Search

The history of hemophilia is well documented, yet reports focus heavily on the male perspective and severe forms of the disease. Although hemophilia was initially believed to only affect men with women seen as silent carriers, it is now universally acknowledged that women and girls can also be affected. In this narrative review, we tracked the progression of beliefs about women and hemophilia as documented in the literature from pre-1800s to the present time. We present a timeline of evolving beliefs and testing practices and identified 9 distinct time periods when key shifts occurred related to various scientific discoveries. Our review highlights how women affected by hemophilia experienced complete dismissal of their health issues despite evidence of bleeding symptoms as early as the 1900s. We identified 1990 as a major timepoint for shifting beliefs when large scale acknowledgment that hemophilia also affects women is documented and systematic testing for bleeding risk is first suggested. Women evolve from being seen as unaffected genetic transmitters only, to being recognized as a population affected by hemophilia in unique ways requiring timely testing and effective treatment. Yet, despite this clear progress, recent publications continue to document many persistent issues such as delayed diagnosis, untreated symptoms, and barriers to care. Ongoing research and advocacy efforts are required to improve knowledge translation until real-world outcomes are seen in screening, diagnosis, treatment, and prevention of bleeding., Competing Interests: Declaration of competing interests P.J. has received research funding from Bayer and consultancy with Star/Vega, Band/Guardian, Roche, and Biomarin. D.L. has received research funding from Biomarin, CSL-Behring, and Sanofi and acted in an advisory role for Biomarin, CSL-Behring, Novo Nordisk, Pfizer, and Takeda. M.S. has received research funding from Octapharma and Pfizer (to institution), and honoraria for speaking engagements from Pfizer, Octapharma, Takeda, Sobi, and Medison. All other authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: It is widely acknowledged that haemophilia affects women and girls, yet current testing recommendations for factor level and genetic testing vary and do not universally incorporate updated research. Canadian parents have expressed frustration at inconsistent recommendations and reported instances where delayed testing led to missed diagnosis and preventable bleeding., Aim: Study aim was to explore and describe the practice of haemophilia-related testing of young girls in Canada., Methods: A mixed methods study was carried out with two populations: (1) Nurses working in haemophilia care completed a survey regarding the current testing recommendations of their Haemophilia Treatment Centre (HTC), (2) Parents of obligate or potential haemophilia carriers completed a structured interview with questions about their family experience of haemophilia and testing decisions for daughters., Results: Twenty-six survey responses were received and showed wide variation in the usual recommendations of Canadian HTCs. Different factor level testing recommendations may be given to obligate and potential carriers despite no difference in bleeding risk. Only a minority of HTCs currently recommend an early baseline factor level (< 10 years) to obligate carriers (27%) or potential carriers (15%). For genetic testing of potential carriers, 70% of HTC would approve a family request for genetic testing of a minor with specific conditions. The majority of parents interviewed felt dissatisfied with their testing experience (58%) and highlighted many issues related to delayed testing recommendations., Conclusion: Updated, nationally affirmed testing recommendations are needed that align with research on bleeding in women and girls affected by haemophilia., (© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.)

MoS 2 nanoribbons have attracted increased interest due to their properties, which can be tailored by tuning their dimensions. Herein, the growth of MoS 2 nanoribbons and triangular crystals formed by the reaction between films of MoOx (22 nanoribbons arising from distinct contributions from the single-layer edges and multilayer core. Nanoscale imaging reveals a blue-shifted exciton emission of the monolayer edge compared to the isolated MoS 2 monolayers due to built-in local strain and disorder. We further report on an ultrasensitive photodetector made of a single MoS 2 nanoribbon with a responsivity of 8.72 × 10 2  A W -1 at 532 nm, among the highest reported up-to-date for single-nanoribbon photodetectors. These findings can inspire the design of MoS 2 semiconductors with tunable geometries for efficient optoelectronic devices., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

The renin-angiotensin system (RAS) is one of the main regulatory systems of cardiovascular homeostasis. It is mainly composed of angiotensin-converting enzyme (ACE) and angiotensin II receptors AT1 and AT2. ACE and AT1 are targets of choice for the treatment of hypertension, whereas the AT2 receptor is still not exploited due to the lack of knowledge of its physiological properties. Peptide toxins from venoms display multiple biological functions associated with varied chemical and structural properties. If Brazilian viper toxins have been described to inhibit ACE, no animal toxin is known to act on AT1/AT2 receptors. We screened a library of toxins on angiotensin II receptors with a radioligand competition binding assay. Functional characterization of the selected toxin was conducted by measuring second messenger production, G-protein activation and β-arrestin 2 recruitment using bioluminescence resonance energy transfer (BRET) based biosensors. We identified one original toxin, A-CTX-cMila, which is a 7-residues cyclic peptide from Conus miliaris with no homology sequence with known angiotensin peptides nor identified toxins, displaying a 100-fold selectivity for AT1 over AT2. This toxin shows a competitive antagonism mode of action on AT1, blocking Gαq, Gαi3, GαoA, β-arrestin 2 pathways and ERK 1/2 activation. These results describe the first animal toxin active on angiotensin II receptors.

This work demonstrates the enhancement in plasmonic sensing efficacy resulting from spatially-localized functionalization on nanostructured surfaces, whereby probe molecules are concentrated in areas of high field concentration. Comparison between SERS measurements on nanostructured surfaces (arrays of nanodisks 110 and 220 nm in diameter) with homogeneous and spatially-localized functionalization with thiophenol demonstrates that the Raman signal originates mainly from areas with high field concentration. TERS measurements with 10 nm spatial resolution confirm the field distribution profiles predicted by the numerical modeling. Though this enhancement in plasmonic sensing efficacy is demonstrated with SERS, results apply equally well to any type of optical/plasmonic sensing on functionalized surfaces with nanostructuring.

Background: Hemophilia carriers experience abnormal bleeding symptoms; however, a lack of awareness about this topic coupled with additional knowledge gaps and barriers leads to suboptimal care for this population., Objective: The primary objective was to describe the current knowledge gaps and challenges from the perspective of both hemophilia carriers and their health care providers., Methods: We carried out a mixed methods descriptive study with two population groups between September and December 2020. The hemophilia carrier perspective was obtained through both focus groups and questionnaires, whereas the health care providers perspective obtained via questionnaire sent to the Association of Hemophilia Care Directors of Canada and the Canadian Association of Nurses in Hemophilia Care. Focus groups were analyzed using descriptive thematic analysis and quantitative survey data was also analyzed., Results: Eleven hemophilia carriers participated along with 19 health care providers (11 physicians, eight nurses). Hemophilia carrier focus group discussions identified four areas representing major challenges or knowledge gaps: (1) negative psychosocial impacts; (2) difficulty determining symptom significance; (3) need for self-advocacy; (4) testing concerns. Survey results from both groups were aligned with the most important topics for ongoing education identified as information on abnormal bleeding symptoms, where to seek treatment, and considerations for heavy menstrual bleeding/menstruation. The majority of both study groups believe obligate or potential carriers should have factor levels checked regardless of age if symptoms of abnormal bleeding occur or before an invasive procedure. However, hemophilia carriers were significantly more in favor of genetic testing under the age of consent than health care providers in all scenarios evaluated., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)