The dispersibility and stability issues of peptide drugs during preparation and storage hinder the widespread adoption of pressurized metered-dose inhaler (pMDI). This study aimed to develop a ...reverse microemulsion (RM) of exenatide (EXE) pMDI through a liquid-based bottom-up method, thus to overcome the stability issue of peptide drugs encountered in traditional top-down methods, such as milling down and high-pressure homogenization. In this study, Pluronic® L64 (L64) was chosen as a surfactant to prepare the EXE-RM pMDI formulations with the assistance of ethanol. The results showed RM possessed a particle size of 123.80 ± 2.91 nm with 0.121 ± 0.024 PdI and a satisfied fine-particle fraction of 41.30 ± 3.73% measured by a next-generation impactor. In addition, the dispersion stability of RM pMDI was maintained after storage at 4 °C for 50 days. The secondary structure of EXE was maintained during the preparation process. Moreover, the results indicated that L64 was compatible with cells and could improve the penetration of EXE through cell monolayers. Through the liquid-based bottom-up method, EXE-RM pMDI was successfully prepared and exhibited favorable stability and aerodynamic performance. This study offers a preparation strategy to enhance the stability of peptides in pMDIs.
IMPORTANCE: Incoming text messages and calls on nurses’ mobile telephones may interrupt medication administration, but whether such interruptions are associated with errors has not been established. ...OBJECTIVE: To assess whether a temporal association exists between mobile telephone interruptions and subsequent errors by pediatric intensive care unit (PICU) nurses during medication administration. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was performed using telecommunications and electronic health record data from a PICU in a children’s hospital. Data were collected from August 1, 2016, through September 30, 2017. Participants included 257 nurses and the 3308 patients to whom they administered medications. EXPOSURES: Primary exposures were incoming telephone calls and text messages received on the institutional mobile telephone assigned to the nurse in the 10 minutes leading up to a medication administration attempt. Secondary exposures were the nurse’s PICU experience, work shift (day vs night), nurse to patient ratio, and level of patient care required. MAIN OUTCOMES AND MEASURES: Primary outcome, errors during medication administration, was a composite of reported medication administration errors and bar code medication administration error alerts generated when nurses attempted to give medications without active orders for the patient whose bar code they scanned. RESULTS: Participants included 257 nurses, of whom 168 (65.4%) had 6 months or more of PICU experience; and 3308 patients, of whom 1839 (55.6%) were male, 1539 (46.5%) were white, and 2880 (87.1%) were non-Hispanic. The overall rate of errors during 238 540 medication administration attempts was 3.1% (95% CI, 3.0%-3.3%) when nurses were uninterrupted by incoming telephone calls and 3.7% (95% CI, 3.4%-4.0%) when they were interrupted by such calls. During day shift, the odds ratios (ORs) for error when interrupted by calls (compared with uninterrupted) were 1.02 (95% CI, 0.92-1.13; P = .73) among nurses with 6 months or more of PICU experience and 1.22 (95% CI, 1.00-1.47; P = .046) among nurses with less than 6 months of experience. During night shift, the ORs for error when interrupted by calls were 1.35 (95% CI, 1.16-1.57; P < .001) among nurses with 6 months or more of PICU experience and 1.53 (95% CI, 1.16-2.03; P = .003) among nurses with less than 6 months of experience. Nurses administering medications to 1 or more patients receiving mechanical ventilation and arterial catheterization while caring for at least 1 other patient had an increased risk of error (OR, 1.21; 95% CI, 1.03-1.42; P = .02). Incoming text messages were not associated with error (OR, 0.97; 95% CI, 0.92-1.02; P = .22). CONCLUSIONS AND RELEVANCE: This study’s findings suggest that incoming telephone call interruptions may be temporally associated with medication administration errors among PICU nurses. Risk of error varied by shift, experience, nurse to patient ratio, and level of patient care required.
Background and aims
Liver transplantation (LT) is the primary curative option for cirrhotic patients with early-stage hepatocellular carcinoma (HCC). However, tumor recurrence occurs in 15–20% of ...cases with unfavorable prognosis. We have developed a library of T cell receptors (TCRs) specific for different hepatitis B virus (HBV) antigens, restricted by different molecules of human leucocyte antigen (HLA)-class I, to redirect T cells against HBV antigens (Banu in Sci Rep 4:4166, 2014). We further demonstrated that these transiently functional T cells specific for HBV obtained through messenger RNA (mRNA) electroporation can eliminate HCC cells expressing HBV antigens in vitro and in vivo (Kah in J Clin Invest 127:3177–3188, 2017). A phase I clinical trial for patients with HCC recurrence post-liver transplant was conducted to assess the safety, tolerability, and anti-tumor efficacy of transiently functional HBV-TCR T cells. Here, we report the clinical findings with regard to the safety and anti-tumor efficacy of mRNA electroporated HBV-specific TCR-T cells. (ClinicalTrials.gov identifier: NCT02719782).
Patients and methods
A total of six patients with HBV-positive recurrent HCC post-liver transplant and HLA-matched to TCR targeting hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) (HLA-A*02:01/HBsAg, HLA-A*11:01/HBcAg, HLA-B*58:01/HBsAg or HLA-C*08:01/HBsAg) were enrolled in this study. The primary objective was to assess the safety of short-lived mRNA electroporated HBV-TCR T cells based on the incidence and severity of the adverse event (AE) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. The secondary objective was to determine the effectiveness of HBV-TCR T cells as per RECIST 1.1 criteria. Patients were followed up for survival for 2 years post-end of treatment.
Results
The median age of the six patients was 35.5 years (range: 28–47). The median number of HBV-TCR T cell infusions administered was 6.5 (range: 4–12). The treatment-related AE included grade 1 pyrexia. This study reported no cytokine release syndrome nor neurotoxicity. One patient remained alive and five were deceased at the time of the data cutoff (30 April 2020).
Conclusion
This study has demonstrated that multiple infusions of mRNA electroporated HBV-specific TCR T cells were well-tolerated in patients with HBV-positive recurrent HCC post-liver transplant.
Biphenotypic acute leukemia (BAL) is an uncommon type of cancer, which accounts for <5% of all adult ALs. Based upon a previously described scoring system, the European Group for the Immunological ...Classification of Leukemias (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based upon the number and degree of specificity of several markers for myeloid or T/B-lymphoid blasts. The present study describes a case of T-cell acute lymphoblastic leukemia (T-ALL) with Burkitt-like cytology, which according to the French-American-British classification, corresponded to a diagnosis of Burkitt type L3 ALL. Flow cytometry analysis demonstrated that the blasts were positive for T-lymphoid markers, cytoplasmic cluster of differentiation (CD)3, CD7 and CD56, and myeloid markers, CD13, CD33 and CD15. At first, a diagnosis of BAL was suggested by the EGIL score, however, according to the 2008 World Health Organization criteria, a case of T-ALL with aberrant myeloid markers was established. The study also reviewed the literature and discussed the limitations of the EGIL scoring system in clinical decision making, to aid in the selection of an appropriate therapeutic regimen.
Transgene expression systems in the Triticeae cereals Hensel, Götz; Himmelbach, Axel; Chen, Wanxin ...
Journal of plant physiology,
2011, 2011-Jan-01, 2011-1-00, 20110101, Letnik:
168, Številka:
1
Journal Article
Recenzirano
The control of transgene expression is vital both for the elucidation of gene function and for the engineering of transgenic crops. Given the dominance of the
Triticeae cereals in the agricultural ...economy of the temperate world, the development of well-performing transgene expression systems of known functionality is of primary importance. Transgenes can be expressed either transiently or stably. Transient expression systems based on direct or virus-mediated gene transfer are particularly useful in situations where the need is to rapidly screen large numbers of genes. However, an unequivocal understanding of gene function generally requires that a transgene functions throughout the plant's life and is transmitted through the sexual cycle, since this alone allows its effect to be decoupled from the plant's response to the generally stressful gene transfer event. Temporal, spatial and quantitative control of a transgene's expression depends on its regulatory environment, which includes both its promoter and certain associated untranslated region sequences. While many transgenic approaches aim to manipulate plant phenotype via ectopic gene expression, a transgene sequence can be also configured to down-regulate the expression of its endogenous counterpart, a strategy which exploits the natural gene silencing machinery of plants. In this review, current technical opportunities for controlling transgene expression in the
Triticeae species are described. Apart from protocols for transient and stable gene transfer, the choice of promoters and other untranslated regulatory elements, we also consider signal peptides, as they too govern the abundance and particularly the sub-cellular localization of transgene products.
A dispersive multiwalled carbon nanotube (MWCNT) based agitation-assisted adsorption and ultrasound-assisted desorption method has been developed for extracting natural estrogenic steroids in ...environmental waters prior to high performance liquid chromatography-diode array detection (HPLC-DAD) analysis. With the aid of agitation, the trace estrogens in bulk aqueous solution were adsorbed onto milligrams of dispersive MWCNTs. After filtration, the estrogens enriched on MWCNT nanoparticles were quickly desorbed into milliliters of organic solvent in an ultrasonic bath. Finally, the analytes in the organic solvent were directly determined by HPLC-DAD. The stability examination of estrogens under the tested ultrasonic irradiation was performed and the results indicated that the estrogens were stable during the extraction process. Several parameters that could influence the extraction efficiency, such as type and volume of desorption solvent, consumed amount of MWCNTs, pH and ionic strength of sample solution, agitation-assisted adsorption and ultrasound-assisted desorption time, were examined. Under the optimized conditions, the recoveries for three analytes in spiked samples were over 82%. The detection limits were 0.076 ng mL −1 for estrone, 0.049 ng mL −1 for 17β-estradiol, and 0.057 ng mL −1 for estriol, respectively, while the relative standard deviations were less than 9% (at the 20 ng mL −1 estrogen level for 10 runs).
► A new SPR platform ‘Phytochip’ was developed and established. ► It provides an improved detection assay to distinguish virus-infected plants from non-infected plants. ► It has a short detection ...time and can be used in a high throughput system to analyze efficiently many samples. ► Phytochip is suitable for practical application in plant breeding and virus control.
The surface plasmon resonance (SPR) based ‘Phytochip’ was developed to distinguish virus-infected plants from non-infected plants. The system detects DNA–RNA hybridization to show the presence of phytopathogenic viruses such as the RNA virus barley stripe mosaic virus (BSMV) in wheat leaves. To achieve this BSMV and wheat specific oligonucleotides, and a negative control yeast oligonucleotide, were immobilized on a SPR gold surface chip. After optimization of the hybridization parameters with purified wheat samples, wheat infected with BSMV resulted in detectable signals with both the BSMV and the wheat probes. In contrast, a hybridization reaction was not be detected with the negative probe. The method is fast and sensitive with a detection time of 3000s (50min), a detection limit of 14.7pgμl−1 BSMV RNA and a measuring range of 14.7–84pgμl−1 BSMV RNA (1.323–7.56ng BSMV RNA per 90μl sample). These characteristics, combined with the high throughput design, make it suitable for application in plant breeding and virus control.
With the aggravation of the global shortage of petroleum resources, the problem of optimizing the motor efficiency of new energy vehicles is imminent. Considering that it is difficult to set the ...speed controller parameters in the traditional brushless DC motor speed system control, and the traditional control has the disadvantages of lag and low-speed prediction accuracy due to the current state feedback signal, a control algorithm based on fuzzy BP neural network is proposed for the energy vehicle. In this paper, based on the mathematical model of DC motor, the space equation is established, the control ability of DC motor is analyzed. Meanwhile, the control theory of BP neural network algorithm is applied to design the related algorithm of a double closed-loop DC speed regulation system. Finally, the motor simulation experiment platform is built through Simulation, and the control effect of the SCM control model is tested through online debugging of Proteus and Keil. The control chip uses AT89C52, the driver module uses L298N chip, and the display module uses LCD1602 display screen. The results show that under the same input conditions, the fuzzy BP network combined with the double closed-loop PID control method has the advantage of significantly reducing the response time and no overshoot. When the disturbance occurs, the time for the system to return to steady-state is short, so it has a high guiding value in engineering.
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