Micropatterning of Cells Reveals Chiral Morphogenesis

Invariant left-right (LR) patterning or chirality is critical for embryonic development. The loss or reversal of LR asymmetry is often associated with malformations and disease. Although several theories have been proposed, the exact mechanism of the initiation of the LR symmetry has not yet been fully elucidated. Recently, chirality has been detected within single cells as well as multicellular structures using several in vitro approaches. These studies demonstrated the universality of cell chirality, its dependence on cell phenotype, and the role of physical boundaries. In this review, we discuss the theories for developmental LR asymmetry, compare various in vitro cell chirality model systems, and highlight possible roles of cell chirality in stem cell differentiation. We emphasize that the in vitro cell chirality systems have great promise for helping unveil the nature of chiral morphogenesis in development

Handheld Raman Spectroscopy in the First UK Home Office Licensed Pharmacist-Led Community Drug Checking Service

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Across the world, the interest in point-of-care drug checking as a harm-reduction intervention is growing. This is an attempt to improve intelligence about current drug trends and reduce drug-related morbidity and mortality. In the UK, drug-related harm is increasing exponentially year after year. As such, specialist community treatment services are exploring new methods to improve engagement with people who use drugs (PWUD), who may require support for their problematic drug use. This need has driven the requirement to pilot an on-site, time-responsive, readily available drug-checking service at point-of-support centres. In this study, we piloted the UK’s first Home Office-licensed drug-checking service that was embedded into a community substance-misuse service and had all on-site analysis and harm-reduction interventions led and delivered by pharmacists. We report on the laboratory findings from the associated confirmatory analysis (UHPLC-MS, GC-MS, and 1H NMR) to assess the performance of the on-site hand-held Raman spectrometer and outline the challenges of providing real-time analysis of psychoactive substances in a clinical setting. Whilst acknowledging the limitation of the small sample size (n = 13), we demonstrate the potential suitability of using this technology for the purposes of screening substances in community-treatment services. Portability of equipment and timeliness of results are important and only very small samples may be provided by people who use the service. The challenges of accurately identifying substances from complex mixtures were equally found with both point-of-care Raman spectroscopy and laboratory confirmatory-analysis techniques. Further studies are required to confirm these findings.Peer reviewe

Benzodiazepine Boom: Tracking Etizolam, Pyrazolam, and Flubromazepam from Pre-UK Psychoactive Act 2016 to Present Using Analytical and Social Listening Techniques

© 2024 The Author(s). Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: The designer benzodiazepine (DBZD) market continues to expand whilst evading regulatory controls. The widespread adoption of social media by pro-drug use communities encourages positive discussions around DBZD use/misuse, driving demand. This research addresses the evolution of three popular DBZDs, etizolam (E), flubromazepam (F), and pyrazolam (P), available on the drug market for over a decade, comparing the quantitative chemical analyses of tablet samples, purchased from the internet prior to the implementation of the Psychoactive Substances Act UK 2016, with the thematic netnographic analyses of social media content. Method: Drug samples were purchased from the internet in early 2016. The characterisation of all drug batches were performed using UHPLC-MS and supported with 1H NMR. In addition, netnographic studies across the platforms X (formerly Twitter) and Reddit, between 2016–2023, were conducted. The latter was supported by both manual and artificial intelligence (AI)-driven thematic analyses, using numerous.ai and ChatGPT, of social media threads and discussions. Results: UHPLC-MS confirmed the expected drug in every sample, showing remarkable inter/intra batch variability across all batches (E = 13.8 ± 0.6 to 24.7 ± 0.9 mg; F = 4.0 ± 0.2 to 23.5 ± 0.8 mg; P = 5.2 ± 0.2 to 11.5 ± 0.4 mg). 1H NMR could not confirm etizolam as a lone compound in any etizolam batch. Thematic analyses showed etizolam dominated social media discussions (59% of all posts), with 24.2% of posts involving sale/purchase and 17.8% detailing new administration trends/poly-drug use scenarios. Artificial intelligence confirmed three of the top five trends identified manually. Conclusions: Purity variability identified across all tested samples emphasises the increased potential health risks associated with DBZD consumption. We propose the global DBZD market is exacerbated by surface web social media discussions, recorded across X and Reddit. Despite the appearance of newer analogues, these three DBZDs remain prevalent and popularised. Reporting themes on harm/effects and new developments in poly-drug use trends, demand for DBZDs continues to grow, despite their potent nature and potential risk to life. It is proposed that greater controls and constant live monitoring of social media user content is warranted to drive active regulation strategies and targeted, effective, harm reduction strategies.Peer reviewe

Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births

Traveler Phase 1A Joint Review

The briefing contains the preliminary findings and suggestions for improvement of methods used in development and evaluation of a multi monitor runtime assurance architecture for autonomous flight vehicles. Initial system design, implementation, verification, and flight testing has been conducted. As of yet detailed data review is incomplete, and flight testing has been limited to initial monitor force fights. Detailed monitor flight evaluations have yet to be performed

Sea Traffic Management : Effektivitet och Cybersäkerhet

Sea Traffic Management has developed with the aim of facilitating work and increasing efficiency at sea, both in terms of productivity and environmental contexts. The technical development and digitization of the equipment on ships has led to new problems that have been developed such as cyber-attacks and technical problems. This study is based on a qualitative research method. The purpose of the work is to investigate how effective STM is and how safe it is to use for merchant vessels. The study showed that STM can have a positive effect on the environment and increase time savings, provided that more vessels in the industry use it as standard equipment. Results indicate that Sea Traffic Management is a helpful tool that will increase safety for navigation and have a positive effect on the environment for longer sea voyages. However, this is assumed if the shipping industry itself is ready for a digitalized world that is constantly developing, where a new type of issues arises with a nuanced threat for both ships and land bases.Sea Traffic Management har utvecklats i syfte att underlätta arbetet och öka effektiviteten till sjöss, både när det gäller i produktivitet samt i miljösammanhang. I samband med den tekniska utvecklingen och digitaliseringen av utrustningen på fartyg så har nya lösningar samt problem uppstått, såsom cyberattacker och tekniska bekymmer. Studien grundar sig i en kvalitativ forskningsmetod. Arbetet har i syfte att undersöka hur effektivt STM är samt hur säker den är för användning av olika handelsfartyg på marknaden. I studien visade det sig att STM kan påverka miljön positivt samt öka tidsbesparingar förutsatt att fler fartyg inom branschen nyttjar det som en standardutrustning. Resultat tyder på att Sea Traffic Management är ett hjälpsamt verktyg som kommer att öka säkerheten för navigeringen samt påverka miljön positivt för längre sjöresor. Detta är dock förutsatt om själva sjöfartsbranschen är redo för en digitaliserad värld som ständigt utvecklas, där en ny typ av problematik uppstår med en nyanserad hotbild för både fartyg och olika land baser

Sea Traffic Management : Effektivitet och Cybersäkerhet

Sea Traffic Management has developed with the aim of facilitating work and increasing efficiency at sea, both in terms of productivity and environmental contexts. The technical development and digitization of the equipment on ships has led to new problems that have been developed such as cyber-attacks and technical problems. This study is based on a qualitative research method. The purpose of the work is to investigate how effective STM is and how safe it is to use for merchant vessels. The study showed that STM can have a positive effect on the environment and increase time savings, provided that more vessels in the industry use it as standard equipment. Results indicate that Sea Traffic Management is a helpful tool that will increase safety for navigation and have a positive effect on the environment for longer sea voyages. However, this is assumed if the shipping industry itself is ready for a digitalized world that is constantly developing, where a new type of issues arises with a nuanced threat for both ships and land bases.Sea Traffic Management har utvecklats i syfte att underlätta arbetet och öka effektiviteten till sjöss, både när det gäller i produktivitet samt i miljösammanhang. I samband med den tekniska utvecklingen och digitaliseringen av utrustningen på fartyg så har nya lösningar samt problem uppstått, såsom cyberattacker och tekniska bekymmer. Studien grundar sig i en kvalitativ forskningsmetod. Arbetet har i syfte att undersöka hur effektivt STM är samt hur säker den är för användning av olika handelsfartyg på marknaden. I studien visade det sig att STM kan påverka miljön positivt samt öka tidsbesparingar förutsatt att fler fartyg inom branschen nyttjar det som en standardutrustning. Resultat tyder på att Sea Traffic Management är ett hjälpsamt verktyg som kommer att öka säkerheten för navigeringen samt påverka miljön positivt för längre sjöresor. Detta är dock förutsatt om själva sjöfartsbranschen är redo för en digitaliserad värld som ständigt utvecklas, där en ny typ av problematik uppstår med en nyanserad hotbild för både fartyg och olika land baser

Development and Validation of a Survey Instrument to Measure Factors that Influence Pharmacist Prescribing

Objective: Study objectives were to develop a questionnaire to assess factors influencing pharmacists’ adoption of prescribing (i.e., continuing, adapting or initiating therapy), describe use of pre-incentive and mixed mode survey, and establish survey psychometric properties. Methods: Questions were developed based on prior qualitative research and Diffusion of Innovation theory. Expert review, cognitive testing, survey pilot, and main survey were used to test the questionnaire. Six content experts reviewed the questionnaire to establish face and content validity. Ten pharmacists from diverse practice settings were purposefully recruited for a cognitive interview to verify question readability. Content analysis was used to analyze the results. A pre-survey introduction letter with a monetary incentive was mailed via post to 100 (i.e. pilot) and 700 (i.e., main survey) randomly selected pharmacists. This was followed by an e-mail with a personalized link to the online questionnaire, e-mail reminders, and a telephone reminder if required. The psychometric properties of scales were evaluated with an exploratory factor analysis and Cronbach’s alpha. Scale responses were described. Results: Engagement of six experts and ten pharmacists clarified definitions (e.g., prescribing), terminology, recall periods, and response options for the 34-item response scale. Fifty-six pharmacists completed the online pilot survey. Based on this data, ambiguous questions and routing issues were addressed. Three hundred and seventy-eight pharmacists completed the online main survey for a response rate of 54.6%. The factors analysis resulted in 27 questions in eight scales: (1) self-efficacy, (2) support from practice environment, (3) support from interprofessional relationship, (4) impact on professionalism, (5) impact on patient care), (6) prescribing beliefs, (7) technical use of electronic health record (EHR) and (8) patient care use of the EHR. Prescribing beliefs and technical use of the EHR scales had low reliability while the remaining six scales had strong evidence for reliability and validity. Conclusion: Through a multi-stage process, a survey instrument was developed to capture pharmacists’ perceptions of prescribing influences. This questionnaire may support future research to develop interventions to enhance adoption of prescribing and enhance direct patient care by pharmacists