Facioscapulohumeral muscular dystrophy (FSHD) represents the third most common form of muscular dystrophy and is characterized by muscle weakness and atrophy. FSHD is caused by the altered expression of the transcription factor double homeobox 4 (DUX4), which is involved in several significantly altered pathways required for myogenesis and muscle regeneration. While DUX4 is normally silenced in the majority of somatic tissues in healthy individuals, its epigenetic de-repression has been linked to FSHD, resulting in DUX4 aberrant expression and cytotoxicity in skeletal muscle cells. Understanding how DUX4 is regulated and functions could provide useful information not only to further understand FSHD pathogenesis, but also to develop therapeutic approaches for this disorder. Therefore, this review discusses the role of DUX4 in FSHD by examining the possible molecular mechanisms underlying the disease as well as novel pharmacological strategies targeting DUX4 aberrant expression.
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder characterized by selective loss of lower and upper motor neurons (MNs) in the brain and spinal cord, resulting in paralysis and eventually death due to respiratory insufficiency. Although the fundamental physiological mechanisms underlying ALS are not completely understood, the key neuropathological hallmarks of ALS pathology are the aggregation and accumulation of ubiquitinated protein inclusions within the cytoplasm of degenerating MNs. Herein, we discuss recent insights into the molecular mechanisms that lead to the accumulation of protein aggregates in ALS. This will contribute to a better understanding of the pathophysiology of the disease and may open novel avenues for the development of therapeutic strategies.
Emergency department (ED) care for psychiatric patients is currently understudied despite being highly utilized. Therefore, we aimed to analyze psychiatric patients' length of stay (LOS) and LOS-related factors at the ED and to investigate and quantify the likelihood of being hospitalized after an emergency psychiatric evaluation. Charts of 408 individuals who sought help at the ED were retrospectively assessed to identify patients' sociodemographic and clinical data upon ED admission and discharge. All interventions performed at the ED (e.g., medications, hospitalization, clinical advice at discharge) were collected as well. The LOS for psychiatric patients was relatively short (6.5 h), and substance/alcohol intoxication was the main factor impacting LOS. Upon ED arrival, hospitalized patients were mostly men, most often had a yellow/severe triage code, and most often had a positive history of psychiatric illness, psychotic symptoms, euphoric mood, or suicidal ideation. Manic symptoms and suicidal ideation were the conditions most frequently leading to hospitalization. Given the paucity of real-world data on psychiatric patients’ LOS and outcomes in the ED context, our findings show that psychiatric patients are evaluated in a reasonable amount of time. Their hospitalization is mostly influenced by clinical conditions rather than predisposing (e.g., age) or system-related factors (e.g., mode of arrival).
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