This clinical trial aimed to determine the influence of attention-deficit/hyperactivity disorder (ADHD) on neuro-ophthalmologic function and brain-derived blood biomarkers following acute ...subconcussive head impacts.
The present trial consisted of age- and sex-matched samples with a ratio of 1:1 between two groups with a total sample size of 60 adults (age ± SD; 20.0 ± 1.8 years). Soccer players diagnosed with and medicated daily for ADHD were assigned into an ADHD group (
= 30). Soccer players without ADHD were assigned into a non-ADHD group (
= 30). Participants performed 10 soccer headers with a soccer ball projected at a velocity of 25mph. King-Devick test (KDT), near point of convergence (NPC), and serum levels of NF-L, tau, GFAP, and UCH-L1 were assessed at baseline (pre-heading) and at 2 h and 24 h post-heading.
There were no statistically significant group-by-time interactions in outcome measures. However, at baseline, the ADHD group exhibited lower neuro-ophthalmologic functions compared to the non-ADHD group (NPC:
= 0.019; KDT:
= 0.018), and persisted at 2 h-post (NPC:
= 0.007; KDT:
= 0.014) and 24 h-post heading (NPC:
= 0.001). NPC significantly worsened over time in both groups compared to baseline ADHD: 2 h-post, 1.23 cm, 95%CI:(0.77, 1.69),
< 0.001; 24 h-post, 1.68 cm, 95%CI:(1.22, 2.13),
= 0.001; Non-ADHD: 2 h-post, 0.96 cm, 95%CI:(0.50, 1.42),
< 0.001; 24 h-post, 1.09 cm, 95%CI:(0.63, 1.55),
< 0.001. Conversely, improvements in KDT time compared to baseline occurred at 2 h-post in the non-ADHD group -1.32 s, 95%CI:(-2.55, -0.09),
= 0.04 and at 24 h-post in both groups ADHD: -4.66 s, 95%CI:(-5.89, -3.43),
< 0.001; Non-ADHD: -3.46 s, 95%CI:(-4.69, -2.23),
< 0.001). There were no group-by-time interactions for GFAP as both groups exhibited increased levels at 2 h-post ADHD: 7.75 pg./mL, 95%CI:(1.41, 14.10),
= 0.019; Non-ADHD: 7.91 pg./mL, 95%CI:(1.71, 14.14),
= 0.015) that returned to baseline at 24 h-post. NF-L levels increased at 2 h-post heading in the ADHD group 0.45 pg./mL, 95%CI:(0.05, 0.86),
= 0.032, but no significant NF-L changes were observed in the non-ADHD group over time.
Ten soccer headers elevated GFAP levels and NPC impairment in both groups. However, persisting group difference in NPC, blunted KDT performance, and increased NF-L levels in the ADHD group suggest that ADHD may reduce neuro-ophthalmologic function and heighten axonal response to soccer headers.
ClinicalTrials.gov, identifier ID: (NCT04880304).
Being strangled, or “choked,” by a sexual partner has emerged as a prevalent, often wanted and consensual sexual behavior among adolescent and young adult women, yet the neurological consequences of ...repeated exposure to this behavior are unknown. The objective of the study was to examine the association between a history of repeated, recent choking/strangling episodes during sex and fMRI activation during working memory tasks in young adult women. This case-control study involved young adult women (18–30 years old) at a large, public university, and consisted of two study groups: a choking group consisting of participants who were recently and frequently choked/strangled during sex by a partner (≥4 times in the past 30 days) and a choking-naïve (control) group who had never been choked/strangled during sex. Participants completed two variations of the N-back (0-back, 1-back, and 2-back) working memory task during functional magnetic resonance imaging (fMRI): verbal and visual N-back tasks. Data from 20 participants per group were available for analysis. Between-group differences for accuracy and reaction time were not significant for either variation of the N-back task. Significant differences in fMRI activation patterns were detected between the choking and the choking-naïve groups for the three contrasts of interest (1-back > 0-back, 2-back > 0-back, and 2-back > 1-back). The choking group exhibited increased activation in multiple clusters relative to the choking-naïve group for the contrasts between the 1-back and 2-back conditions compared to the 0-back conditions (e.g., superior frontal gyrus, corpus callosum). However, the choking-naïve group exhibited increased activation relative to the choking group in several clusters for the 2-back > 1 back contrast (e.g., splenium, middle frontal gyrus). These data indicate that recent, frequent exposure to partnered sexual strangulation is associated with different neural activation patterns during verbal and visual working memory tasks compared to controls, suggesting that being choked/strangled during sex may modify the allocation of neural resources at increasing levels of cognitive load. Further investigation into the neurologic effects of this sexual behavior is warranted, given the prevalence of sexual choking among adolescent and young adult women.
Introduction
Being choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed ...to characterize neuroanatomical differences between young adult women (18–30 years old) who were exposed to frequent sexual choking and their choking naïve controls.
Methods
This cross‐sectional study consisted of two groups (choking ≥4 times in the past 30 days vs. choking‐naïve group). Participants who reported being choked four or more times during sex in the past 30 days were enrolled in the choking group, whereas those without were assigned to the choking naïve group. High‐resolution anatomical magnetic resonance imaging (MRI) data were analyzed using both volumetric features (cortical thickness) and geometric features (fractal dimensionality, gyrification, sulcal depth).
Results
Forty‐one participants (choking n = 20; choking‐naïve n = 21) contributed to the final analysis. The choking group showed significantly increased cortical thickness across multiple regions (e.g., fusiform, lateral occipital, lingual gyri) compared to the choking‐naïve group. Widespread reductions of the gyrification were observed in the choking group as opposed to the choking‐naïve group. However, there was no group difference in sulcal depth. The fractal dimensionality showed bi‐directional results, where the choking group exhibited increased dimensionality in areas including the postcentral gyrus, insula, and fusiform, whereas decreased dimensionality was observed in the bilateral superior frontal gyrus and pericalcarine cortex.
Conclusion
These data in cortical morphology suggest that sexual choking events may be associated with neuroanatomical alteration. A longitudinal study with multimodal assessment is needed to better understand the temporal ordering of sexual choking and neurological outcomes.
Being choked/strangled during partnered sex is an emerging sexual behavior affecting many young adult women. Our cross‐sectional study using multiparameter brain morphology analysis revealed that being choked/strangled during sex is associated with changes in cortical thickness and other metrics related to altered cortical maturation.
PU.1 is a member of the ets family of transcription factors and is expressed exclusively in cells of the hematopoietic lineage. Mice homozygous for a disruption in the PU.1 DNA binding domain are ...born alive but die of severe septicemia within 48 h. The analysis of these neonates revealed a lack of mature macrophages, neutrophils, B cells and T cells, although erythrocytes and megakaryocytes were present. The absence of lymphoid commitment and development in null mice was not absolute, since mice maintained on antibiotics began to develop normal appearing T cells 3–5 days after birth. In contrast, mature B cells remained undetectable in these older mice. Within the myeloid lineage, despite a lack of macrophages in the older antibiotic‐treated animals, a few cells with the characteristics of neutrophils began to appear by day 3. While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages.
Being choked or strangled during partnered sex is an emerging sexual behavior, prevalent among young adult women. The goal of this study was to test whether, and to what extent, frequently being ...choked or strangled during sex is associated with cortical surface functioning and functional connectivity. This case-control study consisted of two groups (choking vs. choking-naïve). Women who were choked 4 or more times during sex in the past 30 days were enrolled into the choking group, whereas those without were assigned to the choking-naïve group. We collected structural and resting-state functional magnetic resonance imaging (fMRI) data and analyzed the data for amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) using cortical surface-based resting-state fMRI analysis, followed by static and dynamic resting-state fMRI connectivity analysis. Forty-one participants (choking
= 20; choking-n-aïve
= 21) contributed to the analysis. An inter-hemispheric imbalance in neuronal activation pattern was observed in the choking group. Specifically, we observed significantly lower ALFF and ReHo in the left cortical regions (e.g., angular gyrus, orbitofrontal gyrus) and higher ALFF and ReHo in the right cortical regions (e.g., pre-central/post-central gyri) in the choking group compared with the choking-naïve group. A significant group difference was found in static functional connectivity between the bilateral angular gyrus and the whole brain, in which the choking group's angular gyrus showed hyperconnectivity with, for example, the post-central gyrus, pre-central gyrus, and Rolandic operculum, relative to the choking-naïve group. The dynamic analysis revealed hyperconnectivity between the left angular gyrus and the bilateral postcentral gyrus in the choking group compared with the choking-naïve group. Taken together, our data show that multiple experiences of sexual choking/strangulation are associated with an inter-hemispheric imbalance in neural activation pattern and hyperconnectivity between the angular gyrus and brain regions related to motor control, consciousness, and emotion. A longitudinal study using multi-modal neurological assessments is needed to clarify the acute and chronic consequences of sexual choking/strangulation.
Altering chromatin structure by blocking histone deacetylase activity with specific inhibitors such as trichostatin A can result in an up-regulation of gene expression. In this report, however, we ...show that expression of the ETS domain transcription factor PU.1 is down-regulated in cells following the addition of trichostatin A. The loss of PU.1 is seen at both the mRNA and protein levels in multiple cell lines and is reversible following removal of the drug. More importantly, we show that the loss of PU.1 results in a loss of PU.1 target gene expression, including CD11b, c-fms, Toll-like receptor 4, and scavenger receptor. Chromatin immunoprecipitation analysis of cells treated with trichostatin A showed a significant increase in the acetylation of histone H4, but not histone H3, across approximately 650 bp of the PU.1 promoter region. Our data suggest that the consequences of using drugs that inhibit histone deacetylase activity may be a loss of blood cell development and/or function due to a block in PU.1 gene expression.
PU.1 recruits the binding of a second B cell-restricted nuclear factor, NF-EM5, to a DNA site in the immunoglobulin κ 3′ enhancer. DNA binding by NF-EM5 requires a protein-protein interaction with ...PU.1 and specific DNA contacts. Dephosphorylated PU.1 bound to DNA but did not interact with NF-EM5. Analysis of serine-to-alanine mutations in PU.1 indicated that serine 148 (Ser$^{148}$) is required for protein-protein interaction. PU.1 produced in bacteria did not interact with NF-EM5. Phosphorylation of bacterially produced PU.1 by purified casein kinase II modified it to a form that interacted with NF-EM5 and that recruited NF-EM5 to bind to DNA. Phosphopeptide analysis of bacterially produced PU.1 suggested that Ser$^{148}$ is phosphorylated by casein kinase II. This site is also phosphorylated in vivo. Expression of wild-type PU.1 increased expression of a reporter construct containing the PU.1 and NF-EM5 binding sites nearly sixfold, whereas the Ser$^{148}$ mutant form only weakly activated transcription. These results demonstrate that phosphorylation of PU.1 at Ser$^{148}$ is necessary for interaction with NF-EM5 and suggest that this phosphorylation can regulate transcriptional activity.
We have isolated a cDNA clone, PU.1, that codes for a new tissue-specific DNA binding protein. Analysis of the binding site by methylation interference and DNAase 1 protection revealed that the PU.1 ...protein recognized a purine-rich sequence, 5'-GAGGAA-3' (PU box). The PU.1 protein was shown to be a transcriptional activator that is expressed in macrophages and B cells. cDNA constructions used to generate proteins lacking portions of either the amino- or carboxy-terminal ends of the PU.1 protein placed the DNA binding domain in the highly basic carboxy-terminal domain of the protein. The amino acid sequence in the binding domain of PU.1 has considerable identity with proteins belonging to the ets oncogene family.
Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue. Some chemokines such as MIP-1 alpha also inhibit hematopoietic progenitor cell proliferation. ...Recently, three chemokines, MIP-1 alpha, MIP-1 beta, and RANTES, have been found to significantly decrease human immunodeficiency virus production from infected T cells. We report here the cloning and characterization of a novel human chemokine termed Exodus for its chemotactic properties. This novel chemokine is distantly related to other chemokines (28% homology with MIP-1 alpha) and shares several biological activities. Exodus is expressed preferentially in lymphocytes and monocytes, and its expression is markedly upregulated by mediators of inflammation such as tumor necrosis factor or lipopolysaccharide. Purified synthetic Exodus was found to inhibit proliferation of myeloid progenitors in colony formation assays. Exodus also stimulated chemotaxis of peripheral blood mononuclear cells. The sequence homology, expression, and biological activity indicate that Exodus represents a novel divergent beta-chemokine.
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