Electroencephalogram Biomarkers from Anesthesia Induction to Identify Vulnerable Patients at Risk for Postoperative Delirium.

BACKGROUND: Postoperative delirium is a common complication in elderly patients undergoing anesthesia. Even though it is increasingly recognized as an important health issue, the early detection of patients at risk for postoperative delirium remains a challenge. This study aims to identify predictors of postoperative delirium by analyzing frontal electroencephalogram at propofol-induced loss of consciousness. METHODS: This prospective, observational single-center study included patients older than 70 yr undergoing general anesthesia for a planned surgery. Frontal electroencephalogram was recorded on the day before surgery (baseline) and during anesthesia induction (1, 2, and 15 min after loss of consciousness). Postoperative patients were screened for postoperative delirium twice daily for 5 days. Spectral analysis was performed using the multitaper method. The electroencephalogram spectrum was decomposed in periodic and aperiodic (correlates to asynchronous spectrum wide activity) components. The aperiodic component is characterized by its offset (y intercept) and exponent (the slope of the curve). Computed electroencephalogram parameters were compared between patients who developed postoperative delirium and those who did not. Significant electroencephalogram parameters were included in a binary logistic regression analysis to predict vulnerability for postoperative delirium. RESULTS: Of 151 patients, 50 (33%) developed postoperative delirium. At 1 min after loss of consciousness, postoperative delirium patients demonstrated decreased alpha (postoperative delirium: 0.3 µV2 [0.21 to 0.71], no postoperative delirium: 0.55 µV2 [0.36 to 0.74]; P = 0.019] and beta band power [postoperative delirium: 0.27 µV2 [0.12 to 0.38], no postoperative delirium: 0.38 µV2 [0.25 to 0.48]; P = 0.003) and lower spectral edge frequency (postoperative delirium: 10.45 Hz [5.65 to 15.04], no postoperative delirium: 14.56 Hz [9.51 to 16.65]; P = 0.01). At 15 min after loss of consciousness, postoperative delirium patients displayed a decreased aperiodic offset (postoperative delirium: 0.42 µV2 (0.11 to 0.69), no postoperative delirium: 0.62 µV2 [0.37 to 0.79]; P = 0.004). The logistic regression model predicting postoperative delirium vulnerability demonstrated an area under the curve of 0.73 (0.69 to 0.75). CONCLUSIONS: The findings suggest that electroencephalogram markers obtained during loss of consciousness at anesthesia induction may serve as electroencephalogram-based biomarkers to identify at an early time patients at risk of developing postoperative delirium.

Unveiling age-independent spectral markers of propofol-induced loss of consciousness by decomposing the electroencephalographic spectrum into its periodic and aperiodic components.

Background: Induction of general anesthesia with propofol induces radical changes in cortical network organization, leading to unconsciousness. While perioperative frontal electroencephalography (EEG) has been widely implemented in the past decades, validated and age-independent EEG markers for the timepoint of loss of consciousness (LOC) are lacking. Especially the appearance of spatially coherent frontal alpha oscillations (8-12 Hz) marks the transition to unconsciousness.Here we explored whether decomposing the EEG spectrum into its periodic and aperiodic components unveiled markers of LOC and investigated their age-dependency. We further characterized the LOC-associated alpha oscillations by parametrizing the adjusted power over the aperiodic component, the center frequency, and the bandwidth of the peak in the alpha range. Methods: In this prospective observational trial, EEG were recorded in a young (18-30 years) and an elderly age-cohort (≥ 70 years) over the transition to propofol-induced unconsciousness. An event marker was set in the EEG recordings at the timepoint of LOC, defined with the suppression of the lid closure reflex. Spectral analysis was conducted with the multitaper method. Aperiodic and periodic components were parametrized with the FOOOF toolbox. Aperiodic parametrization comprised the exponent and the offset. The periodic parametrization consisted in the characterization of the peak in the alpha range with its adjusted power, center frequency and bandwidth. Three time-segments were defined: preLOC (105 - 75 s before LOC), LOC (15 s before to 15 s after LOC), postLOC (190 - 220 s after LOC). Statistical significance was determined with a repeated-measures ANOVA. Results: Loss of consciousness was associated with an increase in the aperiodic exponent (young: p = 0.004, elderly: p = 0.007) and offset (young: p = 0.020, elderly: p = 0.004) as well as an increase in the adjusted power (young: p < 0.001, elderly p = 0.011) and center frequency (young: p = 0.008, elderly: p < 0.001) of the periodic alpha peak. We saw age-related differences in the aperiodic exponent and offset after LOC as well as in the power and bandwidth of the periodic alpha peak during LOC. Conclusion: Decomposing the EEG spectrum over induction of anesthesia into its periodic and aperiodic components unveiled novel age-independent EEG markers of propofol-induced LOC: the aperiodic exponent and offset as well as the center frequency and adjusted power of the power peak in the alpha range.

Working from home during COVID-19: A study of the interruption landscape.

We examine how the shift toward intensive work-from-home during the Coronavirus disease (COVID-19) pandemic has impacted the experience of interruptions during work time. We conducted a two-wave survey of 249 employees working from home during the COVID-19 pandemic. Building on a conceptual framework and typology (Leroy et al., 2020), we examine changes in the prevalence of interruptions since-COVID-19 as a function of interruption type (intrusions, distractions, breaks, multitasking, and surprises), source (work-based vs. nonwork), and timing (pre- vs. since-COVID-19). We find a large increase in interruptions since-COVID, with the largest increases observed for nonwork intrusions, distractions, and multitasking. Women reported a greater increase in interruptions, particularly with regard to nonwork interruptions of all types, in addition to work-based intrusions, multitasking, and surprises, uncovering an important source of gender inequity. A dedicated unshared workspace at home was associated with fewer nonwork interruptions, while more nonwork responsibilities predicted more nonwork interruptions. Further differentiation of interruption types and sources was observed with regard to outcomes of interruptions. Nonwork interruptions predicted higher family-to-work interference, emotional exhaustion, and lower performance. Notably, these relationships varied meaningfully across specific interruption-type/outcome combinations, highlighting the value of differentiating interruptions by type. Work-based interruptions-especially intrusions and multitasking-were associated with higher work-family interference and emotional exhaustion, as well as lower performance. The results of this study provide valuable insights to help understand and, ultimately, improve work experiences in the midst of the COVID-19 pandemic while also contributing to the broader literatures on interruptions and remote work. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Patient compliance and orthodontic treatment efficacy of Planas functional appliances with TheraMon microsensors.

OBJECTIVES: To assess patient compliance and treatment efficacy of preventive expansion treatment with removable Planas functional appliances using an integrated microsensor. MATERIALS AND METHODS: Wear time (WT) and behavior of 69 patients undergoing treatment with Planas functional appliances were assessed and analysed using TheraMon microsensors (Gschladt, Hargelsberg, Austria). Patients were followed up for a period of 9 months, and visits were made every 3 months to download WT data from the microsensor and to assess wearing behavior. From individual WT graphs,10 parameters were derived to characterize compliance for each patient. Treatment efficacy was measured by eight parameters determining the level of expansion after 9 months of treatment. RESULTS: Patients wore their device on average 15.8 ± 5.2 h/d. WT was unrelated to age and gender, but it was positively influenced by patient habits when keeping appliances during eating, sports, care and handling. Treatment efficacy in terms of intercanine and intermolar expansion was 4.4 ± 1.9 mm and 4.6 ± 2.0 mm for the maxilla, and 5.3 ± 2.0 mm and 4.7 ± 2.3 mm for the mandible, respectively. Efficacy was negatively affected by poor compliance (WT < 9 h/d) and by high variability of within-subject WT recordings. CONCLUSIONS: Perfect compliance is not necessary to achieve treatment success, but patients should exhibit sufficient wear time to allow maxillary expansion to occur. The TheraMon microsensor offers a new perspective and aid to individualize treatment prescriptions.

In vitro coagulation triggers anti-Aspergillus fumigatus neutrophil response.

AIM: To explore Aspergillus interactions with platelets in the blood, especially during clot formation. MATERIALS & METHODS: Aspergillus fumigatus resting or swollen conidia, germlings or hyphae were inoculated into blood sampled into tubes with or without anticoagulant. Interactions were explored using microscopy, and chemokine levels were determined. RESULTS: Anatomopathological examination of the clot revealed conidia and germlings colocalization with platelet aggregates, and neutrophil recruitment around aggregates. Transmission electron microscopy showed conidia and hyphae surrounded by neutrophils. Increased CCL5 and CXCL4 when conidia or germlings but not hyphae were added suggested they could be involved in neutrophil recruitment around aggregates. CONCLUSION: These data suggest platelets could trigger coagulopathy and activate neutrophils during aspergillosis. They open up new perspectives for aspergillosis management.

Work-family conflict and self-discrepant time allocation at work.

We examine the relationships between work-to-family conflict, time allocation across work activities, and the outcomes of work satisfaction, well-being, and salary in the context of self-regulation and self-discrepancy theories. We posit work-to-family conflict is associated with self-discrepant time allocation such that employees with higher levels of work-to-family conflict are likely to allocate less time than preferred to work activities that require greater self-regulatory resources (e.g., tasks that are complex, or those with longer term goals that delay rewards and closure) and allocate more time than preferred to activities that demand fewer self-regulatory resources or are replenishing (e.g., those that provide closure or are prosocial). We suggest this self-discrepant time allocation (actual vs. preferred time allocation) is one mechanism by which work-to-family conflict leads to negative employee consequences (Allen, Herst, Bruck, & Sutton, 2000; Mesmer-Magnus & Viswesvaran, 2005). Using polynomial regression and response surface methodology, we find that discrepancies between actual and preferred time allocations to work activities negatively relate to work satisfaction, psychological well-being, and physical well-being. Self-discrepant time allocation mediates the relationship between work-to-family conflict and work satisfaction and well-being, while actual time allocation (rather than the discrepancy) mediates the relationship between work-to-family conflict and salary. We find that women are more likely than men to report self-discrepant time allocations as work-to-family conflict increases.

Polymorphisms of coding trinucleotide repeats of homeogenes in neurodevelopmental psychiatric disorders.

OBJECTIVES: Autism (MIM#209850) and schizophrenia (MIM#181500) are both neurodevelopmental psychiatric disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders. Genetic studies have reported an association between autism and DLX2, HOXA1, EN2, ARX, and FOXP2 genes whereas only three studies of EN2, OTX2, and FOXP2 were performed on schizophrenia. Interestingly, most of these candidate genes contain trinucleotide repeats coding for polyamino acid stretch in which instability can be the cause of neurodevelopmental disorders. Our goal was to identify variations of coding trinucleotide repeats in schizophrenia, autism, and idiopathic mental retardation. METHODS: We screened the coding trinucleotide repeats of OTX1, EN1, DLX2, HOXA1, and FOXP2 genes in populations suffering from schizophrenia (247 patients), autism (98 patients), and idiopathic mental retardation (56 patients), and compared them with control populations (112 super controls and 202 healthy controls). RESULTS: Novel deletions and insertions of coding trinucleotide repeats were found in the DLX2, HOXA1, and FOXP2 genes. Most of these variations were detected in controls and no difference in their distribution was observed between patient and control groups. Two different polymorphisms in FOXP2 were, however, found only in autistic patients and the functional consequences of these variations of repeats have to be characterized and correlated to particular clinical features. CONCLUSION: This study did not identify specific disease risk variants of trinucleotide repeats in OTX1, EN1, DLX2, HOXA1, and FOXP2 candidate genes in neurodevelopmental psychiatric disorders.

Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT: association with childhood ADHD in male African-Caribbean cocaine dependents?

The conflicting results reported by genetic studies with the variants of the genes coding for the dopaminergic system in cocaine addicts could be partially explained by the difficulties to constitute homogenous sample of patients. Childhood attention-deficit/hyperactivity disorder (ADHD), and/or impulsivity are frequently associated with cocaine addiction and could participate in the heterogeneity of the samples in cocaine addicts. Accordingly, it is hypothesized that cocaine addiction would be associated with the variants of the genes coding for the dopamine system in an homogenized sample of cocaine addicts, especially in individuals with childhood ADHD comorbidity, or with a high impulsivity score. The potential association of the variants TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT was examined in African-Caribbean males, smoked-cocaine dependents. All the subjects were assessed with the Diagnostic Interview of Genetic Studies, the Barratt's impulsivity scale, and the Wender Utah rating scale for childhood ADHD. A positive association was found with the DRD2 and DRD4 polymorphisms in the subgroups of patients with childhood ADHD, or with a high impulsivity score, which represented, respectively, 53.3 and 73.0% of the patients. Conversely, no positive association was found for any of the polymorphisms studied when the group of patients was examined as a whole. Therefore, our results suggest that the clinical dimensions of childhood ADHD and of impulsivity could be taken into account to homogenize the samples of patients in cocaine association studies.

Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate.

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

Age at onset of schizophrenia: interaction between brain-derived neurotrophic factor and dopamine D3 receptor gene variants.

One of the main features of schizophrenia is its age at onset in early adulthood. Dopaminergic dysregulation is the most documented neurobiological factor that may be involved in triggering schizophrenia. Recent findings on neurodevelopmental processes show that the brain-derived neurotrophic factor plays a critical role in the development of mesolimbic dopaminergic-related systems and regulates the expression of dopamine D3 receptors. In this study, we examine whether an interaction between dopamine D3 receptors and brain-derived neurotrophic factor gene variants influences age at onset in patients with schizophrenia. Our findings show that this gene-gene interaction was significantly associated with an earlier emergence of psychosis by 3 years.

Population-based and family-based association study of 5'UTR polymorphism of the reelin gene and schizophrenia.

Reelin is a glycoprotein involved in the migration and positioning of proliferating neurons and synaptic connectivity during neurodevelopment. It may also modulate neuronal plasticity throughout life. Therefore, the reelin gene is a candidate gene for schizophrenia. We examined the association of the CGG repeat polymorphism in the 5'-untranslated region of the reelin gene with schizophrenia in 266 unrelated French Caucasian patients, 156 of their parents, and 103 controls. We found no difference in the allele distribution between patients and controls although there was a significant higher prevalence of the genotype 8-8 in controls (CLUMP T3: chi(2) = 6.3, P = 0.035). There was no significant transmission disequilibrium in intrafamilial analysis. To refine our phenotypic characterization and in accordance with converging evidence suggesting that treatment resistance is associated with indices of abnormal neurodevelopment, we studied the association between reelin gene polymorphism and response to antipsychotics. Patients who responded to antipsychotics had a higher frequency of both the (CGG)(10) allele and (CGG)(10)-containing genotypes (P = 0.02; P = 0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]). Our results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia.

Cerebellum development and schizophrenia: an association study of the human homeogene Engrailed 2.

Epidemiological data and family studies in schizophrenia show that genetic factors contribute to the vulnerability to this disorder. The homeogene Engrailed 2 (EN2) is specifically involved in patterning the region that gives rise to the cerebellum and controls the plasticity of midbrain dopaminergic neurons. We carried out an association study for a CA repeat polymorphism located in the 3' region of the homeogene EN2. The subjects consisted of 165 patients with schizophrenia and 97 controls matched for age and ethnicity from a French Caucasian population. We found no significant association of schizophrenia with this bi-nucleotide repeat polymorphism of the EN2 gene.

Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family-based association study of 55 trios. Extended transmission-disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene (P = 0.005). Moreover, in a population-based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically-matched controls (P = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family- and population-based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms.