Rejected

Epilepsy is common in patients with brain tumors and frequently presents as the first clinical manifestation of an underlying tumor. Despite a number of available antiepileptic drugs (AED), brain tumor related epilepsy (BTRE) may still be difficult to control. Recently, the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor antagonist perampanel (PER) is increasingly acknowledged as an attractive novel add-on AED for seizure control in BTRE. We present a single institutional experience reporting five individual cases with refractory BTRE treated with PER. In two of these five brain tumor patients, worsening of seizure control was caused by SMART-syndrome (stroke-like migraine attacks after radiation therapy). Efficacy of PER was assessed by the responder rate and by evaluating overall changes in seizure frequency before and during PER treatment. In our case series, a reduction in seizure frequency was observed in four out of five patients and the responder rate was 40%. In addition, both cases with symptomatic epilepsy associated with SMART-syndrome were successfully treated with PER. This case series supports the growing evidence that PER may become a promising add-on AED for the treatment of refractory BTRE as well as for seizure control in SMART-syndrome.

The FK506-binding protein 51 (FKBP51) emerged as a key player in several diseases like stress-related disorders, chronic pain, and obesity. Linear analogues of FK506 called SAFit were shown to be highly selective for FKBP51 over its closest homologue FKBP52, allowing the proof-of-concept studies in animal models. Here, we designed and synthesized the first macrocyclic FKBP51-selective ligands to stabilize the active conformation. All macrocycles retained full FKBP51 affinity and selectivity over FKBP52 and the incorporation of polar functionalities further enhanced affinity. Six high-resolution crystal structures of macrocyclic inhibitors in complex with FKBP51 confirmed the desired selectivity-enabling binding mode. Our results show that macrocyclization is a viable strategy to target the shallow FKBP51 binding site selectively.

The relationship between atopic dermatitis (AD) severity, sleep disturbance (SD), and health-related outcomes is not fully elucidated.

Studies on structural validity of the Quebec Back Pain Disability Scale (QBPDS) showed uncertain unidimensionality.

The aim of the present study was to detect the prevalence of temporomandibular disorders (TMD) in patients with untreated obstructive sleep apnea (OSA) and to compare the results with healthy controls, matched for sex and age.

Decision-making around tracheostomy placement and chronic respiratory support in children is complicated. Families often seek support and advice from outside the medical care team, including from social media. We undertook this study to characterize the content and nature of online resources created and managed primarily by caregivers of children living with tracheostomy and chronic mechanical ventilation.

Patients with rheumatoid arthritis (RA) or other rheumatic diseases say that pain and stiffness are symptoms affecting their quality of life. Ketoprofen and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and manage mild-to-moderate pain. The aim of this new systematic review of the literature and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical efficacy of ketoprofen and ibuprofen in patients with RA.

Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some CCHD patients are unoperated due to various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in CCHD patients and its association with age. The role of HIF-1α in this process was investigated and potential therapeutic targets were explored. CCHD patients ( = 25) were evaluated for cardiac metabolism and function using positron-emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated using genetically modified animals and isotope-labeled metabolomic-pathway tracing studies. Prepubertal CCHD patients had glucose-dominant cardiac metabolism and normal cardiac function. By comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left-ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In CCHD patients and animals exposed to CH, myocardial HIF-1α was upregulated prior to puberty, but was significantly downregulated during puberty. In cardiomyocyte-specific -knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance (IR) during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial IR, restored glucose metabolism, and improved cardiac function in pubertal CH animals. In CCHD patients, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal IR could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in CCHD patients.

Opioid overdose and abuse have reached epidemic rates in the United States. Medical prescriptions are a large source of opioid misuse. Our quality improvement initiative aimed to reduce opioid exposure from the pediatric emergency department (ED). Objective was to reduce opioid doses prescribed weekly from our ED by 50% within 4 months.

Describe the disease course in a cohort of outpatients with COVID-19 and evaluate factors predicting duration of symptoms.