Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study.

STUDY OBJECTIVES: Previous studies have highlighted the importance of sleep patterns for human health. This study aimed to investigate the association of sleep timing with all-cause and cardiovascular disease mortality. METHODS: Participants were screened from two cohort studies: the Sleep Heart Health Study (SHHS; n = 4,824) and the Osteoporotic Fractures in Men Study (n = 2,658). Sleep timing, including bedtime and wake-up time, was obtained from sleep habit questionnaires at baseline. The sleep midpoint was defined as the halfway point between the bedtime and wake-up time. Restricted cubic splines and Cox proportional hazards regression analyses were used to examine the association between sleep timing and mortality. RESULTS: We observed a U-shaped association between bedtime and all-cause mortality in both the SHHS and Osteoporotic Fractures in Men Study groups. Specifically, bedtime at 11:00 pm and waking up at 7:00 am was the nadir for all-cause and cardiovascular disease mortality risks. Individuals with late bedtime (> 12:00 am) had an increased risk of all-cause mortality in SHHS (hazard ratio 1.53, 95% confidence interval 1.28-1.84) and Osteoporotic Fractures in Men Study (hazard ratio 1.27, 95% confidence interval 1.01-1.58). In the SHHS, late wake-up time (> 8:00 am) was associated with increased all-cause mortality (hazard ratio 1.39, 95% confidence interval 1.13-1.72). No significant association was found between wake-up time and cardiovascular disease mortality. Delaying sleep midpoint (> 4:00 am) was also significantly associated with all-cause mortality in the SHHS and Osteoporotic Fractures in Men Study. CONCLUSIONS: Sleep timing is associated with all-cause and cardiovascular disease mortality. Our findings highlight the importance of appropriate sleep timing in reducing mortality risk. CITATION: Ma M, Fan Y, Peng Y, et al. Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study. J Clin Sleep Med. 2024;20(4):545-553.

Amniotic Fluid Proteomics Analysis and In Vitro Validation to Identify Potential Biomarkers of Preterm Birth.

This study aimed to investigate the regulation of amniotic fibroblast (AFC) function by vitamin K-dependent protein Z (PROZ) during preterm birth (PTB) and its potential role in adverse pregnancy outcomes. Proteomic samples were collected from amniotic fluid in the second trimester, and AFC were isolated from the amniotic membrane and cultured in vitro. The expression of extracellular and intracellular PROZ in AFC was modulated, and their biological properties and functions were evaluated. Clinical analysis revealed a significant upregulation of PROZ expression in amniotic fluid from preterm pregnant women. In vitro experiments demonstrated that PROZ stimulated AFC migration, enhanced their proliferative capacity, and reduced collagen secretion. Overexpression of PROZ further enhanced cell migration and proliferation, while knockdown of PROZ had the opposite effect. PROZ plays a crucial role in promoting the proliferation and migration of amniotic membrane fibroblasts. Increased PROZ expression in amniotic fluid is associated with the occurrence of PTB. These findings shed light on the potential involvement of PROZ in adverse pregnancy outcomes and provide a basis for further research on its regulatory mechanisms during PTB.

Association of Objective and Self-Reported Sleep Duration With All-Cause and Cardiovascular Disease Mortality: A Community-Based Study.

Background Previous studies found an association between self-reported sleep duration and mortality. This study aimed to compare the effects of objective and self-reported sleep duration on all-cause and cardiovascular disease (CVD) mortality. Methods and Results A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in-home polysomnography records, and self-reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self-reported sleep duration with all-cause and CVD mortality. During a mean follow-up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All-cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all-cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J-shaped association of self-reported sleep duration on both weekdays and weekends with all-cause and CVD mortality. Self-reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all-cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self-reported sleep duration. Conclusions This study showed that both objective and self-reported sleep duration were associated with all-cause and CVD mortality, but with different characteristics. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00005275; Unique identifier: NCT00005275.

A comparison of clinical characteristics of psychiatric inpatients in three hospitals from Western China and America.

BACKGROUND: Different countries have differences in social and cultural context and health system, which may affect the clinical characteristics of psychiatric inpatients. This study was the first to compare cross-cultural differences in the clinical characteristics of psychiatric inpatients in three hospitals from Western China and America. METHODS: Overall, 905 and 1318 patients from three hospitals, one in America and two in Western China, respectively, were included. We used a standardised protocol and data collection procedure to record inpatients' sociodemographic and clinical characteristics. RESULTS: Significant differences were found between hospitals from the two countries. Positive symptoms were the main reason for admission in the Chinese hospitals, while reported suicide and self-injury symptoms more frequently led to hospital admission in America. Moreover, there were more inpatients with combined substance abuse in the American hospital (97.6% vs. 1.9%, P < 0.001). The length of stay (LOS) in America was generally shorter than in China (10.5 ± 11.9 vs. 20.7 ± 13.4, P < 0.001). The dosage of antipsychotic drugs used in the American hospital was higher than in China (275.1 ± 306.9 mg vs. 238.3 ± 212.5 mg, P = 0.002). Regression analysis showed that male sex, older age, retirees, being admitted because of physical symptoms, and using higher doses of antipsychotic drugs were significantly associated with longer hospitalisation in the American hospital (P < 0.05). Comparatively, patients who were divorced, experiencing suicidal ideation, admitted involuntarily, admitted because of physical, depression, or anxiety symptoms, and using higher doses of antipsychotic drugs had longer hospitalisation in Chinese hospitals (P < 0.05). CONCLUSION: Significant variations in clinical characteristics of inpatients were found between hospitals from Western China and America. The LOS in Chinese hospitals was significantly longer, but patients used higher doses of antipsychotic drugs in the American hospital. Admission due to physical symptoms and the use of higher dosage drugs were related to longer LOS in both countries.

Coxiella burnetii and Bartonella Endocarditis Diagnosed by Metagenomic Next-Generation Sequencing.

(1) Background: Culture-negative endocarditis is challenging to diagnose. Here, we retrospectively identified 23 cases of Coxiella burnetii and Bartonella endocarditis by metagenomic next-generation sequencing. (2) Methods: Twenty-three patients with culture-negative endocarditis were retrospectively enrolled from Guangdong Provincial People's Hospital (n = 23) between April 2019 and December 2021. Metagenomic next-generation sequencing was performed on blood (n = 22) and excised cardiac valvular tissue samples (n = 22) for etiological identification, and Sanger sequencing was performed for pathogenic diagnostic verification. The demographic and clinical data of the 23 patients were obtained from hospital electronic health records. (3) Results: A total of 23 male patients (median age, 56 years (interquartile range, 16)) with culture-negative endocarditis were diagnosed with Coxiella burnetii (n = 21) or Bartonella (n = 2) species infection by metagenomic next-generation sequencing. All patients underwent cardiac surgery. The resected tissue exhibited both a significantly higher number of unique suspected pathogen read-pairs and more unique pathogen read-pairs than the blood specimens. The results of Sanger sequencing tests on all remaining tissue and blood specimens were positive. Oral doxycycline was added to the antibiotic regimen for at least 1.5 years according to etiology. A total of 21 patients (91%) were discharged, and 20 patients were healthy at the 21-month (interquartile range, 15) follow-up visit. One patient exhibited endocarditis relapse with the same pathogen from inadequate antibiotic administration. The last 2 patients (9%) developed septic shock and multiple organ dysfunction syndrome postoperatively and died shortly after discharge. (4) Conclusions: CNE caused by C. burnetii and Bartonella species is challenging to diagnose and exhibits poor outcome due to delayed treatment. In response, mNGS, characterized by high sensitivity and rapid results, is an effective alternative for the etiological identification of C. burnetii and Bartonella endocarditis.

Grey matter volume and its association with cognitive impairment and peripheral cytokines in excited individuals with schizophrenia.

Although excited behavior in patients with schizophrenia has been linked to brain structural abnormalities, whether cortical abnormalities in this subgroup are related to cognitive impairment or peripheral immune responses is unknown. We included 28 patients with excitability (EC), 28 patients without excitability (NEC), and 48 healthy controls (HCs) to evaluate the associations. Compared with the HC group, the EC and NEC groups showed significant cognitive impairment and increased serum cytokine levels. Analysis of variance in whole-brain grey matter volume (GMV) showed that the volumes of several brain areas, including the superior frontal gyrus (SFG), superior temporal gyrus, and cingulate gyrus, were decreased in patients with schizophrenia. Notably, the left SFG volume was significantly lower in the EC group than in the NEC group. Spearman correlation analysis showed that elevated cytokines were negatively correlated with the GMV of the bilateral SFG, bilateral inferior parietal gyrus, left anterior cingulate gyrus, right fusiform gyrus and parahippocampal gyrus, which were mainly positive correlated with cognitive tests. Moreover, interleukin 4 may contribute to poor scores on Brief Assessment of Cognition and Neuropsychological Assessment Battery by reducing the left SFG volume (17%, Pmediation = 0.044; and 24%, Pmediation = 0.040, respectively). In conclusion, our results confirm GMV changes in excited patients with schizophrenia, and characterize the GMV as an important interface between inflammatory cytokines and cognitive impairment. Therefore, targeted anti-inflammatory adjuvant antipsychotic therapy may improve cognitive function and volumetric brain abnormalities in these patients.

Characterizing serum amino acids in schizophrenic patients: Correlations with gut microbes.

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.

Increased Rapid Eye Movement Sleep Is Associated With a Reduced Risk of Heart Failure in Middle-Aged and Older Adults.

Objectives: Rapid eye movement (REM) sleep is closely related to all-cause mortality. The aim of this study is to explore the role of REM sleep on the incident heart failure (HF). Methods: We selected 4490 participants (2480 women and 2010 men; mean age, 63.2 ± 11.0 years) from the Sleep Heart Health Study. HF was identified as the first occurrence during a mean follow-up period of 10.9 years. REM sleep including percentage of REM sleep and total REM sleep time were monitored using in-home polysomnography at baseline. Multivariable Cox regression analysis was utilized to explore the relationship between REM sleep and HF. Results: In total, 436 (9.7%) cases of HF were observed during the entire follow-up period. After adjusting for potential covariates, an increased percentage of REM sleep (per 5%) was independently associated with a reduced incidence of HF [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.82-0.94, P < 0.001]. A similar result was also found between total REM sleep time (increased per 5 min) and incident HF (HR 0.97, 95% CI 0.95-0.99, P < 0.001). Moreover, the fourth quartile of both percentage of REM sleep (HR 0.65, 95% CI 0.48-0.88, P = 0.005) and total REM sleep time (HR 0.64, 95% CI 0.45-0.90, P = 0.010) had lower risk of incident HF when compared with the first quartile. Conclusion: An increased percentage of REM sleep and total REM sleep time were associated with a reduced risk of HF. REM sleep may be a predictor of the incident HF. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT00005275].

Estimation of the bidirectional relationship between schizophrenia and inflammatory bowel disease using the mendelian randomization approach.

It has been reported that schizophrenia (SCZ) and inflammatory bowel disease (IBD) are related. However, whether there is a bidirectional interaction between them remains unclear. The aim of this study was to conduct a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationship between SCZ and IBD and its subtypes, including Crohn's disease (CD) and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) extracted from the summary data of genome-wide association studies were used as genetic instruments. MR was performed using the inverse-variance-weighted method. The MR-Egger and weighted median methods were used for sensitivity analyses. Analysis using 70 SNPs as genetic instruments showed that SCZ was associated with an increased risk of IBD (OR = 1.14, 95% CI: 1.09-1.20, P = 9.21 × 10-8), CD (OR = 1.16, 95% CI: 1.07-1.25, P = 1.42 × 10-4), and UC (OR = 1.14, 95% CI: 1.07-1.21, P = 2.72 × 10-5). The results of the sensitivity analyses were robust and no evidence of pleiotropy was observed. Bidirectional MR analyses showed no causal effects of IBD, CD, or UC on SCZ. This study suggests that SCZ has causal effects on IBD and its subtypes, whereas IBD has no effect on SCZ. Brain-gut axis interactions may help clarify the causal relationship between SCZ and IBD. However, further studies are needed to elucidate the biological mechanisms behind the brain-gut interactions.

Multi-Omics Analysis Reveals Aberrant Gut-Metabolome-Immune Network in Schizophrenia.

Schizophrenia (SCZ) is associated with several immune dysfunctions, including elevated levels of pro-inflammatory cytokines. Microorganisms and their metabolites have been found to regulate the immune system, and that intestinal microbiota is significantly disturbed in schizophrenic patients. To systematically investigate aberrant gut-metabolome-immune network in schizophrenia, we performed an integrative analysis of intestinal microbiota, serum metabolome, and serum inflammatory cytokines in 63 SCZ patients and 57 healthy controls using a multi-omics strategy. Eighteen differentially abundant metabolite clusters were altered in patients displayed higher cytokine levels, with a significant increase in pro-inflammatory metabolites and a significant decrease in anti-inflammatory metabolites (such as oleic acid and linolenic acid). The bacterial co-abundance groups in the gut displayed more numerous and stronger correlations with circulating metabolites than with cytokines. By integrating these data, we identified that certain bacteria might affect inflammatory cytokines by modulating host metabolites, such as amino acids and fatty acids. A random forest model was constructed based on omics data, and seven serum metabolites significantly associated with cytokines and α-diversity of intestinal microbiota were able to accurately distinguish the cases from the controls with an area under the receiver operating characteristic curve of 0.99. Our results indicated aberrant gut-metabolome-immune network in SCZ and gut microbiota may influence immune responses by regulating host metabolic processes. These findings suggest a mechanism by which microbial-derived metabolites regulated inflammatory cytokines and insights into the diagnosis and treatment of mental disorders from the microbial-immune system in the future.

Stressful events induce long-term gut microbiota dysbiosis and associated post-traumatic stress symptoms in healthcare workers fighting against COVID-19.

OBJECTIVE: The microbiota-gut-brain axis is a key pathway perturbed by prolonged stressors to produce brain and behavioral disorders. Frontline healthcare workers (FHWs) fighting against COVID-19 typically experience stressful event sequences and manifest some mental symptoms; however, the role of gut microbiota in such stress-induced mental problems remains unclear. We investigated the association between the psychological stress of FHW and gut microbiota. METHODS: We used full-length 16S rRNA gene sequencing to characterize the longitudinal changes in gut microbiota and investigated the impact of microbial changes on FHWs' mental status. RESULTS: Stressful events induced significant depression, anxiety, and stress in FHWs and disrupted the gut microbiome; gut dysbiosis persisted for at least half a year. Different microbes followed discrete trajectories during the half-year of follow-up. Microbes associated with mental health were mainly Faecalibacterium spp. and [Eubacterium] eligens group spp. with anti-inflammatory effects. Of note, the prediction model indicated that low abundance of [Eubacterium] hallii group uncultured bacterium and high abundance of Bacteroides eggerthii at Day 0 (immediately after the two-month frontline work) were significant determinants of the reappearance of post-traumatic stress symptoms in FHWs. LIMITATIONS: The lack of metabolomic evidence and animal experiments result in the unclear mechanism of gut dysbiosis-related stress symptoms. CONCLUSION: The stressful event sequences of fighting against COVID-19 induce characteristic longitudinal changes in gut microbiota, which underlies dynamic mental state changes.

Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.

Mendelian randomization analyses reveal novel drug targets for anorexia nervosa.

Among all psychiatric disorders, anorexia nervosa (AN) has the highest mortality rate. However, there is still no pharmacological therapy for AN. The human plasma proteome may be a great cornerstone for the development of new drugs against AN. Here we performed a Mendelian randomization (MR) analysis to identify causal risk proteins for AN. Exposure data were extracted from a large genome-wide association study (GWAS) of 2994 plasma proteins in 3301 subjects of European descent, while outcome data were obtained from another GWAS of AN (16,992 cases and 55,525 controls of European descent). MR analyses were performed using the inverse-variance weighted (IVW) method and other sensitivity analysis methods. Using single nucleotide polymorphisms as instruments, this study suggested that high TXNDC12 levels were associated with a higher risk of AN (IVW Odd's ratio [OR]: 1.12; 95% confidence interval [CI]: 1.08-1.16; P = 2.35 × 10-10), while another protein ADH1B showed the opposite effect (IVW OR: 0.89; 95% CI: 0.85-0.93; P = 2.99 × 10-7). The causal associations were robust in multivariable models, genome-wide significant models, and with additional MR methods. No pleiotropy was observed. Our findings suggest that TXNDC12 was associated with a high risk of AN, while AHD1B was associated with a low risk of AN. They might both have implications in AN by regulating the brain dopamine reward system. In combination with existing knowledge on AN, these proteins may be novel drug targets for AN treatment.

A Modified Technique for Valve Regurgitation After Partial Atrioventricular Septal Defect Repair.

Given its complex pathologic anatomy, recurrent left atrioventricular valve regurgitation after partial atrioventricular septal defect repair remains a challenge for surgical correction. Here, we introduce a modified bridging technique by shortening the anteroposterior leaflet distance in selected patients with inadequate coaptation to compensate for the short leaflet height, specifically that of the anterior leaflet.

Analysis of risk factors of non-suicidal self-harm behavior in adolescents with depression.

BACKGROUND: Adolescents are a high-risk group for non-suicidal self-injury (NSSI), which seriously affects their physical and mental health. This study aimed to explore the risk factors for depressive adolescents with NSSI. METHODS: A total of 153 adolescents with depression were divided into the NSSI group (n=65) and non-NSSI group (n=88) according to the criteria stipulated by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The Beck scale for suicidal ideation (BSS), adolescent self-rating life events checklist (ASLEC), family adaptability and cohesion evaluation scale II-Chinese version (FACES II-CV), childhood trauma questionnaire short form (CTQ SF), and multidimensional scale of perceived social support (MSPSS) were applied to evaluate suicidal ideation, frequency and intensity of stressful life events, family functions, childhood trauma, and perceived support, respectively. We applied two-dimensional logistic regression to identify risk factors for NSSI. RESULTS: Female gender ratio, suicidal ideation, and attempted suicide were significantly higher in the NSSI group than in the non-NSSI group (all P<0.05). Scores of interpersonal relationships in ASLEC, emotional abuse, and emotional neglect in the CTQ-SF were significantly higher in the NSSI group than those in the non-NSSI group (all P<0.001). The scores of family cohesion (P=0.001) and family adaptability (P=0.01) were significantly lower in the NSSI group than in the non-NSSI group. The MSPSS was used to assess support from the family, and the index was significantly lower in the NSSI group (P<0.001). After adjusting for age and gender, BSS score, interpersonal relationship score, emotional abuse score, and emotional neglect score were identified as independent risk factors for NSSI. CONCLUSIONS: The rate of NSSI in adolescents with depression is high. Higher scores of BSS, interpersonal relationship, emotional abuse, and neglect were independently associated with NSSI.

LncRNA TUG1 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR-133b in myocardial fibrosis after myocardial infarction.

Myocardial fibrosis (MF) is one of the basic causes of many cardiovascular diseases. Noncoding RNAs (ncRNAs), including microRNA (miRNA) and long noncoding RNA (lncRNA), have been reported to play an indispensable role in MF. The current work is focused on investigating the biological role of lncRNA taurine upregulation gene 1 (TUG1) in activating cardiac myofibroblasts as well as the underlying mechanism. The outcome revealed that after myocardial infarction TUG1 expression increased and miR-133b expression decreased in the rat model of MF. The expression level of TUG1 increased following AngII treatment in cardiac myofibroblast. TUG1 knockdown inhibited the Ang-II induced cardiac myofibroblast activation and TUG1 overexpression increased proliferation and collagen generation of cardiac myofibroblasts. Bioinformatic prediction programs predicted that TUG1 had MRE directly combined with miR-133b seed sequence, luciferase activity, and RIP experiments indicated that TUG1, acted as a sponger and interacted with miR-133b in cardiac myofibroblasts. Furthermore, a target of miR-133b was CTGF and CTGF knockdown counteracted the promotion of MF by miR-133b knockdown. Collectively, our study suggested that TUG1 mediates CTGF expression by sponging miR-133b in the activation of cardiac myofibroblasts. The current work reveals a unique role of the TUG1/miR-133b/CTGF axis in MF, thus suggesting its immense therapeutic potential in the treatment of cardiac diseases.

Causal relationships between genetically determined metabolites and human intelligence: a Mendelian randomization study.

Intelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (PIVW = 9.25 × 10-5). The causal relationship was robust when sensitivity analyses were applied (PMR-Egger = 0.0001, PWeighted median = 6.29 × 10-6, PMR-PRESSO = 0.0007), and repeated analysis yielded consistent result (PIVW = 0.0087). Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

ECG-gated CT in Aortic Perivalvular Abscess: Comparison with Transesophageal Echocardiography and Intraoperative Findings.

Background The 2015 European Society of Cardiology guidelines acknowledged similar diagnostic performance of electrocardiography (ECG)-gated CT on perivalvular abscesses compared with transesophageal echocardiography (TEE), but data on ECG-gated CT remain insufficient. Purpose To determine the diagnostic performance of ECG-gated CT for assessing aortic root perivalvular abscesses and to compare it with TEE. Materials and Methods Between January 2008 and June 2019, the imaging records of surgically confirmed infective endocarditis were retrospectively reviewed for presence of aortic perivalvular abscesses, their extension, fistulization, vegetations, and valvular destruction. The diagnostic performance of ECG-gated CT was analyzed in all patients (part A) and in an noninferiority analysis (part B; δ = -10%) in patients undergoing TEE. Results A total of 178 patients (median age, 54 years [interquartile range, 15 years]; 147 men) were evaluated (CT, n = 178; TEE, n = 35). In part A, the sensitivity and specificity of CT were 70 of 71 (99% [95% confidence interval (CI): 96%, 100%]) and 102 of 107 (95% [95% CI: 91%, 99%]) for abscess; 65 of 68 (96% [95% CI: 91%, 100%]) and 107 of 110 (97% [95% CI: 94%, 100%]) for extension, 36 of 36 (100% [95% CI: 100%, 100%]) and 139 of 142 (98% [95% CI: 96%, 100%]) for fistulization, 153 of 160 (96% [95% CI: 93%, 99%]) and five of 18 (28% [95% CI: 7%, 49%]) for vegetations, and 90 of 90 (100% [95% CI: 100%, 100%]) and 24 of 88 (27% [95% CI: 18%, 37%]) for valvular destruction. In part B, ECG-gated CT had noninferior sensitivity compared with TEE for detecting abscess (difference, 14 percentage points [lower one-sided 95% CI: -4 percentage points]), extension (difference, 0 percentage points [lower one-sided 95% CI: 0 percentage points]), fistulization (difference, 0 percentage points [lower one-sided 95% CI: 0 percentage points]), and valvular destruction (difference, 5 percentage points [lower one-sided 95% CI: -4 percentage points]). Specificity of CT was inferior for demonstrating perivalvular abscess (difference, 5 percentage points [lower one-sided 95% CI: -11 percentage points]) and valvular destruction (difference, -62 percentage points [lower one-sided 95% CI: -92 percentage points]). ECG-gated CT had inferior sensitivity in detecting vegetations (difference, -6 percentage points [lower one-sided 95% CI: -14 percentage points]). Conclusion Electrocardiography-gated CT had noninferior sensitivity compared with transesophageal echocardiography for identification of aortic perivalvular abscesses, extension of these abscesses, fistulization, and valvular destruction but had inferior sensitivity in detection of vegetations. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Sakuma in this issue.

Metagenome-wide association of gut microbiome features for schizophrenia.

Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

The Role of Cytokines in Predicting the Efficacy of Acute Stage Treatment in Patients with Schizophrenia.

PURPOSE: Inflammatory response in schizophrenia (SCz) is related to its underlying pathological mechanism and might be significant in deciding a patient's prognosis. The current study aims to investigate the differences in the serum inflammation level between schizophrenic patients and healthy controls and identify inflammatory markers that can predict clinical therapeutic effects in early-stage SCz patients at the 6-month follow-up. PATIENTS AND METHODS: In total, 71 subjects were recruited in this study, including 35 patients with Scz and 36 healthy controls. The 35 Scz patients, who were in the first-episode or acute relapse state at admission, had completed the 6-month follow-up. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI) assessment results, demographic details, and blood samples were collected at the baseline and at follow-up. Data were analyzed using the Spearman correlation and multiple linear regression. RESULTS: Serum interleukin (IL-1ß, IL-4, IL-6, and IL-8) levels were significantly elevated in SCz patients at baseline compared with healthy controls, with a reduced IL-8 level at the follow-up. Furthermore, a higher IL-6 level and lower IL-8 level was found to predict better improvement in negative symptoms. The higher IL-6 level also predicted lesser improvement in depressive symptoms. Finally, a higher interferon (IFN)-γ level predicted a lower therapeutic effect for excitatory symptoms. CONCLUSION: The serum levels of inflammatory markers were higher in patients with SCz than in healthy controls. These markers can be considered accurate predictors of therapeutic effects in patients with SCz.