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1.
Exp Neurobiol ; 33(2): 107-117, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38724480

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years' duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups' gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

2.
Exp Neurobiol ; 33(2): 99-106, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38724479

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, high-resolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex-a major region in the extended olfactory network-and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

3.
Sleep ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38666299

STUDY OBJECTIVES: Shift work interferes with circadian rhythms, affecting sleep quality and cognitive function. Poor sleep quality in shift workers can impair psychomotor performance due to fatigue and sleepiness, increasing the risk of errors, accidents, and reduced productivity. Given the potential for atrophic changes in the hippocampus due to sleep disturbances, our study investigates how poor sleep quality correlates with hippocampal structural alterations and impacts psychomotor performance among shift workers. METHODS: We recruited 100 shift workers, classifying them based on sleep quality into two groups: good sleep-SW group (n = 59) and poor sleep-SW group (n = 41). Sleep quality was assessed using both 7-day actigraphy for sleep efficiency and the Pittsburgh Sleep Quality Index. A control group of 106 non-shift workers without sleep problems (non-SW group) was also included for comparison. The outcome measures were psychomotor speed and hippocampal volumes, both total and by subfield. RESULTS: The poor sleep-SW group showed significantly smaller hippocampal volumes than both the good sleep-SW group (P<0.001) and the non-SW group (P=0.003). Longer shift work years correlated with greater reductions in hippocampal volume in this group (r=-0.42, P=0.009), unlike in the good sleep-SW group (r=0.08, P=0.541). Furthermore, they demonstrated declines in psychomotor speed relative to the non-SW group (P=0.006), which correlated with smaller hippocampal volumes (r=0.37, P=0.020). CONCLUSIONS: Shift workers with poor sleep quality exhibit significant hippocampal volume reductions and psychomotor speed decline, underscoring the importance of early intervention and support for sleep issues in this population.

4.
Bioengineering (Basel) ; 11(3)2024 Mar 08.
Article En | MEDLINE | ID: mdl-38534539

Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson's correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.

5.
Compr Psychiatry ; 131: 152463, 2024 May.
Article En | MEDLINE | ID: mdl-38394926

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.


Bipolar Disorder , Outpatients , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Suicide, Attempted/psychology , Bipolar Disorder/psychology , Anxiety Disorders/psychology , Suicidal Ideation , Risk Factors
6.
J Clin Invest ; 134(4)2023 Dec 05.
Article En | MEDLINE | ID: mdl-38051585

Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we used kidney-specific expression of quantitative traits and single-nucleus open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2-KO mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulated de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered that pharmacological inhibition or genetic ablation of fatty acid synthase safeguarded kidney cells against profibrotic gene expression and prevented kidney disease in mice. Lipid accumulation and the expression of genes related to DNL were elevated in the kidneys of patients with fibrosis. Our findings pinpoint ACSS2 as a critical kidney disease gene and reveal the role of DNL in kidney disease.


Acetate-CoA Ligase , Kidney Diseases , Lipogenesis , Animals , Humans , Mice , Acetate-CoA Ligase/genetics , Fibrosis , Kidney/metabolism , Kidney Diseases/genetics , Kidney Diseases/metabolism , Kidney Tubules/metabolism , Lipogenesis/genetics
7.
Glomerular Dis ; 3(1): 258-265, 2023.
Article En | MEDLINE | ID: mdl-38033715

Background: Kidney diseases pose a significant global health burden; there is an urgent need to deepen our understanding of their underlying mechanisms. Summary: This review focuses on new innovative approaches that merge genome-wide association studies (GWAS) and single-cell omics (including transcriptomics) in kidney disease research. We begin by detailing how GWAS has identified numerous genetic risk factors, offering valuable insight into disease susceptibility. Then, we explore the application of scRNA-seq, highlighting its ability to unravel how genetic variants influence cellular phenotypes. Through a synthesis of recent studies, we illuminate the synergy between these two powerful methodologies, demonstrating their potential in elucidating the complex etiology of kidney diseases. Moreover, we discuss how this integrative approach could pave the way for precise diagnostics and personalized treatments. Key Message: This review underscores the transformative potential of combining GWAS and scRNA-seq in the journey toward a deeper understanding of kidney diseases.

8.
Psychiatry Res ; 327: 115345, 2023 09.
Article En | MEDLINE | ID: mdl-37516039

A considerable proportion of individuals exposed to trauma experience chronic and persistent posttraumatic stress disorder (PTSD). However, the specific brain and clinical features that render trauma-exposed individuals more susceptible to enduring symptoms remain elusive. This study investigated 112 trauma-exposed participants who had been diagnosed with PTSD and 112 demographically-matched healthy controls. Trauma-exposed participants were classified into those with current PTSD (persistent PTSD, n = 78) and those without (remitted PTSD, n = 34). Cortical thickness analysis was performed to discern group-specific brain structural characteristics. Coping strategies and resilience levels, assessed as clinical attributes, were compared across the groups. The persistent PTSD group displayed cortical thinning in the superior frontal cortex (SFC), insula, superior temporal cortex, dorsolateral prefrontal cortex, superior parietal cortex, and precuneus, relative to the remitted PTSD and control groups. Cortical thinning in the SFC was associated with increased utilization of maladaptive coping strategies, while diminished thickness in the insula correlated with lower resilience levels among trauma-exposed individuals. These findings imply that cortical thinning in brain regions related to coping strategy and resilience plays a vital role in the persistence of PTSD symptoms.


Emotional Regulation , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/diagnostic imaging , Cerebral Cortical Thinning , Brain , Cerebral Cortex/diagnostic imaging , Magnetic Resonance Imaging
9.
Exp Neurobiol ; 32(2): 110-118, 2023 Apr 30.
Article En | MEDLINE | ID: mdl-37164651

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (ß=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (ß=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

10.
Neuroimage Clin ; 38: 103440, 2023.
Article En | MEDLINE | ID: mdl-37224606

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by continued amplification of pain intensity. Given the pivotal roles of the insula in the perception and interpretation of pain, we examined insular functional connectivity and its associations with clinical characteristics in patients with CRPS. METHODS: Twenty-one patients with CRPS and 49 healthy controls underwent resting-state functional magnetic resonance imaging. The seed-to-seed functional connectivity analysis was performed for the bilateral insulae and cognitive control regions including the dorsal anterior cingulate cortex (dACC) and bilateral dorsolateral prefrontal cortex (DLPFC) between the two groups. Correlations between altered functional connectivity and clinical characteristics were assessed in CRPS patients. RESULTS: CRPS patients exhibited lower functional connectivity within the bilateral anterior insulae, between the insular and cognitive control regions (the bilateral anterior/posterior insulae-dACC; the right posterior insula-left DLPFC), as compared with healthy controls at false discovery rate-corrected p < 0.05. In CRPS patients, pain severity was associated negatively with the left-right anterior insular functional connectivity (r = -0.49, p = 0.03), yet positively with the left anterior insula-dACC functional connectivity (r = 0.51, p = 0.02). CONCLUSIONS: CRPS patients showed lower functional connectivity both within the bilateral anterior insulae and between the insular and cognitive control regions. The current findings may suggest pivotal roles of the insula in dysfunctional pain processing of CRPS patients.


Complex Regional Pain Syndromes , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Complex Regional Pain Syndromes/diagnostic imaging , Complex Regional Pain Syndromes/pathology , Pain , Gyrus Cinguli/diagnostic imaging , Pain Measurement , Cerebral Cortex
11.
Arthritis Rheumatol ; 75(9): 1566-1572, 2023 09.
Article En | MEDLINE | ID: mdl-37011055

OBJECTIVE: Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients. METHODS: We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome-wide single-nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA haplotypes of SLE-risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration. RESULTS: Childhood-onset SLE (<16 years) conferred the highest genetic risk compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (P = 6.8 × 10-6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (ß = 0.143, P = 1.8 × 10-6 ). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10-8 ) and anti-Sm antibody production (HR 1.85, P = 2.8 × 10-5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10-5 ) and class V (HR 2.79, P = 1.0 × 10-3 ), but especially lupus nephritis class V in anti-Sm-positive SLE (area under the curve 0.68, P = 1.8 × 10-4 ). CONCLUSION: Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.


Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Lupus Nephritis/genetics , Lupus Erythematosus, Systemic/genetics , Genotype , Phenotype , Autoantibodies
12.
Mol Psychiatry ; 28(7): 2964-2974, 2023 Jul.
Article En | MEDLINE | ID: mdl-36854717

Trauma elicits various adaptive and maladaptive responses among all exposed people. There may be distinctively different patterns of adaptation/maladaptation or types according to neurobiological predisposition. The present study aims to dissect the heterogeneity of posttraumatic conditions in order to identify clinically meaningful subtypes in recently traumatized individuals and evaluate their neurobiological correlates and long-term prognosis. We implemented a data-driven classification approach in both discovery (n = 480) and replication (n = 220) datasets of trauma-exposed and trauma-unexposed individuals based on the clinical data across a wide range of assessments. Subtype-specific patterns of functional connectivity in higher-order cortical networks, longitudinal clinical outcomes, and changes in functional connectivity were also evaluated. We identified four distinct and replicable subtypes for trauma-exposed individuals according to posttraumatic stress symptoms. Each subtype was distinct in clinical characteristics, brain functional organization, and long-term trajectories for posttraumatic symptoms. These findings help enhance current understanding of mechanisms underlying the human-specific heterogeneous responses to trauma. Furthermore, this study contributes data towards the development of improved interventions, including targeting of subtype-specific characteristics, for trauma-exposed individuals and those with PTSD.


Stress Disorders, Post-Traumatic , Humans , Brain
13.
J Clin Med ; 11(23)2022 Dec 01.
Article En | MEDLINE | ID: mdl-36498718

Percutaneous plasma disc decompression (PPDD) is a minimally invasive treatment for discogenic low back pain and herniated disc-related symptoms. However, there are no known outcome predictive variables during the procedure. The purpose of this study was to evaluate and validate epidurography as an intra-procedure outcome predictor. We retrospectively enrolled 60 consecutive patients who did not respond to conventional treatments. In the next stage of treatment, PPDD was performed, and the epidurography was conducted before and after the PPDD. We analyzed the relationship between epidurographic improvement and the success rate. The Numerical Rating Scale and the Oswestry Disability Index were used to assess pain and functional capacity, respectively, before the procedure and 1 month after the procedure. The pain reduction and the success rate in the epidurographic improvement group were significantly higher than in the epidurographic non-improvement group. Both the Numerical Rating Scale and the Oswestry Disability Index scores were significantly reduced in both groups, but there was no significant difference in Oswestry Disability Index scores. This study's results showed that PPDD is an effective treatment method. We also suggested that epidurography may be a potential outcome predictor for ensuring successful outcomes and determining the endpoint of the procedure.

14.
Ann Rheum Dis ; 2022 May 24.
Article En | MEDLINE | ID: mdl-35609976

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

15.
J Neurosci Res ; 100(6): 1321-1330, 2022 06.
Article En | MEDLINE | ID: mdl-35240720

Loss of olfaction, or anosmia, frequently accompanies emotional dysfunctions, partly due to the overlapping brain regions between the olfactory and emotional processing centers. Here, we investigated whether anosmia was associated with gray matter volume alterations at a network level, and whether these alterations were related to the olfactory-specific quality of life (QOL) and depressive symptoms. Structural brain magnetic resonance imaging was acquired in 22 individuals with postinfectious or idiopathic anosmia (the anosmia group) and 30 age- and sex-matched controls (the control group). Using independent component analysis on the gray matter volumes, we identified 10 morphometric networks. The gray matter volumes of these networks were compared between the two groups. Olfactory-specific QOL and depressive symptoms were assessed by self-report questionnaires and clinician-administered interviews, respectively. The anosmia group showed lower gray matter volumes in the hippocampus-amygdala and the precuneus networks, relative to the control group. Lower gray matter volumes in the hippocampus-amygdala network were also linearly associated with lower olfactory-specific QOL and higher depressive symptom scores. These findings suggest a close relationship between anosmia and gray matter volume alterations in the emotional brain networks, albeit without determined causal relations.


Gray Matter , Quality of Life , Adult , Anosmia , Brain/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Magnetic Resonance Imaging/methods
16.
Semin Immunopathol ; 44(1): 29-46, 2022 01.
Article En | MEDLINE | ID: mdl-34731289

Systemic lupus erythematosus (SLE) is a polygenic chronic autoimmune disease leading to multiple organ damage. A large heritability of up to 66% is estimated in SLE, with roughly 180 reported susceptibility loci that have been identified mostly by genome-wide association studies (GWASs) and account for approximately 30% of genetic heritability. A vast majority of risk variants reside in non-coding regions, which makes it quite challenging to interpret their functional implications in the SLE-affected immune system, suggesting the importance of understanding cell type-specific epigenetic regulation around SLE GWAS variants. The latest genetic studies have been highly fruitful as several dozens of SLE loci were newly discovered in the last few years and many loci have come to be understood in systemic approaches integrating GWAS signals with other biological resources. In this review, we summarize SLE-associated genetic variants in both the major histocompatibility complex (MHC) and non-MHC loci, examining polygenetic risk scores for SLE and their associations with clinical features. Finally, variant-driven pathogenetic functions underlying genetic associations are described, coupled with discussion about challenges and future directions in genetic studies on SLE.


Genome-Wide Association Study , Lupus Erythematosus, Systemic , Epigenesis, Genetic , Genetic Predisposition to Disease , Humans , Lupus Erythematosus, Systemic/etiology , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide
17.
Nat Sci Sleep ; 13: 1507-1517, 2021.
Article En | MEDLINE | ID: mdl-34531693

PURPOSE: To investigate the cerebral blood flow (CBF) alterations associated with poor sleep quality and memory performance in firefighters. PARTICIPANTS AND METHODS: Thirty-seven firefighters (the FF group) and 37 non-firefighter controls (the control group) with sleep complaints were enrolled in this study. We performed brain arterial spin labeling perfusion magnetic resonance imaging (MRI) and compared the CBF between the two groups using whole-brain voxel-wise analyses. Self-reported sleep problems and actigraphy-measured sleep parameters, including the sleep efficiency, wake after sleep onset (WASO), total sleep time, and sleep latency, were assessed. Spatial working memory and learning performances were evaluated on the day of the MRI scan. RESULTS: The FF group, relative to the control group, had lower CBF in the right hemispheric regions: Middle temporal/lateral occipital, orbitofrontal, and insular cortices. Lower CBF in the right orbitofrontal cortex was linearly associated with poor sleep quality, as indicated by lower sleep efficiency and longer WASO. The CBF of the right insular cortex was also associated with longer WASO. Despite comparable degrees of self-reported sleep problems between the two groups, the FF group had lower sleep efficiency and longer WASO in the actigraphy, and lower spatial working memory and learning performance, relative to the control group. Poor sleep efficiency was linearly associated with lower spatial working memory performance. CONCLUSION: These results demonstrated an association of poor sleep quality with decreased brain perfusion in the right orbitofrontal and insular cortices, as well as with reduced working memory performance.

18.
Neurol Sci ; 42(10): 4131-4138, 2021 Oct.
Article En | MEDLINE | ID: mdl-33532950

BACKGROUND: Recent evidence suggests that hyperbaric oxygenation (HBO), which has been used as an effective treatment for certain types of tissue injury, may change neural activities in the human brain and subsequently improve symptoms of psychiatric disorders. To scrutinize the neural mechanism of HBO in the human brain, we investigated whether 20 sessions of HBO changed regional cerebral blood flow (rCBF) of the limbic system in firefighters with mild traumatic brain injury (mTBI) and subjective emotional distress. METHODS: Twenty firefighters with mTBI and mild emotional distress were treated with HBO at a relatively low pressure of 1.3 atmospheres absolute for 45 min a day for 20 consecutive days (the mild emotional distress group). The rCBF of the limbic system was measured using an arterial spin labeling perfusion magnetic resonance imaging before and after the HBO. Analyses were performed on the data from fourteen individuals who completed the study and 14 age- and sex-matched healthy firefighters (the comparison group). RESULTS: Firefighters in the mild emotional distress group showed increase rCBF following HBO in a cluster encompassing the right hippocampal and parahippocampal regions (peak t = 4.31; cluster size = 248 mm3)(post-hoc analysis, z = 5.92, p < 0.001) that had lower rCBF relative to the comparison group at baseline (post-hoc analysis, t = -2.20, p = 0.04). CONCLUSION: The current study demonstrated that low-pressure HBO might increase rCBF of the hippocampal and parahippocampal regions, suggesting a potential underpinning mechanism of HBO in the human brain.


Brain Concussion , Firefighters , Hyperbaric Oxygenation , Psychological Distress , Cerebrovascular Circulation , Hippocampus/diagnostic imaging , Humans
19.
J Surg Res ; 267: 755-761, 2021 11.
Article En | MEDLINE | ID: mdl-33583601

BACKGROUND: We aimed to evaluate the usefulness of neutrophil-to-lymphocyte (N/L) and neutrophil-to-lymphocyte platelet (N/LP) ratios in predicting late mortality of patients with trauma who underwent emergency surgery. MATERIALS AND METHODS: We retrospectively evaluated patients with trauma older than 19 y who underwent emergency surgery at our level I trauma center. Blood count-based ratios (N/L and N/LP at days 1, 3, and 7 of hospitalization) and trauma scores were analyzed. Statistical analysis was performed using univariable logistic regression and receiver operating curves. RESULTS: A total of 209 patients were evaluated. N/LP at day 7, N/L at day 7, Trauma Injury Severity Score, Revised Trauma Score, and Injury Severity Score were significantly associated with late mortality. Area under the receiver operating characteristic curves for predicting mortality was highest for N/LP at day 7 (0.867 [95% confidence interval 0.798-0.936], P < 0.001). The group with N/LP greater than the cutoff value (9.3, sensitivity 77.3%, specificity 83.1%) at day 7 showed higher mortality than the group with N/LP less than the cutoff value (35.4% versus 3.2%, P < 0.001, respectively) at day 7. CONCLUSIONS: N/LP at day 7 may be a superior predictor of late mortality compared with preexisting trauma scores in patients with major trauma undergoing emergency surgery, by better reflecting the systemic inflammation status.


Lymphocytes , Neutrophils , Blood Platelets , Humans , Injury Severity Score , Prognosis , ROC Curve , Retrospective Studies
20.
Sci Rep ; 11(1): 1935, 2021 01 21.
Article En | MEDLINE | ID: mdl-33479442

We hypothesized that deep neuromuscular blockade (NMB) with low-pressure pneumoperitoneum (PP) would improve respiratory mechanics and reduce biotrauma compared to moderate NMB with high-pressure PP in a steep Trendelenburg position. Seventy-four women undergoing robotic gynecologic surgery were randomly assigned to two equal groups. Moderate NMB group was maintained with a train of four count of 1-2 and PP at 12 mmHg. Deep NMB group was maintained with a post-tetanic count of 1-2 and PP at 8 mmHg. Inflammatory cytokines were measured at baseline, at the end of PP, and 24 h after surgery. Interleukin-6 increased significantly from baseline at the end of PP and 24 h after the surgery in moderate NMB group but not in deep NMB group (Pgroup*time = 0.036). The peak inspiratory, driving, and mean airway pressures were significantly higher in moderate NMB group than in deep NMB group at 15 min and 60 min after PP (Pgroup*time = 0.002, 0.003, and 0.048, respectively). In conclusion, deep NMB with low-pressure PP significantly suppressed the increase in interleukin-6 developed after PP, by significantly improving the respiratory mechanics compared to moderate NMB with high-pressure PP during robotic surgery.


Abdomen/surgery , Neuromuscular Blockade/adverse effects , Pneumoperitoneum/surgery , Robotic Surgical Procedures , Abdomen/physiopathology , Adult , Female , Gynecologic Surgical Procedures/methods , Head-Down Tilt , Humans , Injections, Intraperitoneal , Interleukin-6/genetics , Laparoscopy , Neuromuscular Blockade/methods , Neuromuscular Monitoring/methods , Patient Positioning , Pneumoperitoneum/genetics , Pneumoperitoneum/physiopathology , Pressure/adverse effects , Respiratory Mechanics
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