Wendy A Gold, Alan K Percy, Jeffrey L Neul, Stuart R Cobb, Lucas Pozzo-Miller, Jasmeen K Issar, Bruria Ben-Zeev, Aglaia Vignoli, Walter E Kaufmann
{"title":"Rett syndrome.","authors":"Wendy A Gold, Alan K Percy, Jeffrey L Neul, Stuart R Cobb, Lucas Pozzo-Miller, Jasmeen K Issar, Bruria Ben-Zeev, Aglaia Vignoli, Walter E Kaufmann","doi":"10.1038/s41572-024-00568-0","DOIUrl":"https://doi.org/10.1038/s41572-024-00568-0","url":null,"abstract":"<p><p>Rett syndrome (RTT) is a severe, progressive, neurodevelopmental disorder, which affects predominantly females. In most cases, RTT is associated with pathogenic variants in MECP2. MeCP2, the protein product of MECP2, is known to regulate gene expression and is highly expressed in the brain. RTT is characterized by developmental regression of spoken language and hand use that, with hand stereotypies and impaired ambulation, constitute the four core diagnostic features. Affected individuals may present multiple other neurological impairments and comorbidities, such as seizures, breathing irregularities, anxiety and constipation. Studies employing neuroimaging, neuropathology, neurochemistry and animal models show reductions in brain size and global decreases in neuronal size, as well as alterations in multiple neurotransmitter systems. Management of RTT is mainly focused on preventing the progression of symptoms, currently improved by guidelines based on natural history studies. Animal and cellular models of MeCP2 deficiency have helped in understanding the pathophysiology of RTT and guided the development of trofinetide, an IGF1-related compound, which is an approved drug for RTT, as well as of other drugs and gene therapies currently under investigation.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":"10 1","pages":"84"},"PeriodicalIF":76.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marc Michel, Etienne Crickx, Bruno Fattizzo, Wilma Barcellini
{"title":"Autoimmune haemolytic anaemias.","authors":"Marc Michel, Etienne Crickx, Bruno Fattizzo, Wilma Barcellini","doi":"10.1038/s41572-024-00566-2","DOIUrl":"10.1038/s41572-024-00566-2","url":null,"abstract":"<p><p>Adult autoimmune haemolytic anaemias (AIHAs) include different subtypes of a rare autoimmune disease in which autoantibodies targeting autoantigens expressed on the membrane of autologous red blood cells (RBCs) are produced, leading to their accelerated destruction. In the presence of haemolytic anaemia, the direct antiglobulin test is the cornerstone of AIHA diagnosis. AIHAs are classified according to the isotype and the thermal optimum of the autoantibody into warm (wAIHAs), cold and mixed AIHAs. wAIHAs, the most frequent type of AIHAs, are associated with underlying conditions in ~50% of cases. In wAIHA, IgG autoantibody reacts with autologous RBCs at 37 °C, leading to antibody-dependent cell-mediated cytotoxicity and increased phagocytosis of RBCs in the spleen. Cold AIHAs include cold agglutinin disease (CAD) and cold agglutinin syndrome (CAS) when there is an underlying condition. CAD and cold agglutinin syndrome are IgM cold antibody-driven AIHAs characterized by classical complement pathway-mediated haemolysis. The management of wAIHAs has long been based around corticosteroids and splenectomy and on symptomatic measures and non-specific cytotoxic agents for CAD. Rituximab and the development of complement inhibitors, such as the anti-C1s antibody sutimlimab, have changed the therapeutic landscape of AIHAs, and new promising targeted therapies are under investigation.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":"10 1","pages":"82"},"PeriodicalIF":76.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rohan Bir Singh, Shizuka Koh, Namrata Sharma, Fasika A Woreta, Farhad Hafezi, Harminder S Dua, Vishal Jhanji
{"title":"Keratoconus.","authors":"Rohan Bir Singh, Shizuka Koh, Namrata Sharma, Fasika A Woreta, Farhad Hafezi, Harminder S Dua, Vishal Jhanji","doi":"10.1038/s41572-024-00565-3","DOIUrl":"https://doi.org/10.1038/s41572-024-00565-3","url":null,"abstract":"<p><p>Keratoconus is a progressive eye disorder primarily affecting individuals in adolescence and early adulthood. The ectatic changes in the cornea cause thinning and cone-like steepening leading to irregular astigmatism and reduced vision. Keratoconus is a complex disorder with a multifaceted aetiology and pathogenesis, including genetic, environmental, biomechanical and cellular factors. Environmental factors, such as eye rubbing, UV light exposure and contact lens wearing, are associated with disease progression. On the cellular level, a complex interplay of hormonal changes, alterations in enzymatic activity that modify extracellular membrane stiffness, and changes in biochemical and biomechanical signalling pathways disrupt collagen cross-linking within the stroma, contributing to structural integrity loss and distortion of normal corneal anatomy. Clinically, keratoconus is diagnosed through clinical examination and corneal imaging. Advanced imaging platforms have improved the detection of keratoconus, facilitating early diagnosis and monitoring of disease progression. Treatment strategies for keratoconus are tailored to disease severity and progression. In early stages, vision correction with glasses or soft contact lenses may suffice. As the condition advances, rigid gas-permeable contact lenses or scleral lenses are prescribed. Corneal cross-linking has emerged as a pivotal treatment aimed at halting the progression of corneal ectasia. In patients with keratoconus with scarring or contact lens intolerance, surgical interventions are performed.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":"10 1","pages":"81"},"PeriodicalIF":76.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ian J Neeland, Soo Lim, André Tchernof, Amalia Gastaldelli, Janani Rangaswami, Chiadi E Ndumele, Tiffany M Powell-Wiley, Jean-Pierre Després
{"title":"Metabolic syndrome.","authors":"Ian J Neeland, Soo Lim, André Tchernof, Amalia Gastaldelli, Janani Rangaswami, Chiadi E Ndumele, Tiffany M Powell-Wiley, Jean-Pierre Després","doi":"10.1038/s41572-024-00563-5","DOIUrl":"https://doi.org/10.1038/s41572-024-00563-5","url":null,"abstract":"<p><p>The metabolic syndrome (MetS) is a multiplex modifiable risk factor for cardiovascular disease, type 2 diabetes mellitus and other health outcomes, and is a major challenge to clinical practice and public health. The rising global prevalence of MetS, driven by urbanization, sedentary lifestyles and dietary changes, underlines the urgency of addressing this syndrome. We explore the complex underlying mechanisms, including genetic predisposition, insulin resistance, accumulation of dysfunctional adipose tissue and ectopic lipids in abdominal obesity, systemic inflammation and dyslipidaemia, and how they contribute to the clinical manifestations of MetS. Diagnostic approaches vary but commonly focus on abdominal obesity (assessed using waist circumference), hyperglycaemia, dyslipidaemia and hypertension, highlighting the need for population-specific and phenotype-specific diagnostic strategies. Management of MetS prioritizes lifestyle modifications, such as healthy dietary patterns, physical activity and management of excess visceral and ectopic adiposity, as foundational interventions. We also discuss emerging therapies, including new pharmacological treatments and surgical options, providing a forward-looking perspective on MetS research and care. This Primer aims to inform clinicians, researchers and policymakers about MetS complexities, advocating for a cohesive, patient-centred management and prevention strategy. Emphasizing the multifactorial nature of MetS, this Primer calls for integrated public health efforts, personalized care and innovative research to address this escalating health issue.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":"10 1","pages":"77"},"PeriodicalIF":76.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan J Stein, Daniel L C Costa, Christine Lochner, Euripedes C Miguel, Y C Janardhan Reddy, Roseli G Shavitt, Odile A van den Heuvel, H Blair Simpson
{"title":"Author Correction: Obsessive-compulsive disorder.","authors":"Dan J Stein, Daniel L C Costa, Christine Lochner, Euripedes C Miguel, Y C Janardhan Reddy, Roseli G Shavitt, Odile A van den Heuvel, H Blair Simpson","doi":"10.1038/s41572-024-00569-z","DOIUrl":"https://doi.org/10.1038/s41572-024-00569-z","url":null,"abstract":"","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":"10 1","pages":"79"},"PeriodicalIF":76.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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