Optimizing analytical precision in the identification of synthetic cathinones and isomers: a comparative assessment of diverse GC-MS operating parameters.

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.

PS2MS: A Deep Learning-Based Prediction System for Identifying New Psychoactive Substances Using Mass Spectrometry.

The rapid proliferation of new psychoactive substances (NPS) poses significant challenges to conventional mass-spectrometry-based identification methods due to the absence of reference spectra for these emerging substances. This paper introduces PS2MS, an AI-powered predictive system designed specifically to address the limitations of identifying the emergence of unidentified novel illicit drugs. PS2MS builds a synthetic NPS database by enumerating feasible derivatives of known substances and uses deep learning to generate mass spectra and chemical fingerprints. When the mass spectrum of an analyte does not match any known reference, PS2MS simultaneously examines the chemical fingerprint and mass spectrum against the putative NPS database using integrated metrics to deduce possible identities. Experimental results affirm the effectiveness of PS2MS in identifying cathinone derivatives within real evidence specimens, signifying its potential for practical use in identifying emerging drugs of abuse for researchers and forensic experts.

Simultaneous Determination and Stability Analysis of Ten New Psychoactive Substances including Synthetic Cathinones, Phenethylamines, and Ketamine Substitutes in Urine Using Liquid Chromatography-Tandem Mass Spectrometry.

Knowing the stability of drugs is important to ensure accurate and reliable results of drug concentrations. This study evaluated the stability of ten new psychoactive substances (NPSs) in urine and methanol/water at different storage temperatures. Quantitative analyses were performed using liquid chromatography-tandem mass spectrometry. Three replicates of each storage condition were analyzed at day 0 and after 7, 14-, 30-, 60-, and 90 days with storage at +25°C, +4°C, and -20°C. For each analyte, the percent difference at each time interval from day 0 was calculated for each storage condition. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), deschloroketamine (DCK), and 2-fluorodeschloroketamine (2-FDCK) were stable in urine, even when stored for 90-day periods at various temperatures. For synthetic cathinones, the concentrations declined over time at room temperature (+25°C) in urine but were relatively stable in methanol solvent with 0.1% formic acid. The significant degradation was found at +25°C, and the most excellent stability was shown by samples stored at -20°C. Phenethylamines (PMA and PMMA) and ketamine substitutes (DCK and 2-FDCK) were relatively more stable than synthetic cathinones (mephedrone, butylone, pentylone, ephylone, 4-MEAPP, and eutylone).

The Effect of Nursing Internships on the Effectiveness of Implementing Information Technology Teaching.

In nursing education, the diversity of clinical scenarios is complex and dynamic, and it is a challenge for nursing students to learn this clinical knowledge in conventional teaching mechanisms. However, integrating information technology into teaching can promote diversity of learning environment. This study aimed to investigate the effectiveness of teaching mechanisms which combined clinical simulation scenario and Information Technology Integrated Instruction. This study applied innovative experimental teaching in medical-surgical and critical care nursing courses for nursing students in their fourth or fifth year at a five-year junior college. Instructional systems design was combined with clinical simulation scenarios and technology to develop multidimensional teaching strategies. Fifth-year students' overall OSCE mean score was considerably higher than that of fourth-year students; specifically, their scores on basic life support and care for subdural hemorrhage varied substantially. Compared with fourth-year students, fifth-year students performed considerably greater on situational awareness. The results of the present study can be used to develop nursing core competencies and improve the clinical care competency of nursing personnel.

Using data mining technology to predict medication-taking behaviour in women with breast cancer: A retrospective study.

AIMS: Medication-taking behaviours of breast cancer survivors undergoing adjuvant hormone therapy have received considerable attention. This study aimed to determine factors affecting medication-taking behaviours in people with breast cancer using data mining. DESIGN: A longitudinal observational retrospective cohort study with a hospital-based survey. METHODS: A total of 385 subjects were surveyed, analysing existing data from January 2010 to December 2017 in Taiwan. Three data mining approaches-multiple logistic regression, decision tree and artificial neural network-were used to build the prediction models and rank the importance of influencing factors. Accuracy, specificity and sensitivity were used as assessment indicators for the prediction models. RESULTS: Multiple logistic regression was the most effective approach, achieving an accuracy of 96.37%, specificity of 96.75% and sensitivity of 96.12%. The duration of adjuvant hormone therapy discontinuation, duration of adjuvant hormone therapy use and age at diagnosis by data mining were the three most critical factors influencing the medication-taking behaviours of people with breast cancer.

Effects of noise and music on situation awareness, anxiety, and the mental workload of nurses during operations.

This study aims to explore the effects of noise and music types on nurses' anxiety, mental workload and situation awareness during an operation. Participants included 20 circulating nurses (CNs) and 16 nurse anesthetists (NAs) who completed a total of 70 operations in which each operation required one CN and one NA. The experiment was separated into a control group (operating noise only) vs. an experimental group (3 different music types-between subjects and 2 music volume levels-within-subjects). Results showed that all participants had excellent situation awareness performance despite their mental workload showing significant differences in various phases of the surgery. Music at 55-60 dB caused lower mental workloads and anxiousness for nurses than those exposed to levels of 75-80 dB. When Mozart's music was played, the participants' mental workload and situation anxiety were lower than when exposed to other music types. Music played at 60 dB during an operation may be a feasible solution to mitigate the negative effects of extra noise and thus improve the nurses' performance.

Effectiveness of applying clinical simulation scenarios and integrating information technology in medical-surgical nursing and critical nursing courses.

BACKGROUND: To determine the impact of combining clinical simulation scenario training and Information Technology Integrated Instruction (ITII) on the teaching of nursing skills. METHODS: 120 4th-year students in a nursing program who were enrolled in medical and surgical nursing courses. 61 received innovative instruction (experimental group) and 59 received conventional instruction (control group). The ADDIE model, systematic method of course development that includes analysis, design, development, implementation, and evaluation,was used to build simulation teaching and clinical scenarios and to create and modify objective structure clinical examination (OSCE) scenario checklists for acute myocardial infarction (AMI) care, basic life support and operation of automated external defibrillator (BLS), and subdural hemorrhage (SDH) care. The modified OSCE checklists were assessed for reliability, consistency, and validity. The innovative training included flipped classrooms, clinical simulation scenarios, ITII and blended learning formats. RESULTS: The reliability and validity of the OSCE checklists developed in this study were acceptable and comparable or higher than checklists in past studies and could be utilized as an OSCE performance tool. Students in innovative instruction obtained significantly better OSCE performance, lab scores and improvements from the previous year's grades. Significant differences were found in situational awareness (SA). No strong correlations were found between OSCE scores and clinical internship scores, and no significant differences were found between the groups in overall clinical internship performance. CONCLUSIONS: Innovative instruction showed better performance than conventional methods in summative evaluation of knowledge components, OSCE formative evaluation and clinical nursing internship scores, as well as improved situational awareness in nursing students.

Quantitation of serum 25(OH)D2 and 25(OH)D3 concentrations by liquid chromatography tandem mass spectrometry in patients with diabetes mellitus.

Vitamin D has been considered to regulate calcium and phosphorus homeostasis and to preserve skeletal integrity. Serum 25-hydroxyvitamin D (25(OH)D) is the best indicator of vitamin D levels. The association of serum 25(OH)D deficiency with increased risk of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) is controversial. We investigated serum 25(OH)D2 and 25(OH)D3 levels in diabetes patients by using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum 25(OH)D2 and 25(OH)D3 levels were measured with liquid chromatography tandem mass spectrometry in electrospray ionization positive mode. Chromatograms were separated using an ACE5 C18 column on a gradient of methanol. The total 25(OH)D levels were calculated as the sum of 25(OH)D3 and 25(OH)D2 levels. A total of 56 patients with T1DM and 41 patients with T2DM were enrolled in this study. There were 42 and 28 non-diabetic, age-matched volunteers who participated as the T1DM controls and the T2DM controls, respectively. The total 25(OH)D levels were lowest in the 21-40 age group. The levels of both 25(OH)D3 and the total 25(OH)D were significantly higher in the T1DM and T2DM groups than in the controls (p < 0.01 in T1DM and p < 0.05 in T2DM group, respectively). The 25(OH)D2 levels were only significantly higher in T1DM patients than in the controls. The percentages of vitamin D deficiency (total 25(OH)D less than 20 ng/mL) in the T1DM, T2DM, the T1DM controls and the T2DM controls were 7.1%, 0%, 14.3% and 3.6%, respectively. The percentages of vitamin D insufficiency (total 25(OH)D less than 30 ng/mL) in the T1DM, T2DM, the T1DM controls and the T2DM controls were 26.8%, 7.3%, 54.8% and 17.9%, respectively. The percentages of vitamin D deficiency and insufficiency were significantly lower in the T1DM patients than in the T1DM controls (p < 0.01). In the present study, both type 1 and type 2 diabetes patients had higher serum 25(OH)D levels and lower percentages of vitamin D deficiency/insufficiency.

Nanohybrids of silver particles on clay platelets delaminate Pseudomonas biofilms.

AIM: To evaluate the effectiveness of novel nanohybrids, composed of silver nanoparticles and nanoscale silicate platelets, to clear Pseudomonas aeruginosa biofilms. MATERIALS & METHODS: The nanohybrids were manufactured from an in situ reduction of silver salts in the silicate platelet dispersion, and then applied to biofilms in vitro and in vivo. RESULTS: In reference to the biocidal effects of gentamycin, the nanohybrids mitigated the spreading of the biofilms, and initiated robust cell death and exfoliation from the superficial layers of the biofilms in vitro. In vivo, the nanohybrids exhibited significant therapeutic effects by eliminating established biofilms from infected corneas and promoting the recovery of corneal integrity. CONCLUSION: All of the evaluations indicate the high potency of the newly developed silver nanoparticle/nanoscale silicate platelet nanohybrids for eliminating biofilms.

Efficacy and safety of nanohybrids comprising silver nanoparticles and silicate clay for controlling Salmonella infection.

Developing effective and safe drugs is imperative for replacing antibiotics and controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the nanohybrids show a strong and general antibacterial activity in vitro. Here, their efficacy for protecting Salmonella-infected chicks from fatality and septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not AgNPs alone, effectively reduced the systemic Salmonella infection and mortality. In addition, quantitative Ag analyses demonstrated that Ag deposition from AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue and improved the safety of AgNPs. These in vivo results illustrated that both NSP and AgNP/NSP nanohybrid represent potential agents for controlling enteric bacterial infections.

Adjuvant effect of liposome in chicken result from induction of nitric oxide.

Intranasal delivery of liposome-encapsulated inactivated Newcastle Disease virus (NDV) is known to be an effective vaccine for inducing immunity in the respiratory tract from our previous reports. Four-week-old specific pathogen-free chickens were intranasally immunized with NDV entrapped in phosphatidylcholine-liposomes (PC-Lip). The mucosal levels of anti-NDV s-immunoglobulin A (IgA), serum IgG, a high hemagglutination inhibition titer (1:640), and the high survival rate with the PC-Lip vaccine were comparable to those of our previous report. The immune mechanisms of the PC-Lip adjuvant were determined by in vitro cellular experiments using the NO production of chicken spleen macrophages. The most important finding of this study was proving that macrophages were stimulated by PC-Lip via the extracellular regulated kinase (ERK) 1/2 and nuclear factor (NF)-κB activation pathways. This finding may be useful for developing potent mucosal vaccine delivery systems in the future.

The influence of liposomal adjuvant on intranasal vaccination of chickens against Newcastle disease.

The adjuvant effect of liposomes formulated with three phospholipids including phosphatidylcholine-liposomes (PC-Lip), phosphatidylserine-liposomes (PS-Lip), and stearylamine-liposomes (SA-Lip) was compared with virus alone using inactivated Newcastle disease virus (NDV) as a model antigen. The difference in adjuvanticity was evaluated using the haemagglutination-inhibition (HI) test, enzyme-linked immunosorbent assay, and a challenge study following intranasal inoculation of specific pathogen-free chickens. After two inoculations, a liposomal vaccine consisting of NDV in PC-Lip resulted in a significant increase in HI titre, up to 32-fold higher than a vaccine containing virus alone and 320-fold higher than a vaccine containing NDV in SA-Lip. PC-Lip also elicited a significant mucosal secretary immunoglobulin A response (P<0.05) in tracheal lavages and a serum IgG response (P<0.05). In response to viral challenge, all control animals died, whereas 90% of animals which received PC-Lip survived. The results suggest that PC-Lip may be suitable as an adjuvant for mucosal vaccination against NDV in chickens.

Mucoadhesive liposomes for intranasal immunization with an avian influenza virus vaccine in chickens.

The aim of this study was to characterize a nasally delivered bioadhesive liposome using an inactivated H5N3 virus as a model antigen. Bioadhesive liposomes were developed using tremella (T) or xanthan gum (XG) as the bioadhesive polysaccharide. Using chickens as the target animal, we evaluated whether delivery of a bioadhesive liposomal influenza vaccine via a mucosal site of infection could improve vaccine effectiveness. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cytotoxicity assays demonstrated that T, XG and liposomes were non toxic to chicken spleen macrophages. Enzyme-linked immunosorbent assay (ELISA) was used to determine the adjuvant effect of the bioadhesive liposomal-vaccines. Chickens immunized with a low dose (200 microL) of bioadhesive liposomal influenza vaccine had significantly higher mucosal and serum antibody levels (P<0.05). In addition, liposomes mixed with a low-viscosity bioadhesive gel used for nasal delivery resulted in superior antibody responses compared with liposomes mixed with a high-viscosity gel (P<0.05). This suggest that a low-viscosity gel mixed with liposomes is more suitable for nasal delivery, and that chickens elicit higher mucosal secretory immunoglobulin A (s-IgA) and serum IgG after two vaccinations.

Evaluation of encapsulated Newcastle disease virus liposomes using various phospholipids administered to improve chicken humoral immunity.

We propose the adjuvant effects of phospholipid liposome compositions using intranasal inoculation of a liposomal-Newcastle disease virus (NDV) vaccine in chickens. The immunogenicity of three liposome formulations was determined in chickens using the hemagglutination-inhibition (HI) test, nasal secretory immunoglobulin A and serum immunoglobulin A (IgG) antibody titers using the enzyme-linked immunosorbent assay. The immune response against NDV antigens was determined after immunization with neutral charged liposomes composed of egg phosphatidylcholine (EPC) (60 micromol), cholesterol (Chol) (15 micromol), and EPC-liposomes (EPC-Lip), which elicited strong systemic (serum) and local (nasal) humoral responses. However, the intranasal administration with cationic charged liposomes composed of EPC (30 micromol), stearylamine (SA) (15 micromol), Chol (15 micromol), and SA-liposomes (SA-Lip) induced poor humoral immune responses. Only the vaccine formulated with anionic charged liposomes composed of EPC (30 micromol), dipalmitoylphosphatidylserine (15 micromol), Chol (15 micromol), and phosphatidylserine-liposomes (PS-Lip) elicited the highest titers of HI antibodies. These are the first results to suggest that antigen delivery using EPC-Lip is very useful in enhancing antibody production at the mucosal site and in serum.

Effect of lipopolysaccharide on intranasal administration of liposomal Newcastle disease virus vaccine to SPF chickens.

In order to potentiate the low immunogenicity of the inactivated Newcastle disease virus immunized into chickens by mucosal route, liposomes as a drug delivery system and LPS (lipopolysaccharide) as an immuno-stimulator were evaluated. Here, we report a new nasal delivery system of inactivated Newcastle disease virus (NDV) vaccine. The intranasal vaccine was based on different lipids to form MLV (multi-lamellar vehicles) liposomes. The liposomes had combined carrier and adjuvant activities, which induced strong systemic (serum) and local (lung and nasal) humoral responses in SPF (specific-pathogen-free) chickens, and provided protective immunity. PC-Lip (phosphatidylcholine-liposome) elicited significant mucosal secretary immunoglobulin A (s-IgA) levels (p<0.05) in tracheal lavage fluid and serum IgG levels (p<0.05). In response to virulent viral challenge, birds treated with PBS (phosphate buffered saline) as control group died, whereas 80% of chickens which received PC-Lip, PC-Lip-LPS, PS-Lip (phosphatidylserine-liposome), and PS-Lip-LPS survived. HAI titers were 1:2560 in the PS-Lip-LPS group and 1:1280 in the PC-Lip, PC-Lip-LPS, and PS-Lip groups after two vaccinations. The results suggest that PC-Lip or PS-Lip might thus be suitable as a potential adjuvant for mucosal vaccination against NDV in chickens.

The influence of hyperbaric oxygen on hemorheological parameters in diabetic rats.

The effect of hyperbaric oxygen (HBO2) treatment on hemorheological parameters of diabetic rats was investigated. This study is a placebo-controlled, in vivo animal study. 30 streptozocin-induced diabetic rats were divided into two groups; one group received hyperbaric oxygen treatment while the other did not. Hematological and hemorheological parameters were tested with blood samples collected directly from the heart using surgical procedures. Student t-tests with a type I (alpha) error at 0.05 was used to test any significant difference between means of the hematologic and hemorheological parameters of the control (CON) and the HBO2 groups. Compared with the placebo group, hyperbaric oxygen resulted in significant higher lipid peroxidation stress of the erythrocytes and resistance of erythrocytes to deformation in rats of the HBO2 group. Whole blood viscosities measured at shear rates of 5, 150 and 400 s(-1) were all higher for the rats in the HBO2 group than those for rats in the control group. In addition, the oxygen delivery index was found to be significantly lower in rats of the HBO2 group. Thus, our work demonstrates that hyperbaric oxygen treatment significantly changes the hemorheological parameters in diabetic rats.