Risk Factors for Fractures in Renal Transplantation: A Population-Based Cohort Study.

INTRODUCTION: Kidney transplant recipients are at an increased risk of fractures, and targeted preventive strategies are needed. Therefore, in this retrospective cohort study, we investigated a large population-based cohort to identify the transplant recipient-specific risk factors for fractures in Taiwanese kidney transplant recipients. METHODS: We conducted a retrospective cohort study using the National Health Insurance Research Database. Patients who underwent renal transplantation between 2003 and 2015 were identified and followed until December 31, 2015, to observe the development of fractures. Variables associated with the development of post-transplant fractures were identified by calculating hazard ratios in a Cox regression model. RESULTS: 5,309 renal transplant recipients were identified, of whom 553 (10.4%) were diagnosed with post-transplant fractures. Independent predictors of post-transplant fractures included an age at transplant ≥65 years (p < 0.001), female sex (p < 0.001), fractures within 3 years prior to transplantation (p < 0.001), and diabetes mellitus (p < 0.001). In addition, daily prednisolone doses >2.9­5.3 mg/day (p < 0.001), >5.3­8.7 mg/day (p < 0.001), and >8.7 mg/day (p < 0.001) were also independent predictors of post-transplant fractures. Conversely, the use of peritoneal dialysis before renal transplantation (p = 0.021), hypertension (p = 0.005), and the use of tacrolimus (p < 0.001), azathioprine (p = 0.006), mycophenolate mofetil/mycophenolic acid (p = 0.002), mTOR inhibitors (p = 0.004), and calcium supplements (p = 0.009) were inversely correlated with post-transplant fractures. CONCLUSION: We recommend minimizing daily glucocorticoids as early and as far as possible in conjunction with immunosuppressive regimens such as tacrolimus, azathioprine, mycophenolate mofetil/mycophenolic acid, mTOR inhibitors, and calcium supplements, especially in older female recipients and in recipients with diabetes and a history of prior fractures.

Application of Deep Learning Techniques for Detection of Pneumothorax in Chest Radiographs.

With the advent of Artificial Intelligence (AI) and even more so recently in the field of Machine Learning (ML), there has been rapid progress across the field. One of the prominent examples is image recognition in the medical category, such as X-ray imaging, Computed Tomography (CT), and Magnetic Resonance Imaging (MRI). It has the potential to alleviate a doctor's heavy workload of sifting through large quantities of images. Due to the rising attention to lung-related diseases, such as pneumothorax and nodules, ML is being incorporated into the field in the hope of alleviating the already strained medical resources. In this study, we proposed a system that can detect pneumothorax diseases reliably. By comparing multiple models and hyperparameter configurations, we recommend a model for hospitals, as its focus on minimizing false positives aligns with the precision required by medical professionals. Through our cooperation with Poh-Ai Hospital, we acquired a total of over 8000 X-ray images, with more than 1000 of them from pneumothorax patients. We hope that by integrating AI systems into the automated process of scanning chest X-ray images with various diseases, more resources will be available in the already strained medical systems. Our proposed system showed that the best model that is used for transfer learning from our dataset performed with an AP of 51.57 and an AP75 of 61.40, with accuracy at 93.89%, a false positive of 1.12%, and a false negative of 4.99%. Based on the feedback from practicing doctors, they are more wary of false positives. For their use case, we recommend another model due to the lower false positive rate and higher accuracy compared with other models, which in our test shows a rate of only 0.88% and 95.68%, demonstrating the feasibility of the research. This promising result showed that it could be utilized in other types of diseases and expand to more hospitals and medical organizations, potentially benefitting more people.

Deep Learning-based Diagnosis and Localization of Pneumothorax on Portable Supine Chest X-ray in Intensive and Emergency Medicine: A Retrospective Study.

PURPOSE: To develop two deep learning-based systems for diagnosing and localizing pneumothorax on portable supine chest X-rays (SCXRs). METHODS: For this retrospective study, images meeting the following inclusion criteria were included: (1) patient age ≥ 20 years; (2) portable SCXR; (3) imaging obtained in the emergency department or intensive care unit. Included images were temporally split into training (1571 images, between January 2015 and December 2019) and testing (1071 images, between January 2020 to December 2020) datasets. All images were annotated using pixel-level labels. Object detection and image segmentation were adopted to develop separate systems. For the detection-based system, EfficientNet-B2, DneseNet-121, and Inception-v3 were the architecture for the classification model; Deformable DETR, TOOD, and VFNet were the architecture for the localization model. Both classification and localization models of the segmentation-based system shared the UNet architecture. RESULTS: In diagnosing pneumothorax, performance was excellent for both detection-based (Area under receiver operating characteristics curve [AUC]: 0.940, 95% confidence interval [CI]: 0.907-0.967) and segmentation-based (AUC: 0.979, 95% CI: 0.963-0.991) systems. For images with both predicted and ground-truth pneumothorax, lesion localization was highly accurate (detection-based Dice coefficient: 0.758, 95% CI: 0.707-0.806; segmentation-based Dice coefficient: 0.681, 95% CI: 0.642-0.721). The performance of the two deep learning-based systems declined as pneumothorax size diminished. Nonetheless, both systems were similar or better than human readers in diagnosis or localization performance across all sizes of pneumothorax. CONCLUSIONS: Both deep learning-based systems excelled when tested in a temporally different dataset with differing patient or image characteristics, showing favourable potential for external generalizability.

Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c.

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies. We show that rats hemizygous for Cacna1c harbour marked impairments in learning to disregard non-salient stimuli, a behavioural change previously associated with psychosis. This behavioural deficit is accompanied by dys-coordinated network oscillations during learning, pathway-selective disruption of hippocampal synaptic plasticity, attenuated Ca2+ signalling in dendritic spines and decreased signalling through the Extracellular-signal Regulated Kinase (ERK) pathway. Activation of the ERK pathway by a small-molecule agonist of TrkB/TrkC neurotrophin receptors rescued both behavioural and synaptic plasticity deficits in Cacna1c+/- rats. These results map a route through which genetic variation in CACNA1C can disrupt experience-dependent synaptic signalling and circuit activity, culminating in cognitive alterations associated with psychiatric disorders. Our findings highlight targeted activation of neurotrophin signalling pathways with BDNF mimetic drugs as a genetically informed therapeutic approach for rescuing behavioural abnormalities in psychiatric disorder.

A review of epidemic investigation on cold-chain food-mediated SARS-CoV-2 transmission and food safety consideration during COVID-19 pandemic.

COVID-19 has brought speculations on potential transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the pandemic. It is reported that the main route of virus transmission to be person-to-person by respiratory droplets; however, people have raised concerns on the possible transmission of SARS-CoV-2 to humans via food and packaging and its potential effects on food safety. This review discusses food safety issues in the COVID-19 pandemic and reveals its possible transmission in cold-chain food. The first outbreak of COVID-19 in late 2019 was associated with a seafood market in Wuhan, China, while the second outbreak of COVID-19 in June 2020 was also related to a seafood market in Beijing, China. As of 2020, several frozen seafood products linked with SARS-CoV-2 have been reported in China. According to the current survey and scientific studies, the risk of infection by SARS-CoV-2 from cold-chain food, food products, and food packaging is thought to be very low. However, studies on food cold chain contamination have shown that SARS-CoV-2 remained highly stable under refrigerated (4°C) and even in freezing conditions (-10 to -80°C). Since one mode of SARS-CoV-2 transmission appears to be touching contaminated surfaces, it is important to clean and sanitize food contact surfaces properly. Understanding food safety hazard risks is essential to avoid potential negative health effects and SARS-CoV-2 transmission in the food supply chain during the COVID-19 pandemic.

Conditioning with spatio-temporal patterns: Constraining the contribution of the hippocampus to configural learning.

The conditions under which the hippocampus contributes to learning about spatio-temporal configural patterns are not fully established. The aim of Experiments 1-4 was to investigate the impact of hippocampal lesions on learning about where or when a reinforcer would be delivered. In each experiment, the rats received exposure to an identical set of patterns (i.e., spotted+morning, checked+morning, spotted+afternoon and checked+afternoon); and the contexts (Experiment 1), times of day (Experiment 2), or their configuration (Experiments 3 and 4) signalled whether or not a reinforcer would be delivered. The fact that hippocampal damage did not disrupt the formation of simple or configural associations involving spatio-temporal patterns is surprising, and suggests that the contribution of the hippocampus is restricted to mediated learning (or updating) involving spatio-temporal configurations.

Novel sensory preconditioning procedures identify a specific role for the hippocampus in pattern completion.

Successful retrieval of a memory for an entire pattern of stimulation by the presentation of a fragment of that pattern is a critical facet of memory function. We examined processes of pattern completion using novel sensory preconditioning procedures in rats that had either received sham lesions (group Sham) or lesions of the hippocampus (group HPC). After exposure to two audio-visual patterns (AX and BY) rats received fear conditioning with X (but not Y). Subsequent tests assessed fear to stimulus compounds (e.g., AX versus BX; Experiment 1) or elements (A versus B; Experiment 2). There was more fear to AX than BX in group Sham but not group HPC, while there was more fear to A than B in group HPC, but not in group Sham. This double dissociation suggests that pattern completion can be based upon separable processes that differ in their reliance on the hippocampus.

Work stress, occupational burnout and depression levels: a clinical study of paediatric intensive care unit nurses in Taiwan.

AIMS AND OBJECTIVES: This study aimed to examine the relationship between work stress and depression; and investigate the mediating effect of occupational burnout among nurses in paediatric intensive care units. BACKGROUND: The relationships among work stress, occupational burnout and depression level have been explored, neither regarding occupational burnout as the mediating role that causes work stress to induce depression nor considering the paediatric intensive care unit context. DESIGN: A cross-sectional correlational design was conducted. METHODS: One hundred and forty-four female paediatric intensive care unit nurses from seven teaching hospitals in southern Taiwan were recruited as the participants. Data were collected by structured questionnaires including individual demographics, the Nurse Stress Checklist, the Occupational Burnout Inventory and the Taiwan Depression Questionnaire. RESULTS: The results indicated that after controlling for individual demographic variables, the correlations of work stress with occupational burnout, as well as work stress and occupational burnout with depression level were all positive. Furthermore, occupational burnout may exert a partial mediating effect on the relationship between work stress and depression level. CONCLUSION: This study provides information about work stress, occupational burnout and depression level, and their correlations, as well as the mediating role of occupational burnout among paediatric intensive care unit nurses. RELEVANCE TO CLINICAL PRACTICE: It suggests government departments and hospital administrators when formulating interventions to prevent work stress and occupational burnout. These interventions can subsequently prevent episodes of depression in paediatric intensive care unit nurses, thereby providing patients with a safe and high-quality nursing environment.

Configural integration of temporal and contextual information in rats: Automated measurement in appetitive and aversive preparations.

Two experiments investigated the capacity of rats to learn configural discriminations requiring integration of contextual (where) with temporal (when) information. In Experiment 1, during morning training sessions, food was delivered in context A and not in context B, whereas during afternoon sessions food was delivered in context B and not in context A. Rats acquired this discrimination over the course of 20 days. Experiment 2 employed a directly analogous aversive conditioning procedure in which footshock served in place of food. This procedure allowed the acquisition of the discrimination to be assessed through changes in activity to the contextual + temporal configurations (i.e., inactivity or freezing) and modulation of the immediate impact of footshock presentations (i.e., post-shock activity bursts). Both measures provided evidence of configural learning over the course of 12 days, with a final test showing that the presentation of footshock resulted in more post-shock activity in the nonreinforced than reinforced configurations. These behavioral effects reveal important parallels between (i) configural discrimination learning involving components allied to episodic memory and (ii) simple conditioning.

The role of the hippocampus in passive and active spatial learning.

Rats with lesions of the hippocampus or sham lesions were required in four experiments to escape from a square swimming pool by finding a submerged platform. Experiments 1 and 2 commenced with passive training in which rats were repeatedly placed on the platform in one corner-the correct corner-of a pool with distinctive walls. A test trial then revealed a strong preference for the correct corner in the sham but not the hippocampal group. Subsequent active training of being required to swim to the platform resulted in both groups acquiring a preference for the correct corner in the two experiments. In Experiments 3 and 4, rats were required to solve a discrimination between different panels pasted to the walls of the pool, by swimming to the middle of a correct panel. Hippocampal lesions prevented a discrimination being formed between panels of different lengths (Experiment 3), but not between panels showing lines of different orientations (Experiment 4); rats with sham lesions mastered both problems. It is suggested that an intact hippocampus is necessary for the formation of stimulus-goal associations that permit successful passive spatial leaning. It is further suggested that an intact hippocampus is not necessary for the formation of stimulus-response associations, except when they involve information about length or distance.

Characterization and Predictors of Fractures following Hematopoietic Stem Cell Transplantation.

CONTEXT: Bone loss and fractures are common and serious complications following hematopoietic stem cell transplantation (HSCT), and identifying risk predictors for fractures in transplant recipients remains challenging. The Taiwan Bone Marrow Donation Center is the largest databank of donors in Asia. However, no population-based studies have yet been conducted in Asia to accurately assess the risk of fractures. OBJECTIVE: The aims of this study were to determine the incidence and risk factors for fractures in HSCT recipients. METHODS: We conducted a retrospective cohort study of patients >18 years who received a HSCT from January 1, 2003 to September 30, 2015 using the Taiwan National Health Insurance Research Database. Fractures following HSCT were identified using ICD-9-CM codes. Cox regression analysis was used to identify risk factors for fractures. RESULTS: A total of 3327 patients underwent a HSCT, of whom 126 (3.8%) had a fracture after HSCT. The cumulative incidence of fractures was 5.3% at 5 years, and 10.8% at 10 years. Multivariate analysis showed that a fracture in the 3 years prior to transplant (HR = 3.79; 95% CI 2.39-6.03) was associated with a higher risk of fractures post HSCT. With a daily dose equivalent of >0.50-3.75 mg, >3.75-15.23 mg and >15.23 mg prednisolone, the risk of fractures increased by 1.70 (95% CI 1.07-2.71), 2.23 (95% CI 1.32-3.76) and 2.93 (95% CI 1.43-6.01) folds, respectively. CONCLUSIONS: Regular screening to monitor bone loss should be initiated early, and counseling about the importance of general preventive measures for bone loss is warranted in HSCT recipients with a prior fracture and mean daily dose of steroids >0.50 mg.

Fabrication and application of glutathione biosensing SPCE strips with gold nanoparticle modification.

Glutathione (GSH) is a major antioxidant in organisms. An alteration in GSH concentration has been implicated in a number of pathological conditions. Therefore, GSH sensing has become a critical issue. In this study, a disposable strip used for tyrosinase-modified electrochemical testing was fabricated for the detection of GSH levels in vivo. The system is based on tyrosinase as a biorecognition element and a screen-printed carbon electrode (SPCE) as an amperometric transducer. On the tyrosinase-SPCE strips, the oxidation reaction from catechol to o-quinone was catalyzed by tyrosinase. The tyrosinase-SPCE strips were modified with gold nanoparticles (AuNPs). In the presence of AuNPs of 25 nm diameter, the cathodic peak current of cyclic voltammetry (CV) was significantly enhanced by 5.2 fold. Under optimized conditions (250 µM catechol, 50 mM phosphate buffer, and pH 6.5), the linear response of the tyrosinase-SPCE strips ranged from 31.25 to 500 µM GSH, with a detection limit of approximately 35 µM (S/N > 3). The tyrosinase-SPCE strips have been used to detect real samples of plasma and tissue homogenates in a mouse experiment. The mice were orally administrated with N-acetylcysteine (NAC) 100 mg kg-1 once a day for 7 days; the plasma GSH significantly enhanced 2.8 fold as compared with saline-treated mice (1123 vs. 480 µM µg-1 protein). NAC administration also could alleviate the adverse effect of GSH reduction in the mice treated with doxorubicin.

Long-term complications and outcomes of augmentation cystoplasty in children with neurogenic bladder.

Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.

Impact of the implementation of the Intelligent Antimicrobial System (iAMS) on clinical outcomes among patients with bacteraemia caused by methicillin-resistant Staphylococcus aureus.

OBJECTIVES: This study aimed to investigate the clinical impact of the Intelligent Antimicrobial System (iAMS) on patients with bacteraemia due to methicillin-resistant (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). METHODS: A total of 1008 patients with suspected SA infection were enrolled before and after the implementation of iAMS. Among them, 252 with bacteraemia caused by SA, including 118 in the iAMS and 134 in the non-iAMS groups, were evaluated. RESULTS: The iAMS group exhibited a 5.2% (from 55.2% to 50.0%; P = 0.96) increase in the 1-year survival rate. For patients with MRSA and MSSA compared to the non-iAMS group, the 1-year survival rate increased by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57), respectively, both surpassing the rate of the non-iAMS group. The iAMS intervention resulted in a higher long-term survival rate (from 70.9% to 52.3%; P = 0.984) for MRSA patients than for MSSA patients. MRSA patients experienced a reduced length of hospital stay (from 23.3% to 35.6%; P = 0.038), and the 45-day discharge rate increased by 20.4% (P = 0.064). Furthermore, the intervention resulted in a significant 97.3% relative decrease in near miss medication incidents reported by pharmacists (P = 0.013). CONCLUSIONS: Implementation of iAMS platform improved long-term survival rates, discharge rates, hospitalization days, and medical cost (although no significant differences were observed) among patients with MRSA bacteraemia. Additionally, it demonstrated significant benefits in ensuring drug safety.

Myricetin Nanofibers Enhanced Water Solubility and Skin Penetration for Increasing Antioxidant and Photoprotective Activities.

Excessive exposure to ultraviolet radiation (UV) can induce oxidative stress through the over-production of reactive oxygen species (ROS) on the skin. Myricetin (MYR), a natural flavonoid compound, significantly inhibited UV-induced keratinocyte damage; however, its bioavailability is limited by its poor water solubility and inefficient skin penetration ability, which subsequently influences its biological activity. The purpose of the study was to develop a myricetin nanofibers (MyNF) system of hydroxypropyl-ß-cyclodextrin (HPBCD)/polyvinylpyrrolidone K120 (PVP)-loaded with MYR that would enhance the water solubility and skin penetration by changing the physicochemical characteristics of MYR, including reducing the particle size, increasing the specific surface area, and amorphous transformation. The results also revealed that the MyNF can reduce cytotoxicity in HaCaT keratinocytes when compared with MYR; additionally, MyNF had better antioxidant and photoprotective activity than raw MYR for the UVB-induced HaCaT keratinocytes damage model due to the MyNF increased water solubility and permeability. In conclusion, our results demonstrate that MyNF is a safe, photostable, and thermostable topical ingredient of antioxidant nanofibers to enhance the skin penetration of MYR and prevent UVB-induced skin damage.

Risk factors for fractures following liver transplantation: a population-based cohort study.

BACKGROUND: Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant in a Taiwanese population. METHODS: We identified newly diagnosed liver transplant recipients from the National Health Insurance Research Database in Taiwan between 2003 and 2015. Risk factors of post-transplant fractures were analyzed using a Cox proportional hazards model. RESULTS: A total of 4821 patients underwent liver transplantation, of whom 419 (8.7%) had post-transplant fractures. Independent predictors of post-transplant fractures were age ≥65 years at transplantation (hazard ratio (HR): 1.566; 95% confidence interval (CI) 1.122-2.186), female sex (HR: 1.648; 95% CI 1.319-2.057), fractures within 1 year prior to transplant (HR: 3.664; 95% CI 2.503-5.364), hepatitis C carriers (HR: 1.594; 95% CI 1.289-1.970), alcoholism (HR: 1.557; 95% CI 1.087-2.230) and daily prednisolone dose >1.61-3.78 mg/day (HR: 1.354; 95% CI 1.005-1.824), >3.78-9.18 mg (HR: 4.182; 95% CI 3.155-5.544) and >9.18 mg (HR: 13.334; 95% CI 9.506-18.703). Post-transplant fractures were inversely correlated with tacrolimus (HR: 0.617; 95% CI 0.417-0.913) and sirolimus/everolimus (HR: 0.504; 95% CI 0.391-0.650) treatment. CONCLUSIONS: The liver transplant recipients, and especially those who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were associated with an increased risk of post-transplant fractures. Conversely, the use of tacrolimus and sirolimus/everolimus was associated with a decreased risk of fractures.

This study identified risk factors for fractures after liver transplant in a population-based study in an area with high prevalence of hepatitis B and hepatitis C.Recipients who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were independent risk factors for post-transplant fractures.Our findings highlight the importance of identifying individuals at high risk of fractures and concomitant tacrolimus and sirolimus/everolimus treatment to avoid the use of high-dose steroids and prevent post-transplant fractures.

Efficacy of Warfarin Therapy Guided by Pharmacogenetics: A Real-world Investigation Among Han Taiwanese.

PURPOSE: The anticoagulation activity of warfarin in populations with CYP2C9, VKORC1, and CYP4F2 variants differs between individuals and is correlated with poor international normalized ratio (INR) control. Pharmacogenetics-guided warfarin dosing has been successfully developed for patients with genetic variations in recent years. However, few real-world data have been used to investigate the INR and warfarin dosage and the time to target INR. This study examined the largest collection of genetic and clinical real-world data related to warfarin to provide further evidence supporting the benefits of pharmacogenetics in clinical outcomes. METHODS: We retrieved a total of 69,610 INR-warfarin records after the index date from 2,613 patients in the China Medical University Hospital database between January 2003 and December 2019. Each INR reading was obtained from the latest laboratory data after the hospital visit date. Patients with a history of malignant neoplasms or pregnancy before the index date were excluded, as were patients without data on INR measurements after the fifth day of prescription, genetic information, or gender variables. The primary outcomes were the INR and warfarin dosage during days 7, 14, 28, 56, and 84 after prescription. The secondary outcome was the time required to reach the INR ranges of 1.5 to 3.0 and >4.0. FINDINGS: A total of 59,643 INR-warfarin records from 2188 patients were retrieved. The average INR was higher for homozygous carriers of the minor allele at CYP2C9 and VKORC1 during the first 7 days (1.83 [1.03] [CYP2C9*1] and 2.46 [1.44] [CYP2C9*3], P < 0.001; 1.39 [0.36] [rs9923231 G/G], 1.55 [0.79] [rs9923231 G/A], and 1.96 [1.13] [rs9923231 A/A], P < 0.001) than for the wild-type allele. These patients with variants required lower warfarin doses than those with the wild-type allele during the first 28 days. CYP4F2 variant patients seemed to require higher doses of warfarin than those in the wild-type group; however, no significant difference in the average INR was observed (1.95 [1.14] [homozygous V433 carriers], 1.78 [0.98] [heterozygous V433M carriers], and 1.66 [0.91] [homozygous M433 carriers], P = 0.016). IMPLICATIONS: Our study indicates that genetic variants in the Han population may enhance warfarin responsiveness, which holds clinical relevance. An increased warfarin dosage was not linked to a shorter time to therapeutic INR between CYP4F2 variant patients and those with a wild-type allele. Assessing CYP2C9 and VKORC1 genetic polymorphisms before initiating warfarin treatment in real-world practice is essential for potentially vulnerable patients and is likely to optimize therapeutic dosing.

The effect of tetrafluoromethane plasma post-treatment on the electrical property of tungsten oxide nanowires.

The effects of tetrafluoromethane (CF4) plasma on the surface morphology, chemical compositions, and electrical property of tungsten oxide (W18O49) nanowires are investigated. The nanostructured tungsten oxide nanowires with average length of 250-350 nm were self-catalytically grown on Si substrate. By post-treatment with CF4 plasma for 10 min, the W18O49 nanowires on the substrate showed the highest current response. Longer CF4 plasma post-treatment time demonstrated higher etching effect which demolished the nanowires and resulted in lower conductivity of the samples. The disintegration of the W18O49 nanowires layer after CF4 plasma treatment, revealed physically by the decrease of the average thickness and chemically by the decrease of XRD peak ratio (I 23.0/I 26.0), was closely related to the overall electrical performance. The etching effect was further reveled by Raman spectra showing the evolution of O-W-O and W=O characteristics with the increased post-treatment time. Moreover, the improvement of the electrical property of W18O49 nanowires was elucidated by the exposure rate to explain the mechanism of plasma post treatment in three stages: passivation, degradation and ablation. The maximum exposure rate, corresponding to the maximum conductivity, was achieved by 10 min of CF4 plasma treatment. The time-differentiated exposure analyses confirmed the evolution of resistance of W18O49 nanowires on Si with different post-treatment time which supported the results of surface characterizations.

Gas ionization sensors with carbon nanotube/nickel field emitters.

Gas ionization sensors based on the field emission properties of the carbon nanotube/nickel (CNT/Ni) field emitters were first developed in this work. It is found that the breakdown electric field (E(b)) slightly decreases from 2.2 V/microm to 1.9 V/microm as the pressure of H2 gas increases from 0.5 Torr to 100 Torr. On the contrary, E(b) obviously increases from 2.9 V/microm to 6.5 V/microm as O2 gas pressure increases from 0.5 Torr to 100 Torr. This may be explained by the depression of the electron emission that caused by the adsorption of the O2 gas on the CNT emitters. The Raman spectra of the CNT/Ni emitters also show that more defects were generated on the CNTs after O2 gas sensing. The Joule heating effect under high current density as performing H2 sensing was also observed. These effects may contribute the pressure dependence on the breakdown electric field of the CNT/Ni gas ionization sensors.

Pterostilbene Nanoparticles Downregulate Hypoxia-Inducible Factors in Hepatoma Cells Under Hypoxic Conditions.

PURPOSE: Transcatheter arterial chemoembolization (TACE) is a common clinical treatment for hepatocellular carcinoma (HCC). However, hypoxia induction after treatment might trigger tumor invasiveness and metastasis. Although pterostilbene (PTS) has antitumor effects, its chemoprevention in HepG2 cells under hypoxia has not been investigated yet. In addition, the poor water solubility of raw PTS limits its clinical application. Here, we prepared nanoparticles of PTS (PSN) and compared their antihepatoma activities with those of raw PTS in HepG2 under hypoxic conditions. MATERIALS AND METHODS: The PTS nanoparticle formulation was prepared by nanoprecipitation, using Eudragit® e100 (EE) and polyvinyl alcohol (PVA) as carriers. We analyzed the physicochemical properties of raw PTS and PSN, including yield, encapsulation efficiency, water-solubility, particle size, morphology, crystalline-to-amorphous transformation, and molecular interaction between PTS and carriers. We also evaluated their antihepatoma activities under hypoxia treatment in HepG2 cells, including cell viability, hypoxia, and apoptosis. RESULTS: The yield and encapsulation efficiency of PSN were 86.33% and >99%, respectively. The water solubility and drug release of PTS were effectively improved after nanoprecipitation corresponding to the reduction in particle size, amorphous transformation, and formation of hydrogen bonding with carriers. PSN had a better cytotoxic effect than raw PTS in HepG2 under pre- and post-hypoxia conditions. In addition, hypoxia- and apoptosis-related proteins in HepG2 cells under two different hypoxic conditions were significantly inhibited by PSN compared with the control group with hypoxia only, except for HIF-1α in the post-hypoxia group. PSN was also significantly better in inhibiting these proteins, except for Bcl2, under pre-hypoxic conditions. CONCLUSION: Our results suggested that PSN could improve the water solubility and drug release of PTS and enhance the efficacy of HCC treatment under hypoxic conditions.