Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing (RNA-Seq) in 33 ME/CFS patients (20 female, 13 male) and 34 matched healthy controls (20 female and 14 male) before, during, and after an exercise challenge intended to provoke PEM. Our findings revealed that pathways related to immune-cell signaling (including IL-12) and natural killer cell cytotoxicity were activated as a result of exertion in the male ME/CFS cohort, while female ME/CFS patients did not show significant enough changes in gene expression to meet the criteria for the differential expression. Functional analysis during recovery from an exercise challenge showed that male ME/CFS patients had distinct changes in the regulation of specific cytokine signals (including IL-1ß). Meanwhile, female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses, and NF-κß signaling. The functional pathways and differentially expressed genes highlighted in this pilot project provide insight into the sex-specific pathophysiology of ME/CFS.

Stress-Induced Transcriptomic Changes in Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reveal Disrupted Immune Signatures.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, complex multi-organ illness characterized by unexplained debilitating fatigue and post-exertional malaise (PEM), which is defined as a worsening of symptoms following even minor physical or mental exertion. Our study aimed to evaluate transcriptomic changes in ME/CFS female patients undergoing an exercise challenge intended to precipitate PEM. Our time points (baseline before exercise challenge, the point of maximal exertion, and after an exercise challenge) allowed for the exploration of the transcriptomic response to exercise and recovery in female patients with ME/CFS, as compared to healthy controls (HCs). Under maximal exertion, ME/CFS patients did not show significant changes in gene expression, while HCs demonstrated altered functional gene networks related to signaling and integral functions of their immune cells. During the recovery period (commonly during onset of PEM), female ME/CFS patients showed dysregulated immune signaling pathways and dysfunctional cellular responses to stress. The unique functional pathways identified provide a foundation for future research efforts into the disease, as well as for potential targeted treatment options.

Do Admitted COVID-19-Positive Patients on Anticoagulation Therapy Have a Reduced Hospital Stay and Disease Severity?

Background As of December 2021, the coronavirus disease 2019 (COVID-19) pandemic has resulted in the deaths of over 5 million people. It is known that infection with this virus causes a state of hypercoagulability. Because of this, there has been considerable debate on whether or not patients should be placed on anticoagulation prophylaxis/therapy. The goal of our project was to shed light on this topic by examining the effects of preexisting anticoagulation therapy in COVID-19 patients on disease severity (measured by blood clot readmissions, transfusion counts, and length of hospital stay). In this retrospective cohort study, we conducted an analysis based on data from 30,076 COVID-19-positive patients' electronic medical records. Materials and methods This is a retrospective cohort study. Patients included in this study were identified from the HCA Healthcare corporate database. Registry data was sourced from HCA East Florida hospitals. All patients included in this study were COVID-19 positive via polymerase chain reaction (PCR) or rapid antigen testing on admission and over age 18. A total of 30,076 patients were included in this study with hospital admission dates from March 1, 2020 to June 30, 2021. The analysis examined the relationship between age, sex, blood clot history, and most importantly current anticoagulation status on COVID-19 disease severity (through blood clot readmissions, length of stay, and transfusion count). Blood clot readmissions were analyzed with a logistic regression model while the length of hospital stay and transfusion count were analyzed with a linear regression model. Results Our analysis revealed that the odds of experiencing a blood clot readmission is 2.017 times more likely in patients already on anticoagulation therapy compared to those who were not (p = 0.0024). We also found that patients on anticoagulation therapy had a hospital stay of 6.90 days longer on average than patients not on anticoagulation therapy (p < 0.0001). Finally, patients on anticoagulation therapy had, on average, 0.20 more blood transfusions than patients not on anticoagulation therapy (p < 0.001).  Conclusion While these findings may be affected by the underlying conditions of those on preexisting anticoagulation therapy, they provide valuable insight into the debate on whether COVID-19-positive patients should be anticoagulated on admission to a hospital.

Functional MRI findings in personality disorders: A review.

Personality disorders (PDs) have a prevalence of approximately 10% in the United States, translating to over 30 million people affected in just one country. The true prevalence of these disorders may be even higher, as the paucity of objective diagnostic criteria could be leading to underdiagnosis. Because little is known about the underlying neuropathologies of these disorders, patients are diagnosed using subjective criteria and treated nonspecifically. To better understand the neural aberrancies responsible for these patients' symptoms, a review of functional MRI literature was performed. The findings reveal that each PD is characterized by a unique set of activation changes corresponding to individual structures or specific neural networks. While unique patterns of neural activity are distinguishable within each PD, aberrations of the limbic/paralimbic structures and default mode network are noted across several of them. In addition to identifying valuable activation patterns, this review reveals a void in research pertaining to paranoid, schizoid, histrionic, narcissistic, and dependent PDs. By delineating patterns in PD neuropathology, we can more effectively direct future research efforts toward enhancing objective diagnostic techniques and developing targeted treatment modalities. Furthermore, understanding why patients are manifesting certain symptoms can advance clinical awareness and improve patient outcomes.

The effect of stress on the transcriptomes of circulating immune cells in patients with Gulf War Illness.

AIMS: In an effort to gain further insight into the underlying mechanisms tied to disease onset and progression of Gulf War Illness (GWI), our team evaluated GWI patient response to stress utilizing RNA-Seq. MAIN METHODS: The protocol included blood collection before exercise challenge (baseline), at maximal exertion, and after exercise challenge (recovery - four hours post-exercise challenge). Peripheral blood mononuclear cell (PBMC) transcriptomics data were analyzed to understand why GWI patients process stressors differently from their healthy counterparts. KEY FINDINGS: Our findings validate previously identified dysregulation of immune and inflammatory pathways among GWI patients as well as highlight novel immune and inflammatory markers of disease activity. These results provide a foundation for future research efforts in understanding GWI pathophysiology and creating targeted treatments. SIGNIFICANCE: Gulf War Illness is a complex, chronic, and debilitating multi-system illness impacting 25%-30% of the U.S. troops deployed to the 1990-1991 Gulf War. The condition is characterized by medically unexplained fatigue and affects multiple organ systems. Because the underlying mechanisms are largely unknown, patients receive symptom-based treatment, rather than targeting fundamental biological processes. To the best of our knowledge, this is the first study that applies RNA-Seq to analyze the effect of GWI, and the response to stressors in GWI, on the transcriptomic changes in circulating immune cells.