Microglia sense and suppress epileptic neuronal hyperexcitability.

Microglia are the resident immune cells of the central nervous system, undertaking surveillance role and reacting to brain homeostasis and neurological diseases. Recent studies indicate that microglia modulate epilepsy-induced neuronal activities, however, the mechanisms underlying microglia-neuron communication in epilepsy are still unclear. Here we report that epileptic neuronal hyperexcitability activates microglia and drives microglial ATP/ADP hydrolyzing ectoenzyme CD39 (encoded by Entpd1) expression via recruiting the cAMP responsive element binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) from cytoplasm to the nucleus and binding to CREB. Activated microglia in turn suppress epileptic neuronal hyperexcitability in a CD39 dependent manner. Disrupting microglial CREB/CRTC1 signaling, however, decreases CD39 expression and diminishes the inhibitory effect of microglia on epileptic neuronal hyperexcitability. Overall, our findings reveal CD39-dependent control of epileptic neuronal hyperexcitability by microglia is through an excitation-transcription coupling mechanism.

Effects of a virtual voice-based coach delivering problem-solving treatment on emotional distress and brain function: a pilot RCT in depression and anxiety.

Consumer-based voice assistants have the ability to deliver evidence-based treatment, but their therapeutic potential is largely unknown. In a pilot trial of a virtual voice-based coach, Lumen, delivering problem-solving treatment, adults with mild-to-moderate depression and/or anxiety were randomized to the Lumen intervention (n = 42) or waitlist control (n = 21). The main outcomes included changes in neural measures of emotional reactivity and cognitive control, and Hospital Anxiety and Depression Scale [HADS] symptom scores over 16 weeks. Participants were 37.8 years (SD = 12.4), 68% women, 25% Black, 24% Latino, and 11% Asian. Activation of the right dlPFC (neural region of interest in cognitive control) decreased in the intervention group but increased in the control group, with an effect size meeting the prespecified threshold for a meaningful effect (Cohen's d = 0.3). Between-group differences in the change in activation of the left dlPFC and bilateral amygdala were observed, but were of smaller magnitude (d = 0.2). Change in right dlPFC activation was also meaningfully associated (r ≥ 0.4) with changes in self-reported problem-solving ability and avoidance in the intervention. Lumen intervention also led to decreased HADS depression, anxiety, and overall psychological distress scores, with medium effect sizes (Cohen's d = 0.49, 0.51, and 0.55, respectively), compared with the waitlist control group. This pilot trial showed promising effects of a novel digital mental health intervention on cognitive control using neuroimaging and depression and anxiety symptoms, providing foundational evidence for a future confirmatory study.

Gut commensal Parabacteroides distasonis alleviates inflammatory arthritis.

OBJECTIVE: Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA. DESIGN: Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal Parabacteroides distasonis in RA. The effects of P. distasonis-derived microbial metabolites on the differentiation of CD4+ T cells and macrophage polarisation were also investigated. RESULTS: The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of P. distasonis. CONCLUSIONS: P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.

Association of balance control mechanisms with brain structural integrity in older adults with mild cognitive impairment.

BACKGROUND: Older adults with mild cognitive impairment (OAwMCI) exhibit subtle balance control and gait deficits which are predominantly associated with structural brain pathologies such as impaired white matter integrity and reduced gray matter volume. However, the relationship between balance recovery mechanisms and neural substrates in OAwMCI remains unknown. This study thus aimed to explore the associations of volitional (self-initiated) and reactive balance (in response to an external perturbation) control with structural brain integrity. METHODS: Ten OAwMCI (MoCA 18-25/30; greater than 55 years) were examined on the limits of stability test (volitional balance via Equitest), stance perturbation test (reactive balance via ActiveStep treadmill) and underwent magnetic resonance imaging. Forward movement (frequently performed functional activity of daily living) was quantified by maximum excursion (maximum ability to shift one's center of gravity toward the theoretical limit [MXE-%])and directional control (amount of movement exhibited towards the target proportional to the movement away from the target [DCL-%]) on the limits of stability test. Slip-like (prevalent type of accidental falls) perturbations were quantified by postural stability (shortest distance of the COM motion state, i.e., its position and velocity, to the theoretical boundary) on the ActiveStep treadmill. White matter integrity was quantified by fractional anisotropy (FA, movement of water molecules directionality) and gray matter volume measured in mm3. RESULTS: For volitional balance control, reduced forward MXE was significantly (p < 0.05) associated with lower FA in left (R2 = 0.56) and right (R2 = 0.60) corticospinal tract, left (R2 = 0.49) and right (R2 = 0.51) corticothalamic tract, left (R2 = 0.70) and right (R2 = 0.57) frontopontine tract, right (R2 = 0.67) cingulum, anterior commissure (R2 = 0.82), and corpus callosum (R2 = 0.62). Reduced forward DCL was significantly (p < 0.05) associated with reduced gray matter volume in the left (R2 = 0.75) and right (R2 = 0.81) cerebellum, brainstem (R2 = 0.64), right (R2 = 0.49) thalamus. For reactive balance control, reduced postural stability (p < 0.05) was significantly associated with reduced FA in the left (R2 = 0.75) and right (R2 = 0.64) corticospinal tract, left (R2 = 0.67) and right (R2 = 0.65) frontopontine tract. Reduced postural stability was significantly (p < 0.05) associated with reduced gray matter volume in the brainstem (R2 = 0.72) and right cerebellum (R2 = 0.70). CONCLUSION: Our results indicate that structural brain integrity influences stability control in OAwMCI for both volitional and reactive balance tasks, which may share some common cortico-subcortical motor pathways and relay centers. Results also show that the integrity of descending pathways from cortical attentional centers could influence stability control for both tasks.

[Retracted] MicroRNA­454 inhibits non­small cell lung cancer cells growth and metastasis via targeting signal transducer and activator of transcription­3.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration and invasion assay data shown in Figs. 2C and 4D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 3979­3986, 2018; DOI: 10.3892/mmr.2017.8350].

Inhibition of neuronal nitric oxide synthase protects against hippocampal neuronal injuries by increasing neuropeptide Y expression in temporal lobe epilepsy mice.

Neuronal nitric oxide synthase (nNOS) plays a pivotal role in the pathological process of neuronal injury in the development of epilepsy. Our previous study has demonstrated that nitric oxide (NO) derived from nNOS in the epileptic brain is neurotoxic due to its reaction with the superoxide radical with the formation of peroxynitrite. Neuropeptide Y (NPY) is widely expressed in the mammalian brain, which has been implicated in energy homeostasis and neuroprotection. Recent studies suggest that nNOS may act as a mediator of NPY signaling. Here in this study, we sought to determine whether NPY expression is regulated by nNOS, and if so, whether the regulation of NPY by nNOS is associated with the neuronal injuries in the hippocampus of epileptic brain. Our results showed that pilocarpine-induced temporal lobe epilepsy (TLE) mice exhibited an increased level of nNOS expression and a decreased level of NPY expression along with hippocampal neuronal injuries and cognition deficit. Genetic deletion of nNOS gene, however, significantly upregulated hippocampal NPY expression and reduced TLE-induced hippocampal neuronal injuries and cognition decline. Knockdown of NPY abolished nNOS depletion-induced neuroprotection and cognitive improvement in the TLE mice, suggesting that inhibition of nNOS protects against hippocampal neuronal injuries by increasing neuropeptide Y expression in TLE mice. Targeting nNOS-NPY signaling pathway in the epileptic brain might provide clinical benefit by attenuating neuronal injuries and preventing cognitive deficits in epilepsy patients.

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses.

Purpose: Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N6-methyladenosine (m6A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m6A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level. Experimental Design: Single-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m6A regulators and multiple factors. Results: HNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m6A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m6A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m6A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m6A/high ICP and high m6A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance. Conclusion: At the single-cell level, m6A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m6A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.

Integrin α5 Is Regulated by miR-218-5p in Endothelial Progenitor Cells.

BACKGROUND: Endothelial cell injury is a common nidus of renal injury in patients and consistent with the high prevalence of AKI reported during the coronavirus disease 2019 pandemic. This cell type expresses integrin α5 (ITGA5), which is essential to the Tie2 signaling pathway. The microRNA miR-218-5p is upregulated in endothelial progenitor cells (EPCs) after hypoxia, but microRNA regulation of Tie2 in the EPC lineage is unclear. METHODS: We isolated human kidney-derived EPCs (hkEPCs) and surveyed microRNA target transcripts. A preclinical model of ischemic kidney injury was used to evaluate the effect of hkEPCs on capillary repair. We used a genetic knockout model to evaluate the effect of deleting endogenous expression of miR-218 specifically in angioblasts. RESULTS: After ischemic in vitro preconditioning, miR-218-5p was elevated in hkEPCs. We found miR-218-5p bound to ITGA5 mRNA transcript and decreased ITGA5 protein expression. Phosphorylation of 42/44 MAPK decreased by 73.6% in hkEPCs treated with miR-218-5p. Cells supplemented with miR-218-5p downregulated ITGA5 synthesis and decreased 42/44 MAPK phosphorylation. In a CD309-Cre/miR-218-2-LoxP mammalian model (a conditional knockout mouse model designed to delete pre-miR-218-2 exclusively in CD309+ cells), homozygotes at e18.5 contained avascular glomeruli, whereas heterozygote adults showed susceptibility to kidney injury. Isolated EPCs from the mouse kidney contained high amounts of ITGA5 and showed decreased migratory capacity in three-dimensional cell culture. CONCLUSIONS: These results demonstrate the critical regulatory role of miR-218-5p in kidney EPC migration, a finding that may inform efforts to treat microvascular kidney injury via therapeutic cell delivery.

Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis.

Myelin consists of several layers of tightly compacted membranes that form an insulating sheath around axons. These membranes are highly enriched in cholesterol, which is essential for the myelination process. Proper myelination is crucial for various neurophysiological functions while demyelination may cause CNS disease, such as multiple sclerosis (MS). Recent studies demonstrated that demyelination occurs not only in the white matter but also in the grey matter, such as the hippocampus, which may cause cognitive deficits and mental disorders. Valproic acid (VPA) is an anticonvulsant agent prescribed for the treatment of epilepsy and seizure. Recently, VPA was reported to alter cholesterol metabolism in neural cells, suggesting that it may play an important role in myelin biogenesis. Here in this study, we found significant demyelination in the hippocampus of the mouse cuprizone model, which is accompanied by reduced cholesterol biosynthesis and increased anxiety-like behavior. VPA treatment, however, suppressed cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis. These data identify an important role of VPA in the hippocampal demyelination process and the hippocampal demyelination-related behavior deficit via regulation of cholesterol biosynthesis, which provides new insights into the mechanisms of VPA as a protective agent against CNS demyelination.

ADAM10 suppresses demyelination and reduces seizure susceptibility in cuprizone-induced demyelination model.

The metalloproteinase ADAM10 is the most important amyloid precursor protein (APP) α-secretase, preventing the deposit of neurotoxic amyloid ß (Aß) peptide and generating a soluble APP fragment (sAPPα) with neurotrophic functions. Recent studies have suggested that ADAM10 also play a role in the pathogenesis of inflammatory CNS diseases, such as multiple sclerosis (MS). Demyelination is the hallmarks of MS but the mechanisms involved remain unclear. Here in this study, we examined the role that ADAM10 might play in the cuprizone-induced demyelination model. Our results demonstrated that ADAM10 expression and sAPPα production were significantly reduced in the corpus callosum in response to cuprizone treatment. Overexpression of ADAM10 increased sAPPα production and suppressed demyelination as well as neuroinflammation and oxidative stress in cuprizone-induced demyelination model. Pharmacological inhibition of ADAM10 activity, however, abrogates the protective effect of ADAM10 against demyelination, neuroinflammation and oxidative stress. It has been reported that CNS demyelination may induce seizure activity. Here, we found that overexpression of ADAM10 reduced seizure susceptibility in cuprizone-induced demyelination model, suggesting that ADAM10-derived sAPPα suppresses demyelination and reduces seizure susceptibility via ameliorating neuroinflammation and oxidative stress in cuprizone-induced demyelination model.

MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8.

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

Systemic arterial blood pressure and intracerebral hemorrhage after mechanical thrombectomy in anterior cerebral circulation.

The relationship between systemic arterial blood pressure (BP) and intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) of the cerebral artery remains unclear. This study aimed to determine the effect of BP variables on ICH after MT in patients with acute occlusions of the anterior cerebral circulation. Patients undergoing MT due to acute occlusions of the anterior cerebral circulation were enrolled in this single-center study. Non-invasive BP data following MT were obtained within the first 24 hours, including mean, maximum, minimum, difference between maximum and minimum, SD and coefficient of variation for systolic BP (SBP) and diastolic BP (DBP) and mean arterial pressure. ICH was defined and classified according to the European Cooperative Acute Stroke Study-II. In 164 enrolled patients (median age 65 (IQR 56-75) years; 31.7% female), higher maximum (89.5 mm Hg vs 98.5 mm Hg, p=0.001) and SD (9.8 mm Hg vs 10.9 mm Hg, p=0.038) of DBP were associated with higher risk of ICH. The optimal cut-off values associated with ICH for maximum SBP were 155 mm Hg and for maximum DBP 92.5 mm Hg, respectively. Higher BP within 24 hours after MT in acute occlusions of the anterior cerebral circulation is associated with a greater risk of ICH. More studies are needed to further determine optimal BP goals in the acute phase after MT.

MiR34a Regulates Neuronal MHC Class I Molecules and Promotes Primary Hippocampal Neuron Dendritic Growth and Branching.

In the immune system, Major Histocompatibility Complex class I (MHC-I) molecules are located on the surface of most nucleated cells in vertebrates where they mediate immune responses. Accumulating evidence indicates that MHC-I molecules are also expressed in the central nervous system (CNS) where they play important roles that are significantly different from their immune functions. Classical MHC-I molecules are temporally and spatially expressed in the developing and adult CNS, where they participate in the synaptic formation, remodeling and plasticity. Therefore, clarifying the regulation of MHC-I expression is necessary to develop an accurate understanding of its function in the CNS. Here, we show that microRNA 34a (miR34a), a brain enriched noncoding RNA, is temporally expressed in developing hippocampal neurons, and its expression is significantly increased after MHC-I protein abundance is decreased in the hippocampus. Computational algorithms identify putative miR34a target sites in the 3'UTR of MHC-I mRNA, and here we demonstrate direct targeting of miR34a to MHC-I mRNA using a dual-luciferase reporter assay system. MiR34a targeting can decrease constitutive MHC-I expression in both Neuro-2a neuroblastoma cells and primary hippocampal neurons. Finally, miR34a mediated reduction of MHC-I results in increased dendritic growth and branching in cultured hippocampal neurons. Taken together, our findings identify miR34a as a novel regulator of MHC-I for shaping neural morphology in developing hippocampal neurons.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

OBJECTIVE: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). METHODS: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. RESULTS: We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-ß (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. CONCLUSIONS: Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. CLINICALTRIALSGOV IDENTIFIER: NCT03218293. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

Targeted NIRF/MR dual-mode imaging of breast cancer brain metastasis using BRBP1-functionalized ultra-small iron oxide nanoparticles.

Tumor metastasis to brain is the main clinical manifestation of patients with advanced breast cancer, leading to poor survival prognosis. In order to detect the early incidence of brain metastasis, it is urgent to develop hypersensitive contrast agents for multimode imaging. In this study, PEG-phospholipids coated, a phage play derived peptide, BRBP1 peptide modified ultra-small iron oxide nanoparticles were prepared for targeted NIRF and MR imaging of breast cancer brain metastasis. The nanoparticles showed 10 nm core-shell, high relaxivity values and photon emission efficiency in vitro. The nanoparticles offered a T2 contrast imaging effect and near-infrared fluorescent signal enhancement. Compared with control peptide modified nanoparticles, the MR/NIRF imaging signal of BRBP1-modified nanoparticles in tumor tissue was significantly enhanced, which should be induced by the targeting ability of BRBP1 peptide. These results indicated that BRBP1-SPIO@mPEG (DiR) nanoparticles could be applied as an effective targeted delivery system for diagnosis of breast cancer brain metastasis.

COX-2-PGE2 signaling pathway contributes to hippocampal neuronal injury and cognitive impairment in PTZ-kindled epilepsy mice.

Epilepsy is one of the most common neurological diseases. It adversely affects cognitive function. Neuroinflammation has been widely recognized as an important factor involved in the pathophysiology of epilepsy. Cyclooxygenase (COX) is a type of oxidoreductase enzyme that acts in the metabolic pathway converting arachidonic acid to prostaglandins, which mediate inflammatory reactions. The activation of inducible cyclooxygenase-2 (COX-2) is considered to be a precipitating factor of neuroinflammation in the brain. Neuroinflammatory processes in the brain are known to contribute to the cascade of events leading to neuronal injury, which may consequently cause cognitive decline. Here in this study, we showed that pentylenetetrazole (PTZ)-kindled mice exhibited an increased level of COX-2 and its main product prostaglandin E2 (PGE2) along with neuroinflammation and neuronal injury in the hippocampus. Pharmacological inhibition of COX-2 by celecoxib, however, significantly reduced hippocampal neuroinflammation and neuronal injury. Furthermore, inhibition of COX-2 by celecoxib attenuated cognitive impairment in the PTZ-kindled mice, suggesting that COX-2-PGE2 signaling pathway mediated neuroinflammation and neuronal injury contributes to cognitive dysfunction in the PTZ-kindled epilepsy mice. Targeting COX-2-PGE2 signaling pathway in the epileptic brain appears to be a viable strategy for attenuating neuronal injury and preventing cognitive deficits in epilepsy patients.

Personalized application of three different concentrations of iodinated contrast media in coronary computed tomography angiography.

No study has evaluated the impact of different iodinated contrast media on coronary contrast enhancement, using an injection protocol according to body surface area (BSA). Thus, the present study aimed to examine the usefulness and safety of personalized application of different iodine concentrations of contrast media in coronary computed tomographic (CT) angiography with a 2nd dual-source CT scanner in eliminating differences in coronary contrast enhancement based on a BSA-adapted injection protocol of contrast media. A total of 270 enrolled participants were randomly assigned to three groups: ioversol 320, ioversol 350 and iopromide 370 (n = 90 per group). The three groups were administered contrast media at a BSA-adjusted volume and flow rate with a fixed injection time of 15 seconds, and they subsequently received a 30-mL saline flush. All patients were scanned with a prospective electrocardiogram-gated protocol in a craniocaudal direction using a second-generation 128-slice dual-source CT system. The three iodinated contrast media used in coronary CT angiography exhibited similar diagnostic quality and safety. No significant differences were found in the contrast enhancement degrees, image quality scores, radiation doses and incidences of adverse effects among the three groups. The three contrast media used in coronary CT angiography with 320, 350 and 370 mg/mL iodine, respectively, have comparable diagnostic quality and safety. However, more large-scale, multinational, multi-centre and prospective trials are warranted.

Prognostic Potential of Electrocardiographic Parameters in Patients with Multiple Myeloma: A Retrospective Analysis of the Multiple Myeloma Population.

INTRODUCTION: Patients with multiple myeloma (MM) can develop cardiac abnormalities, predisposing them to the development of heart failure, arrhythmias, or infarction with poor prognosis. The purpose of this study is to evaluate the prognostic potential of electrocardiographic (ECG) parameters in patients with MM. METHODS: This study retrospectively included patients with MM from January 2010 to December 2018 in the First Affiliated Hospital of Xi'an Jiao Tong University. Univariate and multivariate Cox proportional hazard models were conducted to evaluate the relationship between ECG parameters and all-cause mortality in patients with MM. RESULTS: A total of 409 patients were included (mean age 61.3 ± 9.7 years, 59.2% male). The relationship between ECG parameters (including PR interval, voltage, QRS axis, QRS duration, and QTc interval) and all-cause mortality in patients with MM was evaluated. Overall, patients with QTc interval ≥ 400 ms have a significantly higher all-cause mortality compared to those with QTc interval < 400 ms (P < 0.001). When stratified by the International Staging System (ISS), this relationship was true for stages II and III (P < 0.01), but not stage I (P > 0.05). Patients with MM and QRS duration ≥ 120 ms had a higher all-cause mortality compared to those with QRS duration < 120 ms for women (P < 0.01) but not for men (P > 0.05). PR interval, voltage, and QRS axis did not predict mortality. CONCLUSION: QTc interval was independently associated with all-cause mortality in patients with MM, especially when QTc interval was more than 400 ms in more advanced stages II and III. ECG parameters may provide prognostic potential in patients with MM and aid risk stratification of these patients.

Seizure-induced neuroinflammation contributes to ectopic neurogenesis and aggressive behavior in pilocarpine-induced status epilepticus mice.

Epilepsy is a chronic neurological disorder often associated with recurrent seizures. A growing body of evidence suggests that seizures cause structural and functional alterations of the brain. It is reported that behavioral abnormalities frequently occur in patients with epilepsy and experimental epilepsy models. However, the precise pathological mechanisms associated with these epilepsy comorbidities remain largely unknown. Neurogenesis persists throughout life in the hippocampal dentate gyrus (DG) to maintain proper brain function. However, aberrant neurogenesis usually generates abnormal neural circuits and consequently causes neuronal dysfunction. Neuroinflammatory responses are well known to affect neurogenesis and lead to aberrant reorganization of neural networks in the hippocampal DG. Here, in this study, we observed a significant increase in neuroinflammation and in the proliferation and survival of newborn granular cells in the hippocampus of pilocarpine-induced status epilepticus (SE) mice. More importantly, these proliferating and surviving newborn granular cells are largely ectopically located in the hippocampal DG hilus region. Our behavior test demonstrated that SE mice displayed severe aggressive behavior. Pharmacological inhibition of neuroinflammation, however, suppressed the ectopic neurogenesis and countered the enhanced aggressive behavior in SE mice, indicating that seizure-induced neuroinflammation may contribute to ectopic neurogenesis and aggressive behavior in SE mice. These findings establish a key role for neuroinflammation in seizure-induced aberrant neurogenesis and aggressive behavior. Suppressing neuroinflammation in the epileptic brain may reduce ectopic neurogenesis and effectively block the pathophysiological process that leads to aggressive behavior in TLE mice.