Rationale: A prolonged, prodromal phase before definitive paediatric precursor B acute lymphoblastic leukaemia (BCP ALL) diagnosis is rarely observed.
Patients Concerns: In the first, the patient presented with an aplastic preleukemic phase, whilst the second presented with a rheumatic-like preliminary phase.
Diagnoses: The case reports of two patients with BCP ALL with a prodromal phase lasting a few weeks are presented.
Interventions And Outcomes: DNA whole genome profile methylation analysis of bone marrow cells obtained at diagnosis revealed a pattern of methylation that was readily distinguishable from both healthy and standard course BCP ALL bone marrow samples.
Lessons: The biological implication of this observation remains unclear, with many differentially methylated loci involved in many processes like neurogenesis, cell projection organization and adhesion along with leucocyte activation and apoptosis. The prevalence and clinical significance of these methylation changes is unknown but this data indicates that the epigenetic basis of BCP ALL with a prolonged, prodromal phase requires a more detailed assessment.
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http://dx.doi.org/10.1097/MD.0000000000012763 | DOI Listing |
Neuroimage
January 2025
Faculty of Health Sciences, University of Macau, Macau SAR 999078, China; Centre for Cognitive and Brain Sciences, University of Macau, Macau SAR 999078, China. Electronic address:
Individuals in the prodromal phase of Parkinson's disease (PD) exhibit significant heterogeneity and can be divided into distinct subtypes based on clinical symptoms, pathological mechanisms, and brain network patterns. However, little has been done regarding the valid subtyping of prodromal PD, which hinders the early diagnosis of PD. Therefore, we aimed to identify the subtypes of prodromal PD using the brain radiomics-based network and examine the unique patterns linked to the clinical presentations of each subtype.
View Article and Find Full Text PDFJAMA Neurol
December 2024
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Importance: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, rapidly progressive and fatal neurodegenerative disease. Definite sCJD diagnosis can only be made post mortem, and little is known about the prodromal phase of the disease.
Objective: To compare drug prescription patterns before the clinical onset of sCJD between patients and matched controls for exploration of potential risk factors and to assess correlations between drug exposure and sCJD survival.
Mol Psychiatry
January 2025
Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.
A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
Genomic sequencing has the potential to revolutionise newborn screening (NBS) programmes. In 2024, Genomics England began to recruit for the Generation Study (GS), which uses whole genome sequencing (WGS) to detect genetic changes in 500 genes in more than 200 rare conditions. Ultimately, its purpose is to facilitate the earlier identification of rare conditions and thereby improve health-related outcomes for individuals.
View Article and Find Full Text PDFInt J Toxicol
January 2025
Allucent, Cary, NC, USA.
Seizures are complex electrophysiological disturbances affecting one or more populations of brain neurons. Seizures following test article (TA) exposure pose significant challenges in drug development. This paper considers the diverse neurological manifestations, mechanisms, and functional and structural assessments needed to investigate TA-related seizure liabilities, with a particular focus on nonclinical species.
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