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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood‐onset SLE (cSLE) versus adult‐onset SLE, negatively impacting school function, self‐management, and psychosocial health, as well as lifelong health‐related quality of life. In this review, we describe pathogenic mechanisms active in cSLE, such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in patients with cSLE, and the role of alterations in protective central nervous system (CNS) barriers (ie, the blood–brain barrier) are also discussed. Recent findings derived from novel neuroimaging approaches are highlighted because the methods employed in these studies hold potential for identifying CNS abnormalities that would otherwise remain undetected with conventional multiple resonance imaging studies (eg, T2‐weighted or fluid‐attenuated inversion recovery sequences). Furthermore, we propose that a more robust presentation of neuropsychiatric symptoms in cSLE is in part due to the harmful impact of a chronic inflammatory insult on a developing CNS. Although the immature status of the CNS may leave patients with cSLE more vulnerable to harboring neuropsychiatric manifestations, the same property may represent a greater urgency to reverse the maladaptive effects associated with a proneuroinflammatory state, provided that effective diagnostic tools and treatment strategies are available. Finally, considering the crosstalk among the CNS and other organ systems affected in cSLE, we postulate that a finer understanding of this interconnectivity and its role in the clinical presentation in cSLE is warranted. [ABSTRACT FROM AUTHOR]

Context: Pain is a poorly managed aspect in fibrous dysplasia/McCune-Albright syndrome (FD/MAS) because of uncertainties regarding the clinical, behavioral, and neurobiological underpinnings that contribute to pain in these patients. Objective: Identify neuropsychological and neurobiological factors associated with pain severity in FD/MAS. Design: Prospective, single-site study. Patients: Twenty patients with FD/MAS and 16 age-sex matched healthy controls. Intervention: Assessments of pain severity, neuropathic pain, pain catastrophizing (pain rumination, magnification, and helplessness), emotional health, and pain sensitivity with thermal quantitative sensory testing. Central nervous system (CNS) properties were measured with diffusion tensor imaging, structural magnetic resonance imaging, and functional magnetic resonance imaging. Main outcome measures: Questionnaire responses, detection thresholds and tolerances to thermal stimuli, and structural and functional CNS properties. Results: Pain severity in patients with FD/MAS was associated with more neuropathic pain quality, higher levels of pain catastrophizing, and depression. Quantitative sensory testing revealed normal detection of nonnoxious stimuli in patients. Individuals with FD/MAS had higher pain tolerances relative to healthy controls. From neuroimaging studies, greater pain severity, neuropathic pain quality, and psychological status of the patient were associated with reduced structural integrity of white matter pathways (superior thalamic radiation and uncinate fasciculus), reduced gray matter thickness (pre-/paracentral gyri), and heightened responses to pain (precentral, temporal, and frontal gyri). Thus, properties of CNS circuits involved in processing sensorimotor and emotional aspects of pain were altered in FD/MAS. Conclusion: These results offer insights into pain mechanisms in FD/MAS, while providing a basis for implementation of comprehensive pain management treatment approaches that addresses neuropsychological aspects of pain. [ABSTRACT FROM AUTHOR]

Maintenance of hepatocyte homeostasis plays an important role in mediating the pathogenesis of many diseases. A growing body of literature has established a critical role played by tumor necrosis factor-α (TNFα) in maintaining hepatocyte homeostasis; however, the transcriptional mechanisms underlying constitutive Tnf expression are unknown. Whole liver fractions and primary hepatocytes from adult control C57BL/6 mice and the murine hepatocyte cell line AML12 were assessed for constitutive Tnf expression. Impacts of glycogen synthase kinase-3 β (GSK3β) and nuclear factor κB (NF-κB) inhibition on constitutive Tnf expression were assessed in AML12 cells. Finally, AML12 cell proliferation following GSK3β and NF-κB inhibition was evaluated. Constitutive Tnf gene expression is present in whole liver, primary hepatocytes, and cultured AML12 hepatocytes. Cytokine-induced Tnf gene expression is regulated by NF-κB activation. Pharmacological inhibition of GSK3β resulted in a time- and dose-dependent inhibition of Tnf gene expression. GSK3β inhibition decreased nuclear levels of the NF-κB subunits p65 and p50. We determined that NF-κB transcription factor subunit p65 binds to consensus sequence elements present in the murine TNFα promoter and inhibition of GSK3β decreases binding and subsequent Tnf expression. Finally, AML12 cell growth was significantly reduced following GSK3β and NF-κB inhibition. These results demonstrate that GSK3β and NF-κB are essential for mediating Tnf expression and constitutive hepatocyte cell growth. These findings add to a growing body of literature on TNFα mediated hepatocyte homeostasis and identify novel molecular mechanisms involved in mediating response to various disease states in the liver. NEW & NOTEWORTHY Maintenance of hepatocyte homeostasis plays an important role in controlling the pathogenesis of many diseases. Our findings add to a growing body of literature on tumor necrosis factor-α (TNFα)-mediated hepatocyte homeostasis and identify novel molecular mechanisms involved in regulating this response.

Imaging modalities such as computed tomography (CT) are critical for monitoring musculoskeletal abnormalities in children with rare diseases. However, CT exposes patients to radiation, which limits its utility in the clinical setting, particularly during longitudinal evaluation. Synthetic CT is a novel, noncontrast, and rapid MRI method that can provide CT-like images without any radiation exposure and is easily performed in conjunction with traditional MRI, which detects soft-tissue and bone marrow abnormalities. To date, an evaluation of synthetic CT in pediatric patients with rare musculoskeletal diseases has been lacking. In this case series, the capability of synthetic CT to identify musculoskeletal lesions accurately in 2 rare disease patients is revealed. In Case 1, synthetic CT, in agreement with routine CT, identified an intraosseous lesion in the right femoral neck in a 16-year-old female with fibrous dysplasia, whereas standard-of-care MRIs additionally revealed mild surrounding edema-like bone marrow signal. For Case 2, synthetic CT applied to a 12-year-old female with fibrodysplasia ossificans progressiva revealed heterotopic ossification present along the cervical spine that had caused the fusion of multiple vertebrae. Our evaluation of synthetic CT offers important insights into the feasibility and utility of this methodology in children with rare diseases affecting the musculoskeletal system., (Copyright © 2023 by the American Academy of Pediatrics.)