Recall and Self-Relevance of Emotional Words Predict Subjective Self-Evaluation of Cognition in Patients with MTLE with or without Depressive Symptoms

We examined whether word processing is associated with subjective self-evaluation of cognition in patients with mesial temporal lobe epilepsy (MTLE) as a function of their depressive symptoms. MTLE patients with (MTLE +d, N = 28) or without (MTLE -d, N = 11) depression were compared to pair-matched healthy control participants on free recall and self-relevance ratings of emotionally valenced words. Correlation and hierarchical analyses were conducted to investigate whether the subjective self-evaluation of cognition in MTLE patients is predicted by the negative emotional bias reflected in task performance. MTLE +d patients endorsed as self-relevant fewer positive words and more negative words than the MTLE -d patients and healthy participants. They also self-evaluated their cognition poorer than the MTLE -d patients. Analyses indicated that recall and self-endorsement of emotional words predicted both self-evaluation of cognition as well as epilepsy duration. Our findings indicate that negative self-relevance emotional bias is observed in MTLE patients and is predictive of subjective self-evaluation of cognition. Application of brief behavioral tasks probing emotional functions could be valuable for clinical research and practice in the patients with MTLE.

The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice

Background Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. Methods Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. Results In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. Conclusion Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.

Long Noncoding RNA RP11-115N4.1 Promotes Inflammatory Responses by Interacting With HNRNPH3 and Enhancing the Transcription of HSP70 in Unexplained Recurrent Spontaneous Abortion

BackgroundUnexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis.ObjectiveTo investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA.MethodsWe profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated in vitro.ResultsRP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients (P = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and in vitro overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes (HSPA1A and HSPA1B) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis (HSPA1A (P = 4.39E-08, Fold change = 4.17), HSPA1B (P = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and HNRNPH3 knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1β, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA.ConclusionOur results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 via binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA.

No association of microRNA-146a rs2910164 polymorphism and risk of primary gout development in Chinese Han populations: a case-control study

Background: Previous studies demonstrated that MicroRNA-146a (miR-146a) plays an important role in the regulation of autoinflammatory diseases including primary gout. The G/C polymorphism (rs2910164) in the precursor sequence of miR-146a caused its stem region to change from G: U to C: U，which can contribute to the susceptibility of human diseases. however, no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. Objective: The purpose of this study was to analyze the association between the miR-146a rs2910164 genetic polymorphism and the susceptibility of Chinese Han population to primary gout. Method：1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5'exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. Method: 1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5'exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. Result: After statistical analysis, no significant differences were observed between gout patients and healthy controls in genotype and allele frequency. Conclusion: Our results indicate that there is no evidence for the involvement of the miR-146a rs2910164 polymorphisms in susceptibility to primary gout in the Chinese Han population.

Novel severe traumatic brain injury blood outcome biomarkers identified with proximity extension assay

Objectives Severe traumatic brain injury (sTBI) patients suffer high mortality. Accurate prognostic biomarkers have not been identified. In this exploratory study, we performed targeted proteomics on plasma obtained from sTBI patients to identify potential outcome biomarkers. Methods Blood sample was collected from patients admitted to the ICU suffering a sTBI, using standardized clinical and computerized tomography (CT) imaging criteria. Age- and sex-matched healthy control subjects and sTBI patients were enrolled. Targeted proteomics was performed on plasma with proximity extension assays (1,161 proteins). Results Cohorts were well-balanced for age and sex. The majority of sTBI patients were injured in motor vehicle collisions and the most frequent head CT finding was subarachnoid hemorrhage. Mortality rate for sTBI patients was 40%. Feature selection identified the top performing 15 proteins for identifying sTBI patients from healthy control subjects with a classification accuracy of 100%. The sTBI proteome was dominated by markers of vascular pathology, immunity/inflammation, cell survival and macrophage/microglia activation. Receiver operating characteristic (ROC) curve analyses demonstrated areas-under-the-curves (AUC) for identifying sTBI that ranged from 0.870-1.000 (p≤0.005). When mortality was used as outcome, ROC curve analyses identified the top 3 proteins as vWF, WIF-1, and CSF-1. Combining vWF with either WIF-1 or CSF-1 resulted in excellent mortality prediction with AUC of 1.000 for both combinations (p=0.011). Conclusions Targeted proteomics with feature classification and selection distinguished sTBI patients from matched healthy control subjects. Two protein combinations were identified that accurately predicted sTBI patient mortality. Our exploratory findings require confirmation in larger sTBI patient populations.

Examining the neural antecedents of tics in Tourette syndrome using electroencephalography

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by ‘premonitory sensory/urge phenomena’ (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued that tics should be viewed as voluntary movements that are executed in response to the presence of PU and bring temporary relief from the uncomfortable bodily sensations that are associated with PU. This issue remains unresolved but has very important implications for the design of clinical interventions for TS. To investigate this issue further, we conducted a study using electroencephalography (EEG). Specifically, we recorded movement-related EEG (mu and beta band oscillations) during (a) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (b) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta band oscillations are not observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, basal ganglia nuclei, and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.

Detection of Atypical porcine pestivirus in Swedish piglets with congenital tremor type A-II

Background Congenital tremor (CT) type A-II is a neurological disorder characterized by tremor of the head and body of newborn piglets. The suggested causative agent of the disease is the recently found atypical porcine pestivirus (APPV). The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far been performed in the Nordic countries. The overarching goal of this study was to investigate if APPV is present in the brain tissue of Swedish piglets suffering from congenital tremor. From June 2017 – June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of congenital tremor and 13 piglets with splay leg originating from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n=8) were also investigated. Two APPV-specific RT-qPCR methods targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed on material from Swedish piglets with congenital tremor sampled in 2004 (n = 11) and 2011/2012 (n = 3) using the described APPV-specific RT-qPCR methods. The total number of piglets with signs of CT in this study was 29. Results Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV, whereas, all of the healthy controls (n = 11) were negative. The piglets with congenital tremor sampled 2017-2018 had an odds ratio of 91,8 (95% CI 3.9128 to 2153.7842, z = 2.807, P = 0.0050) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in the Swedish pig population. Conclusion This is the first description of atypical porcine pestivirus in piglets suffering from congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004.

Detection of Atypical porcine pestivirus in Swedish pigs with congenital tremor type A-II

Background Congenital tremor (CT) type A-II is a neurological disorder characterized by tremor of the head and body of new-born piglets. The suggested causative agent of the disease is the recently found atypical porcine pestivirus. The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far been performed in the Nordic countries. The overarching goal of this study was to investigate if atypical porcine pestivirus are present in the brain tissue of Swedish piglets suffering from congenital tremor. From June 2017 – June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of CT and 13 piglets with splay leg originating from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n=8) were also studied. Two APPV-specific RT-qPCR methods targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed on material from Swedish piglets with CT sampled in 2004 (n = 11) and 2011/2012 (n = 3) using the described APPV-specific RT-qPCR methods. The total number of piglets with signs of CT in this study was 29. Results Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV, whereas, all of the healthy controls (n = 11) were negative. The piglets with CT sampled 2017-2018 had an odds ratio of 271 (95% CI 12.1 to 6096.8, z = 3.5, P = 0.0004) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in the Swedish pig population. Conclusion This is the first description of atypical porcine pestivirus in piglets suffering from congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004. Keywords: congenital tremor, type A-II, atypical porcine pestivirus, splay legs, Sweden, pigs, piglets.

Cognitive mediated eye movements during the SDMT reveal the challenges with processing speed faced by people with MS

Background The Symbol Digit Modalities Test (SDMT) is regarded as the cognitive test of choice for people with MS (pwMS). While deficits are linked to impaired processing speed, the mechanisms by which they arise are unclear. Cognitive-mediated eye movements offer one putative explanation. The objective of this study was to determine the association between eye movements and performance on the SDMT. Methods Thirty-three people with confirmed MS and 25 matched healthy control subjects (HC) were administered the oral SDMT while eye movements were recorded. Results Mean SDMT scores were significantly lower in pwMS (p < 0.038). Shorter mean saccade distance in the key area (p = 0.007), more visits to the key area per response (p = 0.014), and more total number of fixations in the test area (p = 0.045) differentiated pwMS from HCs. A hierarchical regression analysis revealed that the number of visits to the key area per response (p < 0.001; ΔR2 = 0.549) and total number of fixations in the test area (p < 0.001; ΔR2 = 0.782) were the most robust predictors of SDMT scores. Conclusion Cognitive-mediated eye movements help elucidate the processing speed challenges confronted by people with MS. Mechanistic insights such as these can potentially help inform new cognitive rehabilitation strategies.

Detection of Atypical porcine pestivirus in Swedish pigs with congenital tremor type A-II

Background Congenital tremor type A-II is a neurological disorder characterized by tremor of the head and body of new-born piglets. The suggestive causative agent of the disease is the recently found atypical porcine pestivirus. The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far not been performed in the Nordic countries, hence, the aim of this study was to investigate the prevalence of atypical porcine pestivirus in Swedish piglets. From June 2017 – June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of congenital tremor, and 13 piglets with splay leg, from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n=8) were also studied. Two APPV-specific RT-qPCR:s targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed in the same manner on material from Swedish piglets with congenital tremor sampled in 2004 (n=11) and 2011/2012 (n=6). Results Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All samples from piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV. All of the healthy controls (n=8) were negative for APPV. The piglets with congenital tremor sampled 2017-2018 had an odds ratio of 271 (95% CI 12.1 to 6096.8, z = 3.5, P = 0.0004) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in pigs in Sweden, as most of the virus details is unknown to date. Conclusion This is the first description of atypical porcine pestivirus in piglets with congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004.