The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how different neuron types respond to this kind of injury. In this study, we follow neuronal populations over several months after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI. We show that neurons that activate ATF3 upregulate stress-related genes while repressing many genes, including commonly used markers for these cell types. Using an inducible reporter linked to ATF3, we genetically mark damaged cells to track them over time. Notably, we find that a population in layer V undergoes cell death acutely after injury, while another in layer II/III survives long term and retains the ability to fire action potentials. To investigate the mechanism controlling layer V neuron death, we genetically silenced candidate stress response pathways. We found that the axon injury responsive kinase MAP3K12, also known as dual leucine zipper kinase (DLK), is required for the layer V neuron death. This work provides a rationale for targeting the DLK signaling pathway as a therapeutic intervention for traumatic brain injury. Beyond this, our novel approach to track neurons after a mild, subclinical injury can inform our understanding of neuronal susceptibility to repeated impacts.

Dissociating Fibroepithelioma of Pinkus From Internal Malignancy: A Single-Center Retrospective Study.

Fibroepithelioma of Pinkus (FeP) is a rare skin tumor with a clinical presentation similar to benign neoplasms such as acrochordons and seborrheic keratoses. Our study analyzed if there is an association between FeP and internal tumors, specifically gastrointestinal tract tumors. We retrospectively reviewed the medical records of patients with FeP for other tumors throughout their lives until 2020. Although the quality of documentation for each patient may have differed, this study suggests that the presence of FeP does not indicate the presence of gastrointestinal tract tumors, and there is no need for altered cancer screening recommendations for those with FeP.

Clarification of Eosinophilic Esophagitis Treatment in the DoD Retention Standards.

The DoD Instruction 6130.03, Volume 2, outlines the retention standards for the U.S. Military, providing guidance on medical conditions and treatments that are disqualifying for all branches of the military. This document states that patients with conditions requiring immunomodulating or immunosuppressant medications do not meet retention standards. Eosinophilic esophagitis is a common, chronic inflammatory disease of the esophagus that typically presents with dysphagia. Although proton pump inhibitors are effective at treating this disease in some cases, swallowed topical steroids are the most frequently used therapy within the DoD. These medications act locally in the esophagus and do not cause systemic side effects typical of oral steroid therapy, including immunosuppression. They are effective at inducing and maintaining disease remission and are generally well tolerated, with minimal side effects. We propose a brief amendment to this document to clarify the language used and avoid inappropriate Medical Evaluation Board referrals.

A 24-Year-Old Man With Hemoptysis Found to Have a Chest Mass and Contralateral Axillary Lymphadenopathy.

CASE PRESENTATION: A 24-year-old man, never smoker, with no medical or surgical history, not currently on medications, presented to the ED with a second episode of gross hemoptysis, 4 months after an initial episode that had not previously been evaluated. He described the current episode of hemoptysis as "enough to fill the sink"; however, he did not further quantify. He has no history of recurrent epistaxis, hematemesis, or other evidence of clotting disorder. He denied any fevers, chills, night sweats, or recent travel. He denied any sick contacts and has no history of TB exposure or risk factors. The patient denied any shortness of breath, wheezing, or chest pain. He had no lower extremity pain or swelling. He routinely exercises and generally lives a healthy lifestyle. He is a health care worker who has not routinely worked with patients infected with SARS-CoV-2, although he received his second (of two) COVID-19 vaccines 4 days before presentation.

Frontolimbic brain volume abnormalities in bipolar disorder with suicide attempts.

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. We studied the gray matter volume (GMV) of 81 participants with a bipolar-I diagnosis (age-range: 14-34 years old) and 40 healthy participants (age-range 14.7-32 years old) to compare their neuroanatomy and histories of suicide attempt. In the bipolar group, 42 were manic with ages ranging from 14-30.6 years, and 39 were depressed with ages ranging from 14-34.3 years). Twenty three bipolar participants had a suicide attempt history, and 58 had no suicide attempt history. All participants completed behavioral/diagnostic assessments and MRI. We focused on a predefined frontolimbic circuitry in bipolar disorder versus controls to first identify diagnostic GMV correlates and to specifically identify GMV correlates for suicide attempt history. We found reduced GMV in bipolar diagnosis versus controls in the subgenual cingulate and dorsolateral prefrontal cortices. Our observed regional GMV reductions were associated with histories of suicide attempts and measures of individual variations in current suicidal ideation at the time of scanning.