CD3 for treating AML. METHODS: ABL602 candidates were compared in terms of binding activity, T-cell activation, and tumor-killing activities. ABL602-mediated T-cell activation and tumor-killing activities were determined by measuring the expression of activation markers, cytokines, cytolytic proteins, and the proportion of dead cells. We evaluated in vivo tumor growth inhibitory activity in two mouse models bearing subcutaneously and orthotopically engrafted human AML. Direct tumor-killing activity and T-cell activation in patient-derived AML blasts were also evaluated. RESULTS: ABL602 2+1 showed a limited CD3 binding in the absence of CLL-1, suggesting that steric hindrance on the CD3 binding arm could reduce CLL-1 expression-independent CD3 binding. Although the CD3 binding activity was attenuated compared with that of 1+1, ABL602 2+1 exhibited much stronger T-cell activation and potent tumor-killing activities in AML cell lines. ABL602 2+1 efficiently inhibited tumor progression in subcutaneously and orthotopically engrafted AML mouse models. In the orthotopic mouse model, tumor growth inhibition was observed by gross measurement of luciferase activity, as well as a reduced proportion of AML blasts in the bone marrow, as determined by flow cytometry and immunohistochemistry (IHC) staining. ABL602 2+1 efficiently activated T cells and induced the lysis of AML blasts, even at very low effector:target (E:T) ratios (eg, 1:50). Compared with the reference 1+1 antibody, ABL602 did not induce the release of cytokines including interleukin-6 and tumor necrosis factor-α in the healthy donor-derived peripheral blood mononuclear cell. CONCLUSIONS: With its potent tumor-killing activity and reduced cytokine release, ABL602 2+1 is a promising candidate for treating patients with AML and warrants further study.

The use of photovoice in nursing education: A scoping review.

Given the variety of uses of photovoice in nursing education, the importance of clarifying and describing this method is apparent. This scoping review aimed to explore the evidence on the use of photovoice in nursing education, describe the state of knowledge in this area, and identify knowledge gaps within the existing literature. A comprehensive search was performed in seven databases including MEDLINE, CINAHL, Embase, and Education Full Text. Three gray literature databases (ProQuest Dissertations and Theses Global database, EThOS, and PapersFirst) were also searched. This scoping review was conducted with reference to the JBI scoping review guidelines and reported using the PRISMA-ScR statement. A total of 22 studies published between 2001 and 2022 were included in this scoping review. The findings indicate that photovoice is used globally in nursing education to teach in various courses and content areas within online, hybrid, and in-person environments. Despite the heterogeneity within the definition of photovoice and associated pedagogical strategies, the results of this scoping review suggest that photovoice can serve as an educational tool for nursing students.

Job satisfaction and moral distress of nurses working as physician assistants: focusing on moderating role of moral distress in effects of professional identity and work environment on job satisfaction.

BACKGROUND: Physician assistant was created in response to a shortage of physicians. However, this profession is not officially recognized in Korea. Many nurses are working as physician assistants. Their job satisfaction was low due to role conflict. Job satisfaction plays a major role in providing high quality nursing. This study aimed to investigate effects of work environment and professional identity on job satisfaction and identify the mediating role of moral distress in such effects. METHODS: Participants were 112 nurses working as physician assistants. They were recruited from three General Hospitals. A questionnaire scale was used to collect data. Data were analyzed using frequency, descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation, and Macro Model 4 with SPSS Statistics. RESULTS: Job satisfaction of nurses working as physician assistants had a score of 3.08 out of 5. It showed significant associations with work environment and professional identity. Moral distress had a partial mediating role in relationships of job satisfaction with work environment and professional identity. CONCLUSION: Many nurses are working as physician assistants, although physician assistant as a profession is not officially recognized in Korea. Nurses working as physician assistants experience confusion about their professional identity and moral distress. For better nursing outcomes, physician assistant policy should be improved, and various strategies should be provided to improve their job satisfaction.

The experience of resilience in newly graduated nurses: A qualitative metasynthesis.

AIM: The aim of the present study was to understand the experiences and perceptions of newly graduated nurses in relation to resilience by providing an interpretive synthesis of the existing qualitative literature on this topic. BACKGROUND: Resilience in newly graduated nurses has been associated with increased satisfaction and decreased turnover. As the experience of resilience is unique to each individual, qualitative studies are well suited to explore this concept, yet the existing data is heterogenous. DESIGN: A qualitative metasynthesis was conducted using a meta-ethnographic approach. METHODS: The search was performed using PubMed, CINAHL, Embase, PsycINFO, ProQuest Dissertations and Theses Global for the English literature and NDSL, KCI, RISS, KISS and DBpia for the Korean literature. The JBI Critical Appraisal Checklist for Qualitative Research was used to assess the quality of studies. An a priori protocol was created and registered on the Open Science Framework (Randall & De Gagne, 2022). RESULTS: The final review included seven articles published between 2008 and 2021. Three main themes were identified: (1) internal experience of resilience; (2) external sources of resilience; and (3) building resilience over time. Subthemes were also identified. CONCLUSIONS: This study indicates that resilience can be developed over time during the period of transition from student nurse to professional nurse and is impacted by personal and organizational influences. The promotion of resilience presents considerations and opportunities for health care leaders and administrators.

Biosorption of sub-micron-sized polystyrene microplastics using bacterial biofilms.

Microplastics are becoming a global concern because they pose potential ecological and toxicological risks to organisms. Thus, removing microplastics from aquatic environments is important. In this study, we evaluated the capability of bacterial biofilms as a biological source for the biosorptive removal of sub-micron-sized polystyrene (PS) microplastics. Three bacterial strains-specifically, Pseudomonas aeruginosa, Bacillus subtilis, and Acinetobacter sp.-were used to form biofilms, and each biofilm was tested in batch experiments for the removal of sub-micron-sized PS microplastics. The Acinetobacter sp. biofilm demonstrated excellent removal performance against 430 nm-PS microplastics than other bacterial biofilms and showed a removal capacity of 715.5 mg/g upon treatment with the PS microplastics for 20 min, thus it employed further adsorption experiments. The biosorption of 430 nm-PS microplastics onto the Acinetobacter sp. biofilm was well explained by the pseudo-second-order kinetics and Freundlich isotherm models. Fourier transform infrared analysis indicated that biosorption of 430 nm-PS microplastics onto the Acinetobacter sp. biofilm involved chemisorption. Three environmental parameters-temperature, pH, and coexisting ions-marginally affected the biosorption of 430 nm-PS microplastics onto Acinetobacter sp. biofilm. However, the biosorption capability of Acinetobacter sp. biofilm was diminished when the 430 nm-PS microplastics were incubated in environmental freshwaters for 7 d.

Exposure to polystyrene particles causes anxiety-, depression-like behavior and abnormal social behavior in mice.

In the era of plastic use, organisms are constantly exposed to polystyrene particles (PS-Ps). PS-Ps accumulated in living organisms exert negative effects on the body, although studies evaluating their effects on brain development are scarce. In this study, the effects of PS-Ps on nervous system development were investigated using cultured primary cortical neurons and mice exposed to PS-Ps at different stages of brain development. The gene expression associated with brain development was downregulated in embryonic brains following PS-Ps exposure, and Gabra2 expression decreased in the embryonic and adult mice exposed to PS-Ps. Additionally, offspring of PS-Ps-treated dams exhibited signs of anxiety- and depression-like behavior, and abnormal social behavior. We propose that PS-Ps accumulation in the brain disrupts brain development and behavior in mice. This study provides novel information regarding PS-Ps toxicity and its harmful effects on neural development and behavior in mammals.

Cannabinoid enhancement of lncRNA MMP25-AS1/MMP25 interaction reduces neutrophil infiltration and intestinal epithelial injury in HIV/SIV infection.

Intestinal epithelial barrier dysfunction, a hallmark of HIV/SIV infection, persists despite viral suppression by combination antiretroviral therapy (cART). Emerging evidence suggests a critical role for long noncoding RNAs (lncRNAs) in maintaining epithelial homeostasis. We simultaneously profiled lncRNA/mRNA expression exclusively in colonic epithelium (CE) of SIV-infected rhesus macaques (RMs) administered vehicle (VEH) or Δ-9-tetrahydrocannabinol (THC). Relative to controls, fewer lncRNAs were up- or downregulated in CE of THC/SIV compared with VEH/SIV RMs. Importantly, reciprocal expression of the natural antisense lncRNA MMP25-AS1 (up 2.3-fold) and its associated protein-coding gene MMP25 (attracts neutrophils by inactivating alpha-1 anti-trypsin/SERPINA1) (down 2.2-fold) was detected in CE of THC/SIV RMs. Computational analysis verified 2 perfectly matched complementary regions and an energetically stable (normalized binding free energy = -0.2626) MMP25-AS1/MMP25 duplex structure. MMP25-AS1 overexpression blocked IFN-γ-induced MMP25 mRNA and protein expression in vitro. Elevated MMP25 protein expression in CE of VEH/SIV but not THC/SIV RMs was associated with increased infiltration by myeloperoxidase/CD11b++ neutrophils (transendothelial migration) and epithelial CD47 (transepithelial migration) expression. Interestingly, THC administered in combination with cART increased MMP25-AS1 and reduced MMP25 mRNA/protein expression in jejunal epithelium of SIV-infected RMs. Our findings demonstrate that MMP25-AS1 is a potentially unique epigenetic regulator of MMP25 and that low-dose THC can reduce neutrophil infiltration and intestinal epithelial injury potentially by downregulating MMP25 expression through modulation of MMP25-AS1.

Cannabinoids modulate the microbiota-gut-brain axis in HIV/SIV infection by reducing neuroinflammation and dysbiosis while concurrently elevating endocannabinoid and indole-3-propionate levels.

BACKGROUND: Although the advent of combination anti-retroviral therapy (cART) has transformed HIV into a manageable chronic disease, an estimated 30-50% of people living with HIV (PLWH) exhibit cognitive and motor deficits collectively known as HIV-associated neurocognitive disorders (HAND). A key driver of HAND neuropathology is chronic neuroinflammation, where proinflammatory mediators produced by activated microglia and macrophages are thought to inflict neuronal injury and loss. Moreover, the dysregulation of the microbiota-gut-brain axis (MGBA) in PLWH, consequent to gastrointestinal dysfunction and dysbiosis, can lead to neuroinflammation and persistent cognitive impairment, which underscores the need for new interventions. METHODS: We performed RNA-seq and microRNA profiling in basal ganglia (BG), metabolomics (plasma) and shotgun metagenomic sequencing (colon contents) in uninfected and SIV-infected rhesus macaques (RMs) administered vehicle (VEH/SIV) or delta-9-tetrahydrocannabinol (THC) (THC/SIV). RESULTS: Long-term, low-dose THC reduced neuroinflammation and dysbiosis and significantly increased plasma endocannabinoid, endocannabinoid-like, glycerophospholipid and indole-3-propionate levels in chronically SIV-infected RMs. Chronic THC potently blocked the upregulation of genes associated with type-I interferon responses (NLRC5, CCL2, CXCL10, IRF1, IRF7, STAT2, BST2), excitotoxicity (SLC7A11), and enhanced protein expression of WFS1 (endoplasmic reticulum stress) and CRYM (oxidative stress) in BG. Additionally, THC successfully countered miR-142-3p-mediated suppression of WFS1 protein expression via a cannabinoid receptor-1-mediated mechanism in HCN2 neuronal cells. Most importantly, THC significantly increased the relative abundance of Firmicutes and Clostridia including indole-3-propionate (C. botulinum, C. paraputrificum, and C. cadaveris) and butyrate (C. butyricum, Faecalibacterium prausnitzii and Butyricicoccus pullicaecorum) producers in colonic contents. CONCLUSION: This study demonstrates the potential of long-term, low-dose THC to positively modulate the MGBA by reducing neuroinflammation, enhancing endocannabinoid levels and promoting the growth of gut bacterial species that produce neuroprotective metabolites, like indole-3-propionate. The findings from this study may benefit not only PLWH on cART, but also those with no access to cART and more importantly, those who fail to suppress the virus under cART.

Adsorption behavior of polyamide microplastics as a vector of the cyanotoxin microcystin-LR in environmental freshwaters.

Microplastics are ubiquitous environmental contaminants, and concern about microplastics functioning as vectors for coexisting environmental contaminants has been increasing. In this study, we evaluated the potential of microplastics as a vector for microcystins (MCs) in an aquatic environment. Six microplastics-polyvinylidene chloride, polystyrene, polyamide-6 (PA-6), polyvinyl chloride, poly(ethylene terephthalate), and polyethylene-were used in the experiments, and the PA-6 microplastics showed strong affinity toward the cyanotoxin microcystin-leucine arginine (MC-LR) with an adsorption efficiency of 89.5 ± 0.1 %. The adsorption of MC-LR onto PA-6 microplastics was well described by the pseudo-first-order kinetics and Langmuir isotherm models, and the adsorption was considered to be driven mainly by polar-polar interactions. The maximum adsorption capacity (qm) of MC-LR onto PA-6 microplastics was estimated to be 85.64-129.05 µg per g of PA-6 microplastics. Coexisting ions of NaCl, MgSO4, KH2PO4, CaCO3, and Na2HPO4 marginally affected the adsorption of MC-LR onto the PA-6 microplastics. However, water-quality parameters of conductivity and total-nitrogen content in environmental freshwaters influenced the adsorption of MC-LR onto PA-6 microplastics. The adsorption capability of PA-6 microplastics was evaluated using extracellular MCs (i.e., MC-LR, MC-YR, MC-RR, and total MCs) released from Microcystis aeruginosa cells during their growth.

A systematic review of videoconferencing in health professions education: the digital divide revisited in the COVID-19 era.

OBJECTIVES: During the COVID-19 pandemic, educators shifted from traditional lectures to videoconferencing. This systematic review explored the use of videoconferencing as a teaching tool in response to the pandemic as well as issues related to digital equity and inclusion. CONTENT: The review was conducted using the Joanna Briggs Institute for Systematic Reviews methodology and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. SUMMARY: A total of nine studies met eligibility criteria. The participants in the included studies were medical students from various parts of the world. Technical difficulties and lack of human interactions were identified as barriers to learning through videoconferencing. OUTLOOK: To achieve full success, pedagogical videoconferencing must prioritize digital equity and a universal design for learning. Although useful for maintaining education during the pandemic, in the future, videoconferencing will present challenges related to the digital divide as well as opportunities as a teaching tool for nurse educators globally.

Upconverting nanoparticle-containing erythrocyte-sized hemoglobin microgels that generate heat, oxygen and reactive oxygen species for suppressing hypoxic tumors.

Inspired by erythrocytes that contain oxygen-carrying hemoglobin (Hb) and that exhibit photo-driven activity, we introduce homogenous-sized erythrocyte-like Hb microgel (µGel) systems (5-6 µm) that can (i) emit heat, (ii) supply oxygen, and (iii) generate reactive oxygen species (ROS; 1O2) in response to near-infrared (NIR) laser irradiation. Hb µGels consist of Hb, bovine serum albumin (BSA), chlorin e6 (Ce6) and erbium@lutetium upconverting nanoparticles (UCNPs; ∼35 nm) that effectively convert 808 nm NIR light to 660 nm visible light. These Hb µGels are capable of releasing oxygen to help generate sufficient reactive oxygen species (1O2) from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity. Moreover, the Hb µGels emit heat and increase surface temperature due to NIR light absorption by heme (iron protoporphyrin IX) and display photothermal activity. By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation, it is possible to formulate bespoke Hb µGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect. These Hb µGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.

The new insight into the inflammatory response following focused ultrasound-mediated blood-brain barrier disruption.

BACKGROUND: Despite the great potential of FUS-BBB disruption (FUS-BBBD), it is still controversial whether FUS-BBBD acts as an inducing factor of neuro-inflammation or not, and the biological responses after FUS-BBBD triggers the inflammatory process are poorly understood. The aim of this study is to investigate the safety window for FUS levels based on a comprehensive safety assessment. METHODS: The mice were treated with two different ultrasound parameters (0.25 MPa and 0.42 MPa) in the thalamus region of brain. The efficacy of BBB opening was verified by dynamic contrast-enhanced MRI (DCE-MRI) and the cavitation monitoring. The transcriptome analysis was performed to investigate the molecular response for the two BBBD conditions after FUS-mediated BBB opening in time-dependent manners. Histological analysis was used for evaluation of the tissue damage, neuronal degeneration, and activation of glial cells induced by FUS-BBBD. RESULTS: The BBBD, as quantified by the Ktrans, was approximately threefold higher in 0.42 MPa-treated group than 0.25 MPa-treated group. While the minimal tissue/cellular damage was found in 0.25 MPa-treated group, visible damages containing microhemorrhages and degenerating neurons were detected in 0.42 MPa-treated group in accordance with the extent of BBBD. In transcriptome analysis, 0.42 MPa-treated group exhibited highly dynamic changes in the expression levels of an inflammatory response or NF-κB pathway-relative genes in a time-dependent manner whereas, 0.25 MPa was not altered. Interestingly, although it is clear that 0.42 MPa induces neuroinflammation through glial activation, neuroprotective properties were evident by the expression of A2-type astrocytes. CONCLUSIONS: Our findings propose that a well-defined BBBD parameter of 0.25 MPa could ensure the safety without cellular/tissue damage or sterile inflammatory response in the brain. Furthermore, the fact that the excessive sonication parameters at 0.42 MPa could induce a sterile inflammation response via glial activation suggested the possibility that could lead to tissue repair toward the homeostasis of the brain microenvironment through A2-type reactive astrocytes.

Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood-Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and neuroprotective functions. Despite the small molecular size of MB, which can cross the BBB, the therapeutic effective dosage using a BBB-permeable delivery system in a specific brain localization remains unclear. In this study, we presented magnetic resonance-guided focused ultrasound (MRgFUS) as a delivery system to enhance BBB permeability for the effective treatment of AD. MRgFUS using two ultrasound intensities (0.25 and 0.32 MPa) was used to intravenously deliver MB to the hippocampal region. Compared with treatment with 0.25 MPa FUS, treatment with 0.32 MPa FUS significantly enhanced MB brain accumulation. Deposition of amyloid-ß (Aß) plaques and neural cell damage was significantly reduced in 0.32 MPa FUS/MB-treated APP/PS1 mice. Furthermore, aquaporin-4 expression increased significantly in the 0.32 MPa FUS and 0.32 MPa FUS/MB groups without glial fibrillary acidic protein activation. The results from this study demonstrate that FUS improved MB delivery to the brain, and FUS/MB combination treatment reduced the number of Aß plaques. This study revealed the potential of FUS-BBBD as an effective strategy to enhance the efficacy of therapeutic drugs for AD.

Effectiveness of speak-up training programs for clinical nurses: A scoping review.

BACKGROUND: Speaking up about patient safety concerns is critical when bedside nurses encounter unsafe situations. Training programs that encourage nurses' speaking up behavior have been introduced, but there is limited evidence regarding whether such training leads to behavior change or improves patient safety. OBJECTIVE: The aim of this review was to identify the effectiveness of speak-up training programs for clinical nurses, focusing on program content and outcomes. DESIGN: A scoping review was conducted using the Joanna Briggs Institute methodology and reported according to the Cochrane and Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews guidelines. METHODS: This study used bibliographic databases of PubMed, Embase, PsycINFO, Scopus, ProQuest Dissertations and Theses Global for the English language, and NDSL, KCI, RISS, KISS, and DBpia for the Korean language. The literature search used a combination of keywords and subject headings related to speak-up training programs for nurses or any type of nurse training program with an assertiveness component. Training outcomes were evaluated according to the 4-level Kirkpatrick model. RESULTS: A total of 4808 references were retrieved, of which 21 articles were selected. These 21 studies were conducted in different parts of the world and published from 1981 to 2020. Speak-up training primarily increased some degree of nurses' levels of assertiveness and speak-up behavior, and also led to secondary outcomes such as job stress, work motivation, and communication conflicts. Most studies (n = 19) applied traditional training formats which consisted of multi-session lectures and practice, whereas three studies applied new methodologies such as high-fidelity simulations and online learning. According to the Kirkpatrick model, five studies assessed reactions to speak-up training (level 1), all studies evaluated learning as a result of training (level 2), two studies measured the effect of speak-up training on nurses' behavior (level 3), and one study evaluated nurses' results (level 4) while no studies evaluated patient-level outcomes. CONCLUSIONS: Speak-up training for nurses can improve their levels of assertiveness or speak-up behaviors. Despite inconsistent or mixed findings, speak-up training has the potential to improve nurses' psychological well-being, leading to positive organizational performance. New training methods are directed at specialized education for clinical situations. Future speak-up training should consist of training programs based on real clinical situations in which team members participate together to comprehensively evaluate the effect of training on behavioral changes of health professionals as well as patient safety.

Colorimetric Detection of Urease-Producing Microbes Using an Ammonia-Responsive Flexible Film Sensor.

Urease-producing (ureolytic) microbes have given rise to environmental and public health concerns because they are thought to contribute to emissions of ammonia and to be a virulence factor for infections. Therefore, it is highly important to have the ability to detect such microbes. In this study, a poly(dimethylsiloxane) (PDMS)-based colorimetric film sensor was employed for the detection of urease-producing microbes. The sensor was able to detect the enzyme activity of commercially available urease, as the color and absorbance spectrum of the sensor was observed to change upon being exposed to the reaction catalyzed by urease. The ratio of the absorbance of the sensor at 640 nm to that at 460 nm (A640/A460) was linearly proportional to the amount of urease present. The performance of the sensor was validated by the results of a sensitivity and selectivity analysis towards thirteen different bacterial strains. Based on the development of blue color of the sensor, the tested bacteria were classified as strongly positive, moderately positive, weakly positive, or negative urease producers. The response of the sensor to ureolytic bacteria was verified using the urease inhibitor phenyl phosphorodiamidate (PPDA). Additionally, the sensor achieved the selective detection of ureolytic bacteria even in the presence of non-ureolytic bacteria. In addition, a used sensor could be reverted to its original state by being subjected to simple aeration, and in this way the same sensor could be used at least five times for the detection of bacterial urease activity.