Bridging Size and Charge Effects of Mesoporous Silica Nanoparticles for Crossing the Blood-Brain Barrier.

The blood-brain barrier (BBB) is a highly selective cellular barrier that tightly controls the microenvironment of the central nervous system to restrict the passage of substances, which is a primary challenge in delivering therapeutic drugs to treat brain diseases. This study aimed to develop simple surface modifications of mesoporous silica nanoparticles (MSNs) without external stimuli or receptor protein conjugation, which exhibited a critical surface charge and size allowing them to cross the BBB. A series of MSNs with various charges and two different sizes of 50 and 200 nm were synthesized, which showed a uniform mesoporous structure with various surface zeta potentials ranging from +42.3 to -51.6 mV. Confocal microscopic results showed that 50 nm of strongly negatively charged N4-RMSN50@PEG/THPMP (∼-40 mV) could be significantly observed outside blood vessels of the brain in Tg(zfli1:EGFP) transgenic zebrafish embryos superior to the other negatively charged MSNs. However, very few positively charged MSNs were found in the brain, indicating that negatively charged MSNs could successfully penetrate the BBB. The data were confirmed by high-resolution images of 3D deconvoluted confocal microscopy and two-photon microscopy and zebrafish brain tissue sections. In addition, while increasing the size to 200 nm but maintaining the similar negative charge (∼40 mV), MSNs could not be detected in the brain of zebrafish, suggesting that transport across the BBB based on MSNs occurred in charge- and size-dependent manners. No obvious cytotoxicity was observed in the CTX-TNA2 astrocyte cell line and U87-MG glioma cell line treated with MSNs. After doxorubicin (Dox) loading, N4-RMSN50@PEG/THPMP/Dox enabled drug delivery and pH-responsive release. The toxicity assay showed that N4-RMSN50@PEG/THPMP could reduce Dox release, resulting in the increase of the survival rate in zebrafish. Flow cytometry demonstrated N4-RMSN50@PEG/THPMP had few cellular uptakes. Protein corona analysis revealed three transporter proteins, such as afamin, apolipoprotein E, and basigin, could contribute to BBB penetration, validating the possible mechanism of N4-RMSN50@PEG/THPMP crossing the BBB. With this simple approach, MSNs with critical negative charge and size could overcome the BBB-limiting characteristics of therapeutic drug molecules; furthermore, their use may also cause drug sustained-release in the brain, decreasing peripheral toxicity.

The effect of a virtual simulation-based educational application on nursing students' belief and self-efficacy in communicating with patients about complementary and alternative medicine.

BACKGROUND: Simulation-based learning that focuses on the development and assessment of communication and counseling skills can help nursing students achieve better skill performance and gain self-confidence with decision-making ability. It is unknown whether virtual simulation as an instructional design significantly improves educational outcomes than a traditional lecture with low-fidelity simulation in students. OBJECTIVES: The aim was to explore the effect of a virtual simulation-based educational smartphone application on nursing students' beliefs and self-efficacy in communicating with patients about complementary and alternative medicine (CAM) use. DESIGN: A quasi-experimental study with pretest-posttest nonequivalent control group design. SETTINGS AND PARTICIPANTS: A total of 101 nursing students, who were in their second or third-year nursing program at a Southern Taiwan university volunteered to participate in the academic year 2020-2021. Participants were assigned to an experimental or control group in an elective course. METHODS: All participants received a 4-hour lecture that included an in-class lecture with low-fidelity simulation (paper-based scenarios) about the risk-benefit assessment of a patient's CAM use. The experimental group received a series of 13 virtual simulation exercises with clinical scenarios by means of a smartphone application. Data from belief and self-efficacy scales were collected at the beginning and end of the course from September 2020 to February 2021. Descriptive and inferential statistics were analyzed using the IBM® SPSS® version 23.0. RESULTS: Although both groups significantly improved their belief and self-efficacy scale scores, the experimental group had significant differences in overall self-efficacy in communicating with patients about CAM use compared with the control group, specifically the CAM perceptions and self-confidence scores. CONCLUSIONS: Although both in-class and virtual simulation improved nursing students' belief and self-efficacy, the virtual simulation-based educational app is effective as an adjunct learning tool in significantly increasing nursing students' self-efficacy in communicating with patients about CAM use to help minimize their risks.

A Novel Role of Arrhythmia-Related Gene KCNQ1 Revealed by Multi-Omic Analysis: Theragnostic Value and Potential Mechanisms in Lung Adenocarcinoma.

The early diagnosis, prognostic prediction, and personalized therapy of lung adenocarcinoma (LUAD) remains a challenging issue. KCNQ1 (potassium voltage-gated channel subfamily Q Member 1) is implicated in long QT syndrome (LQTS) and cardiac arrhythmia, while its significance in LUAD remains unclear. In this study, we aimed to explore the significance of KCNQ1 in terms of clinical value, tumor immunity, underlying mechanisms, and a precision medicine approach by means of multi-omics analysis. The association of KCNQ1 with LUAD was first explored. Both altered variants and high expression of KCNQ1 in a TCGA-LUAD cohort indicated a favorable outcome. KCNQ1 levels had a negative correlation with tumor proliferation index Ki67 levels. siRNA-knockdown of KCNQ1 promoted the migration ability of lung cancer cells. KCNQ1 levels were decreased in LUAD tissue compared to normal tissue. A receiver operating characteristic (ROC) curve indicated good diagnostic efficiency of KCNQ1. High KCNQ1 is associated with an immunoactive profile of immune infiltration and immunomodulators and is involved in the inhibition of the cell cycle and DNA replication. Lapatinib was identified as a potent drug for LUAD in the context of low KCNQ1. This study unveiled the significance of KCNQ1 in diagnosis and prognosis and provided a corresponding precision medicine strategy for LUAD.

Body volume estimation equation for male laborers in Taiwan.

The purpose of this study was to develop a body volume (BV) estimation equation for male laborers in Taiwan with body weight (W) and stature height (H) as initial estimators. A three-dimensional (3D) body scanner and a 3D foot scanner were used to measure the 3D range data of 100 male laborers in this study. Subjects' BV was extracted from the 3D body model, and H and W were used as independent variables in regression analysis. The results show that the final BV estimation equation is BV = 1122.927 × W0.972, with R2 = 0.949. Thirty extra male subjects were scanned to compare this BV estimation equation with those in previous studies. The results show that this BV estimation equation had the smallest absolute mean difference at 1.1458 L and the smallest standard error of the estimate at 2.48% in comparison.

In-vehicle carbon dioxide and adverse effects: An air filtration-based intervention study.

Drowsiness is considered a potential risk for traffic accidents. Exposure to high carbon dioxide (CO2) levels in vehicles may result in unpleasant feeling, fatigue, drowsiness or lethargy among drivers and passengers. However, little is known about whether reducing CO2 levels in vehicles by air filtration can relieve adverse effects among human subjects during driving. We recruited a panel of 84 healthy participants to drive a vehicle equipped with a CO2 filtration system for 1 h on a coastal road in a Northern Taiwan rural area. The operation modes of the CO2 filtration system, including fresh air from open windows without a CO2 filtration system (Control-mode), fresh air from an air conditioning (AC) system with closed windows and a false CO2 filtration system in operation (Off-mode) or a true CO2 filtration system in operation (On-mode), were examined. The repeated measurements of heart rate (HR), blood pressure (BP), CO2, total volatile organic compounds (TVOCs), particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) and a simple question about drowsiness were obtained for each participant in three different modes. We found that decreased HR, systolic BP (SBP) and diastolic BP (DBP) and increased drowsiness were associated with increased levels of in-vehicle CO2. The effects of in-vehicle CO2 on adverse effects were highest in the Off-mode during driving. In the On-mode, the participants showed slight decreases in HR, SBP and DBP and slight increases in drowsiness. We concluded that the utilization of a CO2 filtration system can reduce in-vehicle CO2 levels and modify the effect of in-vehicle CO2 on HR, BP and drowsiness among human subjects during driving.

A Pilot Study of Five Types of Maximum Hand Strength among Manufacturing Industry Workers in Taiwan.

Background: The purpose of this study is to collect five types of maximum hand strength among workers in the manufacturing industry in Taiwan. Methods: This study is a cross sectional study with a stratified and convenient sample of workers on the production line in manufacturing industries in Central Taiwan. In total, we recruited 198 healthy subjects to participate in this study. Five types of hand strength were measured in both hands three times with 3 min rests between trials. Results: The strength of females for these five types of hand exertions were 52.0% to 67.6% of the strength of males (p < 0.001). For both genders, there was a main effect for the types of hand strength for the right hand (p < 0.001) and the left hand (p < 0.001). In general, the hand strength in U.S. and EU countries was 1.2 to 1.7 times greater than the strength among the three types of hand exertions in this study. Conclusion: These results can be used to evaluate the musculoskeletal burdens on the upper extremities in the manufacturing industry and could also be used for tool and job design and job modifications.

[A Challenge for Home-Based Hospice Care: Good Death at Home].

Taiwan is expected to become a "super-aged" nation in 2065. Modern medical advancements, while extending the average human lifespan, has led to higher incidence of patient suffering and greater medical expenses due to chronic disease and terminal illnesses. As the concept and services of hospice and palliative care have become increasingly accepted by the public, the issue of final care for a good death has become a priority concern for both patients and their families. Experiencing a good death at home is a common last wish for terminal patients. However, guidelines for good death at home are still unavailable in Taiwan. The promotion of this concept thus remains a challenge with many limitations. This article aims to explore: (1) the importance of hospice care; (2) the selection of a proper location for good death; (3) the requirements for nursing education in the care of dying patients; and (4) the challenges and strategies of a good death at home, including "the family dimension-connections with the family members" and "the education dimension-promotion of home-based dying in nursing education". The goal is to help terminal patients experience a good death at home, to assist family members embrace the good death of their loved ones, and, eventually, to facilitate peaceful and successful home-based dying for both the patient and their family members.

Indoor ozone levels, houseplants and peak expiratory flow rates among healthy adults in Taipei, Taiwan.

The association between houseplants and indoor air quality improvement has been reported in previous studies. However, the effect of houseplant-emitted isoprene on the association between ozone (O3) formation and respiratory health remains unclear. We recruited 60 adult subjects from 60 houses with or without houseplants (1:1) in Taipei; twelve house visits were conducted in each home throughout 2014. The indoor air pollutants that were measured consisted of particulate matter less than or equal to 2.5 µm in diameter (PM2.5), O3 and isoprene. Peak expiratory flow rate (PEFR) was measured in each study subject during each house visit. Household information was collected by a questionnaire. Mixed-effects models were used to explore the association between indoor air pollution levels and PEFR. We found that the concentrations of O3 and isoprene in houses with houseplants were higher than those in houses without houseplants. In contrast, PM2.5 levels and % predicted PEFR were higher in houses without houseplants than in those with houseplants. Moreover, increased levels of O3 and PM2.5 in houses with houseplants were associated with a decreased % predicted PEFR, especially in the summer. We concluded that increased levels of indoor O3 and PM2.5 were associated with decreased PEFR. The presence of houseplants was associated with indoor O3, isoprene and PEFR variations in the summer.

[Mutual Support Beyond Suffering and Mortality-Spiritual Care for Families of Terminal Cancer Patients].

With the progression of cancer and the approach of death in terminal cancer patients, the suffering of the family members of patients increases drastically, often leading into a difficult spiritual journey. The needs for spiritual care in this population generally consist of: 1. Empathy: Bearing the psychological stress due to the sharing of physical pain with the patients; 2. Powerlessness: Regretting not having the power to turn the tide; 3. Loneliness: Becoming exhausted due to facing heavy physical workloads alone; 4. Break down: Feeling hopeless in the face of the myriad challenges of care; 5. Despair: Feeling perplexed by the prospects of a desperate future; 6. Sorrow: Feeling bitter due to the realization that the disease is incurable and to being reluctant to acknowledge the parting. The spiritual needs of family members may be met by evaluating the needs for and resistance to spiritual care, followed by the use of religious and non-religious companions and the application of listening and empathy approaches in order to elicit positive thoughts and the values of love, forgiveness, and reconciliation. In strengthening their personal beliefs, family members may find connectedness with god, humanity, and objects; may see hope in life; and may find the meaning of suffering in order to further seek and find inner peace, accomplish themselves, and eventually achieve spiritual sublimation.

Antibody-free isolation of rare cancer cells from blood based on 3D lateral dielectrophoresis.

We present an antibody-free approach for the high-purity and high-throughput dielectrophoretic (DEP) isolation of circulating tumour cells (CTCs) from blood in a microfluidic chip. A hydrodynamic sheath flow is designed upstream in the chip to direct the suspension samples to the channel side walls, thus providing a queue to allow DEP-induced lateral displacements. High-throughput continuous cancer cell sorting (maximum flow rate: ~2.4 mL h(-1), linear velocity: ~4 mm s(-1)) is achieved with a sustained 3D lateral DEP (LDEP) particle force normal to the continuous through-flow. This design allows the continuous fractionation of micro/nanosized particles into different downstream subchannels based on the differences in their different critical negative DEP strengths/mobilities. The main advantage of this separation strategy is that increasing the channel length can effectively increase the throughput proportionally. The effective separation of rare cancer cells (<0.001%) from diluted human blood in a handheld chip is demonstrated. An enrichment factor of 10(5) and a recovery rate of ~85% from a 0.001% cancer cell sample are achieved at an optimal flow rate of 20 µL min(-1) passing through a 6 cm long LDEP channel with an appropriate voltage at a frequency of 10 kHz. A higher throughput of 2.4 mL h(-1) is also achieved with a 13 cm long metal-based microchannel.

Personal exposure to household particulate matter, household activities and heart rate variability among housewives.

BACKGROUND: The association between indoor air pollution and heart rate variability (HRV) has been well-documented. Little is known about effects of household activities on indoor air quality and HRV alteration. To investigate changes in HRV associated with changes in personal exposure to household particulate matter (PM) and household activities. METHODS: We performed 24-h continuous monitoring of electrocardiography and measured household PM exposure among 50 housewives. The outcome variables were log10-transformed standard deviation of normal-to-normal (NN) intervals (SDNN) and the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD). Household PM was measured as the mass concentration of PM with an aerodynamic diameter <2.5 µm (PM2.5). We used mixed-effects models to examine the association between household PM2.5 exposure and log10-transformed HRV indices. RESULTS: After controlling for potential confounders, an interquartile range change in household PM2.5 with 1- to 4-h mean was associated with 1.25-4.31% decreases in SDNN and 0.12-3.71% decreases in r-MSSD. Stir-frying, cleaning with detergent and burning incense may increase household PM2.5 concentrations and modify the effects of household PM2.5 on HRV indices among housewives. CONCLUSIONS: Indoor PM2.5 exposures were associated with decreased SDNN and r-MSSD among housewives, especially during stir-frying, cleaning with detergent and burning incense.

Single-step protein purification by back flush in ion exchange chromatography.

Ion exchange chromatography, one of the major procedures for protein purification, seldom provides single-step purification due to a lack of specific affinity. In this work, a novel and simple method called "back flush" (i.e., reversing the flow direction of elution relative to that of sample loading) was developed to achieve single-step purification on an ion exchanger. Tips for the conditions and operation by back flush are presented. Our study demonstrates, for the first time, the feasibility and dramatic improvement for protein purification by the back-flush method.

Preliminary study of planar RF coils for Magnetic Resonance Microscopy.

In this study, we attempt to do a preliminary study of planar RF coils that are aimed for the application of Magnetic Resonance Microscopy (MRM). We will discuss the requirements and considerations for designing such a device. And at last, we conducted a small experiment to show that the design solution we propose is in the correct direction.