Distinct transcriptomic and epigenomic modalities underpin human memory T cell subsets and their activation potential.

Human memory T cells (MTC) are poised to rapidly respond to antigen re-exposure. Here, we derived the transcriptional and epigenetic programs of resting and ex vivo activated, circulating CD4+ and CD8+ MTC subsets. A progressive gradient of gene expression from naïve to TCM to TEM is observed, which is accompanied by corresponding changes in chromatin accessibility. Transcriptional changes suggest adaptations of metabolism that are reflected in altered metabolic capacity. Other differences involve regulatory modalities comprised of discrete accessible chromatin patterns, transcription factor binding motif enrichment, and evidence of epigenetic priming. Basic-helix-loop-helix factor motifs for AHR and HIF1A distinguish subsets and predict transcription networks to sense environmental changes. Following stimulation, primed accessible chromatin correlate with an augmentation of MTC gene expression as well as effector transcription factor gene expression. These results identify coordinated epigenetic remodeling, metabolic, and transcriptional changes that enable MTC subsets to ultimately respond to antigen re-encounters more efficiently.

An IRF4-MYC-mTORC1 Integrated Pathway Controls Cell Growth and the Proliferative Capacity of Activated B Cells during B Cell Differentiation In Vivo.

Cell division is an essential component of B cell differentiation to Ab-secreting plasma cells, with critical reprogramming occurring during the initial stages of B cell activation. However, a complete understanding of the factors that coordinate early reprogramming events in vivo remain to be determined. In this study, we examined the initial reprogramming by IRF4 in activated B cells using an adoptive transfer system and mice with a B cell-specific deletion of IRF4. IRF4-deficient B cells responding to influenza, 4-hydroxy-3-nitrophenylacetyl-Ficoll, and LPS divided but stalled during the proliferative response. Gene expression profiling of IRF4-deficient B cells at discrete divisions revealed IRF4 was critical for inducing MYC target genes, oxidative phosphorylation, and glycolysis. Moreover, IRF4-deficient B cells maintained an inflammatory gene expression signature. Complementary chromatin accessibility analyses established a hierarchy of IRF4 activity and identified networks of dysregulated transcription factor families in IRF4-deficient B cells, including E-box binding bHLH family members. Indeed, B cells lacking IRF4 failed to fully induce Myc after stimulation and displayed aberrant cell cycle distribution. Furthermore, IRF4-deficient B cells showed reduced mTORC1 activity and failed to initiate the B cell activation unfolded protein response and grow in cell size. Myc overexpression in IRF4-deficient cells was sufficient to overcome the cell growth defect. Together, these data reveal an IRF4-MYC-mTORC1 relationship critical for controlling cell growth and the proliferative response during B cell differentiation.

Knowledge of accurate blood pressure measurement procedures in chiropractic students.

Objective : Blood pressure measurement is a basic clinical procedure. However, studies have shown that many errors are made when health care providers acquire blood pressure readings. Our study assessed knowledge of blood pressure measurement procedures in chiropractic students. Methods : This was an observational, descriptive study. A questionnaire based on one created by the American Heart Association was given to 1st, 2nd, 3rd, and final year students (n = 186). A one way ANOVA was used to analyze the data. Results : Of the students 80% were confident that their knowledge of this clinical skill was adequate or better. However, the overall score on the knowledge test of blood pressure-taking skills was 52% (range, 24%-88%). The only significant difference in the mean scores was between the 1st and 2nd year students compared to the 3rd and 4th year students (p < .005). Of the 16 questions given, the following mean scores were: 1st year 10.45, 2nd year 9.75, 3rd year 7.93, and 4th year 8.33. Of the 16 areas tested, 10 were of major concern (test item score <70%), showing the need for frequent retraining of chiropractic students. Conclusion : Consistent with studies in other health care disciplines, our research found the knowledge of blood pressure skills to be deficient in our sample. There is a need for subsequent training in our teaching program.

Chiropractic care of a patient with thoracic outlet syndrome and arrhythmia.

OBJECTIVE: The purpose of this article is to describe a case report and discuss a possible anatomical explanation of the occurrence of arrhythmias in patients with thoracic outlet syndrome (TOS). CLINICAL FEATURES: A 60-year-old man experienced arrhythmia when he turned his head to the left and had these symptoms for 7 years. The patient attributed his symptoms to TOS. The arrhythmia was triggered while performing an Adson test during the clinical evaluation. INTERVENTION AND OUTCOME: The Grostic procedure as a measure of analysis of the biomechanical relationship of C1 to C0 and the lower cervical spine was performed. According to this analysis, the patient had a right laterality malposition of the atlas. High-velocity, low-amplitude manipulations (adjustments) were applied. The patient's symptoms improved after one visit and demonstrated resolution upon evaluation at the third visit. In the year following the initial presentation, he has had minor recurrent short-lived episodes of arrhythmia that abated with the atlas manipulation/adjustment. CONCLUSION: There is a paucity of published reports describing the management of patients with arrhythmias through manipulative methods. This appears to be the first case that describes the successful amelioration of an arrhythmia associated with TOS using chiropractic adjustment of the atlas vertebra as the sole intervention.

Red blood cell orientation in pulmonary capillaries and its effect on gas diffusion.

When alveoli are inflated, the stretched alveolar walls draw their capillaries into oval cross sections. This causes the disk-shaped red blood cells to be oriented near alveolar gas, thereby minimizing diffusion distance. We tested these ideas by measuring red blood cell orientation in histological slides from rapidly frozen rat lungs. High lung inflation did cause the capillaries to have oval cross sections, which constrained the red blood cells within them to flow with their broad sides facing alveolar gas. Low lung inflation stretched alveolar walls less and allowed the capillaries to assume a circular cross section. The circular luminal profile permitted the red blood cells to have their edges facing alveolar gas, which increased the diffusion distance. Using a finite-element method to calculate the diffusing capacity of red blood cells in the broad-side and edge-on orientations, we found that edge-on red blood cells had a 40% lower diffusing capacity. This suggests that, when capillary cross sections become circular, whether through low-alveolar volume or through increased microvascular pressure, the red blood cells are likely to be less favorably oriented for gas exchange.