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Objective: This study aimed to evaluate the intra- and inter-grader reliability of four evaluators using three different digital intraoral scanners and visual methods for typodontic Class II composite preparations. Materials and methods: Ninety-five typodont teeth of Class II composite preparations were evaluated using traditional visual grading methods (VGM) and digital grading methods (DGM) using the same rubric. Three intraoral scanners were used to scan the Class II cavity preparation for the composite: i700 (Medit, Korea), Trios 4 (3Shape, Denmark), and Shinning 3D (Shinning 3D, China). The same rubric was used to score the visual and digital evaluations by calibrated examiners. Two-way ANOVA was used to compare method- and evaluator-based scores, accounting for the scanner type used. Results: The scores of the prepped typodont teeth were subjected to an interaction between the examiner and the evaluation technique. In addition, the mean total prepped teeth scores differed between examiners using VGM. A statistically significant interaction emerged between examiners and the evaluation technique employed to assess the total score of the prepped teeth: F(9, 1504) = 3.893, P = 0.001, partial η2 = 0.023. The total prepped tooth score differed between the VGM and DGM groups. Lower (P < 0.05) intra-grader consistency was observed for the final scores when Class II preparations were evaluated using the VGM; however, this consistency improved when using the DGM. Conclusion: Examiners and evaluation methods affect student performance in Class II cavity preparations. The DGM may be more reliable and consistent within and between evaluators than the VGM is.

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Syringin, a phenylpropanoid glycoside, is widely distributed in various plants, such as Acanthopanax senticosus (Rupr. et Maxim.) Harms, Syringa reticulata (BL) Hara var. mandshurica (Maxim.) Hara, and Ilex rotunda Thumb. It serves as the main ingredient in numerous listed medicines, health products, and foods with immunomodulatory, anti-tumor, antihyperglycemic, and antihyperlipidemic effects. This review aims to systematically summarize syringin, including its physicochemical properties, plant sources, extraction and separation methods, total synthesis approaches, pharmacological activities, drug safety profiles, and preparations and applications. It will also cover the pharmacokinetics of syringin, followed by suggestions for future application prospects. The information on syringin was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS Elsevier, and Flora of China) and libraries. Syringin, extraction and separation, pharmacological activities, preparations and applications, and pharmacokinetics were chosen as the keywords. According to statistics, syringin can be found in 23 families more than 60 genera, and over 100 species of plants. As a key component in many Chinese herbal medicines, syringin holds significant research value due to its unique sinapyl alcohol structure. Its diverse pharmacological effects include immunomodulatory activity, tumor suppression, hypoglycemic action, and hypolipidemic effects. Additionally, it has been shown to provide neuroprotection, liver protection, radiation protection, cardioprotection, and bone protection. Related preparations such as Aidi injection, compound cantharidin capsule, and Tanreqing injection have been widely used in clinical settings. Other studies on syringin such as extraction and isolation, total synthesis, safety profile assessment, and pharmacokinetics have also made progress. It is crucial for medical research to deeply explore its mechanism of action, especially regarding immunity and tumor therapy. Meanwhile, more robust support is needed to improve the utilization of plant resources and to develop extraction means adapted to the needs of industrial biochemistry to further promote economic development while protecting people's health.

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INTRODUCTION: Veterinary oncology is constituted mainly by human-use drugs with hazardous agents. Occupational risks are present in all stages of handling. Many studies highlighted that veterinarians and pharmacists staff present a lack of knowledge and insufficient structure for promoting safety practices. This study investigated the professional profile and structure of veterinary antineoplastic chemotherapy in Brazilian services. METHODS: A nationwide survey was carried out through digital platforms by a self-applicable from 2020 to 2021. The characteristics of the structure, facilities, professional profiles, practices related to antineoplastic chemotherapy services, and inspections provided by regulatory companies were investigated. Frequency and ranges were used to examine and describe data. RESULTS: This study analyzed 108 respondents from all Brazilian regions where 36 participants worked in veterinary oncology. Dogs and cats comprised more than 90% of animals assisted. Vincristine, doxorubicin, carboplatin, vinblastine, and cyclophosphamide were the most commonly used drugs. Considering pharmacists-led (n = 4) vs veterinarians-led (n = 18) services, structure with safety for handling hazardous drugs (4 vs 9), correct PPE usage (3 vs 0), and occurrence of occupational accident (0 vs 5) were registered. Almost 60% were dissatisfied with the structure and the managerial unwillingness to promote facility improvements. The majority of participants reported an absence of service inspection. CONCLUSION: The results demonstrated worrying concerning the inadequacy of the physical structure of the facilities, human resources, and handling hazardous drugs increased occupational health risk. The lack of competent authority standards and supervision corroborates practices that expose professionals, the population, and the environment to hazardous agents.

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The development of traditional Chinese medicine(TCM) preparations as an incubator for new drugs in medical institutions has flourished, while an evaluation index system remains to be established for comprehensively assessing the development value of these prescriptions. This study established an item pool through literature research, employed the Delphi method to determine the content of evaluation indexes, and adopted the superiority chart to determine the weight of each index. Two-level evaluation index system for the development value of TCM preparations in medical institutions was established, which included 7 first-level items and 36 se-cond-level items, demonstrating scientific validity. The first-level items(weight) were inheritance(10.61%), effectiveness(23.22%), safety(22.71%), innovation(13.21%), economy(10.00%), suitability(8.57%), and accessibility(11.68%). The top three second-level items in terms of weight distribution were adverse reaction monitoring(6.73%), evidence of therapeutic effect(5.71%), and clinical response rate(4.75%). The bottom three second-level items were production advantages(0.86%), medicinal dosage(0.48%), and medicinal smell or taste(0.18%). The content validity of the established system was assessed, which revealed that the index system was reliable, with the overall and average content validity indexes of 0.47 and 0.90, respectively. Furthermore, the established evaluation index system was used to evaluate six TCM preparations in a city-level hospital of TCM in Sichuan Province, which demonstrated that the system had operability. The results indicate that the evaluation index system is scientific, reliable, and operable, providing a reference for developers to selectively develop TCM preparations in medical institutions. In practical application, the system can be adjusted regarding the index weights according to actual conditions.

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BACKGROUND: The COVID-19 pandemic exerted an unprecedented impact on the blood supply from 2020 through 2022. As a result, throughout 2021 there were months our hospital had less than one-day supply of type O RBCs. To meet transfusion needs, whole RBC units were split into half units and issued to stable, non-bleeding patients. This single-institution, retrospective study examines time intervals to subsequent transfusion and total numbers of RBC units subsequently transfused after the first half or whole RBC unit. STUDY DESIGN AND METHODS: Patients who were transfused RBC between May 21, 2021 and November 1, 2021 were divided into in- and outpatient groups, then based on whether they received at least 1 half RBC unit or only whole RBC units during the study period. The time interval between this first half unit transfusion, or first whole unit transfusion in those who did not receive half units, and the subsequent RBC transfusion within 90 days was calculated and compared, as well as the total number of RBC units transfused 30 days after the first unit. RESULTS: In general, patients transfused with half units received a subsequent transfusion significantly earlier than those transfused with whole units. Additionally, receiving an index half unit was associated with more RBC transfusions in the following 30 days (p = .001). CONCLUSION: Transfusion of half RBC units during a severe RBC blood shortage can temporarily decrease RBC usage but will result in a shorter interval to the next transfusion and greater total number of RBC units transfused in subsequent days.

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The medicinal value of Chinese medicines has been recognized since ancient times, and they have also been used to treat various diseases. However, in-depth studies on the active ingredients of Chinese medicines have shown that many of them suffer from poor water-solubility, stability, and bioavailability, which has severely limited their further development. The advent of nanomedicine represents a novel direction and paradigm for addressing these challenges. Particularly, within the framework of nanocrystal technology, enhancements in the water solubility, stability, and bioavailability of Chinese medicines are expected to significantly improve the therapeutic efficiency. This advancement also holds promise for unlocking new therapeutic capabilities. Nanocrystals offer significant advantages in oral, intravenous, intranasal and targeted delivery. The drug loading principle is "all in one", with hydrophobic-drug-in and hydrophilic-drug-out and stabilization by amphiphilic agents. Nanocrystal technology in traditional Chinese medicine (TCM) holds extensive application potential. Continuous refinement of preparation techniques, sound safety assessments, and the promotion of large-scale production are anticipated to augment its pivotal role in TCM formulations, thereby creating novel opportunities for clinical drug therapy.

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Mutations in the human PCDH19 gene lead to epileptic encephalopathy of early childhood. It is characterized by the early onset of serial seizures, cognitive impairment and behavioral disorders (including autistic personality traits). In most cases, difficulties arise in selecting therapy due to pharmacoresistance. The pathogenesis of the disease is complex. The data available to us at the moment from numerous studies present the pathogenesis of «PCDH19 syndrome¼ as multi-level, affecting both the epigenetic support of cell life, and development of stem cells and progenitor cells in the process of neuroontogenesis, and the influence on the neurotransmitter mechanisms of the brain, and disruption of the formation of neural networks with an inevitable increase in the excitability of the cerebral cortex as a whole, and local changes in the highly labile regulatory structures of the hippocampal region. And it is not surprising that all these changes entail not only (and perhaps not so much) epileptization, but a profound disruption of the regulation of brain activity, accompanied by autism spectrum disorders, more profound disorders in the form of schizophrenia or cyclothymia, and the formation of delayed psychomotor development. A «side branch¼ of these pathogenetic processes can also be considered the participation of PCDH19 dysfunctions in certain variants of oncogenesis. The need for polypharmacy (in most cases) confirms the diversity of mechanisms involved in the pathogenesis of the disease and makes the prospects for the development of effective and rational treatment regimens very vague. Cautious optimism is caused only by attempts at relatively specific treatment with ganaxolone.

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Computer-aided design and computer-aided manufacturing (CAD/CAM) dentistry have significantly changed workflows in recent years. Restorations and devices can now be digitally designed and 3D-printed for dental care purposes. This clinical case report provides straightforward protocols for the digital design and 3D manufacture of gingivectomy and tooth preparation guides. These types of guides improved the gingival architecture of the anterior teeth and provided controllable tooth preparations prior to labial ceramic veneers. Thoughtful clinical evaluation started with listening to the patient's chief complaint and extra- and intra-oral evaluations. Then a digital wax-up was performed, followed by an intra-oral mock-up, to evaluate the shape of the proposed restorations. After patient acceptance, the clinical procedure started with the gingivectomy and tooth preparation. Hand-crafted porcelain veneers were bonded under rubber dam isolation to avoid any contamination and maximize the bonding protocol. The esthetic and functional demands were fully satisfied. Predictable outcomes can be obtained whenever a meticulous evaluation and execution of all the steps are performed. Three dimensional printing technology allows the fabrication of devices such as gingivectomy and tooth reduction guides that help accomplish the desired results.

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Trivalent ruthenium (Ru) can catalyse the oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). However, the structure of Ru itself is unstable and is prone to aggregation and oxidation, leading to a decrease in catalytic activity. Therefore, it is necessary to prepare a stable, reliable, Ru-based catalyst. Based on the catalytic properties of trivalent Ru, a stable spinel structure with zinc ferrite was designed and loaded onto different carbon supports to prepare a homogeneous and stable Ru-based catalyst. The structure and physico-chemical properties were characterized through scanning electron microscopy, X-ray diffraction, transmission electron microscopy and other techniques, and the catalyst was applied to the oxidation of HMF for the preparation of FDCA. The results show that the prepared magnetic activated carbon-supported Ru-based catalyst has a concentrated particle size distribution in the range of 5-8 nm, with a loading amount of 3.61 at%. It exhibits strong soft magnetism, which is beneficial for Ru loading. Additionally, it can be reused in the oxidation of HMF to prepare FDCA over 10 cycles, with the product yield remaining essentially unchanged. The catalyst prepared in this study is characterized by recyclability and structural stability, making it promising for practical applications.

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The objectives were to summarise the evidence and clinical experts' views comparing the use of decentralised produced chimeric antigen receptor (CAR) T-cell therapies versus commercially available products, regarding drug costs, time to finalised product and other reported advantages, disadvantages, challenges and facilitators. A literature review according to the PRISMA guidelines was conducted in Medline, Embase and Trip databases. Publications were included if they reported information on cost estimates, time to finalised products and other outcomes of interest of a decentralised CAR T-cell production strategy. A structured interview guide was developed and used for qualitative expert interviews. Five experts were purposively selected, and interviews were either conducted face-to-face or online, and recorded for the purpose of transcription. Transcripts were analysed and categories and codes extracted. Reporting is based on the COREQ checklist for reporting qualitative research. Costs of decentralised produced CAR T-cells appear to be lower by a factor two to 14, compared with commercial products. But there is high uncertainty about this estimate, because it is unclear whether cost components included are comparable and due to the heterogeneity of the studies. The most commonly reported advantages were proximity to patients and decreased product risks and costs, whereas the continuing dependency on centrally manufactured reagents and specific characteristics of 'fresh' CAR T-cells are reported as disadvantages. Compliance with regulatory requirements is mentioned as the biggest challenge. The availability of closed-system production devices is reported as one main facilitator, as are clear commitment, secured financing and knowledge transfer from already experienced centres. Apparent cost differences open a field for healthcare decision-makers to discuss and justify investment costs for implementation of a complementing decentralised production programme and to realise other associated benefits of such a strategy, such as flexibility, patient proximity and expanding patient access.

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BACKGROUND: The cellular and molecular changes during red blood cell (RBC) storage that affect posttransfusion recovery (PTR) remain incompletely understood. We have previously reported that RBCs of different storage biology cross-regulate each other when stored together (co-storage cross-regulation [CSCR]). However, the mechanism of CSCR is unclear. In the current study, we tested the hypothesis that CSCR involves acquisition of molecular signatures associated with PTR. STUDY DESIGN AND METHODS: The whole blood compartment of either B6 or FVB mice was biotinylated in vivo prior to blood collection and storage. Bio-B6 or Bio.FVB were stored with RBCs from B6 mice transgenic for green florescent protein (GFP) (B6.GFP). After storage, avidin-magnetic beads were used to simultaneous purify Bio-RBCs (positive selection) and B6.GFPs (negative selection). Isolated populations were analyzed by transfusion to establish PTR, and subjected to metabolomic and proteomic analysis. RESULTS: B6 RBCs acquired molecular signatures associated with stored FVB RBCs at both the metabolomic and proteomic level including metabolites associated with energy metabolism, oxidative stress regulation, and oxidative damage. Mitochondrial signatures were also acquired by B6 RBCs. Protein signatures acquired by B6 RBCs include proteins associated with vesiculation. CONCLUSION: The data presented herein demonstrate the appearance of multiple molecular changes from poor-storing RBCs in good-storing RBCs during co-storage. Whether this is a result of damage causing intrinsic molecular changes in B6 RBCs or if molecules of FVB RBC origin are transferred to B6 RBCs remains unclear. These studies broaden our mechanistic understanding of RBC storage (in particular) and potentially RBC biology (in general).

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AIM: This study aims to explore and describe self-reported perceptions of nursing students' competence in the administration of medication. BACKGROUND: Medication errors are a significant concern in hospitals, as they can result in serious harm and even death for patients. Nursing students play a crucial role in administering medication and preventing errors, but they are also prone to making mistakes. While numerous studies have extensively examined the factors that contribute to medication errors, few have focused on the assessment of competency among nursing students. DESIGN: This study employed a qualitative exploratory and descriptive design. METHODS: A total of 10 undergraduate nursing students at a higher education institution consented to participate in face-to-face, semi-structured individual interviews. Data were collected between August and September 2022 using an interview guide. The interviews were audio recorded and analysed using Braun and Clarke's six steps of thematic analysis. RESULTS: The study revealed two major themes: (1) 'Perceived barriers to competency', which include participants' concerns regarding making errors, knowledge in pharmacology, self-efficacy in mathematics and level of supervision; and (2) 'Mechanisms for improvement', which centre on enhancing simulation proficiency, improving supervision and integrating pharmacology education in year two of nursing training. CONCLUSION: The study findings suggest that student nurses face various barriers to competence, such as a fear of making mistakes, a lack of pharmacology knowledge and low self-confidence in calculating drug dosages. To address these issues, prioritising supervision is crucial to facilitate student learning and ensure safety. Future research should consider investigating the perspectives of nurse educators on pharmacology curricula.

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BACKGROUND: Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. STUDY DESIGN AND METHODS: Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. RESULTS: TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. DISCUSSION: Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.

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The cyclic peptides, cyclotides, are identified mostly with 29-31-aa (amino acid residues) but rarely with ≥ 34-aa in plants. Viola philippica is a well-known medicinal plant but a rare metallophyte with cyclotides. A hypothesis was hence raised that the potential novel 34-aa cyclotide of Viola philippica would clearly broaden the structural and functional diversities of plant cyclotides. After homology-cloning the cyclotide precursor gene of VpCP5, a 34-aa cyclotide (viphi I) was identified to be larger than 22 other known cyclotides in V. philippica. It had a chimeric primary structure, due to its unusual loop structures (8 residues in loop 2 and 6 residues in loop 5) and aa composition (3 E and 5 R), by using phylogenetic analyses and an in-house cyclotide analysis tool, CyExcel_V1. A plasmid pCYC-viphi_I and a lab-used recombinant process were specially constructed for preparing viphi I. Typically, 0.12 or 0.25 mg ml-1 co-exposed viphi I could significantly remain cell activities with elevating Cd2+-exposed doses from 10-8 to 10-6 mol l-1 in MCF7 cells. In the model nematode Caenorhabditis elegans, IC50 values of viphi I to inhibit adult ratios and to induce death ratios, were 184.7 and 585.9 µg ml-1, respectively; the median lifespan of adult worms decreased from 14 to 2 d at viphi I doses ranging from 0.05 to 2 mg ml-1. Taken together, the newly identified viphi I exhibits functional potentials against cadmium and nematodes, providing new insights into structural and functional diversity of chimeric cyclotides in plants.

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Background/purpose: The success of root canal treatments is influenced by the shape of the access opening and the outcomes of root canal enlargement. The aim of this study was to evaluate the impact of various rotary instruments on the maintenance of the root canal's central alignment post shaping, considering a range of access cavity designs. Materials and methods: Using digital tooth simulation, 4 sets of 12 teeth underwent traditional (TradAC) or conservative (ConsAC) access cavity preparations. Root canals were enlarged with TruNatomy or ProTaper Ultimate rotary instruments. Canal transportation and centering ratio were separately measured. Statistical analysis was performed using JMP trial 17 software. Results: The analysis revealed no significant difference in buccal and lingual canal transportation among different rotary instruments or canal enlargement designs (P > 0.05). TradAC yielded higher centering ratios in MB and ML canals, while ConsAC excelled in the distal canal for the TruNatomy group. Conversely, in the ProTaper Ultimate group, ConsAC demonstrated higher ML canal ratios (P < 0.05). Conclusion: TruNatomy maintained superior canal centering with ConsAC, while ProTaper performed better with TradAC.

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The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

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In recent years, the application of numerical simulation in the research and development(R&D) as well as the pharmaceutical processes of new drugs has expanded considerably. The discrete element method(DEM), an important approach among numerical simulation methods, offers an effective tool for the simulation of discontinuous media. Referring to the research progress of DEM and the formulation of solid traditional Chinese medicine(TCM) preparations in recent years, this paper summarizes and analyzes the application of DEM in the pharmaceutical processes of solid TCM preparations, and discusses the challenges of its application in these processes, in order to provide new methods and ideas for promoting the high-quality production of TCM preparations.

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The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by the European Pharmacopoeia (Ph. Eur.) that requires 2 control reference reagents. The World Health Organization (WHO) positive control International Reference Reagent (IRR; 02/228) with a nominal titre of 8 defines the highest acceptable titre, while the negative control preparation (02/226) has a nominal titre of <2. Working reference preparations (04/132 and 04/140) were subsequently established as Biological Reference Preparations (BRPs) for the Ph. Eur., and for distribution by the United States Food and Drug Administration (US FDA) and the National Institute for Biological Standards and Control (NIBSC). Due to diminishing stocks of these working reference preparations across the 3 institutions, a joint international study was organised to establish harmonised replacement batches. Sixteen laboratories contributed data to the study to evaluate positive and negative candidate replacement batches (13/148 and 12/300, respectively) against the WHO positive and negative control IRRs and the current working reference preparations (BRPs). The results show that the candidate reference preparations (13/148 and 12/300) are indistinguishable from the corresponding IRRs and current BRPs. The candidate preparations 13/148 and 12/300 were adopted by the Ph. Eur. Commission as Immunoglobulin (anti-D antibodies test) BRP batch 2 and Immunoglobulin (anti-D antibodies test negative control) BRP batch 2 with nominal haemagglutination titres of 8 and <2, respectively. The same materials were also adopted as NIBSC and US FDA reference preparations, thus ensuring full harmonisation.

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Congenital pre-extensively drug-resistant tuberculosis is rare, and administration of second-line anti-tuberculosis medications to neonates is challenging due to the small doses required and limited availability of suitable formulations. Paediatric formulations have increasingly become available but may not be readily accessible in all countries. For the extremely preterm and low birth weight neonate, doses equivalent to a fraction of a tablet or capsule are required, with frequent dose adjustment for increasing age and weight during the course of treatment. The pharmaceutical formulation must be suitable for administration via enteral feeding tube and must be free of unsafe excipients. We report on the challenges, considerations and outcome of an extremely premature neonate with congenital pre-extensively drug-resistant tuberculosis who was successfully treated with second-line anti-tuberculosis medications. Child-friendly formulations were procured where available, and extemporaneous compounding of clofazimine, moxifloxacin and prothionamide oral suspensions was undertaken to enable administration of these medications.

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Medicine shortages are an increasing issue, with broad public health implications for patients, health professionals and institutions. Despite national notification mechanisms involving sponsors and national regulators (e.g. Australian Therapeutic Goods Administration), shortages continue to be a significant workload in hospitals, particularly for pharmacy staff. In this article, we describe the implications of medicine shortages and a team approach to their management in an Australian public hospital. The medicine shortages team comprises senior pharmacists, a pharmacy technician, and a purchasing officer, in consultation with medical staff. A 10 week audit recorded 34 medicine shortages and/or discontinuations, comprising 49 usually stocked products. Shortages were more quickly identified by the purchasing officer using established relationships with suppliers, rather than relying on sponsor or government communication. Having a team systematically dealing with these shortages enables expertise in supply chains, finances, therapeutics, and medicine safety to be shared, to identify optimal interventions to mitigate patient risk.