Assessment of myelination in infants and young children by T1 relaxation time measurements using the magnetization-prepared 2 rapid acquisition gradient echoes sequence.

BACKGROUND: Axonal myelination is an important maturation process in the developing brain. Increasing myelin content correlates with the longitudinal relaxation rate (R1=1/T1) in magnetic resonance imaging (MRI). OBJECTIVE: By using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) on a 3-T MRI system, we provide R1 values and myelination rates for infants and young children. MATERIALS AND METHODS: Average R1 values in white and grey matter regions in 94 children without pathological MRI findings (age range: 3 months to 6 years) were measured and fitted by a saturating-exponential growth model. For comparison, R1 values of 36 children with different brain pathologies are presented. The findings were related to a qualitative evaluation using T2, magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and MP2RAGE. RESULTS: R1 changes rapidly in the first 16 months of life, then much slower thereafter. R1 is highest in pre-myelinated structures in the youngest subjects, such as the posterior limb of the internal capsule (0.74-0.76±0.04 s-1) and lowest for the corpus callosum (0.37-0.44±0.03 s-1). The myelination rate is fastest in the corpus callosum and slowest in the deep grey matter. R1 is decreased in hypo- and dysmyelination disorders. Myelin maturation is clearly visible on MP2RAGE, especially in the first year of life. CONCLUSION: MP2RAGE permits a quantitative R1 mapping method with an examination time of approximately 6 min. The age-dependent R1 values for children without MRI-identified brain pathologies are well described by a saturating-exponential function with time constants depending on the investigated brain region. This model can serve as a reference for this age group and to search for indications of subtle pathologies. Moreover, the MP2RAGE sequence can also be used for the qualitative assessment of myelinated structures.

Teachers' Heart Rate Variability and Behavioral Reactions in Aggressive Interactions: Teachers Can Downregulate Their Physiological Arousal, and Progesterone Favors Social Integrative Teacher Responses.

Aggressive student behavior is considered one of the main risk factors for teacher stress. The present study investigated teachers' physiological and behavioral reactions when facing aggressive student behavior and examined which resources favor adaptive teacher reactions. The sample included 42 teachers. We assessed (a) teacher self-reports (i.e., resources, risk factors, and vital exhaustion) (b) classroom observations, (c) ambulatory assessments of teachers' heart rate and heart rate variability, and (d) teachers' progesterone concentrations in the hair. The present study focused on a subsample of ten teachers (9 females, Mage = 34.70, SD = 11.32) managing classes which were potentially very stressful as they had a high density of aggressive behavior. High levels of work satisfaction, hair progesterone, and a low level of work overload fostered social integrative teacher responses. Moreover, in 75% of the cases, teachers succeeded in downregulating their physiological reaction. Our results support the notion that teachers evaluate stressors in light of their resources. When they perceive their resources as insufficient for coping with a challenging situation, stress arises, and subsequently, they react inefficiently to aggressive behavior. Thus, teacher education could benefit from strengthening teacher resources and strategies for coping with aggressive student behavior.

Teachers' perception of aggressive student behavior through the lens of chronic worry and resignation, and its association with psychophysiological stress: An observational study.

Aggressive student behavior is considered a leading risk factor for teacher stress. However, teachers' coping styles may affect how they perceive and respond to aggressive student behavior. This study tests whether teachers' perceptions of aggressive student behavior mainly mirror objectively observed aggression in presence of the teacher (as coded by external observers) or whether teachers' perception of aggressive student behavior primarily reflects teachers' avoidant coping styles, such as chronic worry and resignation. Finally, we examine whether observed and teacher-perceived aggression relates to increased vital exhaustion and psychophysiological stress among teachers (i.e., higher hair cortisol concentration). In an ambulatory assessment study, we administered self-reports to 42 Swiss teachers to assess perceived student aggression, chronic worry, resignation, and vital exhaustion. Additionally, four consecutive lessons per teacher were filmed, and aggressive student behavior in presence of the teacher was coded by four trained external observers. The concentration of cortisol was assessed in hair samples. Results showed that teacher-perceived and observed aggression were moderately associated. Observed aggression was related to teacher perceptions to a much lesser extent than teachers' avoidant coping styles, that is, chronic worry and resignation. While teacher-perceived student aggression was associated with teachers' self-reported vital exhaustion, we did not find any significant association with hair-cortisol concentration. Our findings suggest that teachers perceive student aggression through the lens of their coping styles. Teachers' dysfunctional coping styles are associated with an overestimation of student aggression. Teachers' overestimation of student aggression relates to higher levels of vital exhaustion. Therefore, it is crucial to identify and change teachers' dysfunctional coping styles to prevent a vicious cycle of dysfunctional teacher-student interactions.

Associations between stress, resources, and hair cortisol concentration in teachers.

Challenging interactions are the main source of teacher' stress in the classroom. We investigated the association of chronic stress and characteristics of teacher-student interactions with teachers' Hair Cortisol Concentration (HCC). Forty-one teachers (27 women; Mage = 39.65 ± 12.14 years; Mlesson number = 23.15 ± 3.99 lessons per week; grade: elementary, secondary, high, and vocational school teachers) participated in the present study, with participation lasting over the length of one year. HCC was assessed from a 3 cm hair segment near the scalp. Self-reported chronic stress in the last three months was further assessed using the 'Trier Inventory for Chronic Stress' (TICS). Additionally, four consecutive, same-day lectures of each teacher were videotaped and coded offline in an event sampling procedure by trained external observers. The videos were analyzed for two stressors, i.e., classroom disruptions and total student aggression, as well as two resources, i.e., teacher-student relationship and classroom management. Overall, hair samples were collected M = 120.34 days (SD = 84.39) after the distribution of the questionnaires, and M = 67.63 days (SD = 18.40) prior to the observations. Lesson number, classroom disruptions, as well as total student aggression were all significantly positively correlated with HCC. In addition, both teacher-student relationship and classroom management were significantly negatively related to HCC. With regard to self-rated chronic stress, only the TICS subscale 'Pressure to perform' was positively related to HCC. Exploratory moderation analyses revealed that an increasingly good, observed teacher-student relationship buffered the positive association between lesson number and HCC. Our findings show significant associations between HCC and mainly objectively assessable stress, supporting HCC as a biological indicator of chronic stress. In this association, a good relationship between teachers and students acts as a buffer. While the findings underline the importance of examining objective and behavioral data for better understanding the psychobiology of stress, they also support the importance of boostering teachers' (social) resources to increase their overall resilience.

Predictors of Psychological Strain and Allostatic Load in Teachers: Examining the Long-Term Effects of Biopsychosocial Risk and Protective Factors Using a LASSO Regression Approach.

Teacher stress significantly challenges teachers' health, teaching quality, and students' motivation and achievement. Thus, it is crucial to identify factors that effectively prevent it. Using a LASSO regression approach, we examined which factors predict teachers' psychological strain and allostatic load over two years. The study included 42 teachers (28 female, Mage = 39.66, SD = 11.99) and three measurement time points: At baseline, we assessed teachers' (a) self-reports (i.e., on personality, coping styles, and psychological strain), (b) behavioral data (i.e., videotaped lessons), and (c) allostatic load (i.e., body mass index, blood pressure, and hair cortisol concentration). At 1- and 2-year follow-ups, psychological strain and allostatic load biomarkers were reassessed. Neuroticism and perceived student disruptions at baseline emerged as the most significant risk factors regarding teachers' psychological strain two years later, while a positive core self-evaluation was the most important protective factor. Perceived support from other teachers and the school administration as well as adaptive coping styles were protective factors against allostatic load after two years. The findings suggest that teachers' psychological strain and allostatic load do not primarily originate from objective classroom conditions but are attributable to teachers' idiosyncratic perception of this environment through the lens of personality and coping strategies.

The diurnal course of salivary cortisol and alpha-amylase on workdays and leisure days in teachers and the role of social isolation and neuroticism.

Teachers are among the occupational groups with the highest sick leave rates due to workplace stress and burnout symptoms. A substantial body of research has suggested social isolation and neuroticism to be related to physiological stress activity. However, the relationship between such characteristics and stress experiences has rarely been studied in conjunction with physiological stress indicators in the teachers' natural settings. Thus, the present study examines salivary cortisol and α-amylase as physiological stress indicators on teachers' work and leisure days and their relationship with social isolation. Furthermore, we test whether neuroticism moderates the relationship between social isolation and salivary biomarkers. Forty-two teachers completed questionnaires assessing social isolation (Trier Inventory for the Assessment of Chronic Stress) and neuroticism (Big-Five Inventory). Participants collected eight saliva samples on three days, two workdays, and one leisure day to measure the concentration of cortisol and α-amylase as biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), respectively. Results showed a significantly higher Cortisol Awakening Response (CAR) and diurnal cortisol slope (DCS) on workdays than on the leisure day but no significant differences regarding measures of α-amylase. We found a significant positive relationship between social isolation and the CAR on the leisure day but no association with the α-amylase measures. Furthermore, after controlling for confounders, social isolation was unrelated to neuroticism, and the latter did not moderate between social isolation and the CAR. Our findings suggest an association between social isolation and the HPA axis, i.e., the CAR, but do not support an association with the ANS, which would be indicated by the α-amylase assessments. Finally, our findings could not support an association of neuroticism with the HPA axis and ANS.

Real-world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study.

OBJECTIVE: Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes. METHODS: In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers. RESULTS: The study cohort comprised 311 patients with epilepsy with a median age of 11.3 (0-72) years (235 children and adolescents, 76 adults). Therapy with CBD was off-label in 91.3% of cases due to age, epilepsy subtype, lack of adjunct therapy with clobazam, and/or higher dose applied. CBD titration regimens were slower than recommended, with good tolerability of higher doses particularly in children. Of all patients, 36.9% experienced a reduction in seizure frequency of >50%, independent of their epilepsy subtype or clobazam co-medication. The median observation period was 15.8 months. About one third of all patients discontinued therapy within the observation period due to adverse effects or lack of efficacy. Adverse effects were reported frequently (46.9%). SIGNIFICANCE: Our study highlights that CBD has an antiseizure effect comparable to other antiseizure medications with a positive safety profile independent of the epilepsy subtype. Comedication with clobazam was not associated with a better outcome. Higher doses to achieve seizure frequency reduction were safe, particularly in children. These findings call for further trials for an extended approval of CBD for other epilepsy subtypes and for children <2 years of age.

Is cannabidiol worth a trial in Rasmussen encephalitis?

We report 3 patients (age 8, 13 and 14 years) with drug-resistant epilepsy due to Rasmussen encephalitis treated with cannabidiol in addition to their current antiseizure medication (ASM). In all three patients we observed a positive effect, which seemed to surpass the efficacy that would be expected from a different fourth or fifth antiseizure drug used during the course of the disease.

Longitudinal Associations Between Core Self-Evaluation, Vital Exhaustion and Hair Cortisol in Teachers and the Mediating Effects of Resignation Tendency.

Work-related stress appears to be especially high among teachers. However, most research on teacher stress relies exclusively on teachers' self-reports. Little is known about the physiological correlates of affective stress in teachers. This longitudinal study investigates the relationship between core self-evaluation and adverse psychological and physiological stress outcomes in 42 teachers. Self-report questionnaires were used to assess core self-evaluation, vital exhaustion, and resignation tendency. The concentration of cortisol was assessed using hair samples. One year after the initial measurement, vital exhaustion and hair cortisol were assessed again. Path-analytic mediational models showed that core self-evaluation strongly predicted vital exhaustion, and resignation tendency partially mediated this relationship. However, core self-evaluation did not predict hair cortisol concentration. These findings suggest that core self-evaluation plays a crucial role in preventing vital exhaustion among teachers. A positive core self-evaluation seems beneficial for teachers' primary and secondary appraisal and an essential resource for the long-term prevention of self-reported vital exhaustion.

Modified Zipper Method, a Promising Treatment Option in Severe Pediatric Immune-Mediated Neurologic Disorders.

OBJECTIVE: To introduce and evaluate a modified version of the "zipper method"-a treatment strategy alternating intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) first reported for 9 pediatric cases of Guillain-Barré syndrome in 2018-for treatment of severe immune-mediated neurologic disorders in children. METHODS: The modified zipper method comprised longer intervals between PLEX-IVIG cycles (48 hours instead of 24 hours), more cycles (7-10 instead of 5), a consistent plasma volume exchange (instead of the original multistep approach), and variable infusion times for IVIGs (4-8 hours). The modified zipper method was applied as an individual treatment approach once standard therapy failed. The follow-up ranged from 6 months to 2 years. Cases were analyzed retrospectively. Disease severity was mainly quantified by the Guillain-Barré syndrome disability score. RESULTS: Four children (9-15 years) with (1) Miller-Fisher syndrome, (2) Bickerstaff brainstem encephalitis, (3) common Guillain-Barré syndrome, and (4) severe acute disseminated encephalomyelitis were treated by the modified zipper method. Results for duration of mechanical ventilation (median of 12 days, interquartile range [IQR] 8-16), hospital stay (median of 23 days, IQR 22-24), and time to unaided walking (median of 22 days, IQR 21-37) outperformed previous studies with IVIG/PLEX alone or IVIG + PLEX combinations unlike the zipper method. CONCLUSION: The modified zipper method is associated with a low mortality, a short mechanical ventilation time, a short hospital stay, and an excellent outcome in children with severe Guillain-Barré syndrome or acute disseminated encephalomyelitis. Our regimen is streamlined for applicability. Results emphasize its robust effectiveness as an option for therapy escalation in severe neuroimmunologic diseases. Now, multicenter trials are needed to evaluate this novel treatment strategy.

Ambulatory Assessment of Psychological and Physiological Stress on Workdays and Free Days Among Teachers. A Preliminary Study.

OBJECTIVE: Teachers are affected by high levels of job stress, leading to one of the highest rates of burnout. The purpose of our pilot study was to investigate the diurnal course of teachers' psychological and physiological stress responses [cortisol levels, alpha-amylase, heart rate (HR), and heart rate variability (HRV)]. Another aim of the project was to test the applicability of ambulatory assessment methods in daily teaching situations. METHODS: In a non-clinical sample of eight primary school teachers (mean age = 43, SD = 15.22, 6 females) in Switzerland, continuous biopsychological data on two workdays and a free day were assessed. The teachers' HRs and HRV were measured continuously using an ambulatory ECG. Additionally, eight saliva samples were collected from the teachers repeatedly throughout the day to determine the diurnal course of salivary cortisol and alpha-amylase (sAA). Perceived stress and anger ratings were assessed simultaneously. RESULTS: As hypothesized, the teachers' morning cortisol levels, perceived stress, and anger levels were significantly higher, and their overall HRV was significantly lower on workdays than on a free day. Conversely, sAA levels and HRs showed no significant differences between working and free days. Salivary markers exhibited the expected diurnal course, with decreasing cortisol and increasing sAA levels over the course of the day, while self-rated stress reached the maximum at midday during working days. CONCLUSION: The results of the present explorative study show that physiological and psychological parameters differ within working and free days for teachers. A comparison between working and free days resulted in differences in morning cortisol levels, HRV as well as stress and anger levels. The ambulatory assessment method was found to be applicable in daily teaching situations.