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"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]

Purpose: To evaluate the effects of metreleptin in patients with partial lipodystrophy (PL). Methods: Patients aged ≥ 6 months with PL, circulating leptin < 12.0 ng/mL, and diabetes mellitus, insulin resistance, or hypertriglyceridemia received metreleptin doses (once or twice daily) titrated to a mean of 0.124 mg/kg/day. Changes from baseline to month 12 in glycated hemoglobin (HbA1c) and fasting serum triglycerides (TGs; co-primary endpoints), fasting plasma glucose (FPG), and liver volume were evaluated. Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at month 12, long-term treatment effects, and treatment-emergent adverse events (TEAEs). Results: Significant (p < 0.05) reductions in HbA1c (−0.6%), fasting TGs (−20.8%), FPG (−1.2 mmol/L), and liver volume (−13.4%) were observed in the overall PL population at month 12. In a subgroup of patients with baseline HbA1c ≥ 6.5% or TGs ≥ 5.65 mmol/L, significant (p < 0.05) reductions were seen in HbA1c (−0.9%), fasting TGs (−37.4%), FPG (−1.9 mmol/L), and liver volume (−12.4%). In this subgroup, 67.9% of patients had a ≥ 1% decrease in HbA1c or ≥ 30% decrease in fasting TGs, and 42.9% had a ≥ 2% decrease in HbA1c or ≥ 40% decrease in fasting TGs. Long-term treatment in this subgroup led to significant (p < 0.05) reductions at months 12, 24, and 36 in HbA1c, fasting TGs, and FPG. Metreleptin was well tolerated with no unexpected safety signals. The most common TEAEs were abdominal pain, hypoglycemia, and nausea. Conclusions: In patients with PL, treatment with metreleptin was well tolerated and resulted in improvements in glycemic control, hypertriglyceridemia, and liver volume. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to summarize the effectiveness and safety of metreleptin in patients with congenital or acquired generalized lipodystrophy.Methods: Patients (n = 66) aged ≥6 months had lipodystrophy, low circulating leptin, and ≥1 metabolic abnormality (diabetes mellitus, insulin resistance, or hypertriglyceridemia). Metreleptin dose (once or twice daily) was titrated to a mean dose of 0.10 mg/kg/day with a maximum of 0.24 mg/kg/day. Means and changes from baseline to month 12 were assessed for glycated hemoglobin (HbA1c), fasting triglycerides (TGs), and fasting plasma glucose (FPG). Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at months 4, 12, and 36, medication changes, and estimates of liver size. Treatment-emergent adverse events (TEAEs) were recorded.Results: Significant mean reductions from baseline were seen at month 12 for HbA1c (-2.2%, n = 59) and FPG (-3.0 mmol/L, n = 59) and mean percent change in fasting TGs (-32.1%, n = 57) (all p ≤ 0.001). Reductions from baseline over time in these parameters were also significant at month 36 (all p < 0.001, n = 14). At month 4, 34.8% of patients had a ≥1% reduction in HbA1c and 62.5% had a ≥30% reduction in fasting TGs; at month 12, 80% of patients had a ≥1% decrease in HbA1c or ≥30% decrease in TGs, and 66% had a decrease of ≥2% in HbA1c or ≥40% decrease in TGs. Of those on medications, 41%, 22%, and 24% discontinued insulin, oral antidiabetic medications, or lipid-lowering medications, respectively. Mean decrease in liver volume at month 12 was 33.8% (p < 0.001, n = 12). Most TEAEs were of mild/moderate severity.Conclusions: In patients with generalized lipodystrophy, long-term treatment with metreleptin was well tolerated and resulted in sustained improvements in hypertriglyceridemia, glycemic control, and liver volume. [ABSTRACT FROM AUTHOR]

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]

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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]

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. Microfluidics: 3-D microfluidic gradient generator for antimicrobial susceptibility testing Microfluidic concentration gradient generators (μ-CGGs) have been used to identify optimal drug compositions through antimicrobial susceptibility testing (AST) to treat antimicrobial-resistant infections, and a new method has been developed to overcome previous 2-D limitations. Conventional μ-CGGs fabricated through photolithography-based micromachining processes are limited to 2-D fluidic routing, which allows only two distinct antimicrobial drugs to be tested simultaneously. However, a team headed by Eric Sweet at the University of California, Berkeley, United States employed 3-D-printed microchannel networks that are capable of 3-D fluidic routing to generate symmetrical multi-drug concentration gradients. The authors were able to confirm their 3-D μ-CGG prototype by means of both theoretical simulations and experimental validations. The team believes that its 3-D μ-CGG platform offers considerable potential for conducting multi-drug AST evaluations for a variety of biomedical and diagnostic applications. [ABSTRACT FROM AUTHOR]

Editorial. Discusses the need for a national arthroplasty register in Great Britain. Aim of effecting unbiased scientific evaluation of the outcome of any total joint replacement; Alternatives to a register; Potential difficulties of a national register; Role of hospital trusts in selecting implants.