Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision.

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.

Virtual (Zoom) Interactions Alter Conversational Behavior and Interbrain Coherence.

A growing number of social interactions are taking place virtually on videoconferencing platforms. Here, we explore potential effects of virtual interactions on observed behavior, subjective experience, and neural "single-brain" and "interbrain" activity via functional near-infrared spectroscopy neuroimaging. We scanned a total of 36 human dyads (72 participants, 36 males, 36 females) who engaged in three naturalistic tasks (i.e., problem-solving, creative-innovation, socio-emotional task) in either an in-person or virtual (Zoom) condition. We also coded cooperative behavior from audio recordings. We observed reduced conversational turn-taking behavior during the virtual condition. Given that conversational turn-taking was associated with other metrics of positive social interaction (e.g., subjective cooperation and task performance), this measure may be an indicator of prosocial interaction. In addition, we observed altered patterns of averaged and dynamic interbrain coherence in virtual interactions. Interbrain coherence patterns that were characteristic of the virtual condition were associated with reduced conversational turn-taking. These insights can inform the design and engineering of the next generation of videoconferencing technology.SIGNIFICANCE STATEMENT Videoconferencing has become an integral part of our lives. Whether this technology impacts behavior and neurobiology is not well understood. We explored potential effects of virtual interaction on social behavior, brain activity, and interbrain coupling. We found that virtual interactions were characterized by patterns of interbrain coupling that were negatively implicated in cooperation. Our findings are consistent with the perspective that videoconferencing technology adversely affects individuals and dyads during social interaction. As virtual interactions become even more necessary, improving the design of videoconferencing technology will be crucial for supporting effective communication.

Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis.

BACKGROUND: Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1ß cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis. METHODS: We conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed. RESULTS: A total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as compared with 23 of 31 patients (74%) in the placebo group. In the run-in period, 4 patients had adverse events leading to the discontinuation of rilonacept therapy. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections. CONCLUSIONS: Among patients with recurrent pericarditis, rilonacept led to rapid resolution of recurrent pericarditis episodes and to a significantly lower risk of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110.).

Real-World Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion: Results of the BArONIS Study.

OBJECTIVE: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. RESULTS: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. INTERPRETATION: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60.

Expressing appreciation is linked to interpersonal closeness and inter-brain coherence, both in person and over Zoom.

Expressing appreciation is essential for establishing interpersonal closeness, but virtual interactions are increasingly common and create social distance. Little is known about the neural and inter-brain correlates of expressing appreciation and the potential effects of virtual videoconferencing on this kind of interaction. Here, we assess inter-brain coherence with functional near-infrared spectroscopy while dyads expressed appreciation to one another. We scanned 36 dyads (72 participants) who interacted in either an in-person or virtual (Zoom®) condition. Participants reported on their subjective experience of interpersonal closeness. As predicted, expressing appreciation increased interpersonal closeness between dyad partners. Relative to 3 other cooperation tasks (i.e. problem-solving task, creative-innovation task, socio-emotional task), we observed increased inter-brain coherence in socio-cognitive areas of the cortex (anterior frontopolar area, inferior frontal gyrus, premotor cortex, middle temporal gyrus, supramarginal gyrus, and visual association cortex) during the appreciation task. Increased inter-brain coherence in socio-cognitive areas during the appreciation task was associated with increased interpersonal closeness. These findings support the perspective that expressing appreciation, both in-person and virtually, increases subjective and neural metrics of interpersonal closeness.

Alterations in cortical and subcortical neuroanatomy and associations with behavior in females with fragile X syndrome.

AIM: To address substantial gaps in the literature on neuroanatomical variations in females with fragile X syndrome (FXS). METHOD: Surface-based modeling techniques were applied to the magnetic resonance imaging of 45 females with FXS (mean age = 10 years 9 months, range 6 years-16 years 4 months, SD = 2 years 9 months) and 33 age-matched and developmentally matched females without FXS to elucidate differences in cortical gray matter volume, surface area, and thickness. Gray matter volumes in subcortical regions were examined to ascertain differences in subcortical volume. RESULTS: In females with FXS, cortical volume was greater bilaterally in the occipital pole and smaller in the right postcentral gyrus. Seven regions demonstrated lower surface area in participants with FXS, while cortical thickness was significantly greater over the posterior and medial surfaces in the group with FXS. Subcortical region of interest analyses demonstrated greater volume in the caudate nucleus, globus pallidus, and nucleus accumbens in the group with FXS. Global gray matter volume, pial thickness, and surface area were associated with behavioral outcomes in the group with FXS but not in the comparison group. INTERPRETATION: Females with FXS demonstrated unique cortical and subcortical gray matter anatomy relative to a matched comparison group. These findings may be relevant to the pathogenesis of the FXS behavioral phenotype and provide insights into behavioral interventions targeted to this population.

Towards assessing subcortical "deep brain" biomarkers of PTSD with functional near-infrared spectroscopy.

Assessment of brain function with functional near-infrared spectroscopy (fNIRS) is limited to the outer regions of the cortex. Previously, we demonstrated the feasibility of inferring activity in subcortical "deep brain" regions using cortical functional magnetic resonance imaging (fMRI) and fNIRS activity in healthy adults. Access to subcortical regions subserving emotion and arousal using affordable and portable fNIRS is likely to be transformative for clinical diagnostic and treatment planning. Here, we validate the feasibility of inferring activity in subcortical regions that are central to the pathophysiology of posttraumatic stress disorder (PTSD; i.e. amygdala and hippocampus) using cortical fMRI and simulated fNIRS activity in a sample of adolescents diagnosed with PTSD (N = 20, mean age = 15.3 ± 1.9 years) and age-matched healthy controls (N = 20, mean age = 14.5 ± 2.0 years) as they performed a facial expression task. We tested different prediction models, including linear regression, a multilayer perceptron neural network, and a k-nearest neighbors model. Inference of subcortical fMRI activity with cortical fMRI showed high prediction performance for the amygdala (r > 0.91) and hippocampus (r > 0.95) in both groups. Using fNIRS simulated data, relatively high prediction performance for deep brain regions was maintained in healthy controls (r > 0.79), as well as in youths with PTSD (r > 0.75). The linear regression and neural network models provided the best predictions.

Prenatal and childhood exposure to organophosphate pesticides and functional brain imaging in young adults.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment from infancy to adolescence. In our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort, we previously reported that residential proximity to OP use during pregnancy was associated with altered cortical activation using functional near infrared spectroscopy (fNIRS) in a small subset (n = 95) of participants at age 16 years. METHODS: We administered fNIRS to 291 CHAMACOS young adults at the 18-year visit. Using covariate-adjusted regression models, we estimated associations of prenatal and childhood urinary dialkylphosphates (DAPs), non-specific OP metabolites, with cortical activation in the frontal, temporal, and parietal regions of the brain during tasks of executive function and semantic language. RESULTS: There were some suggestive associations for prenatal DAPs with altered activation patterns in both the inferior frontal and inferior parietal lobes of the left hemisphere during a task of cognitive flexibility (ß per ten-fold increase in DAPs = 3.37; 95% CI: -0.02, 6.77 and ß = 3.43; 95% CI: 0.64, 6.22, respectively) and the inferior and superior frontal pole/dorsolateral prefrontal cortex of the right hemisphere during the letter retrieval working memory task (ß = -3.10; 95% CI: -6.43, 0.22 and ß = -3.67; 95% CI: -7.94, 0.59, respectively). We did not observe alterations in cortical activation with prenatal DAPs during a semantic language task or with childhood DAPs during any task. DISCUSSION: We observed associations of prenatal OP concentrations with mild alterations in cortical activation during tasks of executive function. Associations with childhood exposure were null. This is reasonably consistent with studies of prenatal OPs and neuropsychological measures of attention and executive function found in CHAMACOS and other birth cohorts.

Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome. METHODS: We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed. RESULTS: We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition. CONCLUSION: Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.

Diagnosis, Risk Stratification, and Treatment of Pericarditis: A Review.

Importance: Pericarditis accounts for up to 5% of emergency department visits for nonischemic chest pain in North America and Western Europe. With appropriate treatment, 70% to 85% of these patients have a benign course. In acute pericarditis, the development of constrictive pericarditis (<0.5%) and pericardial tamponade (<3%) can be life-threatening. Observations: Acute pericarditis is diagnosed with presence of 2 or more of the following: sharp, pleuritic chest pain that worsens when supine (≈90%); new widespread electrocardiographic ST-segment elevation and PR depression (≈25%-50%); a new or increased pericardial effusion that is most often small (≈60%); or a pericardial friction rub (<30%). In North America and Western Europe, the most common causes of acute pericarditis are idiopathic or viral, followed by pericarditis after cardiac procedures or operations. Tuberculosis is the most common cause in endemic areas and is treated with antituberculosis therapy, with corticosteroids considered for associated constrictive pericarditis. Treatment of acute idiopathic and pericarditis after cardiac procedures or operations involves use of high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), with doses tapered once chest pain has resolved and C-reactive protein level has normalized, typically over several weeks. These patients should receive a 3-month course of colchicine to relieve symptoms and reduce the risk of recurrence (37.5% vs 16.7%; absolute risk reduction, 20.8%). With a first recurrence of pericarditis, colchicine should be continued for at least 6 months. Corticosteroids are often used if pericarditis does not improve with NSAIDs and colchicine. In certain patients with multiple recurrences, which can occur for several years, interleukin 1 (IL-1) blockers have demonstrated efficacy and may be preferred to corticosteroids. Conclusions: Acute pericarditis is a common cause of nonischemic chest pain. Tuberculosis is the leading cause of pericarditis in endemic areas and is treated with antitubercular therapy. In North America and Western Europe, pericarditis is typically idiopathic, develops after a viral infection, or develops following cardiac procedures or surgery. Treatment with NSAIDs and colchicine leads to a favorable prognosis in most patients, although 15% to 30% of patients develop recurrence. Patients with multiple recurrent pericarditis can have a disease duration of several years or more, are often treated with corticosteroids, and IL-1 blockers may be used for selected patients as steroid-sparing therapy.

Cortical potentials time-locked to discrete postural events during quiet standing are facilitated during postural threat exposure.

During unperturbed bipedal standing, postural control is governed primarily by subcortical and spinal networks. However, it is unclear if cortical networks begin to play a greater role when stability is threatened. This study investigated how initial and repeated exposure to a height-related postural threat modulates cortical potentials time-locked to discrete centre of pressure (COP) events during standing. Twenty-seven young adults completed a series of 90-s standing trials at LOW (0.8 m above the ground, away from edge) and HIGH (3.2 m above the ground, at edge) threat conditions. Three LOW trials were completed before and after 15 consecutive HIGH trials. Participants stood on a force plate while electroencephalographic (EEG) activity was recorded. To examine changes in cortical activity in response to discrete postural events, prominent forward and backward peaks in the anterior-posterior COP time series were identified. EEG data were waveform-averaged to these events and the amplitude of event-related cortical activity was calculated. At the LOW condition, event-related potentials (ERPs) were scarcely detectable. However, once individuals stood at the HIGH condition, clear ERPs were observed, with more prominent potentials being observed for forward (edge-directed), compared to backward, COP events. Since forward COP peaks accelerate the centre of mass away from the platform edge, these results suggest there is intermittent recruitment of cortical networks that may be involved in the detection and minimization of postural sway toward a perceived threat. This altered cortical engagement appears resistant to habituation and may contribute to threat-related balance changes that persist following repeated threat exposure. KEY POINTS: While standing balance control is regulated primarily by subcortical and spinal processes, it is unclear if cortical networks play a greater role when stability is threatened. This study examined how cortical potentials time-locked to prominent peaks in the anterior-posterior centre of pressure (COP) time series were modulated by exposure to a height-related postural threat. While cortical potentials recorded over the primary sensorimotor cortices were scarcely detectable under non-threatening conditions, clear cortical potentials were observed when individuals stood under conditions of height-related threat. Cortical potentials were larger in response to COP peaks directed toward, compared to away from, the platform edge, and showed limited habituation with repeated threat exposure. Since forward COP peaks accelerate the centre of mass away from the platform edge, these findings suggest that when balance is threatened, there is intermittent recruitment of cortical networks, which may minimize the likelihood of falling in the direction of a perceived threat.

Genomic virulence features of Beauveria bassiana as a biocontrol agent for the mountain pine beetle population.

BACKGROUND: The mountain pine beetle, Dendroctonus ponderosae, is an irruptive bark beetle that causes extensive mortality to many pine species within the forests of western North America. Driven by climate change and wildfire suppression, a recent mountain pine beetle (MPB) outbreak has spread across more than 18 million hectares, including areas to the east of the Rocky Mountains that comprise populations and species of pines not previously affected. Despite its impacts, there are few tactics available to control MPB populations. Beauveria bassiana is an entomopathogenic fungus used as a biological agent in agriculture and forestry and has potential as a management tactic for the mountain pine beetle population. This work investigates the phenotypic and genomic variation between B. bassiana strains to identify optimal strains against a specific insect. RESULTS: Using comparative genome and transcriptome analyses of eight B. bassiana isolates, we have identified the genetic basis of virulence, which includes oosporein production. Genes unique to the more virulent strains included functions in biosynthesis of mycotoxins, membrane transporters, and transcription factors. Significant differential expression of genes related to virulence, transmembrane transport, and stress response was identified between the different strains, as well as up to nine-fold upregulation of genes involved in the biosynthesis of oosporein. Differential correlation analysis revealed transcription factors that may be involved in regulating oosporein production. CONCLUSION: This study provides a foundation for the selection and/or engineering of the most effective strain of B. bassiana for the biological control of mountain pine beetle and other insect pests populations.

Adolescent brain development in girls with Turner syndrome.

Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio-emotional phenotypes. However, few studies have examined TS-associated alterations in the development of cortical gray matter volume and the two components that comprise this measure-surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X-monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface-based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X-monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X-monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X-chromosome haploinsufficiency on brain development in TS.

European Respiratory Society/American Thoracic Society technical statement: standardisation of the measurement of lung volumes, 2023 update.

This document updates the 2005 European Respiratory Society (ERS) and American Thoracic Society (ATS) technical standard for the measurement of lung volumes. The 2005 document integrated the recommendations of an ATS/ERS task force with those from an earlier National Heart, Lung, and Blood Institute workshop that led to the publication of background papers between 1995 and 1999 and a consensus workshop report with more in-depth descriptions and discussion. Advancements in hardware and software, new research and emerging approaches have necessitated an update to the 2005 technical standard to guide laboratory directors, physiologists, operators, pulmonologists and manufacturers. Key updates include standardisation of linked spirometry, new equipment quality control and validation recommendations, generalisation of the multiple breath washout concept beyond nitrogen, a new acceptability and grading system with addition of example tracings, and a brief review of imaging and other new techniques to measure lung volumes. Future directions and key research questions are also noted.

Neural responses to gender-based microaggressions in academic medicine.

Gender-based microaggressions have been associated with persistent disparities between women and men in academia. Little is known about the neural mechanisms underlying those often subtle and unintentional yet detrimental behaviors. Here, we assessed the neural responses to gender-based microaggressions in 28 early career faculty in medicine (N = 16 female, N = 12 male sex) using fMRI. Participants watched 33 videos of situations demonstrating gender-based microaggressions and control situations in academic medicine. Video topics had been previously identified through real-life anecdotes about microaggression from women faculty and were scripted and reenacted using professional actors. Primary voxel-wise analyses comparing group differences in activation elucidated a significant group by condition interaction in a right-lateralized cluster across the frontal (inferior and middle frontal gyri, frontal pole, precentral gyrus, postcentral gyrus) and parietal lobes (supramarginal gyrus, angular gyrus). Whereas women faculty exhibited reduced activation in these regions during the microaggression relative to the control condition, the opposite was true for men. Posthoc analyses showed that these patterns were significantly associated with the degree to which participants reported feeling judged for their gender in academic medicine. Lastly, secondary exploratory ROI analyses showed significant between-group differences in the right dorsolateral prefrontal cortex and inferior frontal gyrus. Women activated these two regions less in the microaggression condition compared to the control condition, whereas men did not. These findings indicate that the observation of gender-based microaggressions results in a specific pattern of neural reactivity in women early career faculty.

Is the mRNA COVID-19 Vaccine Safe in Patients With a Prior History of Myocarditis?

BACKGROUND: Numerous studies have reported myocarditis resulting from messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination. However, to date, there have been no reports highlighting the safety of mRNA COVID-19 vaccines in children and adults with a prior history of myocarditis, which was the intent of this study. METHODS AND RESULTS: Children and adults cared for at the Cleveland Clinic were identified through the electronic health records, who had a history of myocarditis before the COVID-19 pandemic and had subsequently received at least 2 doses of the mRNA COVID-19 vaccines (n = 34). Only 1 patient in this series had recurrence of myocarditis confirmed by cardiac magnetic resonance imaging after receiving the second dose. He was a White man who had his first episode of myocarditis at age 20 and was 27 years of age at the time of recurrence. He was hospitalized for 2 days with no need for cardiac support or reported arrhythmias and was stable at outpatient follow-up. CONCLUSIONS: In patients with an old history of non-COVID-19 myocarditis, the risk of recurrent myocarditis after receipt of mRNA COVID-19 vaccination is low, and when it occurs it seems to be self-limiting. Our study will be valuable to clinicians while discussing the risk-benefit ratio of vaccinations in patients with a prior history of myocarditis.

Multimodality cardiovascular imaging in hypertension.

PURPOSE OF THE REVIEW: Hypertension accounts for the largest proportion of cardiovascular (CV) mortality worldwide and its prevalence continues to rise. While prominent CV societies have offered strong recommendations on the management of hypertension in adults, the role of noninvasive CV imaging in the evaluation of hypertensive patients remains incompletely defined. RECENT FINDINGS: Noninvasive imaging is a rapidly expanding field with a growing number of sophisticated and readily applicable modalities to assess how cardiac structure and function changes after periods of sustained, elevated blood pressure. Echocardiography remains the initial modality to screen these patients while developments in nuclear, computed tomography and cardiac magnetic resonance complement and expand investigations for alternative diagnoses that may complement or conflict with the diagnosis of left ventricular hypertrophy. SUMMARY: In this review article, we summarize the application of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging in the evaluation and management of hypertensive heart disease.

Altered canonical and striatal-frontal resting state functional connectivity in children with pathogenic variants in the Ras/mitogen-activated protein kinase pathway.

Mounting evidence supports the role of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway in neurodevelopmental disorders. Here, the authors used a genetics-first approach to examine how Ras/MAPK pathogenic variants affect the functional organization of the brain and cognitive phenotypes including weaknesses in attention and inhibition. Functional MRI was used to examine resting state functional connectivity (RSFC) in association with Ras/MAPK pathogenic variants in children with Noonan syndrome (NS). Participants (age 4-12 years) included 39 children with NS (mean age 8.44, SD = 2.20, 25 females) and 49 typically developing (TD) children (mean age 9.02, SD = 9.02, 33 females). Twenty-eight children in the NS group and 46 in the TD group had usable MRI data and were included in final analyses. The results indicated significant hyperconnectivity for the NS group within canonical visual, ventral attention, left frontoparietal and limbic networks (p < 0.05 FWE). Higher connectivity within canonical left frontoparietal and limbic networks positively correlated with cognitive function within the NS but not the TD group. Further, the NS group demonstrated significant group differences in seed-based striatal-frontal connectivity (Z > 2.6, p < 0.05 FWE). Hyperconnectivity within canonical brain networks may represent an intermediary phenotype between Ras/MAPK pathogenic variants and cognitive phenotypes, including weaknesses in attention and inhibition. Altered striatal-frontal connectivity corresponds with smaller striatal volume and altered white matter connectivity previously documented in children with NS. These results may indicate delayed maturation and compensatory mechanisms and they are important for understanding the pathophysiology underlying cognitive phenotypes in NS and in the broader population of children with neurodevelopmental disorders.

Aberrant brain network and eye gaze patterns during natural social interaction predict multi-domain social-cognitive behaviors in girls with fragile X syndrome.

Girls with fragile X syndrome (FXS) often manifest significant symptoms of avoidance, anxiety, and arousal, particularly in the context of social interaction. However, little is currently known about the associations among neurobiological, biobehavioral such as eye gaze pattern, and social-cognitive dysfunction in real-world settings. In this study, we sought to characterize brain network properties and eye gaze patterns in girls with FXS during natural social interaction. Participants included 42 girls with FXS and 31 age- and verbal IQ-matched girls (control). Portable functional near-infrared spectroscopy (fNIRS) and an eye gaze tracker were used to investigate brain network alterations and eye gaze patterns associated with social-cognitive dysfunction in girls with FXS during a structured face-to-face conversation. Compared to controls, girls with FXS showed significantly increased inter-regional functional connectivity and greater excitability within the prefrontal cortex (PFC), frontal eye field (FEF) and superior temporal gyrus (STG) during the conversation. Girls with FXS showed significantly less eye contact with their conversational partner and more unregulated eye gaze behavior compared to the control group. We also demonstrated that a machine learning approach based on multimodal data, including brain network properties and eye gaze patterns, was predictive of multiple domains of social-cognitive behaviors in girls with FXS. Our findings expand current knowledge of neural mechanisms and eye gaze behaviors underlying naturalistic social interaction in girls with FXS. These results could be further evaluated and developed as intermediate phenotypic endpoints for treatment trial evaluation in girls with FXS.

Longitudinal investigation of cognition, social competence, and anxiety in children and adolescents with Turner syndrome.

Turner syndrome (TS), a common neurogenetic disorder caused by complete or partial absence of an X chromosome in females, is characterized by distinct physical, cognitive, and social-emotional features. Girls with TS typically display average overall intellectual functioning with relative strength in verbal abilities and weaknesses in visuospatial processing, executive function (EF), and social cognition. This study was designed to better understand longitudinal trajectories of cognitive and social-emotional domains commonly affected in TS. Participants included 57 girls with monosomic 45,X TS and 55 age- and verbal-IQ matched girls who completed behavioral, child-report, and parent-report measures across four timepoints. Group differences in visuospatial processing, EF, social cognition, and anxiety were assessed longitudinally. Potential effects of estrogen replacement therapy (ERT) were assessed cross-sectionally on an exploratory basis. The TS group showed poorer performance on measures of visuospatial processing, EF, and social cognition, but not anxiety, compared to controls throughout childhood and adolescence. There were no significant group differences in the trajectory of skill development over time. Exploratory analyses within the TS group revealed that girls who were receiving ERT showed better performance on measures of overall IQ, expressive vocabulary, and visuospatial processing compared to those not receiving ERT. Consistent with existing literature, weaknesses in visuospatial processing, EF, and social competence among girls with TS persisted throughout childhood and adolescence. Exploratory analyses suggest that ERT may help improve some aspects of cognitive function in TS, although other pre-existing, nonhormonal differences between the two TS subgroups may alternatively explain these findings, given our study design. Future studies are needed to examine potential impacts of ERT on cognitive and social-emotional development in TS.