Evaluation of Hedera species as herbal medicine raw materials.

This study aimed to evaluate the potential of Hedera colchica as an alternative to Hedera helix species for the treatment of mild inflammatory conditions of the upper respiratory tract and chronic inflammatory bronchial diseases. The H. colchica extract with the highest saponin content (C3S; 468.19 ± 16.01 mg HE/g dry weight) and the extract with the highest total phenol content (C1F; 108.60 ± 5.61 mg GAE/g dry weight). Chemical analysis and standardisation of the extract with the highest selective COX-2 inhibitory effect was performed using the LC-MS/MS technique. It was determined that the substances found in the highest ratio in the C1F extract were quinic acid (45.909 µg/g extract) and hesperidin (37.077 µg/g extract). As a result, secondary metabolites, in addition to saponins, found in Hedera species may also contribute to the extract's effectiveness, more potent extracts can be obtained compared to the total extract-containing preparations available in the market.

C-Reactive Protein and Brain Natriuretic Peptides Harmonization.

The harmonization of laboratory biomarkers is pivotal in ensuring consistent and reliable diagnostic outcomes across different clinical settings. This systematic review examines the harmonization of C-Reactive Protein (CRP) and N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) measurements, both of which are jointly utilized in the diagnosis and management of cardiovascular diseases. To identify relevant studies, we searched the PubMed electronic database using specific medical subject headings and keywords such as C-Reactive Protein, CRP, high sensitivity C-Reactive Protein (hs-CRP), N-terminal pro B-type natriuretic peptide, and NT-proBNP, focusing on publications from June 1 to September 26, 2021. The query filtered studies to include only those in English involving human subjects. From our search, 97 articles met the inclusion criteria and were included for in-depth analysis. Despite their widespread use, significant variability remains in the measurements of CRP and NT-proBNP due to a lack of standardized pre-analytical, analytical, and post-analytical practices. This review highlights the consequences of this variability on clinical decision-making and patient outcomes and emphasizes the need for international standards and guidelines to achieve better harmonization. Our findings advocate for the establishment of universal protocols to enhance the reliability of these biomarker measurements across different clinical environments, ensuring improved healthcare delivery.

Benchmarking breath analysis using peppermint approach with gas chromatography ion mobility spectrometer coupled to micro thermal desorber.

The Peppermint Initiative, established within the International Association of Breath Research, introduced the peppermint protocol, a breath analysis benchmarking effort designed to address the lack of inter-comparability of outcomes across different breath sampling techniques and analytical platforms. Benchmarking with gas chromatography-ion mobility spectrometry (GC-IMS) using peppermint has been previously reported however, coupling micro-thermal desorption (µTD) to GC-IMS has not yet, been benchmarked for breath analysis. To benchmarkµTD-GC-IMS for breath analysis using the peppermint protocol. Ten healthy participants (4 males and 6 females, aged 20-73 years), were enrolled to give six breath samples into Nalophan bags via a modified peppermint protocol. Breath sampling after peppermint ingestion occurred over 6 h att= 60, 120, 200, 280, and 360 min. The breath samples (120 cm3) were pre-concentrated in theµTD before being transferred into the GC-IMS for detection. Data was processed using VOCal, including background subtractions, peak volume measurements, and room air assessment. During peppermint washout, eucalyptol showed the highest change in concentration levels, followed byα-pinene andß-pinene. The reproducibility of the technique for breath analysis was demonstrated by constructing logarithmic washout curves, with the average linearity coefficient ofR2= 0.99. The time to baseline (benchmark) value for the eucalyptol washout was 1111 min (95% CI: 529-1693 min), obtained by extrapolating the average logarithmic washout curve. The study demonstrated thatµTD-GC-IMS is reproducible and suitable technique for breath analysis, with benchmark values for eucalyptol comparable to the gold standard GC-MS.

Standardisation of the definition of the types of oncological colectomy. Delphi method for consensus of experts of the Spanish association of surgeons.

There is no international consensus on the definition of the type of oncological resection that corresponds to each of the colectomies existing in the current literature. The objective is to define for each colectomy described in the literature: embryological dissection plane, vascular pedicles in which to perform central ligation, the extent of the colectomy, and the need for resection of the greater momentum. A consensus of experts is carried out through the Delphi methodology through two rounds from the Coloproctology Section of the Spanish Association of Surgeons. Study period: November 2021-January 2023. 120 experts were surveyed. Degrees of consensus: Very strong: >90%, Strong: 80-90%, Moderate: 50-80%, No consensus: <50%. The definition for each oncological colectomy was established by very strong, and strong recommendations. Each oncological colectomy was established as Right hemicolectomy (RHC), RHC with D3 lymphadenectomy, Extended-RHC, transverse colon segmental colectomy, splenic flexure segmental colectomy, subtotal colectomy, total colectomy, left hemicolectomy (LHC), extended-LHC, sigmoidectomy.

Toward an international standardisation roadmap for nanomedicine.

The French National Metrology Institute (LNE) initiated a series of events to identify priorities for test methods and their harmonisation that directly address regulatory needs in Nanomedicine. One of these workshops entitled "The International Standardisation Roadmap for Nanomedicine" held in October 2023 (Paris, France) brought together key experts in the characterisation of nanomedicines and medical products containing nanomaterials, including the Joint Research Centre of the European Commission, SINTEF Industry and the metrology institutes of France, the UK, the USA and Canada, two flagship initiatives of the European Commission (PHOENIX and SAFE-n-MEDTECH Open Innovation Test Beds), representatives of a working party on mRNA vaccines at the European Directorate for the Quality of Medicines (EDQM) and members of international standardisation and pre-normative organisations (including CEN, ISO, ASTM, VAMAS). Two take-home message came out from the discussion. First, developing standard test methods and Reference Materials (RMs) for nanomedicines is a key priority for the European Commission and various stakeholders. Furthermore, there was a unanimous recognition of the need for a unified approach between standardisation committees, regulators and the nanomedicine community. At the USA, Canadian and European level, examples of success stories and of future initiative have been discussed. Future perspectives include the creation of a dedicated Working Group under CEN/TC 352 to consolidate efforts and develop a nanomedicine standardisation roadmap.

Inter-laboratory multiplex bead-based surface protein profiling of MSC-derived EV preparations identifies MSC-EV surface marker signatures.

Mesenchymal stromal cells (MSCs) are promising regenerative therapeutics that primarily exert their effects through secreted extracellular vesicles (EVs). These EVs - being small and non-living - are easier to handle and possess advantages over cellular products. Consequently, the therapeutic potential of MSC-EVs is increasingly investigated. However, due to variations in MSC-EV manufacturing strategies, MSC-EV products should be considered as highly diverse. Moreover, the diverse array of EV characterisation technologies used for MSC-EV characterisation further complicates reliable interlaboratory comparisons of published data. Consequently, this study aimed to establish a common method that can easily be used by various MSC-EV researchers to characterise MSC-EV preparations to facilitate interlaboratory comparisons. To this end, we conducted a comprehensive inter-laboratory assessment using a novel multiplex bead-based EV flow cytometry assay panel. This assessment involved 11 different MSC-EV products from five laboratories with varying MSC sources, culture conditions, and EV preparation methods. Through this assay panel covering a range of mostly MSC-related markers, we identified a set of cell surface markers consistently positive (CD44, CD73 and CD105) or negative (CD11b, CD45 and CD197) on EVs of all explored MSC-EV preparations. Hierarchical clustering analysis revealed distinct surface marker profiles associated with specific preparation processes and laboratory conditions. We propose CD73, CD105 and CD44 as robust positive markers for minimally identifying MSC-derived EVs and CD11b, CD14, CD19, CD45 and CD79 as reliable negative markers. Additionally, we highlight the influence of culture medium components, particularly human platelet lysate, on EV surface marker profiles, underscoring the influence of culture conditions on resulting EV products. This standardisable approach for MSC-EV surface marker profiling offers a tool for routine characterisation of manufactured EV products in pre-clinical and clinical research, enhances the quality control of MSC-EV preparations, and hopefully paves the way for higher consistency and reproducibility in the emerging therapeutic MSC-EV field.

An international perspective on young stroke incidence and risk factors: a scoping review.

BACKGROUND: Stroke among younger age groups is increasing globally. While there is a focus on research conducted on people under 65 years who have had a stroke, there is a paucity of data on the incidence and risk factors of stroke among younger people (≤ 30 years). This scoping review examines evidence on incidence and risk factors for perinatal, paediatric and young adult stroke globally. METHODS: The review was guided by the Joanna Briggs Institute's scoping review methodology. A systematic search was conducted on 23rd March 2022 across Medline Ovid, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The eligibility criteria included all study designs providing information on the incidence and risk factors of stroke among young people (≤ 30 years) in the last ten years. RESULTS: A total of 5750 articles were identified. After screening, 471 articles (224 cohort studies (47.6%), 164 case studies/case series (34.8%), 35 reviews (7.4%), 30 case-control (6.4%) and 18 combinations of designs (3.8%) were included. There was data from 50 different countries, 199 studies were from high-income countries, upper and middle income (n = 38), lower middle-income (n = 39), low-income (n = 3) countries, international study (n = 7) and a further 185 articles did not state the country of research. Most of the studies (63%) focused on risk factors while incidence constituted 37%. Incidence data were reported heterogeneously across studies, leading to an inability to synthesise data. The three most frequently reported risk factors for perinatal stroke were infections, cardiac conditions, and intrapartum factors. Vasculopathies, infection and cardiac conditions accounted for most reported risk factors for paediatric stroke, while chronic conditions such as diabetes mellitus, vasculopathies and cardiac conditions accounted for the most reported risk factors among young adults. CONCLUSION: This review has highlighted different stroke risk factors for each age cohort of people under 30 years. The low number of epidemiological studies suggests that further research of this type is needed to fully understand the incidence and risk factors in young stroke. A standardised reporting of age groupings of incidence data is imperative to enable the comparison of data from different geographical locations.

Development and characterisation of buccal dispersible film, syrup and effervescent granules of extemporaneous antigout remedy.

Homemade medicinal remedies used to treat both acute and chronic ailments for centuries need to be transformed into modern evidence-based dosage forms. Therefore, the present study aimed to develop buccal dispersible film, syrup and effervescent granules of an extemporaneous antigout homemade remedy. The dosage forms were prepared using holistic remedy (HR) as an active entity and excipients masking disagreeable features. The dosage forms and HR were subjected to physicochemical evaluation, and standardised by a reversed-phase HPLC method using chlorogenic acid, caffeic acid, vanillin, and ferulic acid as analytical standards. The standardised dosage forms were investigated for antigout activity using an appropriate model. The dosage forms were found to be physically elegant and phytochemically aligned with HR. The developed dosage forms contained the selected markers and possessed antigout activity. Hence, these standardised and evidence-based dosage forms may have wider acceptance in the market compared to HR.

Myths and Methodologies: Standardisation in Human Physiology Research-Should We Control the Controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Best practices for machine learning in antibody discovery and development.

In the past 40 years, therapeutic antibody discovery and development have advanced considerably, with machine learning (ML) offering a promising way to speed up the process by reducing costs and the number of experiments required. Recent progress in ML-guided antibody design and development (D&D) has been hindered by the diversity of data sets and evaluation methods, which makes it difficult to conduct comparisons and assess utility. Establishing standards and guidelines will be crucial for the wider adoption of ML and the advancement of the field. This perspective critically reviews current practices, highlights common pitfalls and proposes method development and evaluation guidelines for various ML-based techniques in therapeutic antibody D&D. Addressing challenges across the ML process, best practices are recommended for each stage to enhance reproducibility and progress.

Perceptions of social class through Chinese speech cues.

Speech is a complex auditory signal that contains multiple layers of linguistic and non-linguistic structure, it contains both linguistic and social class information. Perceivers are exquisitely sensitive to this layered structure and extract not only linguistic properties, but also indexical characteristics that provide information about individual talkers and groups of talkers. Social class information involves inferring the speaker's social class or forming an impression of their social status based on their speech. Previous research on social class perception in speech has primarily focused on English, with relatively little research on Chinese. This study examines social class perception in Chinese speech. Study 1 employed class judgment and evaluation tasks with a subjective social class scale as the main measure to examine whether listeners could infer class information from Chinese speech and how their own class background influenced their perception. The results of Study 1 showed that subjects could accurately discriminate between speakers' social classes, but there may be a response bias that overestimates lower-class speakers as upper-class speakers. Study 2 focused on whether the speech of different classes of speakers actually differed on a number of indicators. It was found that the speech of higher class speakers was perceived to be more standardised, more pleasant to listen to and less accent-intensive. Overall, listeners can perceive class information from Chinese speech; different classes of Chinese speech do contain different levels of indexical information. In Chinese language societies, individuals can also judge their class information through the speech, which is consistent with the relevant research results in English.

Measurement protocols and determinants of peak oxygen consumption in adults with Down syndrome: a systematic review.

This systematic review aimed to provide an overview of test protocols used to measure peak oxygen uptake (VO2peak) in adults with Down syndrome (DS) and to determine how generalisable the outcomes are for the entire population of adults with DS by describing the sample characteristics of these studies and their impact on VO2peak. A literature search (PROSPERO CRD42022309560) was performed (18 July 2023) using the following databases: PubMed, CINAHL, APA PsycINFO, Web of Science, Embase and SPORTDiscus. For articles to be included, they had to be peer-reviewed pubications, reporting VO2peak or VO2max for individuals with DS separately, with a sample of n ≥ 5 and a mean age ≥18 years. Systematic reviews and meta-analyses were excluded but their reference lists were searched for additional papers to include. Studies were evaluated for risk of bias following the guidelines of Kmet et al. The results were summarised with frequency statistics. Forty-three studies were included in this systematic review. Sample sizes of included adults with DS ranged from n = 4-226, with a total of n = 1498 adults with DS being included. Most studies (29/43) used the same standardised maximal exercise treadmill protocol to measure VO2peak in adults with DS, and 33 out of 43 studies used at least one objective criterion to determine a valid maximal effort. Participants were predominantly male, under 40 years old, and overweight or obese. Additionally, the diversity of study samples was lacking or not reported. The most widely used, standardised, maximal exercise test treadmill protocol is recommended for future use in research and practice, including objective criteria to determine valid maximal effort. The current study samples are not representative of the population of adults with DS in terms of sex, age and diverse backgrounds and therefore likely overestimate VO2peak of this population.

Effect of clinical engagement on value, standardisation, decision-making and savings in NHS product procurement.

BACKGROUND: UK healthcare expenditure is now £193.8 billion a year. The procurement function is seen as central to driving efficiencies within the NHS. This comes with an increasing onus on clinicians, including nurses and allied health professionals, to accept procurement outcomes to realise efficiency savings, with or without prior engagement. AIMS: This empirical study seeks to examine whether clinical engagement in the procurement of healthcare products in the NHS is necessary to achieve value, savings and standardisation; it will thereby address a gap in the research. METHODS: A multi-method qualitative case study design was used, which included a survey and eight semi-structured interviews. FINDINGS: Results identified three factors that influence the achievement of value, savings and standardisation around clinical engagement: micro-level processes for clinical engagement; clinical stakeholders and clinical procurement professionals as experts at the centre of procurement activity; and clinical value in standardisation. A shift away from standardisation to resilience was identified, resulting from current market supply pressures. CONCLUSION: This research brings empirically derived findings to address gaps in research, supports the benefit of clinical engagement through specific forums for collaboration at a trust level and provides a clinical/expert impact/preference matrix as a resource for procurement professionals to facilitate clinical engagement.

The Getting It right First Time (GIRFT) programme in urology; rationale and methodology.

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.

Standardisation is the key to the sustained, rapid and healthy development of stem cell-based therapy.

BACKGROUND: Stem cell-based therapy (SCT) is an important component of regenerative therapy that brings hope to many patients. After decades of development, SCT has made significant progress in the research of various diseases, and the market size has also expanded significantly. The transition of SCT from small-scale, customized experiments to routine clinical practice requires the assistance of standards. Many countries and international organizations around the world have developed corresponding SCT standards, which have effectively promoted the further development of the SCT industry. METHODS: We conducted a comprehensive literature review to introduce the clinical application progress of SCT and focus on the development status of SCT standardization. RESULTS: We first briefly introduced the types and characteristics of stem cells, and summarized the current clinical application and market development of SCT. Subsequently, we focused on the development status of SCT-related standards as of now from three levels: the International Organization for Standardization (ISO), important international organizations, and national organizations. Finally, we provided perspectives and conclusions on the significance and challenges of SCT standardization. CONCLUSIONS: Standardization plays an important role in the sustained, rapid and healthy development of SCT.

How comprehensive is our comprehensive geriatric assessment in clinical practice? An Irish perspective.

PURPOSE: Comprehensive geriatric assessment (CGA) is the cornerstone of high-quality care for older adults. There is no current gold standard to guide what should be included as the baseline measure for CGAs. We examined what metrics are being captured in CGA baseline assessments completed by community based integrated care teams in Ireland. METHODS: CGA's care pathways in Ireland are usually initiated with a written document that establish patients baseline in various assessment areas. These documents were the focus of this study. We completed a cross-sectional study of the components captured in CGA baseline assessments completed in a community setting. We contacted operational leads in each of the community health organisations in Ireland and requested a copy of their current initial baseline screening document for CGA. RESULTS: We reviewed 16 individual CGA baseline documents for analysis in this study. Common assessment areas in all documents included frailty (with the Rockwood Clinical frailty scale used in 94%, n = 15), cognition (4AT-56% of CGAs, MMSE-25%, MOCA-25%, AMTS-19%, AD8-19%, Addenbrookes-13%, 6CIT-13%, mini cog-6%), mobility (100%, n = 16), falls (100%, n = 16), continence (100% n = 16), nutrition (100% n = 16). Mood (94%, n = 15), pain (44%, n = 7), bone health (63%, n = 10), sleep (62%, n = 10) and skin integrity (56%, n = 9). Formal functional assessment was completed in 94% (n = 15) of CGAs with the Barthel index being the tool most used 81% (n = 13). Half of the CGAs included a section describing carer strain (50%, n = 8). The majority of CGAs included a patient centred question which was some variation of 'what matters most to me' (75% n = 11). 87.5% of assessments included a care plan summary (n = 14). CONCLUSIONS: This report highlights that the core tenets of CGA are being assessed across different community based initial CGA screening instruments. There was significant variability in the discussion of challenging topics such as carer strain and social well-being. Our results should prompt a discussion about whether a minimum dataset should be developed for inclusion in nationwide initial baseline CGA document, aiming to improve standardisation of assessments, which will impact areas highlighted for intervention and ultimately guide population health policy.

Post-hoc standardisation of parametric T1 maps in cardiovascular magnetic resonance imaging: a proof-of-concept.

BACKGROUND: In cardiovascular magnetic resonance imaging parametric T1 mapping lacks universally valid reference values. This limits its extensive use in the clinical routine. The aim of this work was the introduction of our self-developed Magnetic Resonance Imaging Software for Standardization (MARISSA) as a post-hoc standardisation approach. METHODS: Our standardisation approach minimises the bias of confounding parameters (CPs) on the base of regression models. 214 healthy subjects with 814 parametric T1 maps were used for training those models on the CPs: age, gender, scanner and sequence. The training dataset included both sex, eleven different scanners and eight different sequences. The regression model type and four other adjustable standardisation parameters were optimised among 240 tested settings to achieve the lowest coefficient of variation, as measure for the inter-subject variability, in the mean T1 value across the healthy test datasets (HTE, N = 40, 156 T1 maps). The HTE were then compared to 135 patients with left ventricular hypertrophy including hypertrophic cardiomyopathy (HCM, N = 112, 121 T1 maps) and amyloidosis (AMY, N = 24, 24 T1 maps) after applying the best performing standardisation pipeline (BPSP) to evaluate the diagnostic accuracy. FINDINGS: The BPSP reduced the COV of the HTE from 12.47% to 5.81%. Sensitivity and specificity reached 95.83% / 91.67% between HTE and AMY, 71.90% / 72.44% between HTE and HCM, and 87.50% / 98.35% between HCM and AMY. INTERPRETATION: Regarding the BPSP, MARISSA enabled the comparability of T1 maps independently of CPs while keeping the discrimination of healthy and patient groups as found in literature. FUNDING: This study was supported by the BMBF / DZHK.