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The authors present a 24-year-old male with a history of class III occlusal deformity who underwent a maxillary advancement with LeFort I osteotomies. Eighteen months after surgery, he was diagnosed with bothersome Eustachian tube dysfunction (ETD). Anatomical shifts secondary to the LeFort osteotomies required for maxillary advancement result in vector changes of muscles that regulate the function of the Eustachian tube. This realignment of muscles is suspected to be a major contributing factor in causing this patient's new onset Eustachian tube dysfunction. This article represents a pilot project as data are collected for a retrospective and, ultimately, prospective studies on this topic., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death. The corticosteroids prednisone/prednisolone and deflazacort are used to treat DMD as the standard of care; however, only deflazacort is FDA approved for DMD. The novel atypical corticosteroid vamorolone is being investigated for treatment of DMD. We compared the pharmaceutical properties as well as the efficacy and safety of the three corticosteroids across multiple doses in the B10-mdx DMD mouse model. Pharmacokinetic studies in the mouse and evaluation of p-glycoprotein (P-gP) efflux in a cellular system demonstrated that vamorolone is not a strong P-gp substrate resulting in measurable central nervous system (CNS) exposure in the mouse. In contrast, deflazacort and prednisolone are strong P-gp substrates. All three corticosteroids showed efficacy, but also side effects at efficacious doses. After dosing mdx mice for two weeks, all three corticosteroids induced changes in gene expression in the liver and the muscle, but prednisolone and vamorolone induced more changes in the brain than did deflazacort. Both prednisolone and vamorolone induced depression-like behavior. All three corticosteroids reduced endogenous corticosterone levels, increased glucose levels, and reduced osteocalcin levels. Using micro-computed tomography, femur bone density was decreased, reaching significance with prednisolone. The results of these studies indicate that efficacious doses of vamorolone, are associated with similar side effects as seen with other corticosteroids. Further, because vamorolone is not a strong P-gp substrate, vamorolone distributes into the CNS increasing the potential CNS side-effects., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Dysfunction of dopaminergic pathways has been considered to play a pivotal role in Parkinson's disease (PD), affecting the processing of emotional and rewarding information, and potentially leading to symptoms of depression or apathy. However, some aspects of motivation in PD might be affected by non-dopaminergic mechanisms., Aim and Method: The objective of this experimental medicine study was to investigate the contribution of serotonergic modulation via administration of citalopram (20 mg) for 7 days on motivated decision-making in twenty PD patients, measured using several different computerised tasks and clinical questionnaires that probe different aspects of decision-making. Twenty healthy controls were additionally tested without medication to assess any baseline differences between the two groups., Results: Results indicated that PD patients were overall less motivated than controls on an effort- and reward-based decision-making task. Citalopram increased or decreased willingness to exert effort for reward, depending on whether baseline motivation was high or low, respectively. A task assessing decision-making under risk revealed higher levels of risk aversion for potential losses in PD patients, which neither serotonin nor the patient's regular dopaminergic medication seemed to restore. However, citalopram in PD was associated with more risk-seeking choices for gains, although patients and controls did not differ on this at baseline., Conclusion: The results provide evidence for a role of the serotonergic system in influencing some aspects of motivated decision-making in PD processes.

To determine the error rate of transcription in human cells, we analyzed the transcriptome of H1 human embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing of the transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species in human cells. Our results indicate that different RNA species display different error rates, suggesting that human cells prioritize the fidelity of some RNAs over others. Cross-referencing the errors that we detected with various genetic and epigenetic features of the human genome revealed that the in vivo error rate in human cells changes along the length of a transcript and is further modified by genetic context, repetitive elements, epigenetic markers, and the speed of transcription. Our experiments further suggest that BRCA1, a DNA repair protein implicated in breast cancer, has a previously unknown role in the suppression of transcription errors. Finally, we analyzed the distribution of transcription errors in multiple tissues of a new mouse model and found that they occur preferentially in neurons, compared to other cell types. These observations lend additional weight to the idea that transcription errors play a key role in the progression of various neurological disorders, including Alzheimer's disease.

The disposition of at-risk students who fail to meet nursing program progression standards is a challenging predicament for both students and faculty. There is little evidence to inform progression decisions regarding remediation and/or probation. More needs to be known about the phenomenon of at-risk students, and the interventions that can transform these individuals into successful graduates and nurses. The purpose of this descriptive study was to investigate factors related to academic success for at-risk senior nursing students. Sixteen at-risk senior students, enrolled in a nursing course called Academic Improvement Strategies, participated in the study which included faculty mentoring, journaling, tutorials, and various self-directed student activities. The mean semester grade point average significantly improved by the end of the semester, increasing from 2.48 to 2.92 (Z = -4.26, p <.0001). Upon graduation, 87% of the participants successfully passed the NCLEX-RN examination. The study findings suggest that faculty mentoring can facilitate behavioral changes that may contribute to academic success for at-risk nursing students.