Evaluating a novel high-density EEG sensor net structure for improving inclusivity in infants with curly or tightly coiled hair.

Electroencephalography (EEG) is an important tool in the field of developmental cognitive neuroscience for indexing neural activity. However, racial biases persist in EEG research that limit the utility of this tool. One bias comes from the structure of EEG nets/caps that do not facilitate equitable data collection across hair textures and types. Recent efforts have improved EEG net/cap design, but these solutions can be time-intensive, reduce sensor density, and are more difficult to implement in younger populations. The present study focused on testing EEG sensor net designs over infancy. Specifically, we compared EEG data quality and retention between two high-density saline-based EEG sensor net designs from the same company (Magstim EGI, Whitland, UK) within the same infants during a baseline EEG paradigm. We found that within infants, the tall sensor nets resulted in lower impedances during collection, including lower impedances in the key online reference electrode for those with greater hair heights and resulted in a greater number of usable EEG channels and data segments retained during pre-processing. These results suggest that along with other best practices, the modified tall sensor net design is useful for improving data quality and retention in infant participants with curly or tightly-coiled hair.

Use of Donor-derived Cell-free DNA to Inform Tapering of Immunosuppression Therapy in Kidney Transplant Recipients: An Observational Study.

Background: Immunosuppression therapy (IST) is required for allograft survival but can cause significant adverse effects. Donor-derived cell-free DNA (dd-cfDNA) is a validated noninvasive biomarker for active rejection in kidney transplant (KTx). Evidence supporting dd-cfDNA testing use in IST management is limited. Methods: In this single-center observational study, dd-cfDNA testing was performed in 21 KTx patients considered good candidates for mycophenolic acid (MPA) reduction. Patients with dd-cfDNA <1% at the first visit (enrollment) had their MPA dosage reduced; those with dd-cfDNA ≥1% had their MPA dosage maintained. Patients were monitored with dd-cfDNA for 6 additional visits. Results: Of 21 patients enrolled in the study, 17 were considered low risk for rejection by dd-cfDNA and underwent MPA reduction; 4 patients were considered high risk for rejection by dd-cfDNA and had their initial MPA dosage maintained. Of the 4 patients considered high risk for rejection by dd-cfDNA, 1 experienced chronic allograft nephropathy and graft loss, and another received an indication biopsy that showed no evidence of rejection. Of the 17 patients considered low risk for rejection by dd-cfDNA, none experienced allograft rejection. dd-cfDNA was used for surveillance in a 6-mo period following MPA reduction; no untoward results were noted. Conclusions: This proof-of-concept study reports the use of dd-cfDNA to directly inform IST management in a cohort of KTx who were candidates for IST reduction.

Antepartum and intrapartum stillbirth rates across gestation: a cross-sectional study using the revised foetal death reporting system in the U.S.

BACKGROUND: There is a renewed call to address preventable foetal deaths in high-income countries, especially where progress has been slow. The Centers for Disease Control and Prevention released publicly, for the first time, the initiating cause and estimated timing of foetal deaths in 2014. The objective of this study is to describe risk and characteristics of antepartum versus intrapartum stillbirths in the U.S., and frequency of pathological examination to determine cause. METHODS: We conducted a cross-sectional study of singleton births (24-43 weeks) using 2014 U.S. Fetal Death and Natality data available from the National Center for Health Statistics. The primary outcome was timing of death (antepartum (n = 6200), intrapartum (n = 453), and unknown (n = 5403)). Risk factors of interest included maternal sociodemographic, behavioural, medical and obstetric factors, along with foetal sex. We estimated gestational week-specific stillbirth hazard, risk factors for intrapartum versus antepartum stillbirth using multivariable log-binomial regression models, conditional probabilities of intrapartum and antepartum stillbirth at each gestational week, and frequency of pathological examination by timing of death. RESULTS: The gestational age-specific stillbirth hazard was approximately 2 per 10,000 foetus-weeks among preterm gestations and > 3 per 10,000 foetus-weeks among term gestations. Both antepartum and intrapartum stillbirth risk increased in late-term and post-term gestations. The risk of intrapartum versus antepartum stillbirth was higher among those without a prior live birth, relative to those with at least one prior live birth (RR 1.32; 95% CI 1.08-1.61) and those with gestational hypertension, relative to those with no report of gestational hypertension (RR 1.47; 95% CI 1.09-1.96), and lower among Black, relative to white, individuals (RR 0.70; 95% CI 0.55-0.89). Pathological examination was not performed/planned in 25% of known antepartum stillbirths and 29% of known intrapartum stillbirths. CONCLUSION: These findings suggest greater stillbirth risk in the late-term and post-term periods. Primiparous mothers had greater risk of intrapartum than antepartum still birth, suggesting the need for intrapartum interventions for primiparous mothers in this phase of pregnancy to prevent some intrapartum foetal deaths. Efforts are needed to improve understanding, prevention and investigation of foetal deaths as well as improve stillbirth data quality and completeness in the United States.

Association Between Total Cell Free DNA and SARS-CoV-2 In Kidney Transplant Patients: A Preliminary Study.

BACKGROUND: Kidney transplant (KT) recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in KT recipients with COVID-19 encourages native immune responses but can raise the risk of rejection. Donor-derived cell-free DNA (dd-cfDNA), reported as a fraction of total cfDNA, is a proven biomarker for KT rejection. Total cfDNA levels are elevated in patients with COVID-19, which may depress dd-cfDNA fractions, potentially leading to missed rejections. METHODS: A retrospective analysis of 29 KT recipients hospitalized with COVID-19 between April and November 2020 examined total and dd-cfDNA levels. Blood samples were collected after onset of COVID-19, with follow-up samples collected from a subset of patients, when infection had likely subsided. RESULTS: After COVID-19 diagnosis, the median total cfDNA level was elevated (7.9 multiples of median [MoM]). A significant decrease in total cfDNA levels was observed between the first and second time points (6.2 MoM, 1.0 MoM; P <001). A significant positive association was identified between total cfDNA levels and COVID-19 severity (P = .02; R2 = .19). Two patients with biopsy-proven acute cellular rejection had dd-cfDNA fractions below the 1% cutoff for rejection (0.20% and 0.78%), with elevated total cfDNA levels of 7.9 MoM and 41.8 MoM, respectively. CONCLUSIONS: In this preliminary study, total cfDNA levels were elevated in KT patients with COVID-19, subsiding after resolution of infection. High total cfDNA levels may confound dd-cfDNA results, leading to failure to identify rejection. Considering total cfDNA levels is important in interpretation of dd-cfDNA tests for assessment of rejection in KT patients with COVID-19 or other infection.

Household clutter and crowding constrain associations between maternal sensitivity and child theory of mind.

Social interactions between parents and children are important for developing theory of mind, but these may be disrupted by aspects of the proximal home environment. The current study observed maternal sensitivity and its associations with child theory of mind and the housing environment (index by clutter and crowding) in a sample of mothers and their 3.5-year-old twins (N = 250 children). Maternal sensitivity and housing environment were measured from experimenter report and child theory of mind was measured through behavioural tasks. Results show that the association between maternal sensitivity and child theory of mind was moderated by the housing environment, where the positive associations between maternal sensitivity and child theory of mind were only observed at lower levels of clutter and crowding in the housing environment. Additional contextual variables and processes are discussed.

Infants' neural responses to emotional faces are related to maternal anxiety.

BACKGROUND: Postnatal maternal anxiety is common (estimates as high as 40% prevalence) and is associated with altered mother-infant interactions (e.g., reduced maternal emotional expression and engagement). Neural circuitry supporting infants' face and emotion processing develops in their first year. Thus, early exposure to maternal anxiety may impact infants' developing understanding of emotional displays. We examine whether maternal anxiety is associated with individual differences in typically developing infants' neural responses to emotional faces. METHODS: One hundred and forty two mother-infant dyads were assessed when infants were 5, 7, or 12 months old. Infants' electroencephalographic (EEG) data were recorded while passively viewing female happy, fearful, and angry faces. Three event-related potential (ERP) components, each linked to face and emotion processing, were evaluated: NC, N290, and P400. Infant ERP amplitude was related to concurrent maternal-report anxiety assessed with the Spielberger State-Trait Anxiety Inventory (Trait form). RESULTS: Greater maternal anxiety predicted more negative NC amplitude for happy and fearful faces in left and mid-central scalp regions, beyond covarying influences of maternal depression symptoms, infant negative emotionality, and infant age. CONCLUSIONS: Postnatal maternal anxiety is related to infants' neural processing of emotional expressions. Infants of mothers endorsing high trait anxiety may need additional attentional resources to process happy and fearful faces (expressions less likely experienced in mother-infant interactions). Future research should investigate mechanisms underlying this association, given possibilities include experiential, genetic, and prenatal factors.

High-resolution CT with arch/neck/head CT angiography on a mobile stroke unit.

BACKGROUND: Mobile stroke units (MSUs) performance dependability and diagnostic yield of 16-slice, ultra-fast CT with auto-injection angiography (CTA) of the aortic arch/neck/circle of Willis has not been previously reported. METHODS: We performed a prospective observational study of the first-of-its kind MSU equipped with high resolution, 16-slice CT with multiphasic CTA. Field CT/CTA was performed on all suspected stroke patients regardless of symptom severity or resolution. Performance dependability, efficiency and diagnostic yield over 365 days was quantified. RESULTS: 1031 MSU emergency activations occurred; of these, 629 (61%) were disregarded with unrelated diagnoses, and 402 patients transported: 245 (61%) ischemic or hemorrhagic stroke, 17 (4%) transient ischemic attack, 140 (35%) other neurologic emergencies. Total time from non-contrast CT/CTA start to images ready for viewing was 4.0 (IQR 3.5-4.5) min. Hemorrhagic stroke totaled 24 (10%): aneurysmal subarachnoid hemorrhage 3, hemorrhagic infarct 1, and 20 intraparenchymal hemorrhages (median intracerebral hemorrhage score was 2 (IQR 1-3), 4 (20%) spot sign positive). In 221 patients with ischemic stroke, 73 (33%) received alteplase with 31.5% treated within 60 min of onset. CTA revealed large vessel occlusion in 66 patients (30%) of which 9 (14%) were extracranial; 27 (41%) underwent thrombectomy with onset to puncture time averaging 141±90 min (median 112 (IQR 90-139) min) with full emergency department (ED) bypass. No imaging needed to be repeated for image quality; all patients were triaged correctly with no inter-hospital transfer required. CONCLUSIONS: MSU use of advanced imaging including multiphasic head/neck CTA is feasible, offers high LVO yield and enables full ED bypass.

Incorporation of Donor-derived Cell-free DNA Into Clinical Practice for Renal Allograft Management.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)-based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients. METHODS: To assess the clinical utility of a clinically available SNP-based massively multiplexed polymerase chain reaction dd-cfDNA assay, we analyzed biopsy data contemporaneous to dd-cfDNA results at 33 participating clinics and calculated the rate of rejection in dd-cfDNA-matched biopsy results. RESULTS: A total of 1347 dd-cfDNA test samples from 879 patients were accessioned from October 3, 2019, to November 2, 2020. The dd-cfDNA testing classified 25.2% (340/1347) of samples as high-risk (dd-cfDNA fraction ≥ 1%). Clinical follow-up was available for 32.1% (109/340) of the high-risk results, which included samples from 28 patients with definitive biopsy results within 2 weeks of dd-cfDNA testing. Pathology reports indicated a 64% (18/28) rate of active rejection in biopsy result-matched samples. Total cfDNA measurements indicated a skewed distribution and a correlation with dd-cfDNA-derived patient risk classification. CONCLUSIONS: This is the first report showing the impact of dd-cfDNA on patient management in a multicenter real-world clinical cohort. The data indicate that incorporating dd-cfDNA testing into practice may improve physician decision making regarding renal allograft recipients.

Household Chaos, Parental Responses to Emotion, and Child Emotion Regulation in Middle Childhood.

Parents' responses to children's negative emotional states play a key role in the socialization of emotion regulation skills in childhood. Much of the prior research on child ER has focused on early development using cross-sectional designs. The current study addresses these gaps by using a longitudinal design to examine individual differences of ER at two times points in middle childhood. We examined the development of children's ER by testing hypotheses about the interplay of parent response to emotions and household chaos in the prediction of individual differences in children's ER. Participants were the mothers of children at 6 and 9 years of age among 224 families in a socioeconomically diverse sample that was part of an ongoing longitudinal study. Mothers completed questionnaires regarding themselves, their children, and their home environment. Mothers' reports of better child ER at both time points were positively associated with mothers' more supportive responses and negatively associated with mothers' less non-supportive responses, as well as lower household chaos. Chaos statistically moderated the link between non-supportive parental responses to emotion and child ER, but only at 6 years of age. The strength of the link between child ER and non-supportive parental responses to emotions was strong only at lower levels of household chaos. At the beginning of middle childhood, family processes linking parent responses to child emotions and children's developing ER may not function at higher levels of household chaos.

Parenting and Children's Executive Function Stability Across the Transition to School.

When children transition to school between the ages of 4 and 6 years, they must learn to control their attention and behavior to be successful. Concurrently, executive function (EF) is an important skill undergoing significant development in childhood. To understand changes occurring during this period, we examined the role of parenting in the development of children's EF from 4 to 6 years old. Participants were mother and child dyads (N = 151). Children completed cognitive tasks to assess overall EF at age 4 and age 6. At both time points, mothers and children completed interaction tasks which were videotaped and coded to assess various parenting dimensions. Results indicated that children with high EF at age 4 were more likely to have high EF at age 6. In addition, results suggested that higher levels of positive parenting across the transition to school promote stability of individual differences in EF.

Rapid face processing for positive and negative emotions in 5-, 7-, and 12-month-old infants: An exploratory study.

Processing of positive and negative facial expressions in infancy follows a distinct course with a bias towards fearful facial expressions starting at 7 months of age; however, little is known about the developmental trajectory of fear processing and other facial expressions, and if this bias is driven by specific regions of the face. This study used eye tracking to examine the processing of positive and negative emotional faces in independent groups of 5- (n = 43), 7- (n = 60), and 12-month-old infants (n = 70). Methods: Infants were shown static images of female faces exhibiting happy, anger, and fear expressions, for one-second each. Total looking time and looking time for areas of interest (AOIs) including forehead and eyes (top), mouth and chin (bottom), and contour of each image were computed. Infants across all ages looked longer to fear faces than angry or happy faces. Negative emotions generally elicited greater looking times for the top of the face than did happy faces. In addition, we also found that at 12 months of age infants looked longer for the bottom of the faces than did 5-month-olds. Our study suggests that the visual bias to attend longer to fearful faces may be in place by 5 months of age, and between 5 and 12 months of age, there seems to be a developmental shift towards looking more to the bottom of the faces. STATEMENT OF CONTRIBUTION: What is already known in this subject? Bias for fear face processing is present at 7 months of age. Using older data collection systems, we have some idea about which facial features recruit infant attention. What the present study adds? Well-controlled paradigm that examines both positive and negative facial expressions, to different areas of interest in the face. Use of the same paradigm to test a cross-sectional sample of infants in distinct developmental stages - 5, 7, and 12 months.

Neural correlates of facial emotion processing in infancy.

In the present study we examined the neural correlates of facial emotion processing in the first year of life using ERP measures and cortical source analysis. EEG data were collected cross-sectionally from 5- (N = 49), 7- (N = 50), and 12-month-old (N = 51) infants while they were viewing images of angry, fearful, and happy faces. The N290 component was found to be larger in amplitude in response to fearful and happy than angry faces in all posterior clusters and showed largest response to fear than the other two emotions only over the right occipital area. The P400 and Nc components were found to be larger in amplitude in response to angry than happy and fearful faces over central and frontal scalp. Cortical source analysis of the N290 component revealed greater cortical activation in the right fusiform face area in response to fearful faces. This effect started to emerge at 5 months and became well established at 7 months, but it disappeared at 12 months. The P400 and Nc components were primarily localized to the PCC/Precuneus where heightened responses to angry faces were observed. The current results suggest the detection of a fearful face in infants' brain can happen shortly (~200-290 ms) after the stimulus onset, and this process may rely on the face network and develop substantially between 5 to 7 months of age. The current findings also suggest the differential processing of angry faces occurred later in the P400/Nc time window, which recruits the PCC/Precuneus and is associated with the allocation of infants' attention.

The role of mental health and specific responsivity in juvenile justice rehabilitation.

Understanding the role that mental health issues play in justice-involved youth poses challenges for research, policy, and practice. While mental health problems are generally not risk factors for criminal behavior according to the risk-needs-responsivity (RNR) framework of correctional psychology practice, prevalence rates are very high and RNR principles suggest that mental health as a responsivity variable may moderate the success of interventions targeted to criminogenic needs. In this study we investigated the relationships among mental health status, criminogenic needs treatment, and recidivism in a sample of 232 youth referred for court-ordered assessments and followed through their community supervision sentence (probation). Youth with mental health needs were no more likely than youth without these needs to reoffend, regardless of whether those needs were treated. Youth who received mental health treatment also more frequently had their criminogenic needs matched across several domains, suggesting an association between mental health treatment and intermediate treatment targets. However, mental health did not moderate the effect of criminogenic needs treatment: youth who had a greater proportion of criminogenic needs targeted through appropriate services were less likely to reoffend, regardless of mental health status. Findings are consistent with the RNR stance that, within a correctional context in which the primary goal of intervention is preventing recidivism, treatment for mental health needs should be in addition to criminogenic needs treatment, not in replacement of it. They also point to the need for continued research to understand precisely how mental health treatment interacts with intervention targeting criminogenic needs. (PsycINFO Database Record

Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome.

Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 did not affect either. By co-immunoprecipitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after IL-4 stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our findings provide novel insight into how dysregulated expression of SOCS increases IL-4 responses in allergic monocytes, and this may represent a new therapeutic avenue for managing allergic disease.

Bacteremia in Early Infancy: Etiology and Management.

We reviewed the literature regarding bacteremia in early infancy (age ≤ 90 days). Bacteremia remains a major cause of morbidity and mortality in young infants. However, recent epidemiologic data suggest that the incidence of bacteremia is decreasing and the pathogens responsible for invasive disease are changing. These changes will impact the evaluation and management of young infants. We review the current epidemiology of community-acquired bacteremia in early infancy with particular emphasis on the causative agents, diagnostic evaluation, and empiric and definitive antimicrobial treatment.

Regulation of Macrophage, Dendritic Cell, and Microglial Phenotype and Function by the SOCS Proteins.

Macrophages are innate immune cells of dynamic phenotype that rapidly respond to external stimuli in the microenvironment by altering their phenotype to respond to and to direct the immune response. The ability to dynamically change phenotype must be carefully regulated to prevent uncontrolled inflammatory responses and subsequently to promote resolution of inflammation. The suppressor of cytokine signaling (SOCS) proteins play a key role in regulating macrophage phenotype. In this review, we summarize research to date from mouse and human studies on the role of the SOCS proteins in determining the phenotype and function of macrophages. We will also touch on the influence of the SOCS on dendritic cell (DC) and microglial phenotype and function. The molecular mechanisms of SOCS function in macrophages and DCs are discussed, along with how dysregulation of SOCS expression or function can lead to alterations in macrophage/DC/microglial phenotype and function and to disease. Regulation of SOCS expression by microRNA is discussed. Novel therapies and unanswered questions with regard to SOCS regulation of monocyte-macrophage phenotype and function are highlighted.

Commentary: IL-4 and IL-13 receptors and signaling.

Interleukin (IL)-4 and IL-13 were discovered approximately 30years ago and were immediately linked to allergy and atopic diseases. Since then, new roles for IL-4 and IL-13 and their receptors in normal gestation, fetal development and neurological function and in the pathogenesis of cancer and fibrosis have been appreciated. Studying IL-4/-13 and their receptors has revealed important clues about cytokine biology and led to the development of numerous experimental therapeutics. Here we aim to highlight new discoveries and consolidate concepts in the field of IL-4 and IL-13 structure, receptor regulation, signaling and experimental therapeutics.

Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function.

Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.

Looking to the eyes influences the processing of emotion on face-sensitive event-related potentials in 7-month-old infants.

Previous studies in infants have shown that face-sensitive components of the ongoing electroencephalogram (the event-related potential, or ERP) are larger in amplitude to negative emotions (e.g., fear, anger) versus positive emotions (e.g., happy). However, it is still unclear whether the negative emotions linked with the face or the negative emotions alone contribute to these amplitude differences. We simultaneously recorded infant looking behaviors (via eye-tracking) and face-sensitive ERPs while 7-month-old infants viewed human faces or animals displaying happy, fear, or angry expressions. We observed that the amplitude of the N290 was greater (i.e., more negative) to angry animals compared to happy or fearful animals; no such differences were obtained for human faces. Eye-tracking data highlighted the importance of the eye region in processing emotional human faces. Infants that spent more time looking to the eye region of human faces showing fearful or angry expressions had greater N290 or P400 amplitudes, respectively.