High signal intensity of the intraaneurysmal sac on T1 CUBE imaging as a predictor of aneurysm stability after coil embolization.

OBJECTIVE: Histopathological studies of aneurysms after coil embolization showed that thrombus formation during the first month after endovascular treatment (EVT) played an important role in the healing process. The authors hypothesized that dedicated T1-weighted imaging may be used to predict stable aneurysms by visualizing the thrombus status within coil-treated aneurysms. Therefore, this study investigated the relationship between the signal intensity (SI) of the intraaneurysmal sac after coil embolization and aneurysm stability. METHODS: The study population included 82 patients with 86 aneurysms who underwent T1-weighted 3D black-blood fast spin-echo (T1 CUBE) imaging within 1 month after coil embolization between 2019 and 2022. The relative SI of a coil-treated aneurysm (RSIcoiled) was calculated as follows: the mean SI of the intraaneurysmal sac/the mean SI of the genu of the corpus callosum. Aneurysms with enlarged remnants on MR angiography (MRA) within 6 months after EVT were defined as recurrence, while a decrease of intraaneurysmal flow on MRA was defined as improved embolization status. Stable aneurysms were defined as improvement or no change in embolization status 6 months after coil embolization. The volume embolization ratio (VER) was calculated as the ratio of the packed coil volume to the aneurysm volume. Differences between stable and recurrent aneurysms were examined. All aneurysms were divided into high and low RSIcoiled groups based on the cutoff value of RSIcoiled, and differences between the two groups were also evaluated. RESULTS: Recurrence was confirmed for 26 of 86 aneurysms. A univariable analysis showed that small aneurysms, high VER, and high RSIcoiled were associated with aneurysm stability. In the receiver operating characteristic curve analysis, the optimal cutoff value for RSIcoiled to differentiate stable from recurrent aneurysms was 0.54. The cutoff value for RSIcoiled was selected as 0.50 (sensitivity 0.77, specificity 0.70) because it was half the value of the SI of the corpus callosum and close to the optimal cutoff value. In a multivariable analysis, RSIcoiled > 0.50 (OR 8.1, 95% CI 2.5-27) remained a significant factor for aneurysm stability. The high RSIcoiled group showed a higher rate of an improved embolization status (26% vs 6.1%, p = 0.022) and stable aneurysms (85% vs 15%, p = 0.0002). CONCLUSIONS: RSIcoiled was associated with postcoiling aneurysm stability. High RSIcoiled might imply intraaneurysmal thrombus formation associated with the healing process of coil-treated aneurysms.

Distribution of osteoprotegerin in unruptured intracranial aneurysms in humans: association with aneurysm wall protective remodeling.

OBJECTIVE: Aneurysm wall inflammation is associated with lesion instability in unruptured intracranial aneurysms (UIAs). However, most UIAs remain unruptured during lifelong follow-ups because of simultaneous protective remodeling against the inflammatory response. The protective effects of osteoprotegerin (OPG) in intracranial and abdominal aortic aneurysms have been suggested using rodent models; however, the role of this protein in UIAs in humans remains unclear. Herein, the authors examined the relationship between OPG expression and aneurysm wall integrity in intraoperatively resected UIAs by using immunohistochemical and immunofluorescence staining. METHODS: Sixteen UIA wall tissue specimens resected between 2017 and 2022 were analyzed. Aneurysm growth was defined as an enlargement > 1 mm or an obvious morphological change over the course of more than 6 months. Three high-power fields were randomly selected from areas expressing high and low levels of OPG within the same aneurysm. To clarify the role of OPG in the human aneurysm wall, the authors compared averaged values for the following pathological features between the 2 OPG expression groups: aneurysm wall thickness, collagen, macrophages, smooth muscle cells, and transforming growth factor beta 1 (TGF-ß1). Immunohistochemical staining within the entire tissue area was also analyzed to determine the relationships between OPG expression and different aneurysm growth patterns. Pathological findings were compared between high and low OPG expression levels using the Wilcoxon signed-rank test. RESULTS: The heterogeneous expression of OPG was detected in the walls of UIAs. Lesions expressing high OPG levels had thicker aneurysm walls (327 vs 180 µm, p = 0.002) and higher expression levels of TGF-ß1 (8.5% vs 5.4%, p = 0.002) than those expressing low OPG levels. The expression of TGF-ß1 was colocalized with that of OPG mainly in the tunica media. Furthermore, lesions expressing high OPG levels had larger α-SMA+ areas (25% vs 13%, p = 0.002). Aneurysm growth was observed in 6 of 9 UIAs with available data: whole sac expansion in 4 and secondary aneurysm formation in 2. Among the 6 UIAs with aneurysm growth, OPG expression was relatively higher in the UIAs with an internal elastic lamina than in those without (17% vs 6.9%). CONCLUSIONS: Aneurysm wall integrity was associated with OPG expression in the aneurysm wall. Collectively, the study results indicated that OPG is associated with protective remodeling, which may contribute to the retention of aneurysm wall structures.

Dual-energy Computed Tomography Iodine Map for Breast Cancer: Comparison With Dynamic Contrast-enhanced Magnetic Resonance Imaging.

BACKGROUND/AIM: The characteristics of different breast cancers imaged using dual-energy computed tomography (DECT) are unknown. Furthermore, the differences between DECT and magnetic resonance imaging (MRI) in the ability to assess tumor extent have not been clarified. Therefore, this study aimed to evaluate the effectiveness of DECT iodine maps compared to contrast-enhanced MRI in patients with operable breast cancer. PATIENTS AND METHODS: Clinicopathological data from 858 patients with breast cancer who underwent resection after DECT (100/140 kv) and MRI during 2012-2021 were collected. Tumoral iodine concentration (IC; max/Δ) was analyzed from iodine maps. Factors associated with the ability of iodine maps and MRI to predict tumor extent were analyzed with reference to resected specimens' pathological diagnosis. RESULTS: IC parameters varied according to the tumors' histological types and were correlated with the estrogen receptor, histological grade, and Ki-67 labeling index. In 86.2% of patients with invasive carcinoma with intraductal extension, images and resected specimen mapping were matched. Iodine maps were less accurate than MRI in identifying tumor borders in 9.8% and more accurate in 2.1% of patients. The discrepancies in assessing tumor borders between imaging modalities were associated with the tumor's IC parameters and mammary gland status. CONCLUSION: Differences in assessment between DECT and MRI in operable breast cancer are associated with IC parameters and background parenchymal enhancement. Therefore, evaluating tumor extent using DECT considering these characteristics appears to be a feasible approach.

The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain.

Background: Evaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples. Methods: We isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis. Results: We identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing. Conclusion: The current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.

Comprehensive evaluation of machine learning algorithms for predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability.

Introduction: Perinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV). Methods: Nine HRV indicators (features) and sleep-wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep-wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated-shallow sleep, deep sleep, and the two types of wake conditions-was also tested. Results and Discussion: In the test for predicting three types of sleep-wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82-0.88) and accuracy (0.78-0.81). The test using four types of sleep-wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep-wake conditions. Among the seven features, "the number of interval differences of successive RR intervals greater than 50 ms (NN50)" and "the proportion dividing NN50 by the total number of RR intervals (pNN50)" were useful to predict sleep-wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

Association between low levels of anti-inflammatory cytokines during pregnancy and postpartum depression.

AIM: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. METHODS: A nested, case-control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age-matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three-generation cohort. Concentrations of nine plasma cytokines (IFN-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, and TNF-α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. RESULTS: Cross-sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL-4 levels during pregnancy and after delivery than the control group, and that plasma IL-4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL-10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL-10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN-γ, IL-6, IL-12p40, and TNF-α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. CONCLUSIONS: These results suggest a potential protective effect of the anti-inflammatory cytokines IL-4 and IL-10 during pregnancy against the development of PPD.

Headache characteristics to screen for cervicocerebral artery dissection in patients with acute onset unusual headache.

OBJECTIVES: The aim of this preplanned primary analysis was to investigate the clinical manifestations of headache to screen for CAD patients with acute onset headache only. BACKGROUND: Spontaneous cervicocerebral artery dissection (CAD) with acute onset headache is not rare in clinical practice; however, it is underdiagnosed. On the other hand, subsequent infarction or subarachnoid hemorrhage mainly occurs within 1 week of headache onset. METHODS: Between April 2017 and January 2022, we conducted a single-center, cross-sectional retrospective study on 197 consecutive referred patients from neurosurgical outpatient clinics with acute onset unusual headache (stronger or longer headache than usual). All patients underwent magnetic resonance imaging to screen for secondary headache and were diagnosed based on the diagnostic protocol. We examined patient background data and the following headache characteristics: distribution, condition at the onset of headache, accompanying vomiting or nausea, worsening headache, and analgesic effects against headache. These factors were analyzed to identify independent diagnostic predictors of CAD. In this study, the rate of missing data was 41% for improvement of headache by analgesia and multiple imputation by chained equations was performed. RESULTS: A total of 93 patients (46 men and 47 women; mean age: 48 years, range: 25-73 years) were diagnosed with CAD. Univariate logistic regression analysis showed CAD was associated with current smoking, systolic blood pressure >140 mmHg, unilateral headache, worsening headache, and no headache improvement by analgesia. Unilateral, worsening headache and no headache improvement by analgesia remained independent diagnostic predictors in multivariable logistic regression after multiple imputation. No headache improvement by analgesia had the highest sensitivity (86%), while worsening headache had the highest specificity (84%). CONCLUSIONS: CAD needs to be considered in patients with unilateral, worsening headache and no headache improvement by analgesia.

N-Acetylcysteine Suppresses Microglial Inflammation and Induces Mortality Dose-Dependently via Tumor Necrosis Factor-α Signaling.

N-acetylcysteine (NAC) is an antioxidant that prevents tumor necrosis factor (TNF)-α-induced cell death, but it also acts as a pro-oxidant, promoting reactive oxygen species independent apoptosis. Although there is plausible preclinical evidence for the use of NAC in the treatment of psychiatric disorders, deleterious side effects are still of concern. Microglia, key innate immune cells in the brain, play an important role in inflammation in psychiatric disorders. This study aimed to investigate the beneficial and deleterious effects of NAC on microglia and stress-induced behavior abnormalities in mice, and its association with microglial TNF-α and nitric oxide (NO) production. The microglial cell line MG6 was stimulated by Escherichia coli lipopolysaccharide (LPS) using NAC at varying concentrations for 24 h. NAC inhibited LPS-induced TNF-α and NO synthesis, whereas high concentrations (≥30 mM) caused MG6 mortality. Intraperitoneal injections of NAC did not ameliorate stress-induced behavioral abnormalities in mice, but high-doses induced microglial mortality. Furthermore, NAC-induced mortality was alleviated in microglial TNF-α-deficient mice and human primary M2 microglia. Our findings provide ample evidence for the use of NAC as a modulating agent of inflammation in the brain. The risk of side effects from NAC on TNF-α remains unclear and merits further mechanistic investigations.

Microarray dataset of gene transcription in mouse microglia and peripheral monocytes in contextual fear conditioning.

The transcription profile of microglia related to fear conditioning remains unclear. Here, we used Illumina MouseWG-6v2 microarrays to investigate the gene transcription changes in microglia and peripheral monocytes after contextual fear conditioning of C57BL/6 J mice. Mice were trained with or without a single minimized footshock stimulation (0-s or 2-s, 0.4 mA) and re-exposed to the training context without footshock for three different durations 24 h later: 0 min (FS0), 3 min (FS3), or 30 min (FS30). Whole brain microglia and peripheral monocytes were prepared 24 h after re-exposure using a neural tissue dissociation kit, including non-footshock controls for two re-exposure durations (Con3 and Con30). The data can be valuable for researchers interested in glial cells and neurotransmission studies and are related to the research article "Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia".

Sex-Specific Differences in the Transcriptome of the Human Dorsolateral Prefrontal Cortex in Schizophrenia.

Schizophrenia presents clinical and biological differences between males and females. This study investigated transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) using postmortem data from the largest RNA-sequencing (RNA-seq) database on schizophrenic cases and controls. Data for 154 male and 113 female controls and 160 male and 93 female schizophrenic cases were obtained from the CommonMind Consortium. In the RNA-seq database, the principal component analysis showed that sex effects were small in schizophrenia. After we analyzed the impact of sex-specific differences on gene expression, the female group showed more significantly changed genes compared with the male group. Based on the gene ontology analysis, the female sex-specific genes that changed were overrepresented in the mitochondrion, ATP (phosphocreatine and adenosine triphosphate)-, and metal ion-binding relevant biological processes. An ingenuity pathway analysis revealed that the differentially expressed genes related to schizophrenia in the female group were involved in midbrain dopaminergic and γ-aminobutyric acid (GABA)-ergic neurons and microglia. We used methylated DNA-binding domain-sequencing analyses and microarray to investigate the DNA methylation that potentially impacts the sex differences in gene transcription using a maternal immune activation (MIA) murine model. Among the sex-specific positional genes related to schizophrenia in the PFC of female offspring from MIA, the changes in the methylation and transcriptional expression of loci ACSBG1 were validated in the females with schizophrenia in independent postmortem samples by real-time PCR and pyrosequencing. Our results reveal potential genetic risks in the DLPFC for the sex-dependent prevalence and symptomology of schizophrenia.

Plasma metabolic disturbances during pregnancy and postpartum in women with depression.

Examining plasma metabolic profiling during pregnancy and postpartum could help clinicians understand the risk factors for postpartum depression (PPD) development. This analysis targeted paired plasma metabolites in mid-late gestational and 1 month postpartum periods in women with (n = 209) or without (n = 222) PPD. Gas chromatogram-mass spectrometry was used to analyze plasma metabolites at these two time points. Among the 170 objected plasma metabolites, principal component analysis distinguished pregnancy and postpartum metabolites but failed to discriminate women with and without PPD. Compared to women without PPD, those with PPD exhibited 37 metabolites with disparate changes during pregnancy and the 1-month postpartum period and an enriched citrate cycle. Machine learning and multivariate statistical analysis identified two or three compounds that could be potential biomarkers for PPD prediction during pregnancy. Our findings suggest metabolic disturbances in women with depression and may help to elucidate metabolic processes associated with PPD development.

Effects of additives on reaction of nucleosides with UV light in presence of uric acid and salicylic acid.

Recently, we reported that uric acid and salicylic acid are photosensitizers of the reaction of nucleosides with UV light via radical formation and energy transfer, respectively. In the present study, effects of 45 biologically relevant compounds on nucleoside reactions photosensitized by uric acid and salicylic acid were examined. When a mixed solution of 2'-deoxycytidine, 2'-deoxyguanosine, thymidine, and 2'-deoxyadenosine with uric acid was irradiated with UV light of a wavelength longer than 300 nm, all the nucleosides decreased. The addition of antioxidants suppressed the consumption of nucleosides. When the UV reaction of nucleosides was conducted with salicylic acid, thymidine decreased almost exclusively. Several antioxidants such as ascorbates, thiols, catecholamines, trans-2-hexen-1-ol, penicillin G, and NaHSO3 enhanced the consumption of thymidine, although the other antioxidants suppressed it. The results suggest that antioxidants may be beneficial to protect against DNA damage by photosensitization via radical formation, but that several of them may be detrimental as they facilitate DNA damage by photo-sensitization via energy transfer.

Diagnostic accuracy of MR vessel wall imaging at 2 weeks to predict morphological healing of vertebral artery dissection.

OBJECTIVES: The spontaneous healing of non-hemorrhagic intracranial vertebral artery dissection (VAD) may be associated with the stabilization of intramural hematoma (IMH). We previously suggested that the signal intensity of IMH increases until approximately 2 weeks in VAD with spontaneous healing. We herein investigated the diagnostic accuracy of the signal intensity of IMH at 2 weeks to predict the spontaneous healing of VAD. METHODS: From April 2017 to April 2021, we prospectively investigated patients with non-hemorrhagic VAD who underwent vessel wall imaging (VWI). Morphological healing of VAD was evaluated by MR angiography three months after its onset. The relative signal intensity (RSI) of IMH against the posterior cervical muscle on VWI was calculated. Univariate and multivariate analyses were performed on factors associated with the spontaneous healing of VAD among patient baseline data, vascular morphology at the diagnosis, and RSI parameters. RESULTS: Forty-eight patients (23 men and 25 women; mean age: 51 years, range: 34-73 years) with 50 non-hemorrhagic VAD were included in the present study. Spontaneous healing was observed in 28 VAD (56%). RSI two weeks after the onset of VAD (RSI2w) and morphological feature such as the string sign were associated with spontaneous healing, respectively. The multivariate logistic regression analysis identified RSI2w as an independent predictive factor of spontaneous healing (OR: 7.3; 95% CI, 1.9-28, p = 0.004). The cut-off value for RSI2w to predict spontaneous healing was 1.22 (AUC = 0.90, sensitivity: 91%, specificity: 82%). CONCLUSION: RSI2w predicted the spontaneous healing of non-hemorrhagic VAD 3 months after its onset.

Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia.

Microglia have been suggested to be involved in the underlying mechanism of conditional fear memory formation by regulating inflammatory cytokines. However, the mechanism linking microglia and neuronal activity related to fear conditioning remains unclear. This study characterized the transcription profile of microglia in a fear memory conditional mouse model. Compared with those in control mice microglia, the most significantly induced genes were synapse-related, whereas immune-related genes were reduced due to fear memory consolidation. Whilst the increased expression of synapse-related genes was reversed after fear memory extinction, that of immunological genes was not, strongly suggesting a connection between microglia, neurons, and a dysregulated immune response following contextual fear conditioning. Furthermore, in the hippocampal microglia, we found that the expression of neurotransmitter release regulators, γ-aminobutyric acid (GABA) receptor GABRB3 and synapsin 1/2, increased under fear memory consolidation and restored (decreased) after extinction. In addition, compared with the transcription profile in peripheral monocytes, few overlapping genes were not enriched in biological processes. Taken together, the identified conditional fear stress-induced changes in mouse microglial transcription profiles suggest that microglia-neuron communication mediates contextual fear conditioning.

Deficient Autophagy in Microglia Aggravates Repeated Social Defeat Stress-Induced Social Avoidance.

Major depressive disorder (MDD) is associated with repeated exposure to environmental stress. Autophagy is activated under various stress conditions that are associated with several diseases in the brain. This study was aimed at elucidating the autophagy signaling changes in the prefrontal cortex (PFC) under repeated social defeat (RSD) to investigate the involvement of microglial autophagy in RSD-induced behavioral changes. We found that RSD stress, an animal model of MDD, significantly induced initial autophagic signals followed by increased transcription of autophagy-related genes (Atg6, Atg7, and Atg12) in the PFC. Similarly, significantly increased transcripts of ATGs (Atg6, Atg7, Atg12, and Atg5) were confirmed in the postmortem PFC of patients with MDD. The protein levels of the prefrontal cortical LC3B were significantly increased, whereas p62 was significantly decreased in the resilient but not in susceptible mice and patients with MDD. This indicates that enhanced autophagic flux may alleviate stress-induced depression. Furthermore, we identified that FKBP5, an early-stage autophagy regulator, was significantly increased in the PFC of resilient mice at the transcript and protein levels. In addition, the resilient mice exhibited enhanced autophagic flux in the prefrontal cortical microglia, and the autophagic deficiency in microglia aggravated RSD-induced social avoidance, indicating that microglial autophagy involves stress-induced behavioral changes.

α-Tocopherol phosphate as a photosensitizer in the reaction of nucleosides with UV light: formation of 5,6-dihydrothymidine.

INTRODUCTION: α-Tocopherol phosphate, a natural water-soluble α-tocopherol analog, exists in biological tissues and fluids. Synthesized α-tocopherol phosphate is used as an ingredient of cosmetics. FINDINGS: When a neutral mixed solution of 2'-deoxycytidine, 2'-deoxyguanosine, thymidine, and 2'-deoxyadenosine was irradiated with UV light at wavelengths longer than 300 nm in the presence of α-tocopherol phosphate, thymidine was markedly consumed in an α-tocopherol phosphate dose-dependent manner, whereas other nucleosides only slightly decreased. Two major product peaks were detected in an HPLC chromatogram. The products were identified as diastereomers of 5,6-dihydrothymidine. The addition of radical scavengers had almost no effects on the generation of 5,6-dihydrothymidine, whereas the reactions of nucleosides other than thymidine were suppressed. Trolox, another water-soluble α-tocopherol analog, did not generate 5,6-dihydrothymidine, although all nucleosides were slightly consumed. When UV irradiation of thymidine with α-tocopherol phosphate was conducted in D2O, two deuterium atoms were added to 5 and 6 positions of thymidine with both syn and anti configurations. The ratio of syn and anti configurations alternated depending on pD of the solution. CONCLUSIONS: The results indicate that α-tocopherol phosphate is a photosensitizer of nucleosides, especially thymidine, and that it introduces two hydrogen atoms to thymidine from H2O, generating 5,6-dihydrothymidine.

The influence of NRXN1 on systemizing and the brain structure in healthy adults.

Certain behavioral characteristics of autism spectrum disorder can be found in otherwise healthy people. Individuals with difficulties in social adaptation may have subclinical autistic traits; however, effective biomarkers of these traits have not yet been established. There is a dire need for objective indices of these traits that combine behavior, brain images, and genetic information. In this study, we examined the association among a single nucleotide polymorphism of NRXN1 (rs858932; C/G), autistic traits, and brain structure in 311 healthy adults. We found that carriers of minor alleles (carriers of the G-allele) had significantly higher systemizing scores than major-allele (C-allele) homozygotes. Furthermore, the regional white matter volume in the right anterior limb of the internal capsule was significantly greater in carriers of the G-allele than in C-allele homozygotes. To the best of our knowledge, this is the first report of NRXN1 rs858932 being involved in systemizing and the brain structure of healthy adults. Our findings provide insight into the effects of genetics on autistic traits and their respective neural substrates.

Segmentation of aneurysm wall enhancement in evolving unruptured intracranial aneurysms.

OBJECTIVE: Morphological changes in unruptured intracranial aneurysms (UIAs) are an imaging marker of aneurysm instability. Recent studies have indicated the ability of MR vessel wall imaging (VWI) to stratify unstable UIAs based on a correlation with histopathological aneurysm wall inflammation. In the present study the authors investigated the relationships between aneurysm growth patterns and the segmentation of aneurysm wall enhancement (AWE) in VWI. METHODS: A total of 120 aneurysms with serial angiography from a follow-up period of at least 2 years (mean 65 months, range 24-215 months) were assessed by VWI. Two readers independently evaluated the patterns of morphological changes (stable, whole sac expansion, and secondary aneurysm formation) and the segmentation of AWE (no, focal, and circumferential AWE). The contrast enhancement ratio of the aneurysm wall versus the pituitary stalk (CRstalk) was calculated for the quantitative assessment of AWE. Statistical analyses were performed to investigate the relationships between AWE patterns and patient baseline profiles, aneurysm characteristics, and morphological modifications. RESULTS: Forty-one of 120 UIAs (34%) exhibited aneurysm growth (whole sac expansion in 19 and secondary aneurysm formation in 22). AWE was detected in 35 of 120 UIAs (focal AWE in 25 and circumferential AWE in 10). The maximum diameter of, irregularities in, and morphological modifications in aneurysms were associated with the segmentation of AWE. Focal AWE correlated with secondary aneurysm formation, and circumferential AWE correlated with whole sac expansion. In focal AWE, CRstalk was significantly higher in secondary aneurysm formation than in stable UIAs. UIAs without AWE (categorized as no AWE) correlated with aneurysm stability. CONCLUSIONS: The segmentation of AWE was associated with aneurysm growth scenarios and may provide a novel insight into the evaluation of unstable UIAs.