Waking qEEG in older adults with insomnia and its associations with sleep reactivity and dysfunctional beliefs about sleep.

Sleep quality often deteriorates with age, and insomnia among the elderly increases the risks of both physical and psychiatric disorders. To elucidate the mechanisms and identify useful diagnostic biomarkers for insomnia in the elderly, the current study investigated the associations of waking brain activity patterns with susceptibility to stress-induced insomnia (sleep reactivity) and dysfunctional beliefs about sleep, major factors precipitating and maintaining insomnia, respectively. Forty-five participants aged 60 years or older with insomnia completed self-reported measures assessing depression, anxiety, sleep quality, dysfunctional beliefs about sleep, and sleep reactivity. Participants were then examined by quantitative electroencephalography (qEEG) during wakefulness, and spectral analysis was conducted to examine associations of regional frequency band power with these insomnia-precipitating and -maintaining factors. Dysfunctional beliefs about sleep were significantly correlated with higher beta/high-beta frequency band powers, while sleep reactivity was correlated with higher theta and delta frequency band powers. These findings suggest that sleep reactivity of older adults is associated with widespread cortical deactivation leading to poor stress coping, while their dysfunctional beliefs about sleep are associated with hyperactivation which is related to cognitive processes. These associations suggest that cognitive inflexibility and maladaptive stress-coping contribute to insomnia among the elderly.

Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression.

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.

Moderating effect of shift work on sleep and depression in individuals at high risk of bipolar disorder.

BACKGROUND: Social Zeitgeber Theory posits that disruptions in social rhythms can increase susceptibility to bipolar disorder (BD). Shift work (SW) is one of the external factors that cause instability in social rhythms and the sleep-wake cycle. This study evaluated the moderating influences of SW on the risks of BD and sleep-related parameters and depressive symptoms. Furthermore, we evaluated the specific work schedules including daytime, nighttime, and regular and irregular rotating SW. METHODS: An online survey was administered to 6665 participants, with 3379 (50.7 %) classified as individuals with high scores of Mood Disorder Questionnaire (MDQ). The survey included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Scale (ISI), Epworth Sleepiness Scale (ESS), and Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: A multivariate regression model revealed significant interactive effects of MDQ positivity and SW on PSQI, ISI, and CES-D scores, but not ESS scores. In a secondary analysis of the high MDQ screen group, daytime workers had lower scores in sleep disturbances and depressive symptoms compared to those engaged in other forms of SW. LIMITATIONS: Online surveys were accessible voluntarily, leading to potential selection bias. Cross-sectional data identified associations, not causal relationships. Only a self-reported questionnaire was used. CONCLUSIONS: Our findings emphasize the advantages of a daytime work schedule for individuals at high risk of BD. In accordance with the principles of social rhythm interpersonal therapy, sleep interventions for individuals at high risk of BD should include the maintenance of a consistent daytime schedule.

Shift schedules and circadian preferences: the association with sleep and mood.

Object: We explored the circadian preferences of non-shift workers (non-SWs) and various types of shift workers (SWs), and the associations of these preferences with sleep and mood. Methods: In total, 4,561 SWs (2,419 women and 2,142 men aged 37.00 ± 9.80 years) and 2,093 non-SWs (1,094 women and 999 men aged 37.80 ± 9.73 years) completed an online survey. Of all SWs, 2,415 (1,079 women and 1,336 men aged 37.77 ± 9.96 years) reported regularly rotating or fixed schedules ("regular SWs"), and 2,146 (1,340 women and 806 men aged 36.12 ± 9.64 years) had irregular schedules ("irregular SWs"). Of the regular SWs, 2,040 had regularly rotating schedules, 212 had fixed evening schedules, and 163 had fixed night schedules. All participants completed the Morningness-Eveningness Questionnaire (MEQ) exploring circadian preferences, the short form of the Center for Epidemiological Studies-Depression Scale (CES-D) evaluating depression, the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). Results: Compared to non-SWs, SWs had lower MEQ scores, i.e., more eveningness, after controlling for age, gender, income, occupation, and weekly work hours (F = 87.97, p < 0.001). Irregular SWs had lower MEQ scores than regular SWs (F = 50.89, p < 0.001). Among regular SWs, the MEQ scores of fixed evening and fixed night SWs were lower than those of regularly rotating SWs (F = 22.42, p < 0.001). An association between the MEQ and ESS scores was apparent in non-SWs (r = -0.85, p < 0.001) but not in SWs (r = 0.001, p = 0.92). Conclusion: SWs exhibited more eveningness than non-SWs; eveningness was particularly prominent in SWs with irregular or fixed evening/night shifts. Eveningness was associated with sleepiness only in non-SWs, but not in SWs.

Brain structural correlates of subjective sleepiness and insomnia symptoms in shift workers.

Background: Studies on the brain structures of shift workers are limited; thus, this cross-sectional study aimed to compare the brain structures and the brain structural correlates of subjective sleepiness and insomnia symptoms between shift workers and non-shift workers. Methods: Shift workers (n = 63) and non-shift workers (n = 58) completed questionnaires assessing subjective sleepiness and insomnia symptoms. Cortical thickness, cortical surface area, and subcortical volumes were measured by magnetic resonance imaging. The brain morphometric measures were compared between the groups, and interaction analyses using the brain morphometric measures as the dependent variable were performed to test the interactions between the study group and measures of sleep disturbance (i.e., subjective sleepiness and insomnia symptoms). Results: No differences in cortical thickness, cortical surface area, or subcortical volumes were detected between shift workers and non-shift workers. A single cluster in the left motor cortex showed a significant interaction between the study group and subjective sleepiness in the cortical surface area. The correlation between the left motor cortex surface area and the subjective sleepiness level was negative in shift workers and positive in non-shift workers. Significant interaction between the study group and insomnia symptoms was present for the left/right putamen volumes. The correlation between the left/right putamen volumes and insomnia symptom levels was positive in shift workers and negative in non-shift workers. Conclusion: Left motor cortex surface area and bilateral putamen volumes were unique structural correlates of subjective sleepiness and insomnia symptoms in shift workers, respectively.

Identifying unique subgroups in suicide risks among psychiatric outpatients.

BACKGROUND: The presence of psychiatric disorders is widely recognized as one of the primary risk factors for suicide. A significant proportion of individuals receiving outpatient psychiatric treatment exhibit varying degrees of suicidal behaviors, which may range from mild suicidal ideations to overt suicide attempts. This study aims to elucidate the transdiagnostic symptom dimensions and associated suicidal features among psychiatric outpatients. METHODS: The study enrolled patients who attended the psychiatry outpatient clinic at a tertiary hospital in South Korea (n = 1, 849, age range = 18-81; 61% women). A data-driven classification methodology was employed, incorporating a broad spectrum of clinical symptoms, to delineate distinctive subgroups among psychiatric outpatients exhibiting suicidality (n = 1189). A reference group of patients without suicidality (n = 660) was included for comparative purposes to ascertain cluster-specific sociodemographic, suicide-related, and psychiatric characteristics. RESULTS: Psychiatric outpatients with suicidality (n = 1189) were subdivided into three distinctive clusters: the low-suicide risk cluster (Cluster 1), the high-suicide risk externalizing cluster (Cluster 2), and the high-suicide risk internalizing cluster (Cluster 3). Relative to the reference group (n = 660), each cluster exhibited distinct attributes pertaining to suicide-related characteristics and clinical symptoms, covering domains such as anxiety, externalizing and internalizing behaviors, and feelings of hopelessness. Cluster 1, identified as the low-suicide risk group, exhibited less frequent suicidal ideation, planning, and multiple attempts. In the high-suicide risk groups, Cluster 2 displayed pronounced externalizing symptoms, whereas Cluster 3 was primarily defined by internalizing and hopelessness symptoms. Bipolar disorders were most common in Cluster 2, while depressive disorders were predominant in Cluster 3. DISCUSSION: Our findings suggest the possibility of differentiating psychiatric outpatients into distinct, clinically relevant subgroups predicated on their suicide risk. This research potentially paves the way for personalizing interventions and preventive strategies that address cluster-specific characteristics, thereby mitigating suicide-related mortality among psychiatric outpatients.

Direct and Indirect Chimeric Antigen Receptor T-Cell Imaging with PET/MRI in a Tumor Xenograft Model.

Background Chimeric antigen receptor (CAR) T cells are a promising cancer therapy; however, reliable and repeatable methods for tracking and monitoring CAR T cells in vivo remain underexplored. Purpose To investigate direct and indirect imaging strategies for tracking the biodistribution of CAR T cells and monitoring their therapeutic effect in target tumors. Materials and Methods CAR T cells co-expressing a tumor-targeting gene (anti-CD19 CAR) and a human somatostatin receptor subtype 2 (hSSTr2) reporter gene were generated from human peripheral blood mononuclear cells. After direct labeling with zirconium 89 (89Zr)-p-isothiocyanatobenzyl-desferrioxamine (DFO), CAR T cells were intravenously injected into immunodeficient mice with a CD19-positive and CD19-negative human tumor xenograft on the left and right flank, respectively. PET/MRI was used for direct in vivo imaging of 89Zr-DFO-labeled CAR T cells on days 0, 1, 3, and 7 and for indirect cell imaging with the radiolabeled somatostatin receptor-targeted ligand gallium 68 (68Ga)-DOTA-Tyr3-octreotide (DOTATOC) on days 6, 9, and 13. On day 13, mice were euthanized, and tissues and tumors were excised. Results The 89Zr-DFO-labeled CAR T cells were observed on PET/MRI scans in the liver and lungs of mice (n = 4) at all time points assessed. However, they were not visualized in CD19-positive or CD19-negative tumors, even on day 7. Serial 68Ga-DOTATOC PET/MRI showed CAR T cell accumulation in CD19-positive tumors but not in CD19-negative tumors from days 6 to 13. Notably, 68Ga-DOTATOC accumulation in CD19-positive tumors was highest on day 9 (mean percentage injected dose [%ID], 3.7% ± 1.0 [SD]) and decreased on day 13 (mean %ID, 2.6% ± 0.7) in parallel with a decrease in tumor volume (day 9: mean, 195 mm3 ± 27; day 13: mean, 127 mm3 ± 43) in the group with tumor growth inhibition. Enhanced immunohistochemistry staining of cluster of differentiation 3 (CD3) and hSSTr2 was also observed in excised CD19-positive tumor tissues. Conclusion Direct and indirect cell imaging with PET/MRI enabled in vivo tracking and monitoring of CAR T cells in an animal model. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Bulte in this issue.

18F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation.

BACKGROUND: The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury. METHODS: Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5). RESULTS: 18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796). CONCLUSIONS: Our results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.

Sleep Reactivity and Sleep Efforts in Shift Workers.

OBJECTIVE: The current study aimed to investigate the differences in sleep reactivity and sleep effort differs among late night shift workers (LSWs) and non-late night shift workers (non-LSWs), and non-shift workers (non-SWs). METHODS: In total, 6,023 participants (1,613 non-SWs, 3,339 LSWs, and 1,071 non-LSWs) were recruited. Non-SWs was defined as those who works at fixed schedules during standard daylight. LSWs was defined as who work late night hours (10 PM-6 AM), while non-LSWs was SWs who did not work during late night. All completed the Ford Insomnia Response to Stress Test (FIRST), the Glasgow Sleep Effort Scale (GSES), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISI), and the short-term Center for Epidemiologic Studies-Depression scale (CES-D) through online survey. RESULTS: LSWs and non-LSWs reported higher FIRST, GSES scores than non-SWs. In addition, LSWs reported higher FIRST, GSES scores than non-LSWs. FIRST scores were correlated with CES-D, PSQI, ISI, and ESS for LSWs, non-LSWs, and non-SWs alike. GSES scores were also correlated with CES-D, PSQI, ISI, and ESS for LSWs, non-LSWs, and non-SWs alike. CONCLUSION: SWs showed higher sleep reactivity and sleep effort than non-SWs. LSWs had higher sleep reactivity and sleep effort than non-LSWs, and these variables are associated with insomnia, daytime sleepiness, and depressive symptoms. Our findings suggests that late night schedule, may increase sleep reactivity and sleep effort, which are associated with sleep and mood disturbances.

Effects of co-sleeping with a shift worker on sleep, mood and cognition.

Objective: Although the negative effects of shift work on workers' sleep and mood are well-known, the effects of shift work on their sleep partners' sleep and mood have rarely been investigated. The current study explored the effects of co-sleeping with a shift worker (SW) on the partner's subjective sleep quality, daytime sleepiness, depressive symptoms, and cognitive disturbances. Methods: Online sleep and work-environment self-report questionnaires (e.g., including the presence of co-sleepers, work schedules of the co-sleepers, and their work schedules) were administered. The questionnaires also included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Cognitive Failures Questionnaire (CFQ), and the short-term Center for Epidemiologic Studies-Depression scale (CES-D). Participants consisted of co-sleepers of SWs (n = 657), co-sleepers of non-SWs (n = 2186), and solo sleepers (n = 2432). Results: Significant between-group differences in the PSQI, ESS, CFQ, and CES-D were observed after controlling for age, gender, work shift, and parenting (p < 0.001). Co-sleepers of SWs showed higher PSQI, ESS, CFQ, and CES-D scores than co-sleepers of non-SWs and solo sleepers. Solo sleepers reported significantly higher PSQI and CES-D scores than co-sleepers of non-SWs. The PSQI, ESS, CFQ, and CES-D scores were significantly correlated in all groups. The association between the ESS and PSQI was stronger in co-sleepers of SWs than in solo sleepers. The association between the ESS and CES-D was stronger in co-sleepers of SWs than in solo sleepers. Conclusions: Co-sleeping with SWs is associated with poor sleep quality, daytime sleepiness, depressive symptoms, and cognitive disturbances in the partner.

Circadian misalignment alters resting-state functional connectivity of the salience network in rotating shift workers.

STUDY OBJECTIVES: This study compared resting-state functional connectivity (rsFC) of the salience network (SN) between rotating shift workers (RSWs) and controls. Furthermore, we examined whether rsFC of the SN was correlated with sleep, emotion, cognition, and attention. METHODS: The 60 RSWs and 57 controls enrolled in this study completed self-report questionnaires and sleep diaries to assess subjective sleep quality, and polysomnography and actigraphy to evaluate objective sleep and 24-hour rest-activity rhythm parameters. The participants also underwent resting-state functional magnetic resonance imaging and structural T1 scans. We performed a seed-based rsFC analysis of the SN using the anterior cingulate cortex (ACC) and anterior insula (AI) as seed regions. Furthermore, AI and ACC rsFC were compared in RSWs and controls, and we analyzed correlations between rsFC and variables of interest showing significant group differences. RESULTS: Compared with controls, RSWs showed reduced rsFC between the ACC and right insula, and increased rsFC of the ACC with the left occipital lobe and right superior frontal gyrus extending to the supplementary motor area (SFG/SMA). Moreover, RSWs showed reduced rsFC between the right AI and right superior parietal lobule (SPL). Finally, rsFC between the ACC and right AI was correlated with 24-hour rest-activity rhythmicity. CONCLUSIONS: Although RSWs did not show sleep disturbance, emotional distress, cognitive impairment, or attention deficits, alterations of right insula, left occipital lobe, right SFG/SMA, and right SPL rsFC in the SN indicate that impairments in salience detection and top-down attentional control may emerge in shift workers over time.

Job burnout among workers with different shift regularity: interactive factors between sleep, depression, and work environment.

Object: We investigated burnout and associated factors in non-shift workers (NSWs), shift workers with regular rotating shifts (RRSWs), and shift workers with irregular or unpredictable rotating shifts (IRSWs). Methods: In total, 5,125 adult workers (1,966 NSWs, 1,936 RRSWs, and 1,223 IRSWs) participated in an online self-reported survey. Job burnout and three dimensions thereof (exhaustion, cynicism, and professional efficacy) were assessed using the Maslach Burnout Inventory-General Survey (MBI-GS). The Center for Epidemiological Studies Depression Scale (CES-D) (depressive symptoms), Pittsburgh Sleep Quality Index (PSQI) (subjective sleep quality), and Korean Occupational Stress Scale (KOSS) (stressful job environment) were also used. Results: Both types of shift workers scored higher in terms of exhaustion, cynicism, and poor professional efficacy on the MBI-GS compared with NSWs after controlling for age and gender. IRSWs exhibited higher scores on the exhaustion and professional efficacy dimensions of the MBI-GS compared with RRSWs. After controlling for the CES-D and PSQI scores, we found no significant difference in cynicism among the groups. After controlling for the KOSS score, we found no significant difference in professional efficacy. All MBI-GS dimensional scores were correlated significantly with the CES-D, PSQI, and KOSS scores in all three groups. Conclusion: The job burnout level of rotating shift workers, especially those with irregular shifts, was higher than that of other workers. Cynicism in shift workers may be largely attributable to poor sleep or depression; the poor efficacy of shift workers may be explained by their stressful work environment.

Fatigue and somatization in shift-workers: Effects of depression and sleep.

OBJECTIVE: We investigated the differences in fatigue and somatization between shift and non-shift workers and explored the effects of sleep and depression on fatigue and somatization in shift workers. METHODS: In total, 4543 shift workers and 2089 non-shift workers completed self-reported questionnaires. The Center for Epidemiologic Studies Depression Scale (CESD), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), and Somatization subscale of the Symptom Checklist 90-item version (SCL-SOM) were used to measure depression, sleep quality, fatigue, and somatization, respectively. Fatigue and somatization were compared between shift and non-shift workers after controlling for different sets of covariates. RESULTS: Compared to non-shift workers, shift workers reported higher FSS (mean difference: 2.19 ± 0.30, p < 0.01) and SCL-SOM (mean difference: 1.77 ± 0.21, p < 0.01) scores after controlling for age, gender, presence of medical illness, occupational category, monthly income, length of service, and weekly working hours. The between-group difference in FSS score was no longer significant after additionally controlling for CES-D (p = 0.15) or PSQI (p = 0.18). The between-group difference in SCL-SOM score showed only non-significant trends after additionally controlling for CES-D (p = 0.09) or PSQI (p = 0.07). The group difference in SCL-SOM scores disappeared after controlling for both CES-D and PSQI scores (p = 0.99). CONCLUSIONS: Shift workers had higher fatigue and somatization levels than non-shift workers and the group difference was associated with disturbed sleep and depressed mood in shift workers.

Effects of sleep and impulsivity on suicidality in shift and non-shift workers.

INTRODUCTION: Shift workers are known to have a higher suicide risk than non-shift workers. Sleep disturbance and impulsivity are also risk factors for suicidality. This study investigated the effects of poor sleep and impulsivity on suicidality in shift and non-shift workers. METHODS: In total, 4572 shift workers (37.0 ± 9.84 years, 2150 males) and 2093 non-shift workers (37.8 ± 9.73 years, 999 males) participated in an online self-report survey. Suicidality was assessed using the Suicidal Behaviors Questionnaire. The Pittsburgh Sleep Quality Index was employed to explore subjective sleep quality, the Insomnia Severity Index to detect insomnia, the Epworth Sleepiness Scale (ESS) to evaluate excessive daytime sleepiness (EDS), the Center for Epidemiological Studies-Depression (CES-D) Scale to assess depressive symptoms, and the Impulsive Behavior Scale (UPPS-P) to explore impulsivity. RESULTS: Shift workers showed poorer sleep quality, and greater impulsivity and suicidality, than non-shift workers. Impulsivity, sleep duration, sleep quality, and insomnia were significantly associated with suicidality, independent of depression. For both shift and non-shift workers, sleep quality moderated the association between impulsivity and suicidality. However, the moderating effects of sleep duration and EDS on the association between impulsivity and suicidality were apparent only in non-shift workers, while a moderating effect of insomnia was observed only in shift workers. CONCLUSION: Shift work, sleep disturbances and impulsivity may exacerbate suicide risk. In addition, the interrelationships among insomnia, EDS, impulsivity, and suicidality may differ between shift and non-shift workers.

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.

Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs. BMNCs cultured under the defined conditions synergistically expressed multiple genes, including those for PDX1, NKX6.1, MAFA, NEUROG3, GLUT2, and insulin, related to pancreatic beta cell development and function. They produced insulin/C-peptide and PDX1, as assessed using immunofluorescence and flow cytometry. The induced cells secreted insulin in a glucose-responsive manner, similar to normal pancreatic beta cells. Grafting BMNC-derived IPCs under kidney capsules of mice with streptozotocin (STZ)-induced diabetes alleviated hyperglycemia by lowering blood glucose levels, enhancing glucose tolerance, and improving glucose-stimulated insulin secretion. Insulin- and PDX1-expressing cells were observed in the IPC-bearing graft sections of nephrectomized mice. Therefore, this study provides a simple protocol for BMNC differentiation, which can be a novel approach for cell-based therapy in diabetes mellitus.

The Influence of Life Stress and Sleep Disturbance on White Matter Integrity.

OBJECTIVE: This study investigated whether sleep and stress mutually interact to induce changes in white matter integrity. METHODS: Diffusion tensor imaging (DTI) was conducted on 36 participants (male=22, female=14; mean age=38.33±12.78 years). Participants were divided into three groups depending on their sleep quality and stress levels: poor sleepers with stress, poor sleepers without stress, and good sleepers. Sleep quality and stress level were evaluated using the Pittsburgh Sleep Quality Index and the Life Experiences Survey, respectively. Fractional anisotropy (FA) values were calculated employing DTI tractography. RESULTS: After controlling for age and sex, poor sleepers with stress exhibited a lower FA of the left inferior cerebellar peduncle (ICP) than did poor sleepers without stress (t=2.81, p=0.02). Poor sleepers without stress showed a higher FA of the right middle longitudinal fasciculus (MdLF) than did good sleepers (t=3.35, p=0.006). CONCLUSION: The current study reports the effects of sleep, stress, and their interaction on the white matter integrities of the ICP and MdLF. ICP change seems to be associated with sleep disturbances related to stress, while MdLF change would be associated with sleep disturbances unrelated to stress.

Sleep disturbances and depressive symptoms of shift workers: Effects of shift schedules.

This study explored sleep disturbances and depression among various types of shift workers (SWs) and non-SWs, focusing on work schedule diversity. We enrolled 6,654 adults (4,561 SWs, 2,093 non-SWs). Based on self-report questionnaires on work schedules, the participants were classified according to shift work type: non-shift work; and fixed evening, fixed night, regularly rotating, irregularly rotating, casual, and flexible shift work. All completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and short-term Center for Epidemiologic Studies-Depression scale (CES-D). SWs reported higher PSQI, ESS, ISI, and CES-D than non-SWs. Fixed SWs (fixed evenings and fixed nights) and true SWs (regularly and irregularly rotating SWs) scored higher on the PSQI, ISI, and CES-D than non-SWs. True SWs scored higher on the ESS than fixed SWs and non-SWs. Among fixed SWs, fixed night SWs scored higher on the PSQI and ISI than fixed evening SWs. Among true SWs, irregular SWs (irregularly rotating and casual SWs) scored higher on the PSQI, ISI, and CES-D compared to regularly rotating SWs. The PSQI, ESS, and ISI independently were associated with the CES-D of all SWs. We found an interaction between the ESS and the work schedule on the one hand, and the CES-D on the other, which was stronger in SWs than non-SWs. Fixed night and irregular shifts were linked with sleep disturbances. The depressive symptoms of SWs are associated with sleep problems. The effects of sleepiness on depression were more prominent in SWs than non-SWs.

MR Template-Based Individual Brain PET Volumes-of-Interest Generation Neither Using MR nor Using Spatial Normalization.

For more anatomically precise quantitation of mouse brain PET, spatial normalization (SN) of PET onto MR template and subsequent template volumes-of-interest (VOIs)-based analysis are commonly used. Although this leads to dependency on the corresponding MR and the process of SN, routine preclinical/clinical PET images cannot always afford corresponding MR and relevant VOIs. To resolve this issue, we propose a deep learning (DL)-based individual-brain-specific VOIs (i.e., cortex, hippocampus, striatum, thalamus, and cerebellum) directly generated from PET images using the inverse-spatial-normalization (iSN)-based VOI labels and deep convolutional neural network model (deep CNN). Our technique was applied to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer's disease. Eighteen mice underwent T2-weighted MRI and 18F FDG PET scans before and after the administration of human immunoglobin or antibody-based treatments. To train the CNN, PET images were used as inputs and MR iSN-based target VOIs as labels. Our devised methods achieved decent performance in terms of not only VOI agreements (i.e., Dice similarity coefficient) but also the correlation of mean counts and SUVR, and CNN-based VOIs was highly accordant with ground-truth (the corresponding MR and MR template-based VOIs). Moreover, the performance metrics were comparable to that of VOI generated by MR-based deep CNN. In conclusion, we established a novel quantitative analysis method both MR-less and SN-less fashion to generate individual brain space VOIs using MR template-based VOIs for PET image quantification. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00772-4.

Neural activation underlying emotional interference of cognitive control in rotating shift workers: moderating effects of the prefrontal cortex response on the association between sleep disturbance and depressive symptoms.

STUDY OBJECTIVES: This study investigated the altered neural function involved in emotional interference and its role in linking sleep disturbance and depressive/anxiety symptoms in rotating shift workers. METHODS: Sixty rotating shift workers and 61 controls performed the emotional Stroop task in three blocks (emotional-related, sleep-related, and neutral words) during functional magnetic resonance imaging (fMRI) assessments. Sleep disturbance and depressive/anxiety symptoms were assessed using self-report measures and sleep diaries. Actigraphy was used to assess the sleep and circadian variables. fMRI scans were performed to compare brain activation during the emotional Stroop task. The proposed moderating models were tested using the PROCESS macro in SPSS software. RESULTS: A significant condition effect on reaction time was detected. Regardless of the group, reaction times were longer in the negative emotional word and sleep-related conditions than in the neutral word condition. Whole-brain analysis revealed that rotating shift workers show greater neural activation in the left dorsolateral prefrontal cortex (DLPFC) compared with controls while performing the emotional Stroop task with negative emotional words. Sleep disturbance was more strongly associated with depressive symptoms when activation of the left DLPFC was higher during the emotional Stroop task with negative words. CONCLUSIONS: The left DLPFC may play important roles in increased sensitivity to emotional information, possibly due to circadian misalignment, and has moderating effects on the association between sleep disturbance and depressive symptoms in rotating shift workers. These findings will help to identify possible brain regions where interventions can be performed to correct sleep and mood problems in rotating shift workers.