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Microfluidic concentration gradient generators (µ-CGGs) have been utilized to identify optimal drug compositions through antimicrobial susceptibility testing (AST) for the treatment of antimicrobial-resistant (AMR) infections. Conventional µ-CGGs fabricated via photolithography-based micromachining processes, however, are fundamentally limited to two-dimensional fluidic routing, such that only two distinct antimicrobial drugs can be tested at once. This work addresses this limitation by employing Multijet-3D-printed microchannel networks capable of fluidic routing in three dimensions to generate symmetric multidrug concentration gradients. The three-fluid gradient generation characteristics of the fabricated 3D µ-CGG prototype were quantified through both theoretical simulations and experimental validations. Furthermore, the antimicrobial effects of three highly clinically relevant antibiotic drugs, tetracycline, ciprofloxacin, and amikacin, were evaluated via experimental single-antibiotic minimum inhibitory concentration (MIC) and pairwise and three-way antibiotic combination drug screening (CDS) studies against model antibiotic-resistant Escherichia coli bacteria. As such, this 3D µ-CGG platform has great potential to enable expedited combination AST screening for various biomedical and diagnostic applications.

"Esperanto and Languages of Internationalism in Revolutionary Russia" by Brigid O'Keeffe is a comprehensive study that challenges the perception of constructed languages like Esperanto as mere hobbies or grandiose schemes. The book explores the history of Esperantism in Russia, from its origins in Zamenhof's early life and Jewish heritage to its fate under Stalin. O'Keeffe argues that Esperanto was seen by early Soviet Esperantists as a means of communication across the diverse peoples of the Russian Empire and as a tool for international socialism. However, the language ultimately faced opposition and persecution under Stalinism, leading to its decline. This book provides valuable insights into the ideas surrounding globalization in the early 20th century and offers a detailed analysis of Esperantism in Revolutionary Russia. [Extracted from the article]

Prior to 2009, it had been generally accepted that Captain Crozier was born in September 1796 and most likely on the 17th of that month. Further research, published in this Journal, then suggested that upon a fresh scrutiny of the evidence the alternative date of 16 August 1796 was more probable. This note proposes that whilst the date of 16 August was of significance to Captain Crozier, that significance was other than natal and furthermore that alternative evidence, namely a letter dated 20 March 1810 from his father to the 3rd Marquess of Downshire, records his date of birth as being 17 October 1796. [ABSTRACT FROM AUTHOR]

Https://doi.org/10.1093/ced/llad073 Dear Editor, For 95 years, sunscreens have been available to protect the skin from the harsh effects of ultraviolet (UV) radiation. [Extracted from the article]

Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1a, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis. [ABSTRACT FROM AUTHOR]

The number of women in the UK seeking genetic counselling, testing and preventative treatment is rapidly increasing. In Manchester 600–800 women are now referred annually to the Family History Clinic. As yet there is no formal provision for this service within the NHS, but research is underway to evaluate such clinics and to identify the psychosocial sequelae of genetic risk counselling. To date, findings have been based on questionnaire data from which it is difficult to ascertain support needs accurately. We interviewed 158 women 3 months after genetic risk counselling because of a family history of breast cancer. Using standard assessment and diagnostic criteria, 21 (13%) women were diagnosed with an affective disorder. This compared with a prevalence of 26% using the 28 item General Health Questionnaire (GHQ). We did not find a relationship between GHQ distress levels and women's understanding of their risk before genetic counselling, but women with accurate risk knowledge post-counsel had significantly lower GHQ scores than those who continued to over or under-estimate and this finding warrants further investigation. Of women referred for psychological help, few reported risk of breast cancer as their main concern, but themes of loss, unresolved grief and relationship problems were common. The value of the GHQ as a screening instrument is discussed and we suggest a new threshold value based on our analysis. We conclude that risk counselling does not adversely affect the general mental health of attenders but a minority of women may need help with the impact of breast cancer in the family. © 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B.Methods: In this multicenter, open-label, phase 1-2 trial, we assessed the safety and efficacy of varying doses of FLT180a in patients with severe or moderately severe hemophilia B (factor IX level, ≤2% of normal value). All the patients received glucocorticoids with or without tacrolimus for immunosuppression to decrease the risk of vector-related immune responses. After 26 weeks, patients were enrolled in a long-term follow-up study. The primary end points were safety and efficacy, as assessed by factor IX levels at week 26.Results: Ten patients received one of four FLT180a doses of vector genomes (vg) per kilogram of body weight: 3.84×1011 vg, 6.40×1011 vg, 8.32×1011 vg, or 1.28×1012 vg. After receiving the infusion, all the patients had dose-dependent increases in factor IX levels. At a median follow-up of 27.2 months (range, 19.1 to 42.4), sustained factor IX activity was observed in all the patients except one, who resumed factor IX prophylaxis. As of the data-cutoff date (September 20, 2021), five patients had normal factor IX levels (range, 51 to 78%), three patients had levels from 23 to 43%, and one had a level of 260%. Of the reported adverse events, approximately 10% were related to FLT180a and 24% to immunosuppression. Increases in liver aminotransferase levels were the most common FLT180a-related adverse events. Late increases in aminotransferase levels occurred in patients who had received prolonged tacrolimus beyond the glucocorticoid taper. A serious adverse event of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels.Conclusions: Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444 and NCT03641703; EudraCT numbers, 2017-000852-24 and 2017-005080-40.). [ABSTRACT FROM AUTHOR]

User perception is an important consideration when assessing the educational value of multimedia resources. A media tool may be proven educationally, but if the users (normally the students) perceive it as anything less than helpful, they are unlikely to obtain maximum utility from it. The aim of this study is to assess the perceived educational value of multimedia tools currently available to MPharm students (i.e. DVD, CD-ROM, handouts/practical schedules and internet resources, including streaming video media) and the factors that influenced students' perception. MPharm students from all four cohorts of the Brighton MPharm degree pathway participated in this study. Respondents identified handouts and schedules for workshops and laboratory classes as the most useful resource, followed by internet-based resources and DVD/CD-ROM resources. Printed resources were perceived as more reliable and trustworthy compared to multimedia resources. DVD-based resources were perceived to captivate attention and maintain focus more than other resources and respondents favoured a combination of printed and electronic resources to be available. Generally, although electronic resources (particularly those which are internet-based) were positively perceived, the use of printed media, such as laboratory schedules and lecture notes, was preferred in conjunction with multimedia resources. [ABSTRACT FROM AUTHOR]

Handouts are an established and recognised way for teaching staff to facilitate learning within higher education, by supplementing traditional didactic Learning and Teaching (L&T) methods. Traditionally, teaching in UK Schools of Pharmacy has often relied upon the use of handouts as part of the L&T strategy. However, their use is inconsistent, and dependent upon the teaching style of the educator. To our knowledge, a systematic analysis of their impact on the student learning experience has not been conducted with respect to their use in the Master of Pharmacy (M.Pharm) degree programme. In this article, we survey the attitudes of undergraduate M.Pharm students with respect to the use of handouts and the effect on their learning at two UK schools of pharmacy and compare the results with an Australian (University of Queensland) school of veterinary science. We report that most students' stated preference is for comprehensive learning support in the form of handouts. This is at slight variance with one of our previous works which, although reported a similar result, also reported that there is in some cases an inversely proportional relationship between the number of handouts given to students and the value they place upon them, as well as that students place greater value on material that they have downloaded themselves by means of an intranet or Managed Learning Environment. Two hundred and eighty five School of Pharmacy and Biomolecular Sciences, University of Brighton students (Levels 1-4) and 19 staff responded to questionnaire and 150 School of Pharmacy and Biomolecular Sciences, University of Portsmouth students responded. Reporting from the view that handouts can be a coherent and effective educational strategy to promote lifelong learning, we compare attitudes of the staff and students of the schools and whether or not these influence the manner in which students and staff approach their subjects. We report significant differences in the way five major questions were answered between each school. Comparisons of the responses from the different schools indicated that students from different universities and from both countries have different beliefs regarding handout usage. Eighty-three percent of Brighton students requested comprehensive handouts as an integral component of the lectures, compared to 56% of Queensland students, and 53% of Portsmouth students. Whilst staff favour the limited use of handouts as supplements to lecture materials and tended to agree on most responses, with only 32% of Brighton staff and 34% of Queensland staff agreeing that students should receive comprehensive handouts. More staff than students also agreed that handouts discourage further reading in a subject. Other factors that were significantly related to student responses were gender, year of study, choice of pre-registration field, the presence or absence of a part-time job and whether or not the student was studying in their native country. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest the authors declare no conflicts of interest.

The initial choice of anticoagulant therapy administered in emergency departments for acute coronary syndromes (ACS) has important consequences for subsequent patient care, as neither unfractionated heparin (UFH) nor low-molecular-weight heparin (LMWH) are ideally suited for all potential clinical treatment pathways. UFH remains widely used for surgical interventions because of the ability to rapidly reverse its anticoagulant activity. However, the unpredictable pharmacokinetic profile of UFH presents safety issues, and the low subcutaneous bioavailability limits the utility of UFH for patients who are medically managed. LMWH has superior pharmacokinetic properties, but its anticoagulant activity cannot be effectively monitored or reversed during surgery. There is an unmet medical need for a baseline anticoagulant therapy that addresses these shortcomings while retaining the beneficial properties of both UFH and LMWH. We describe here M118, a novel LMWH designed specifically for use in the treatment of ACS. M118 shows broad anticoagulant activity, including potent activity against both factor Xa (~240 IU/mg) and thrombin (factor IIa; ~170 IU/mg), low polydispersity, high (78%) subcutaneous bioavailability in rabbits, and predictable subcutaneous and intravenous pharmacokinetics. Additionally, the anticoagulant activity of M118 is monitorable by standard coagulation assays and is reversible with protamine. M118 demonstrates superior activity to conventional LMWH in a rabbit model of abdominal arterial thrombosis without increasing bleeding risk, and is currently being evaluated in a phase II clinical trial evaluating efficacy and safety in patients undergoing percutaneous coronary intervention.