Search

Craniosynostosis is the premature fusion of the sutures of the calvaria and is principally designated as being either syndromic (demonstrating characteristic extracranial malformations) or non-syndromic. While many forms of syndromic craniosynostosis are known to be caused by specific mutations, the genetic etiology of non-syndromic, single-suture craniosynostosis (SSC) is poorly understood. Based on the low recurrence rate (4–7%) and the fact that recurrent mutations have not been identified for most cases of SSC, we propose that some cases of isolated, single suture craniosynostosis may be polygenic. Previous work in our lab identified a disproportionately high number of rare and novel gain-of-function IGF1R variants in patients with SSC as compared to controls. Building upon this result, we used expression array data from calvarial osteoblasts isolated from infants with and without SSC to ascertain correlations between high IGF1 expression and expression of other osteogenic genes of interest. We identified a positive correlation between increased expression of IGF1 and RUNX2, a gene known to cause SSC with increased gene dosage. Subsequent phosphorylation assays revealed that osteoblast cell lines from cases with high IGF1 expression demonstrated inhibition of GSK3β, a serine/threonine kinase known to inhibit RUNX2, thus activating osteogenesis through the IRS1-mediated Akt pathway. With these findings, we have utilized established mouse strains to examine a novel model of polygenic inheritance (a phenotype influenced by more than one gene) of SSC. Compound heterozygous mice with selective disinhibition of RUNX2 and either overexpression of IGF1 or loss of function of GSK3β demonstrated an increase in the frequency and severity of synostosis as compared to mice with the RUNX2 disinhibition alone. These polygenic mouse models reinforce, in-vivo, that the combination of activation of the IGF1 pathway and disinhibition of the RUNX2 pathway leads to an increased risk of developing craniosynostosis and serves as a model of human SSC. [ABSTRACT FROM AUTHOR]

Several reports indicate crosstalk between the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and estrogen, which has a protective effect in colorectal cancer (CRC). The aim of this study was to investigate the role of Nrf2 signaling in the anti-inflammatory effect of estrogen using Nrf2 knockout (Nrf2 KO) mouse embryonic fibroblasts (MEFs), a powerful system to test the function of target genes due to their easy accessibility, and rapid growth rates. After inducing inflammation by tumor necrosis factor alpha (TNF-α), the effects of 17β-estradiol (E2) on the expression of proinflammatory mediators [i.e., NF-κB and inducible nitric oxide synthase (iNOS)] and estrogen receptors were evaluated by Western blot. In wild type (WT) MEFs, E2 treatment ameliorated TNF-α-induced nuclear translocation of NF-κB and expression of its target protein iNOS. Estrogen receptor beta (ERβ) expression was decreased by TNF-α-induced inflammation and restored by E2 treatment. When treated to WT MEFs, E2 induced nuclear translocation of Nrf2. The inhibitory effect of E2 on TNF-α-induced enhancement of iNOS was markedly dampened in Nrf2 KO MEFs. Notably, ERβ expression was significantly diminished in Nrf2 KO MEFs compared to that in WT cells. Promoter Database (EPD) revealed two putative anti-oxidant response elements (AREs) within the mouse ERβ promoter. Furthermore, in WT MEFs, E2 treatment repressed TNF-α-induced expression of iNOS protein and recovered by 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol (PHTPP), a selective ERβ antagonist, treatment, but not in Nrf2 KO MEFs. In conclusion, Nrf2 plays a pivotal role in the anti-inflammatory of estrogen by direct regulating the expression of ERβ. [ABSTRACT FROM AUTHOR]

Freely crawling cells are often viewed as randomly moving Brownian particles but they generally exhibit some directional persistence. This property is often related to their zigzag motile behaviors that can be described as a noisy but temporally structured sequence of “runs” and “turns.” However, its underlying biophysical mechanism is largely unexplored. Here, we carefully investigate the collective actin wave dynamics associated with the zigzag-crawling movements of microglia (as primary brain immune cells) employing a number of different quantitative imaging modalities including synthetic aperture microscopy and optical diffraction tomography, as well as conventional fluorescence imaging and scanning electron microscopy. Interestingly, we find that microglia exhibit two distinct types of actin waves working at two quite different time scales and locations, and they seem to serve different purposes. One type of actin waves is fast “peripheral ruffles” arising spontaneously with an oscillating period of about 6 seconds at some portion of the leading edge of crawling microglia, where the vigorously biased peripheral ruffles seem to set the direction of a new turn (in 2-D free space). When the cell turning events are inhibited with a physical confinement (in 1-D track), the peripheral ruffles still exist at the leading edge with no bias but showing phase coherence in the cell crawling direction. The other type is “dorsal actin waves” which also exhibits an oscillatory behavior but with a much longer period of around 2 minutes compared to the fast “peripheral ruffles”. Dorsal actin waves (whether the cell turning events are inhibited or not) initiate in the lamellipodium just behind the leading edge, travelling down toward the core region of the cell and disappear. Such dorsal wave propagations seem to be correlated with migration of the cell. Thus, we may view the dorsal actin waves are connected with the “run” stage of cell body, whereas the fast ruffles at the leading front are involved in the “turn” stage. [ABSTRACT FROM AUTHOR]

Pentraxin-3 (PTX3) is a multifunctional protein involved in both innate and adaptive immunity. Glucocorticoid (GC) is the first-line therapy to mitigate airway inflammation in asthma. Previous pieces of evidence showed that GC has divergent effects on PTX3 production in various cell types. The molecular mechanisms controlling PTX3 expression in HASMC are, however, not yet characterized. In this study, we demonstrate that the synthetic GC, dexamethasone (DEX) increases the expression of PTX3 both at the protein and mRNA levels. We also found that such an effect of DEX was dependent on de novo protein synthesis and the GC receptor (GR). While DEX increases PTX3 mRNA stability, it did not affect its promoter activity. Interestingly, HASMC pre-treated with p42/p44 ERK inhibitor, but not with p38 or JNK-MAPK inhibitors, significantly interfered with DEX-induced PTX3 secretion. Taken together, our data suggest that GC regulates PTX3 expression in HASMC through transcriptional and post-transcriptional mechanisms in a GR and ERK-dependent manner. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Owing to the incorporation of risk-adapted therapy and the arrival of new directed agents, the cure rate and survival of patients with ALL have improved dramatically, get near to 90%. In Latin American countries, the mortality rates of ALL are high, for example in Colombia, during the last decade, ALL has been the most prevalent cancer among children between 0–14 years of age. In the face of this public health problem and coupled with the fact that the knowledge of the proteome of the child population is little, our investigation proposes the study of the plasma proteome of Colombian children diagnosed with B-cell ALL (B-ALL) to determine potential disease markers that could reflect processes altered by the presence of the disease or in response to it. A proteomic study by LC-MS/MS and quantification by label-free methods were performed in search of proteins differentially expressed between healthy children and those diagnosed with B-ALL. We quantified a total of 472 proteins in depleted blood plasma, and 25 of these proteins were differentially expressed (fold change >2, Bonferroni-adjusted P-values <0.05). Plasma Aggrecan core protein, alpha-2-HS-glycoprotein, coagulation factor XIII A chain and gelsolin protein were examined by ELISA assay and compared to shotgun proteomics results. Our data provide new information on the plasma proteome of Colombian children. Additionally, these proteins may also have certain potential as illness markers or as therapeutic targets in subsequent investigations. [ABSTRACT FROM AUTHOR]

Introduction: Long-term treatment is used in patients with osteoporosis, and bisphosphonates (BPs) are the most commonly prescribed medications. However, in some patients this therapy is not effective, cause different side effects and complications. Unfortunately, at least one year is needed to identify and confirm an ineffectiveness of BPs therapy on bone mineral density (BMD). Among other factors, a response to BPs therapy may also be explained by genetic factors. The aim of this study was to analyze the influence of SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 gene variants on the response to treatment with aminobisphosphonates. Materials and methods: Women with postmenopausal osteoporosis were included to this study if they used aminobisphosphonates for at least 12 months. Exclusion criteria were: persistence on BPs therapy less than 80%, bone metabolic diseases, diseases deemed to affect bone metabolism, malignant tumours, using of any medications influencing BMD. The study protocol was approved by the local ethics committee. The BMD at the lumbar spine and femoral neck were measured using dual x-ray absorptiometry (GE Lunar) before and at least 12 months after treatment with BPs. According to BMD change, patients were divided in two groups–responders and non-responders to BPs terapy. Polymorphic variants in SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). Results: In total, 201 women with BPs therapy were included in the study. No statistically significant differences were observed in age, age at menopause, weight, height, BMI and baseline BMD levels between responders (122 subjects) and non-responders (79 subjects). As single markers, the SOST rs1234612 T/T (OR = 2.3; P = 0.02), PTH rs7125774 T/T (OR = 2.8, P = 0.0009), FDPS rs2297480 G/G (OR = 29.3, P = 2.2×10−7), and GGPS1 rs10925503 C/C+C/T (OR = 2.9; P = 0.003) gene variants were over-represented in non-responders group. No significant association between FGF2 rs6854081 and LRP5 rs3736228 gene variants and response to BPs treatment was observed. The carriers of T-T-G-C allelic combination (constructed from rs1234612, rs7125774, rs2297480, and rs10925503) were predisposed to negative response to BPs treatment (OR = 4.9, 95% CI 1.7–14.6, P = 0.005). The C-C-T-C combination was significantly over-represented in responders (OR = 0.1, 95% CI 0.1–0.5, P = 0.006). Conclusions: Our findings highlight the importance of identified single gene variants and their allelic combinations for pharmacogenetics of BPs therapy of osteoporosis. Complex screening of these genetic markers could be used as a new strategy for personalized antiresorptive therapy. [ABSTRACT FROM AUTHOR]

Candidemia has been considered a persistent public health problem with great impact on hospital costs and high mortality. We aimed to evaluate the epidemiology and prognostic factors of candidemia in a tertiary hospital in Northeast Brazil from January 2011 to December 2016. Demographic and clinical data of patients were retrospectively obtained from medical records and antifungal susceptibility profiling was performed using the broth microdilution method. A total of 68 episodes of candidemia were evaluated. We found an average incidence of 2.23 episodes /1000 admissions and a 30-day mortality rate of 55.9%. The most prevalent species were Candida albicans (35.3%), Candida tropicalis (27.4%), Candida parapsilosis (21.6%) and Candida glabrata (11.8%). Higher mortality rates were observed in cases of candidemia due to C. albicans (61.1%) and C. glabrata (100%), especially when compared to C. parapsilosis (27.3%). Univariate analysis revealed some variables which significantly increased the probability of death: older age (P = 0.022; odds ratio [OR] = 1.041), severe sepsis (P < 0.001; OR = 8.571), septic shock (P = 0.035; OR = 3.792), hypotension (P = 0.003; OR = 9.120), neutrophilia (P = 0.046; OR = 3.080), thrombocytopenia (P = 0.002; OR = 6.800), mechanical ventilation (P = 0.009; OR = 8.167) and greater number of surgeries (P = 0.037; OR = 1.920). Multivariate analysis showed that older age (P = 0.040; OR = 1.055), severe sepsis (P = 0.009; OR = 9.872) and hypotension (P = 0.031; OR = 21.042) were independently associated with worse prognosis. There was no resistance to amphotericin B, micafungin or itraconazole and a low rate of resistance to fluconazole (5.1%). However, 20.5% of the Candida isolates were susceptible dose-dependent (SDD) to fluconazole and 7.7% to itraconazole. In conclusion, our results could assist in the adoption of strategies to stratify patients at higher risk for developing candidemia and worse prognosis, in addition to improve antifungal management. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterised by behavioural, communication and social impairments. The prevalence of sleep disturbances in children with ASD is 40–80%, with significant effects on quality of life for the children and carers. This systematic review aimed to synthesise evidence of the effects of behavioural interventions to improve sleep among children with ASD. Methods: Databases (MEDLINE, PsycINFO, CINAHL, ScienceDirect, Autism Data, CENTRAL, ClinicalTrials.gov and Current Controlled Trials) were searched for published, unpublished and ongoing randomised controlled trials evaluating the effect of non-pharmacological interventions for insomnia in children with autism spectrum conditions. Results: Three studies met the inclusion criteria, one provided actigraphy data, one Children’s Sleep Habits Questionnaire (CSHQ) data, and one both actigraphy and CSHQ data for use in meta-analyses. There were significant differences between the behavioural intervention and comparison groups (actigraphy data) for total sleep time (24.41 minutes, 95% CI 5.71, 43.11, P = 0.01), sleep latency (-18.31 minutes, 95% CI -30.84, -5.77, P = 0.004) and sleep efficiency (5.59%, 95% CI 0.87, 10.31, P = 0.02). There was also a favourable intervention effect evident for the subjective CSHQ data (-4.71, 95% CI -6.70, -2.73, P<0.00001). Risk of bias was low across several key domains (randomisation, allocation concealment and reporting), with some studies being unclear due to poor reporting. Conclusions: There are very few high quality randomised controlled trials in this area. Here we provide initial synthesised quantitative evidence of the effectiveness of behavioural interventions for treating sleep problems in children with ASD. Trial registration: Protocol was registered () on the International Prospective Register of Systematic Reviews (). [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) can provide objective continuous intervertebral disc (IVD) measures in low back pain (LBP) patients. However, there are limited studies comparing quantitative IVD measures of symptomatic and asymptomatic individuals. Purpose: This study aimed to investigate possible differences in IVD tissue composition in patients with chronic LBP and controls using quantitative MRI and correlate IVD measures with the phenotype High-Intensity Zone (HIZ). Methods: The lumbar spine of 25 LBP-patients (25-69y, mean 38y, 11 males) and 12 controls (25-59y, mean 38y, 7 males) was examined with T2-mapping on a 1.5T MRI scanner. The mean T2-map value and standard deviation were determined in three midsagittal IVD slices and five sub-regions dividing each IVD in the sagittal plane. The distribution of T2-map values over the IVD was also determined with histogram analysis (Δμ = distribution width). Results: When compared to controls, patient IVDs displayed lower values for all metrics, with significant differences for the T2-map value, standard deviation (p = 0.026) and Δμ (p = 0.048). Significantly different T2-map values were found between cohorts in the region representing nucleus pulposus and the border zone between nucleus pulposus and posterior annulus fibrosus (p = 0.047–0.050). Excluding all IVDs with HIZs resulted in no significant difference between the cohorts for any of the analyzed metrics (p = 0.053–0.995). Additionally, the T2-map values were lower in patients with HIZ in comparison without HIZ. Conclusions: Differences in IVD characteristics, measured with quantitative MRI, between LBP patients and controls were found. The T2-differences may reflect altered IVD function associated with HIZ. Future studies are recommended to explore IVD functionality in relation to HIZ and LBP. [ABSTRACT FROM AUTHOR]

Complex network theory has been successful at unveiling the topology of the brain and showing alterations to the network structure due to brain disease, cognitive function and behavior. Functional connectivity networks (FCNs) represent different brain regions as the nodes and the connectivity between them as the edges of a graph. Graph theoretic measures provide a way to extract features from these networks enabling subsequent characterization and discrimination of networks across conditions. However, these measures are constrained mostly to binary networks and highly dependent on the network size. In this paper, we propose a novel graph-to-signal transform that overcomes these shortcomings to extract features from functional connectivity networks. The proposed transformation is based on classical multidimensional scaling (CMDS) theory and transforms a graph into signals such that the Euclidean distance between the nodes of the network is preserved. In this paper, we propose to use the resistance distance matrix for transforming weighted functional connectivity networks into signals. Our results illustrate how well-known network structures transform into distinct signals using the proposed graph-to-signal transformation. We then compute well-known signal features on the extracted graph signals to discriminate between FCNs constructed across different experimental conditions. Based on our results, the signals obtained from the graph-to-signal transformation allow for the characterization of functional connectivity networks, and the corresponding features are more discriminative compared to graph theoretic measures. [ABSTRACT FROM AUTHOR]

Background and aims: The revised Atlanta classification is widely used for the evaluation of acute pancreatitis (AP) severity. However, this classification cannot be used within 48 hours of AP onset. The aim of this study was to investigate the predictive factors of mortality in patients with AP on admission. Methods: We evaluated the association between AP mortality and clinical parameters at the time of admission in patients with AP from April 2013 to December 2017 at one university hospital and one tertiary care referral center. Results: A total of 203 consecutive patients were enrolled. Nine patients (4.4%) died despite multidisciplinary treatment. In a multivariable analysis, hematocrit ≥ 40% (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01–1.13; P = 0.021), blood urea nitrogen (BUN) ≥ 40 mg/dL (OR, 1.26; 95% CI, 1.11–1.42; P < 0.001), base excess < -3.0 mmol/L (OR, 1.15; 95% CI, 1.04–1.26; P = 0.004), and inflammation extending to the rectovesical excavation (OR, 1.19; 95% CI, 1.10–1.30; P < 0.001) on admission were significantly associated with mortality. Conclusion: Among the imaging findings, inflammation extending to the rectovesical excavation was the only independent predictive factor for mortality in AP. This simple finding, obtained on computed tomography without contrast agent on admission, might be a promising prognostic factor for AP. [ABSTRACT FROM AUTHOR]

Background: Hypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1α) in ovarian cancer (OC). Materials and methods: Thirty-eight patients with primary OC were enrolled in this prospective study approved by the local ethical committee. Patients underwent dynamic gadolinium-enhanced 3.0 T MRI as part of their staging investigations. Pharmacokinetic perfusion parameters, including a rate constant for transfer of contrast agent from plasma to extravascular extracellular space (EES) (Ktrans) and a rate constant from EES to plasma (Kep), were measured by drawing two types of regions of interest (ROIs): a large solid lesion (L-ROI) and a solid, most enhancing small area (S-ROI) (NordicICE platform). Tissue samples for immunohistochemical analysis were collected during surgery. Kruskal–Wallis, Mann–Whitney U and Chi-square tests were used in statistical analyses. Receiver Operating Characteristic curve analyzes were done for DCE parameters to discriminate high HIF-1α expression. Results: Pharmacokinetic perfusion parameters Ktrans and Kep were inversely associated with HIF-1α expression (Ktrans L-ROI P = 0.021; Ktrans S-ROI P = 0.018 and Kep L-ROI P = 0.032; Kep S-ROI P = 0.033). Ktrans and Kep showed good accuracy in identifying high HIF-1α expression (AUC = 0.832 Ktrans L-ROI; 0.840 Ktrans S-ROI; 0.808 Kep L-ROI and 0.808 Kep L-ROI). Conclusion: This preliminary study demonstrated that pharmacokinetic DCE-MRI perfusion parameters are associated with the hypoxia specific marker, HIF-1α in OC. DCE-MRI may be a useful supplementary tool in the characterization of OC tumors in a staging investigation. [ABSTRACT FROM AUTHOR]

Objective: Detection of vascular endothelial growth factor (VEGF) levels in ocular tissue may perhaps provide insight into the role of VEGF in the pathogenesis and progression of diabetic retinopathy (DR). The aim of this study was to evaluate the levels of VEGF in tears and serum amongst type 2 diabetes mellitus (DM) patients. Methods: A comparative cross-sectional study was conducted between August 2016 and May 2018 involving type 2 DM patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Tear samples were collected using no.41 Whatman filter paper (Schirmer strips) and 5 mL blood samples were drawn by venous puncture. VEGF levels in tears and serum were measured by enzyme-linked immunosorbent assay. Results: A total of 88 type 2 DM patients (no DR: 30 patients, NPDR: 28 patients, PDR: 30 patients) were included in the study. Mean tear VEGF levels were significantly higher in the NPDR and PDR groups (114.4 SD 52.5 pg/mL and 150.8 SD 49.7 pg/mL, respectively) compared to the no DR group (40.4 SD 26.5 pg/mL, p < 0.001). There was no significant difference in the mean serum VEGF levels between the three groups. There was a fair correlation between serum and tear VEGF levels (p = 0.015, r = 0.263). Conclusion: VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR. There was a fair correlation between serum and tear VEGF levels. Detection of VEGF in tears is a good non-invasive predictor test for the severity of DR. A large cohort study is needed for further evaluation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the accuracy of heart rate to estimate energy cost during eight resistance exercises performed at low intensities: half squat, 45° inclined leg press, leg extension, horizontal bench press, 45° inclined bench press, lat pull down, triceps extension and biceps curl. 56 males (27.5 ± 4.9 years, 1.78 ± 0.06 m height, 78.67 ± 10.7 kg body mass and 11.4 ± 4.1% estimated body fat) were randomly divided into four groups of 14 subjects each. Two exercises were randomly assigned to each group and subjects performed four bouts of 4-min constant-intensity at each assigned exercise: 12%, 16%, 20% and 24% 1-RM. Exercise and intensity order were random. Each subject performed no more than 2 bouts in the same testing session. A minimum recovery of 24h was kept between sessions. During testing VO2 was measured with Cosmed K4b2 and heart rate was measured with Polar V800 monitor. Energy cost was calculated from mean VO2 during the last 30-s of each bout by using the energy equivalent 1 ml O2 = 5 calorie. Linear regressions with heart rate as predictor and energy cost as dependent variable were build using mean data from all subjects. Robustness of the regression lines was given by the scatter around the regression line (Sy.x) and Bland-Altman plots confirmed the agreement between measured and estimated energy costs. Significance level was set at p≤0.05. The regressions between heart rate and energy cost in the eight exercises were significant (p<0.01) and robustness was: half squat (Sy.x = 0,48 kcal·min-1), 45° inclined leg press (Sy.x = 0,54 kcal·min-1), leg extension (Sy.x = 0,59 kcal·min-1), horizontal bench press (Sy.x = 0,47 kcal·min-1), 45° inclined bench press (Sy.x = 0,54 kcal·min-1), lat pull down (Sy.x = 0,28 kcal·min-1), triceps extension (Sy.x = 0,08 kcal·min-1) and biceps curl (Sy.x = 0,13 kcal·min-1). We conclude that during low-intensity resistance exercises it is possible to estimate aerobic energy cost by wearable heart rate monitors with errors below 10% in healthy young trained males. [ABSTRACT FROM AUTHOR]

Rejection of solid organ grafts is regarded to be dependent on T cell responses. Nonetheless, numerous studies have focused on the contribution of NK cells in this process, resulting in contradictory theories. While some conclude that there is no participation of NK cells, others found an inflammatory or regulative role of NK cells. However, the experimental settings are rarely comparable with regard to challenged species, strain combinations or the nature of the graft. Thus, clear definition of NK cell contribution might be impeded by these circumstances. In this study we performed heterotopic heart transplantation (HTx) in rats, choosing one donor-recipient-combination leading to a fast and a second leading to a prolonged course of graft rejection. We intervened in the rejection process, by depletion of recipient NK cells on the one hand and by injection of activated NK cells syngeneic to the recipients on the other. The fast course of rejection could not be influenced by any of the NK cell manipulative treatments. However, the more prolonged course of rejection was highly susceptible to depletion of NK cells, resulting in significant acceleration of rejection, while injection of NK cells induced acceptance of the grafts. We suggest that, depending on the specific setting, NK cells can attenuate the first trigger of immune response, which allows establishing the regulatory activity leading to tolerance of the graft. [ABSTRACT FROM AUTHOR]

Glycoprotein G (gG) is a conserved protein, and it has been described as a chemokine-binding protein in most members of the alphaherpesviruses. In case of the infectious laryngotracheitis virus (ILTV), an alphaherpesvirus that infects chickens, this protein is a virulence factor that plays an immunomodulatory role in the chicken immune response. Nevertheless, the gG production profile during ILTV infection has not yet been studied. In this study, we developed monoclonal antibodies in order to determine the gG production profile during ILTV infection in chicken hepatocellular carcinoma (LMH) cell cultures as well as embryonated specific-pathogen-free (SPF) chicken eggs and SPF chickens using a sandwich enzyme-linked immunosorbent assay (ELISA). Despite the fact that inoculated LMH cell cultures showed an increase in both gG production and viral genome copy number up to 96 h after inoculation, we observed that gG production started earlier than the increase in viral genome copy number in ILTV infected embryonated SPF chicken eggs. Likewise, a gG production peak and an increase of viral genome copy number was observed prior to the appearance of clinical signs in infected SPF chickens. According to the production profiles, gG was also produced quite early in eggs and chickens inoculated with ILTV. These findings contribute to the knowledge of the gG role during the ILTV infection as a virulence factor. [ABSTRACT FROM AUTHOR]

In the ultimatum game (UG), mid-value offers are unfair but not so unreasonable as to be rejected immediately. As a consequence, they are difficult for responders to evaluate because of the conflict that arises between two key processes, namely inequity aversion and self-interests. Since there is no clear consensus in the literature on event-related potential (ERP) as to how mid-value offers are processed, we designed an experiment to explore how the ability to reject offers influences key ERP signatures. By manipulating the right to reject offers based on game type (ultimatum game, UG or dictator game, DG), our study explored how ERPs were influenced by three types of offers available to participants (fair, unfair and mid-value). We recorded the electroencephalogram results of 28 participants while they responded to the three kinds of offers in the UG and the DG. We observed that mid-value offers in the UG elicited more negative feedback-related negativity and N400 than did the unfair offers. However, these ERP patterns were specific to the UG. Furthermore, we interpreted these results as further electrophysiological evidence of the interaction between the two processing systems during the UG. [ABSTRACT FROM AUTHOR]

Foraminifera are expected to be particularly susceptible to future changes in ocean carbonate chemistry as a function of increased atmospheric CO2. Studies in an experimental recirculating seawater system were performed with a dominant benthic foraminiferal species collected from intertidal mudflats. We investigated the experimental impacts of ocean acidification on survival, growth/calcification, morphology and the biometric features of a calcareous species Elphidium williamsoni. Foraminifera were exposed for 6 weeks to four different pH treatments that replicated future scenarios of a high CO2 atmosphere resulting in lower seawater pH. Results revealed that declining seawater pH caused a decline in foraminiferal survival rate and growth/calcification (mainly through test weight reduction). Scanning electron microscopy image analysis of live specimens at the end of the experimental period show changes in foraminiferal morphology with clear signs of corrosion and cracking on the test surface, septal bridges, sutures and feeding structures of specimens exposed to the lowest pH conditions. These findings suggest that the morphological changes observed in shell feeding structures may serve to alter: (1) foraminiferal feeding efficiency and their long-term ecological competitiveness, (2) the energy transferred within the benthic food web with a subsequent shift in benthic community structures and (3) carbon cycling and total CaCO3 production, both highly significant processes in coastal waters. These experimental results open-up the possibility of modelling future impacts of ocean acidification on both calcification and dissolution in benthic foraminifera within mid-latitude intertidal environments, with potential implications for understanding the changing marine carbon cycle. [ABSTRACT FROM AUTHOR]

Introduction: Over the past decades, obesity stigma has become a substantial public health issue as studies have highlighted its negative consequences for mental and physical health. However, comparative studies are scarce. In this cross-national study, we focus on the following research questions: (1) Are there differences in the magnitude of public obesity stigma between Germany and the United States (US), and (2) are there differences in the associations of sociodemographic as well as experience (i.e. former obesity experience) and contact-related (i.e. contact to a person with obesity) factors with public obesity stigma between these two countries? Material and methods: National telephone surveys in Germany and the United States were conducted (total sample = 2,802) by using vignettes for the description of a person with obesity. Fat Phobia Scale, negative reactions, and desire for social distance were assessed as components of public obesity stigma. All three stigma components were examined with multilevel linear regression analyses. Results: Overall, results show that public obesity stigma is significantly more pronounced in the US than in Germany. Relationships between obesity stigma and sociodemographic as well as experience and contact-related factors remain rather inconclusive, though, in general, stronger associations are shown in the US. Conclusions: Contrary to the normalization hypothesis, findings indicate that a comparatively high prevalence of obesity like in the US is associated with a higher level of obesity stigma. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) remains a clinical diagnosis but biomarkers from cerebrospinal fluid (CSF) and more lately amyloid imaging with positron emission tomography (PET), are important to support a diagnosis of AD. Objective: To compare amyloid-β (Aβ) PET imaging with biomarkers in CSF and evaluate the prediction of Aβ PET on diagnosis in a memory clinic setting. Methods: We included 64 patients who had lumbar puncture and Aβ PET with 18F-Flutemetamol performed within 190 days. PET was binary classified (Flut+ or Flut-) and logistic regression analyses for correlation to each CSF biomarker; Aβ 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), were performed. Cut-off values were assessed by receiver operating characteristic (ROC) curves. Logistic regression was performed for prediction of clinical AD diagnosis. We assessed the interrater agreement of PET classification as well as for diagnoses, which were made both with and without knowledge of PET results. Results: Thirty-two of the 34 patients (94%) in the Flut+ group and nine of the 30 patients (30%) in the Flut- group had a clinical AD diagnosis. There were significant differences in all CSF biomarkers in the Flut+ and Flut- groups. Aβ42 showed the highest correlation with 18F-Flutemetamol PET with a cut-off value of 706.5 pg/mL, corresponding to sensitivity of 88% and specificity of 87%. 18F-Flutemetamol PET was the best predictor of a clinical AD diagnosis. We found a very high interrater agreement for both PET classification and diagnosis. Conclusions: The present study showed an excellent correlation of Aβ42 in CSF and 18F-Flutemetamol PET and the presented cut-off value for Aβ42 yields high sensitivity and specificity for 18F-Flutemetamol PET. 18F-Flutemetamol PET was the best predictor of clinical AD diagnosis. [ABSTRACT FROM AUTHOR]

Background: The quantitative fluorescent polymerase chain reaction (QF-PCR) has proven to be a reliable method for detection of common fetal chromosomal aneuploidies. However, there are some technical shortcomings, such as uncertainty of aneuploidy determination when the short tandem repeats (STR) height ratio is unusual due to a large size difference between alleles or failure due to the presence of maternal cell contamination (MCC). The aim of our study is to facilitate the implementation of the QF-PCR as a rapid diagnostic test for common fetal aneuploidies. Methods: Here, we describe an in-house one-tube multiplex QF-PCR method including 20 PCR markers (15 STR markers and 5 fixed size) for rapid prenatal diagnosis of chromosome 13, 18, 21, X and Y aneuploidies. In order to improve the aneuploidy classification of a given diallelic STR marker, we have employed a multilevel logistic regression analysis using "height-ratio" and "allele-size-difference" as fixed effects and "marker" as a random effect. We employed two regression models, one for the 2:1 height ratio (n = 48 genotypes) and another for the 1:2 height ratio (n = 41 genotypes) of the trisomic diallelic markers while using the same 9015 genotypes with normal 1:1 height ratio in both models. Furthermore, we have described a simple procedure for the treatment of the MCC, prior DNA isolation and QF-PCR analysis. Results: For both models, we have achieved 100% specificity for the marker aneuploidy classification as compared to 98.60% (2:1 ratio) and 98.04% (1:2 ratio) specificity when using only the height ratio for classification. Treatment of the MCC enables a successful diagnosis rate of 76% among truly contaminated amniotic fluids. Conclusions: Adjustment for the allele size difference and marker type improves the STR aneuploidy classification, which, complemented with appropriate treatment of contaminated amniotic fluids, eliminates sample re-testing and reinforces the robustness of the QF-PCR method for prenatal testing. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH), a commonly abused drug, elevates extracellular dopamine (DA) levels by inducing DA efflux through the DA transporter (DAT). Emerging evidence in rodent models suggests that locomotor responses to a novel inescapable open field may predict behavioral responses to abused drugs; METH produces more potent stimulant effects in high responders to novelty than in low responders. We herein found that mice deficient in protein tyrosine phosphatase receptor type Z (Ptprz-KO) exhibited an enhanced behavioral response to novelty; however, METH-induced hyperlocomotion was significantly lower in Ptprz-KO than in wild-type mice when METH was administered at a non-toxic dose of 1 mg per kg body weight (bdw). Single-cell RT-PCR revealed that the majority of midbrain DA neurons expressed PTPRZ. No histological alterations were observed in the mesolimbic or nigrostriatal dopaminergic pathways in Ptprz-KO brains; however, a significant decrease was noted in brain DA turnover, suggesting functional alterations. In vivo microdialysis experiments revealed that METH-evoked DA release in the nucleus accumbens was significantly lower in Ptprz-KO mice than in wild-type mice. Consistent with this result, Ptprz-KO mice showed significantly fewer cell surface DAT as well as weaker DA uptake activity in striatal synaptosomes prepared 1 hr after the administration of METH than wild-type mice, while no significant differences were observed in the two groups treated with saline. These results indicate that the high response phenotype of Ptprz-KO mice to novelty may not be simply attributed to hyper-dopaminergic activity, and that deficits in PTPRZ reduce the effects of METH by reducing DAT activity. [ABSTRACT FROM AUTHOR]

People with schizophrenia (SZ) or bipolar disorder (BD) experience dysfunction in visual processing. Dysfunctional neural tuning, in which neurons and neuronal populations are selectively activated by specific features of visual stimuli, may contribute to these deficits. Few studies have examined this possibility and there are inconsistent findings of tuning deficits in the literature. We utilized an event-related potential (ERP) paradigm to examine neural adaptation for visual objects, a measure of neural tuning whereby neurons respond less strongly to the repeated presentation of the same stimulus. Seventy-seven SZ, 53 BD, and 49 healthy comparison participants (HC) were examined. In three separate conditions, pictures of objects were presented repeatedly: the same object (SS), different objects from the same category (e.g., two different vases; SD), or different objects from different categories (e.g., a barrel and a clock, DD). Mass-univariate cluster-based permutation analyses identified electrodes and time-windows in which there were significant differences between the SS vs. DD and the SD vs. DD conditions. Mean ERP amplitudes were extracted from these clusters and analyzed for group differences. Results revealed a significant condition difference over parieto-occipital electrodes for the SS-DD comparison between 109–164 ms and for the SD-DD comparison between 78–203 ms, with larger amplitudes in the DD compared to either SS or SD condition. However, there were no significant differences in the pattern of results between groups. Thus, while we found neural adaptation effects using this ERP paradigm, we did not find evidence of group differences. Our results suggest that people with SZ or BD may not exhibit deficits in neural tuning for processing of visual objects using this EEG task with rapidly presented stimuli. However, the results are inconsistent with other studies using different methodologies (e.g., fMRI, behavioral tasks) that have found tuning deficits in people with schizophrenia. [ABSTRACT FROM AUTHOR]

The simultaneous utilization of electrophysiological recordings and two-photon imaging allows the observation of neural activity in a high temporal and spatial resolution at the same time. The three dimensional monitoring of morphological features near the microelectrode array makes the observation more precise and complex. In vitro experiments were performed on mice neocortical slices expressing the GCaMP6 genetically encoded calcium indicator for monitoring the neural activity with two-photon microscopy around the implanted microelectrodes. A special filtering algorithm was used for data analysis to eliminate the artefacts caused by the imaging laser. Utilization of a special filtering algorithm allowed us to detect and sort single unit activities from simultaneous two-photon imaging and electrophysiological measurement. [ABSTRACT FROM AUTHOR]

Chronic pain patients enter treatment with different problem profiles making careful assessment a necessity for more individualized treatment plans. In this cross-sectional study we assigned 320 patients entering tertiary multidisciplinary pain treatment into four categories based on whether they scored low or high on the activity and the affective pain interference dimensions of the Brief Pain Inventory (BPI). To determine whether this categorization system delineates issues that should be assessed further, the categories were compared with ANOVA and MANOVA analyses on three domains: variables affecting physical well-being (body mass index, exercise, substance use), psychological resources (mood), and pain-specific psychological factors (pain anxiety, pain acceptance). The results indicated that subjects who scored low on both interference dimensions compared similarly in weight: mean Body Mass Index (BMI) 27.0 (SD 6.0) kg/m2, and exercise: mean of 2.4 (SD 1.7) exercising sessions over 20 minutes per week, to the general population, had no depressive symptoms on average: mean Beck Depression Index II (BDI-II) score 11.7 (SD 7.5), and had the most favorable psychological reactions to pain relative to the other categories: mean total Pain Anxiety Symptoms Scale-20 (PASS-20) score 36.4 (SD 17.9). In contrast, when interference was high on activity, more physical well-being problems were evident e.g. weight: mean BMI 31.0 (SD 7.3) kg/m2, diminished exercise: mean of 1.5 (SD 1.6) exercising sessions per week, and avoidance behavior: mean PASS-20 Escape/Avoidance subscale 3.7 (95% CI: 1.7 to 5.8) scores higher in comparison to activity interference remaining low. With high affective interference, more depressive symptoms: mean BDI-II score 17.7 (SD 7.3), and more cognitive pain anxiety: mean PASS-20 Cognitive Anxiety subscale 2.8 (95% CI 0.7 to 4.8) scores higher in comparison to affective interference remaining low, emerged. Having high interference on both dimensions indicated accumulated risks for reduced physical well-being: mean BMI 29.9 (SD 6.1) kg/m2, mean of 1.2 (SD 1.7) exercising sessions per week, mood problems: mean BDI-II 20.3 (SD 10.6), and negative psychological reactions to pain: mean total PASS-20 score 53.2 (18.4). The results suggest that low interference on both dimensions may allow assessment with only physician consultations, while high interference on either dimension may call attention to distinct issues to be addressed with the help of a physiotherapist or a psychologist, whereas high interference on both dimensions highlights the need for a full multidisciplinary assessment. [ABSTRACT FROM AUTHOR]

Limb girdle muscular dystrophy (LGMD) types 2D and 2F are caused by mutations in the genes encoding for α- and δ-sarcoglycan, respectively, leading to progressive muscle weakness. Mouse models exist for LGMD2D (Sgca-/-) and 2F (Sgcd-/-). In a previous natural history study, we described the pathology in these mice at 34 weeks of age. However, the development of muscle pathology at younger ages has not been fully characterised yet. We therefore performed a study into age-related changes in muscle function and pathology by examining mice at different ages. From 4 weeks of age onwards, male mice were subjected to functional tests and sacrificed at respectively 8, 16 or 24 weeks of age. Muscle histopathology and expression of genes involved in muscle pathology were analysed for several skeletal muscles, while miRNA levels were assessed in serum. In addition, for Sgcd-/- mice heart pathology was assessed. Muscle function showed a gradual decline in both Sgca-/- and Sgcd-/- mice. Respiratory function was also impaired at all examined timepoints. Already at 8 weeks of age, muscle pathology was prominent, and fibrotic, inflammatory and regenerative markers were elevated, which remained relatively constant with age. In addition, Sgcd-/- mice showed signs of cardiomyopathy from 16 weeks of age onwards. These results indicate that Sgca-/- and Sgcd-/- are relevant disease models for LGMD2D and 2F. [ABSTRACT FROM AUTHOR]

Introduction: Several non-comparative phase II studies have evaluated metronomic oral vinorelbine (MOV) in metastatic non-small cell lung cancer (NSCLC) but the small size of each study limits their conclusions. Purpose: To perform an individual patient-data metaanalysis of studies evaluating MOV in metastatic NSCLC in order to measure survival and safety of treatment with this regimen. Methods: Studies were selected if (1) administration of oral vinorelbine thrice a week; (2) fixed daily dose comprised between 30 and 50 mg, and; (3) being published before October 4th 2018. Database encompassed 8 variables characterizing disease and demography, 3 informing therapy, and 12 describing survival and toxicity. Results: Nine studies encompassing 418 patients fulfilled the selection criteria, 80% of them having frailty characteristics. Median overall survival (OS) was 8.7 months (95%CI: 7.6–9.5). OSrates at 6 months, one year and at two years after starting vinorelbine were 64%, 30.3% and 8.9%, respectively. In the Cox model, Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2, and anemia of any grade were significant determinants of shorter OS. Median progression-free survival(PFS) was 4.2 months (95%CI: 3.9–5). At 6 months and at one-year, PFS rates were 35% and 11.9% respectively. In the Cox model stratified for the variable "study", PS = 2and stage IV were significant determinants of shorter PFS. No toxicity was reported for 40% of patients, and 66 (15.8%) patients experienced a grade 3–4 toxicity. The most frequent toxicity was anemia of any grade (35.8%) that was higher with the 50 mg dosage. Conclusion: MOV is an active and well-tolerated chemotherapy in metastatic NSCLC and is a manageable therapy in frail patients. [ABSTRACT FROM AUTHOR]

Nanometre-scale observation of specimens in water is indispensable in several scientific fields, such as biology, chemistry, materials science and nanotechnology. Scanning electron microscopy (SEM) obtains high-resolution images of biological samples under high vacuum conditions but requires specific sample-preparation protocols. Observations of unstained biological samples in water require more convenient and less invasive methods. Herein, we have developed a new type of impedance microscopy, namely impedance SEM (IP-SEM), which allows the imaging and sub-micrometer scale examination of various specimens in water. By varying the frequency of the input signal, the proposed system can detect the impedance properties of the sample's composition at sub-micrometer scale resolution. Besides examining various unstained biological specimens and material samples in water. Furthermore, the proposed system can be used for diverse liquid samples across a broad range of scientific fields, such as nanoparticles, nanotubes and organic and catalytic materials. [ABSTRACT FROM AUTHOR]

A promising strategy for the enhancement of vaccine-mediated immune responses is by directly targeting protein antigens to immune cells. Targeting of antigens to the dendritic cell (DC) molecule Clec9A has been shown to enhance antibody affinity and titers for model antigens, and influenza and enterovirus antigens, and may be advantageous for immunogens that otherwise fail to elicit antibodies with sufficient titers and breadth for broad protection, such as the envelope protein (Env) of HIV. Previously employed targeting strategies often utilize receptor-specific antibodies, however it is impractical to conjugate a bivalent IgG antibody to oligomeric antigens, including HIV Env trimers. Here we designed single chain variable fragment (scFv) and single chain Fab (scFab) constructs of a Clec9A-targeting antibody, expressed as genetically fused conjugates with the soluble ectodomain of Env, gp140. This conjugation did not affect the presentation of Env neutralising antibody epitopes. The scFab moiety was shown to be more stable than scFv, and in the context of gp140 fusions, was able to mediate better binding to recombinant and cell surface-expressed Clec9A, although the level of binding to cell-surface Clec9A was lower than that of the anti-Clec9A IgG. However, binding to Clec9A on the surface of DCs was not detected. Mouse immunization experiments suggested that the Clec9A-binding activity of the scFab-gp140 conjugate was insufficient to enhance Env-specific antibody responses. This is an important first proof of principle study demonstrating the conjugation of a scFab to an oligomeric protein antigen, and that an scFab displays better antigen binding than the corresponding scFv. Future developments of this technique that increase the scFab affinity will provide a valuable means to target oligomeric proteins to cell surface antigens of interest, improving vaccine-generated immune responses. [ABSTRACT FROM AUTHOR]

L-5-methyltetrahydrofolate is the predominant folate form in human milk but is currently not approved as a folate source for infant and follow-on formula. We aimed to assess the suitability of L-5-methyltetrahydrofolate as a folate source for infants. Growth and tolerance in healthy term infants fed formulae containing equimolar doses of L-5-methyltetrahydrofolate (10.4 μg/ 100 ml, n = 120, intervention group) or folic acid (10.0 μg/ 100 ml, n = 120, control group) was assessed in a randomized, double-blind, parallel, controlled trial. A reference group of breastfed infants was followed. Both formulae were well accepted without differences in tolerance or occurrence of adverse events. The most common adverse events were common cold, poor weight gain or growth, rash, eczema, or dry skin and respiratory tract infection. Weight gain (the primary outcome) was equivalent in the two groups (95% CI -2.11; 1.68 g/d). In line with this, there was only a small difference in absolute body weight adjusted for birth weight and sex at visit 4 (95% CI -235; 135 g). Equivalence was also shown for gain in head circumference but not for recumbent length gain and increase in calorie intake. Given the nature of the test, this does not indicate an actual difference, and adjusted means at visit 4 were not significantly different for any of these parameters. Infants receiving formula containing L-5-methyltetrahydrofolate had lower mean plasma levels of unmetabolized folic acid (intervention: 0.73 nmol/L, control: 1.15 nmol/L, p<0.0001) and higher levels of red cell folate (intervention: 907.0 ±192.8 nmol/L, control: 839.4 ±142.4 nmol/L, p = 0.0095). We conclude that L-5-methyltetrahydrofolate is suitable for use in infant and follow-on formula, and there are no indications of untoward effects. Trial registration: This trial was registered at ClinicalTrials.gov (). [ABSTRACT FROM AUTHOR]

The brown planthopper, Nilaparvata lugens (Stål), severely damages rice production and develops high level resistance to several classes of insecticides. To find potential insecticidal resources is always important. As an environmentally friendly compound, aconitine exhibits potential pesticide features. In the present study, the pesticide and knockdown effects of aconitine were first tested on the brown planthopper. The results showed that the knockdown rates for an aconitine concentration of 200 ppm was 83.6%. The insecticidal LD50 was 22.68 ng/pest (95% CI, 17.75–28.99). The molecular mechanisms responding to aconitine application were analyzed through transcriptional sequencing. Compared to that of the knockdown nymphs of the brown planthoppers, the enzymes CYP3A4, UDP-glucuronosyltransferase (UGT), GST, carboxylesterase (EC3.1.1.1), and GABAergic synapse were up-regulated. We inferred that aconitine might be neurotoxic to the brown planthoppers, and the conscious nymphs resist the drug neurotoxicity through the upregulation of CYP3A4, UGT, and GABA receptor mutation. Although aconitine is not safe for mammals, it may be a leading compound to develop novel insecticides. [ABSTRACT FROM AUTHOR]

Background: Although evidence of a disseminated intravascular coagulation (DIC)-like reaction has been identified in the lung parenchyma of patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF), an association between DIC and IPF outcome has not been elucidated. Therefore, we retrospectively investigated the association between the Japanese Association for Acute Medicine (JAAM)-DIC score and mortality in patients with acute exacerbation of fibrosing idiopathic interstitial pneumonia (AE-fIIP). Methods: Between January 2008 and December 2016, consecutive patients with chronic fIIP who were admitted for the first time for AE-fIIP were recruited into the study. Associations between clinical data and JAAM-DIC score at the time of admission and mortality were examined. Results: During the study period, a total of 91 patients with fIIP (73.0±8.4 y.o.) were hospitalized for AE-fIIP for the first time. The 30-day and hospital mortality were 8.7% and 17.5%, respectively. A multivariate analysis showed that the JAAM-DIC score on admission was an independent predictor of 30-day mortality (odds ratio [OR] 2.57, 95% confidential interval [CI] 1.50–4.40, P = 0.0006). The APACHE II score (OR 1.29, 95% CI 1.01–1.63, P = 0.03) and the JAAM-DIC score (OR 3.47, 95% CI 1.73–6.94, P = 0.0004) were independent predictors of hospital mortality. Conclusions: The JAAM-DIC scoring system can predict survival in patients with AE-fIIP. The role of DIC in the pathogenesis of AE-fIIP merits further investigation. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a primary malignant tumor of the epithelial lining of biliary track associated with endemic Opisthorchis viverrini (Ov) infection in northeastern Thailand. Ov-associated periductal fibrosis (PDF) is the precancerous lesion for CCA, and can be detected by ultrasonography (US) to facilitate early detection. However, US cannot be used to distinguish PDF from cancer. Therefore, the objective of this study was to discover and qualify potential urine biomarkers for CCA detection in at-risk population. Biomarker discovery was conducted on pooled urine samples, 42 patients per group, with PDF or normal bile duct confirmed by ultrasound. After depletion of high abundance proteins, 338 urinary proteins were identified from the 3 samples (normal-US, PDF-US, CCA). Based on fold change and literature review, 70 candidate proteins were selected for qualification by multiple reaction monitoring mass spectrometry (MRM-MS) in 90 individual urine samples, 30 per group. An orthogonal signal correction projection to latent structures discriminant analysis (O-PLS-DA) multivariate model constructed from the 70 candidate biomarkers significantly discriminated CCA from normal and PDF groups (P = 0.003). As an independent validation, the expression of 3 candidate proteins was confirmed by immunohistochemistry in CCA tissues: Lysosome associated membrane glycoprotein 1 (LAMP1), lysosome associated membrane glycoprotein 2 (LAMP2) and cadherin-related family member 2 (CDHR2). Further evaluation of these candidate biomarkers in a larger cohort is needed to support their applicability in a clinical setting for screening and monitoring early CCA and for CCA surveillance. [ABSTRACT FROM AUTHOR]

The pathophysiological mechanisms of sepsis-induced cardiac dysfunction are largely unknown. The Toll-like receptor 4 (TLR4) is expressed in cardiac myocytes and is involved in bacterial endotoxin-mediated inflammatory disorders. TLR4 signaling leads to activation of the nuclear factor kappa B followed by increased expression of cytokines. Several protein phosphatases including PP2Cβ, PP2A or PP1 are known to act as regulators of this signaling pathway. Here, we examined the role of PP5 for the inflammatory response to the bacterial endotoxin lipopolysaccharide in the heart using a transgenic mouse model with cardiac myocyte directed overexpression of PP5. In these transgenic mice, basal cardiac contractility was reduced, in vivo as well as in vitro, but LPS-induced cardiac dysfunction was less pronounced compared to wild type mice. Quantitative RT-PCR suggested an attenuated NF-κB signaling in the heart and cardiac expression of heat shock protein 25 (HSP25) was increased in PP5 transgenic mice. From our data we assume that PP5 increases stress tolerance of cardiac myocytes by downregulation of NF-κB signaling and upregulation of HSP25 expression. [ABSTRACT FROM AUTHOR]

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is characterized by irreversible loss of macular retinal tissue and retinal pigment epithelium (RPE) cells. Several studies have revealed that accumulation of Alu RNA in RPE cell causes RPE cell degeneration in AMD. In the present study, systemic Alu RNA expression levels were determined in 33 subjects with GA and 40 control subjects using a proprietary Alu RNA quantification method. It was observed that the expression level of Alu RNA was not significantly different between GA and Control groups (median = 21.3 in both GA and Control groups, P = 0.251). In addition, the systemic level of Alu RNA was not associated with subject characteristics, such as GA lesion size and SNP profiles of complement factors associated with increased risk of AMD. In conclusion, the usability of systemic Alu RNA expression level as a biomarker of GA secondary to AMD could not be established in this study. [ABSTRACT FROM AUTHOR]

This study investigated the prevalence of Orientia tsutsugamushi, Anaplasma phagocytophilum, and Leptospira interrogans in wild rodents through molecular detection using organ samples and through serological assay using blood samples of mice collected from two distinct sites in Gwangju Metropolitan City, Republic of Korea (ROK). A total of 47 wild rodents, identified as Apodemus agrarius (A. agrarius), were captured from June to August 2016. The seroprevalence of antibodies against bacterial pathogens in A. agrarius sera was analyzed; 17.4% (8/46) were identified as O. tsutsugamushi through indirect immunofluorescence assay and 2.2% (1/46) were identified as Leptospira species through passive hemagglutination assay. Using polymerase chain reaction, the spleen, kidney and blood samples were investigated for the presence of O. tsutsugamushi, A. phagocytophilum, and L. interrogans. Out of the 47 A. agrarius, 19.1% (9/47) were positive for A. phagocytophilum and 6.4% (3/47) were positive for L. interrogans, while none were positive for O. tsutsugamushi. Four out of 46 (8.7%) blood samples, six out of 45 (13.3%) spleen samples, and one out of 47 (2.1%) kidney samples were positive for A. phagocytophilum. Three out of 47 (6.4%) kidney samples were positive for L. interrogans. The sequencing results of PCR positive samples demonstrated > 99% similarity with A. phagocytophilum and L. interrogans sequences. A. phagocytophilum was mostly detected in the spleen, whereas L. interrogans was mostly detected in the kidneys. Notably, A. phagocytophilum and L. interrogans were detected in A. agrarius living in close proximity to humans in the metropolitan suburban areas. The results of this study indicate that rodent-borne bacteria may be present in wild rodents in the metropolitan suburban areas of ROK. [ABSTRACT FROM AUTHOR]

Batroxobin, isolated from Bothrops moojeni, is a defibrinogenating agent used as a thrombin-like serine protease against fibrinogen for improving microcirculation. Here, we investigated whether, and if so, how batroxobin restores ischemic tissue injury in terms of anti-inflammatory effects. In an in vitro flow cytometry assay for human neutrophil extracellular traps (NETs), batroxobin (DF-521; Defibrase) inhibited human NETs induced by tumor necrosis factor-α (TNF-α) in the presence of human fibrinogen. Next, the effect of batroxobin was investigated by immunohistochemistry of the anterior tibial muscle (ATM) in an ischemic hindlimb model using C57BL/6J mice intraperitoneally injected with DF-521 versus the saline control. NETs and fibrinogen deposition in the ischemic ATM decreased in DF-521-treated mice on day 2 after ischemia. Meanwhile, reverse transcription-quantitative PCR assay of the ischemic ATM unveiled continuous downregulation in the expression of the genes; Tnf-α and nitric oxide synthase2 (Nos2) with hypoxia-inducible factor-1α (Hif-1α) and vascular endothelial growth factor-a (Vegf-a) from day 3 to day 7, but the upregulation of arginase-1 (Arg-1) and placental growth factor (Plgf) with myogenin (Myog) on day 7. Daily intraperitoneal DF-521 injection for the initial 7 days into mice with ischemic hindlimbs promoted angiogenesis and arteriogenesis on day 14. Moreover, DF-521 injection accelerated myofiber maturation after day 14. Laser doppler imaging analysis revealed that blood perfusion in DF-521-injected mice significantly improved on day 14 versus the saline control. Thus, DF-521 improves microcirculation by protecting NETs with tissue defibrinogenation, thereby protecting against severe ischemic tissue injury and accelerating vascular and skeletal muscular regeneration. To our knowledge, batroxobin might be the first clinically applicable NET inhibitor against ischemic diseases. [ABSTRACT FROM AUTHOR]

While treatment of serious infectious diseases may require high-dose amoxicillin, continuous infusion may be limited by lack of knowledge regarding the chemical stability of the drug. Therefore, we have performed a comprehensive study so as to determine the chemical stability of high-dose amoxicillin solutions conducive to safe and effective continuous intravenous administration using portable elastomeric pumps. First, amoxicillin solubility in water was assessed within the range of 25 to 300 mg/mL. Then, amoxicillin solutions were prepared at different concentrations (25, 50, 125, 250 mg/mL) and stored in different conditions (5±2°C, 25±1°C, 30±1°C and 37±1°C) to investigate the influence of concentration and temperature on the chemical stability of amoxicillin. Finally, its stability was assessed under optimized conditions using a fully validated HPLC-UV stability-indicating method. Degradation products of amoxicillin were investigated by accurate mass determination using high-resolution mass spectrometry. Amoxicillin displayed limited water solubility requiring reconstitution at concentrations below or equal to 150 mg/mL. Amoxicillin degradation were time, temperature as well as concentration-dependent, resulting in short-term stability, in particular at high concentrations. Four degradation products of amoxicillin have been identified. Among them, amoxicilloic acid and diketopiperazine amoxicillin are at risk of allergic reaction and may accumulate in the patient. Optimized conditions allowing for continuous infusion of high-dose amoxicillin has been determined: amoxicillin should be reconstituted at 25 mg/mL and stored up to 12 hours at room temperature (22 ± 4°C) or up to 24 hours between 4 and 8°C. [ABSTRACT FROM AUTHOR]

Background: Active living approaches seek to promote physical activity and reduce sedentary time across different domains, including through active travel. However, there is little information on how movement behaviours in different domains relate to each other. We used compositional data analysis to explore associations between active commuting and patterns of movement behaviour during discretionary time. Methods and findings: We analysed cross-sectional and longitudinal data from the UK Biobank study. At baseline (2006–2010) and follow up (2009–2013) participants reported their mode of travel to work, dichotomised as active (walking, cycling or public transport) or inactive (car). Participants also reported activities performed during discretionary time, categorised as (i) screen time; (ii) walking for pleasure; and (iii) sport and do-it-yourself (DIY) activities, summed to produce a total. We applied compositional data analysis to test for associations between active commuting and the composition and total amount of discretionary time, using linear regression models adjusted for covariates. Adverse events were not investigated in this observational analysis. The survey response rate was 5.5%. In the cross-sectional analysis (n = 182,406; mean age = 52 years; 51% female), active commuters engaged in relatively less screen time than those who used inactive modes (coefficient -0.12, 95% confidence interval [CI] -0.13 to -0.11), equating to approximately 60 minutes less screen time per week. Similarly, in the longitudinal analysis (n = 4,323; mean age = 51 years; 49% female) there were relative reductions in screen time in those who used active modes at both time points compared with those who used inactive modes at both time points (coefficient -0.15, 95% confidence interval [CI] -0.24 to -0.06), equating to a difference between these commute groups of approximately 30 minutes per week at follow up. However, as exposures and outcomes were measured concurrently, reverse causation is possible. Conclusions: Active commuting was associated with a more favourable pattern of movement behaviour during discretionary time. Active commuters accumulated 30–60 minutes less screen time per week than those using inactive modes. Though modest, this could have a cumulative effect on health over time. [ABSTRACT FROM AUTHOR]

The bacterial species, Faecalibacterium prausnitzii, beneficial to humans and animals and found in mammalian and avian gut, is also occasionally found in dairy cow milk. It is one of the butyrate-producing bacteria of the colon, has anti-inflammatory properties and its abundance in the gut is negatively correlated with obesity in humans. Several strains differing in their functional capability, have been identified. It is important therefore, milk being a potential source of F. prausnitzii as a novel probiotic, to investigate the diversity of this species in bovine milk. Using 16s rRNA gene amplicons we find 292 different dereplicated Faecalibacterium-related amplicons in a herd of 21 dairy cows. The distribution of the 20 most abundant amplicons with >97% identity to a Greengenes OTU varies from cow to cow. Clustering of the 292 pooled sequences from all cows at 99.6% identity finds 4 likely Faecalibacterium phylotypes with >98.5% identity to an F. prausnitzii reference sequence. Sequence alignment and phylogenetic analysis shows these phylotypes are distinct from 34 other species from the Ruminococcaceae family and displaying the sequence clusters as a network illustrates how each cluster is composed of sequences from multiple cows. We conclude there are several phylotypes of Faecalibacterium prausnitzii (the only species so far defined for the genus) in this dairy herd with cows being inoculated with a mixture of several strains from a common source. We conclude that not only can Faecalibacterium be detected in dairy cow milk (as noted by others) but that there exist multiple different strains in the milk of a dairy herd. Therefore milk, as an alternative to faeces, offers the opportunity of discovering new strains with potential probiotic application. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF) is a signal protein, implicated in various physiological and pathophysiological processes together with other common inflammatory biomarkers. However, their associations have not yet been fully elucidated. In the present study, we investigated associations between VEGF and four specific VEGF mRNA isoforms with levels of 11 inflammation molecules, derived from peripheral blood mononuclear cells (PBMCs) extracts. Methods: Healthy participants from the STANISLAS Family Study (n = 285) were included. Levels of VEGF (four mRNA isoforms and protein levels) and inflammatory molecules (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, INF-γ, TNF-α, MCP-1, EGF) were measured in PBMCs extracts. Multiple regression analyses were performed, adjusted for age and gender. Results: The analyses revealed significant associations between VEGF protein levels and levels of IL-4 (β = 0.028, P = 0.013), MCP-1 (β = 0.015, P<0.0001) and EGF (β = 0.017, P<0.0001). Furthermore, mRNA isoform VEGF165 was associated with MCP-1 and IL-1α (P = 0.002 and P = 0.008, respectively); and mRNA isoform VEGF189 was associated with IL-4 and IL-6 (P = 0.019 and P = 0.034, respectively). Conclusions: To our knowledge, the present study represents the first investigation that successfully demonstrates links between VEGF protein levels and inflammatory molecules levels derived from PBMCs extracts and identifies associations between specific VEGF mRNA isoforms and inflammatory molecules. Impact: These findings provide novel insights that may assist in the development of new tissue and mRNA isoform specific measurements of VEGF levels, which may positively contribute to predicting the risk of common complex diseases and response of currently used anti-VEGF agents, and developing of novel targeted therapies for VEGF-related pathophysiology. [ABSTRACT FROM AUTHOR]

ND7/23 cells are gaining traction as a host model to express peripheral sodium channels such as NaV1.8 and NaV1.9 that have been difficult to express in widely utilized heterologous cells, like CHO and HEK293. Use of ND7/23 as a model cell to characterize the properties of sodium channels requires clear understanding of the endogenous ion channels. To define the nature of the background sodium currents in ND7/23 cells, we aimed to comprehensively profile the voltage-gated sodium channel subunits by endpoint and quantitative reverse transcription-PCR and by whole-cell patch clamp electrophysiology. We found that untransfected ND7/23 cells express endogenous peak sodium currents that average –2.12nA (n = 15) and with kinetics typical of fast sodium currents having activation and inactivation completed within few milliseconds. Furthermore, sodium currents were reduced to virtually nil upon exposure to 100nM tetrodotoxin, indicating that ND7/23 cells have essentially null background for tetrodotoxin-resistant (TTX-R) currents. qRT-PCR profiling indicated a major expression of TTX-sensitive (TTX-S) NaV1.6 and NaV1.7 at similar levels and very low expression of TTX-R NaV1.9 transcripts. There was no expression of TTX-R NaV1.8 in ND7/23 cells. There was low expression of NaV1.1, NaV1.2, NaV1.3 and no expression of cardiac or skeletal muscle sodium channels. As for the sodium channel auxiliary subunits, β1 and β3 subunits were expressed, but not the β2 and β4 subunits that covalently associate with the α-subunits. In addition, our results also showed that only the mouse forms of NaV1.6, NaV1.7 and NaV1.9 sodium channels were expressed in ND7/23 cells that was originally generated as a hybridoma of rat embryonic DRG and mouse neuroblastoma cell-line. By molecular profiling of auxiliary β- and principal α-subunits of the voltage gated sodium channel complex, our results define the background sodium channels expressed in ND7/23 cells, and confirm their utility for detailed functional studies of emerging pain channelopathies ascribed to mutations of the TTX-R sodium channels of sensory neurons. [ABSTRACT FROM AUTHOR]

Acylcarnitines are fatty acyl esters of L-carnitine and facilitate the entry of long-chain fatty acids into mitochondria via the carnitine shuttle, where they are metabolized via ß-oxidation. Alterations of acylcarnitine species can be diagnostic for fatty acid oxidation disorders and organic aciduria and are thus frequently used to screen newborns. Only a subfraction of all known acylcarnitines is thereby monitored and quantified. Therefore, a method for the simultaneous fast and robust detection of all known acylcarnitines was developed using a single concise liquid chromatography mass spectrometry (LC-MS) approach. Derivatization by 3-nitrophenylhydrazine increased the signal intensity of the acylcarnitines and a linear elution from a reversed phase column was observed that was dependent on the length of the carbon chain. This allowed a precise prediction of the exact elution time for each acylcarnitine class, which depended solely on the chemical nature of the carbon chain. This method can be further used to screen for yet unknown acylcarnitine species and adds a layer of confidence for their correct identification. Altogether 123 acylcarnitines species were used to establish a targeted low-resolution LC-MS method. The method was applied to acylcarnitine profiling in several mouse tissues and fluids, in order to identify large differences in the quantity and composition of acylcarnitines. [ABSTRACT FROM AUTHOR]

Novel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer polyethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated 98.51 % of 2ME while liberation of 2ME was constant during 7 days at pH 2, 5 and 7.35. Finally, the MgO-PEG-2ME NPs decreased the viability of the prostate cancer cell line LNCap suggesting that this nanocomposite is suitable as a drug delivery system for anticancer prostate therapy. [ABSTRACT FROM AUTHOR]

Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1’s function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. Finally, we propose a model to explain how a metabolic defect could ultimately lead to marked changes in neuronal signaling. [ABSTRACT FROM AUTHOR]

Measles virus is highly infectious and remains a leading cause of vaccine preventable deaths in children. Neutralizing antibody responses elicited by measles virus infection or immunization are a serological correlate of protection. We describe a high-throughput neutralization assay to improve surveillance for measles immunity. Measles virus-antibody mixtures were incubated on Vero cell monolayers and 24 hours later cell-lysates harvested and subjected to one-step SYBR green RT-qPCR to amplify a target sequence within the measles virus nucleoprotein gene. Neutralization endpoint titers were interpolated to determine the dilution that inhibited the relative amplicon copy number by at least 90% compared to the mean signal obtained in virus control wells in the absence of serum. Anti-measles virus and anti-measles hemagglutinin antisera specifically neutralized measles virus in the microneutralization RT-qPCR assay while pre-immune sera and sera raised against other viruses did not. The microneutralization RT-qPCR assay obeyed the Percentage Law for measles virus inputs ranging from 100–5000 TCID50/well. The linear range of the assay corresponds to measles antibody concentrations of 30 to 3000 mIU/mL. Bland-Altman analysis and two-way analysis of variance demonstrated that results obtained using the microneutralization RT-qPCR assay were comparable to those obtained using a plaque reduction neutralization test and correctly identified human serum samples that were seropositive (95% and 100%, sensitivity and specificity, respectively). Furthermore, these comparisons suggest that a concentration of 300 mIU/mL may be a conservative cut-point to use to identify individuals likely to be protected against severe measles disease when the endpoint is based on 90% inhibition of virus replication. Measles virus microneutralization RT-qPCR is a rapid, sensitive, specific, and robust assay for detecting measles neutralizing antibodies that may help to improve immunization strategies nationally and achieve measles elimination globally. [ABSTRACT FROM AUTHOR]

Interleukin-11 (IL-11) is an interleukin-6 (IL-6) family cytokine shown to play a protective role in acute inflammatory settings including systemic infection. In this study we addressed the role of IL-11 in acute bacterial pneumonia using a mouse model of E. coli pneumonia. Compared with other related cytokines, IL-11 protein was maintained at high levels in the lung at baseline, with only mild alterations in whole lung and BALF levels during acute infection. The primary source of IL-11 in the lung was the epithelium, but steady state production was not dependent on the inflammatory transcription factor nuclear factor kappa B in cells of either myeloid or epithelial lineage. Blockade of IL-11 with neutralizing antibodies resulted in a mild but significant decrease in neutrophil recruitment and increase in pulmonary edema during pneumonia, without detectable alterations in bacterial clearance. Exogenous IL-11 administration, however, had no effect at baseline or during infection. Overall, we conclude that maintenance of lung IL-11 concentrations may influence acute pulmonary inflammation during infection, albeit modestly. [ABSTRACT FROM AUTHOR]

The energy expenditure and substrate utilisation were measured in 5 men pre- and post- a 67 day, 1750km unassisted Antarctic traverse from the Hercules Inlet to the Ross Sea Ice via the South pole pulling sledges weighing 120kg whilst experiencing temperatures as low as -57°C. A 36-hours protocol in a whole body calorimeter was employed to measure periods of rest, sleep and three periods of standardised stepping exercises at 80, 100 and 120 steps min-1; participants were fed isocalorically. Unlike previous expeditions where large weight loss was reported, only a modest loss of body weight (7%, P = 0.03) was found; fat tissue was reduced by 53% (P = 0.03) together with a small, but not statistically significant, increase in lean tissue weight (P = 0.18). This loss occurred despite a high-energy intake (6500 kcal/day) designed to match energy expenditure. An energy balance analysis suggested the loss in body weight could be due to the energy requirements of thermoregulation. Differences in energy expenditure [4.9 (0.1) vs 4.5 (0.1) kcal/min. P = 0.03], carbohydrate utilisation [450 (180) vs 569 (195) g/day; P = 0.03] and lipid utilisation [450 (61) vs 388 (127) g/day, P = 0.03] at low levels of exertion were different from pre-expedition values. Only carbohydrate utilisation remained statistically significant when normalised to body weight. The differences in energy expenditure and substrate utilisation between the pre- and post-expedition for other physiological states (sleeping, resting, higher levels of exercise, etc) were small and not statistically significant. Whilst inter-subject variability was large, there was a tendency for increased carbohydrate utilisation, post-expedition, when fasted that decreased upon feeding. [ABSTRACT FROM AUTHOR]

Background: Transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) have been described as promising alternatives to treat different pain syndromes. This study evaluated the effects of TMS and tDCS in the treatment of chronic orofacial pain, through a systematic review. Methods: An electronic search was performed in major databases: MEDLINE, Scopus, Web of Science, Cochrane, Embase, LILACS, BBO, Open Gray and CINAHL. The eligibility criteria comprised randomized clinical trials (RCTs) that applied TMS or tDCS to treat chronic orofacial pain. The variables analyzed were pain, functional limitation, quality of life, tolerance to treatment, somatosensory changes, and adverse effects. The risk of bias was assessed through the Cochrane Collaboration tool, and the certainty of evidence was evaluated through GRADE. The protocol was registered in the PROSPERO database (CRD42018090774). Results: The electronic search resulted in 636 studies. Thereafter, the eligibility criteria were applied and the duplicates removed, resulting in eight RCTs (four TMS and four tDCS). The findings of these studies suggest that rTMS applied to the Motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC) and the secondary somatosensory cortex (S2) provide adequate orofacial pain relief. Two studies reported significant pain improvement with tDCS applied over M1 while the other two failed to demonstrate significant effects compared to placebo. Conclusions: rTMS, applied to M1, DLPFC or S2, is a promising approach for the treatment of chronic orofacial pain. Moreover, tDCS targeting M1 seems to be also effective in chronic orofacial pain treatment. The included studies used a wide variety of therapeutic protocols. In addition, most of them used small sample sizes, with a high risk of biases in their methodologies, thus producing a low quality of evidence. The results indicate that further research should be carried out with caution and with better-standardized therapeutic protocols. [ABSTRACT FROM AUTHOR]

Background: This systematic review aimed to summarise and critically appraise the evidence for the effect of bodily illusions on corticomotoneuronal excitability. Methods: Five databases were searched, with two independent reviewers completing study inclusion, risk of bias, transcranial magnetic stimulation (TMS) reporting quality, and data extraction. Included studies evaluated the effect of an illusion that altered perception of the body (and/or its movement) on excitability of motor circuitry in healthy, adult, human participants. Studies were required to: use TMS to measure excitability and/or inhibition; report quantitative outcomes (e.g., motor evoked potentials); compare the illusion to a control or active comparison condition; evaluate that an illusion had occurred (e.g., measured illusion strength/presence). Results: Of 2,257 studies identified, 11 studies (14 experiments) were included, evaluating kinaesthetic illusions (n = 5), a rubber hand illusion (RHI) paradigm (n = 5), and a missing limb illusion (n = 1). Kinaesthetic illusions (induced via vision/tendon vibration) increased corticomotoneuronal excitability. Conflicting effects were found for traditional, visuotactile RHIs of a static hand. However, embodying a hand and then observing it move (“self-action”) resulted in decreased corticomotoneuronal excitability and increased silent period duration (a measure of Gamma-Aminobutynic acid [GABA]B-mediated intracortical inhibition in motor cortex), with the opposite occurring (increased excitability, decreased inhibition) when the fake hand was not embodied prior to observing movement (“other-action”). Visuomotor illusions manipulating agency had conflicting results, but in the lower risk study, illusory agency over movement resulted in a relative decrease in corticomotoneuronal excitability. Last, an illusion of a missing limb reduced corticomotoneuronal excitability. Conclusion: While evidence for the effect of bodily illusions on corticomotoneuronal excitability was limited (only 14 experiments) and had a high risk of bias, kinaesthetic illusions and illusions of embodying a hand (and seeing it move), had consistent effects. Future investigations into the role of embodiment and the illusion strength on corticomotoneuronal excitability and inhibition are warranted. [ABSTRACT FROM AUTHOR]