Patient-Reported Burden of Severe Alopecia Areata: First Results from the Multinational Alopecia Areata Unmet Need Survey

Purpose: Alopecia areata (AA) is an autoimmune disease characterized by hair loss that has significant psychosocial implications. This study aims to describe the patient -reported burden of severe AA, coping mechanism and information needs using data from the multinational AA Patient Satisfaction and Unmet Need Survey. Patients and Methods: Participants with current or previous >= 50% scalp hair loss (n = 747) were recruited from 11 countries and completed a web -based survey that assessed demographics, clinical characteristics, disease burden and psychosocial impact. Data were stratified according to sex, current age, disease duration and current severity of scalp hair loss. Results: The mean (SD) age of participants was 43.8 (7.1) years, 55.3% were women, and 63.5% reported AA symptoms within 6 months of diagnosis. Most participants had black or brown hair (88.4%), reported a disease duration of 2 years or more (75.6%) and had current scalp hair loss of >= 50% (87.4%). Severe hair loss also extended to eyebrow (46.9%), eyelash (48.7), beard (61.5%) and body hair (73.2%). Participants commonly reported comorbidities such as anxiety (26.1%), depression (18.1%) and sleep problems (28.1%). The Dermatology Life Quality Index revealed a severe impact on quality of life; 86.2% of participants scored >10. Mental health/mood was significantly affected; 55.8% of participants reported a substantial impact. Long-term effects included decreased selfesteem (32.9%), poor mental health (28.1%) and challenges in day-to-day activities (27.2%). Information needs were centered around treatment expectations, mental health, and available treatment options. More severe symptoms and a greater daily impact were reported by women and those with a longer disease duration. Conclusion: The study emphasizes the substantial burden, including impaired quality of life and psychological well-being, of severe AA on the lives of surveyed participants. The findings highlight the importance of comprehensive disease management strategies that address both physical and psychosocial aspects of AA. Plain language summary: Alopecia areata (AA) is a disease that results in hair loss and can greatly affect quality of life and well-being. The authors wanted to understand how this condition affects people's lives and what they need to cope with it. A survey was completed by adults from 11 different countries who had current or past severe AA. The participants were asked about their demographics, their experiences with the condition and how it impacted their daily lives. The results showed that AA has a severe impact on their quality of life, including their mental health and daily activities. Participants also experienced decreased self-esteem and faced challenges in their relationships and daily routines, and many reported feeling anxious, depressed, and having trouble sleeping. Participants found different ways to cope with their condition and expressed a need for realistic expectations about treatment results, information about mental health, and treatment options. The study also found that women and those with a longer duration of AA tended to have more severe symptoms and the impact on their lives was greater. Overall, this study shows that current or previous episodes of severe AA had a significant impact on people's lives, including their mental health and daily activities. It emphasizes the need for information about the condition and treatment options with realistic expectations. The findings help to better understand the experiences of people with AA and may aid the provision of appropriate support and information

A mutated factor X activatable by thrombin corrects bleedings in vivo in a rabbit model of antibody-induced hemophilia A

Rendering coagulation factor X sensitive to thrombin was proposed as a strategy that can bypass the need for factor VIII. In this paper, this non-replacement strategy was evaluated in vitro and in vivo in its ability to correct factor VIII but also factor IX, X and XI deficiencies. A novel modified factor X, named Actiten, was generated and produced in the HEK293F cell line. The molecule possesses the required post-translational modifications, partially keeps its ability to be activated by RVV-X, factor VIIa/tissue factor, factor VIIIa/factor IXa and acquires the ability to be activated by thrombin. The potency of the molecule was evaluated in respective deficient plasmas or hemophilia A plasmas, for some with inhibitors. Actiten corrects dose dependently all the assayed deficient plasmas. It is able to normalize the thrombin generation at 20 μg/mL showing however an increased lagtime. It was then assayed in a rabbit antibody-induced model of hemophilia A where, in contrast to recombinant factor X wild-type, it normalized the bleeding time and the loss of hemoglobin. No sign of thrombogenicity was observed and the generation of activated factor X was controlled by the anticoagulation pathway in all performed coagulation assays. This data indicates that Actiten may be considered as a possible non replacement factor to treat hemophilia's with the advantage of being a zymogen correcting bleedings only when needed

The Dual Targeting of FcRn and FcγRs via Monomeric Fc Fragments Results in Strong Inhibition of IgG-Dependent Autoimmune Pathologies

Novel molecules that directly target the neonatal Fc receptor (FcRn) and/or Fc gamma receptors (FcγRs) are emerging as promising treatments for immunoglobulin G (IgG)-dependent autoimmune pathologies. Mutated Fc regions and monoclonal antibodies that target FcRn are currently in clinical development and hold promise for reducing the levels of circulating IgG. Additionally, engineered structures containing multimeric Fc regions allow the dual targeting of FcRn and FcγRs; however, their tolerance needs to first be validated in phase I clinical studies. Here, for the first time, we have developed a modified monomeric recombinant Fc optimized for binding to all FcRns and FcγRs without the drawback of possible tolerance associated with FcγR cross-linking. A rational approach using Fc engineering allowed the selection of LFBD192, an Fc with a combination of six mutations that exhibits improved binding to human FcRn and FcγR as well as mouse FcRn and FcγRIV. The potency of LFBD192 was compared with that of intravenous immunoglobulin (IVIg), an FcRn blocker (Fc-MST-HN), and a trimeric Fc that blocks FcRn and/or immune complex-mediated cell activation through FcγR without triggering an immune reaction in several in vitro tests and validated in three mouse models of autoimmune disease

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

Frequency Domain Block Turbo-Equalization for Single-Carrier Transmission over MIMO Broadband Wireless Channel

International audienc

Turbo-Equalization for Single-Carrier Transmission over MIMO Broadband Wireless Channel: Performance vs. complexity trade-offs

International audienc

A comparison analysis of prefiltering methods in space-time trellis-based reduced-state turbo-detection

National audienceIn this paper, we investigate two different prefiltering strategies, i.e., multiple input multiple output (MIMO) channel shortening and MIMO whitened matched filtering, to decode iteratively a space time bit interleaved coded modulation transmitted over MIMO block fading intersymbol interference channels using a trellis-based post-detector. Indeed, resorting to such front-ends allows significant complexity gain when compared to the optimal maximum a posteriori-based turbo-receiver. While those two approaches have been exhaustively visited in the past, their fair comparison in terms of trade-off between complexity and performance has - to our knowledge - never been tackled before. This paper aims at giving some valuable insights about the respective benefits of these two prefiltering methods with respect to the channel characteristics and overall receiver complexity