Differences in working memory coding of biological motion attributed to oneself and others.

The question how the brain distinguishes between information about self and others is of fundamental interest to both philosophy and neuroscience. In this functional magnetic resonance imaging (fMRI) study, we sought to distinguish the neural substrates of representing a full-body movement as one's movement and as someone else's movement. Participants performed a delayed match-to-sample working memory task where a retained full-body movement (displayed using point-light walkers) was arbitrarily labeled as one's own movement or as performed by someone else. By using arbitrary associations we aimed to address a limitation of previous studies, namely that our own movements are more familiar to us than movements of other people. A searchlight multivariate decoding analysis was used to test where information about types of movement and about self-association was coded. Movement specific activation patterns were found in a network of regions also involved in perceptual processing of movement stimuli, however not in early sensory regions. Information about whether a memorized movement was associated with the self or with another person was found to be coded by activity in the left middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), bilateral supplementary motor area, and (at reduced threshold) in the left temporoparietal junction (TPJ). These areas are frequently reported as involved in action understanding (IFG, MFG) and domain-general self/other distinction (TPJ). Finally, in univariate analysis we found that selecting a self-associated movement for retention was related to increased activity in the ventral medial prefrontal cortex.

Response modality-dependent categorical choice representations for vibrotactile comparisons.

Previous electrophysiological studies in monkeys and humans suggest that premotor regions are the primary loci for the encoding of perceptual choices during vibrotactile comparisons. However, these studies employed paradigms wherein choices were inextricably linked with the stimulus order and selection of manual movements. It remains largely unknown how vibrotactile choices are represented when they are decoupled from these sensorimotor components of the task. To address this question, we used fMRI-MVPA and a variant of the vibrotactile frequency discrimination task which enabled the isolation of choice-related signals from those related to stimulus order and selection of the manual decision reports. We identified the left contralateral dorsal premotor cortex (PMd) and intraparietal sulcus (IPS) as carrying information about vibrotactile choices. Our finding provides empirical evidence for an involvement of the PMd and IPS in vibrotactile decisions that goes above and beyond the coding of stimulus order and specific action selection. Considering findings from recent studies in animals, we speculate that the premotor region likely serves as a temporary storage site for information necessary for the specification of concrete manual movements, while the IPS might be more directly involved in the computation of choice. Moreover, this finding replicates results from our previous work using an oculomotor variant of the task, with the important difference that the informative premotor cluster identified in the previous work was centered in the bilateral frontal eye fields rather than in the PMd. Evidence from these two studies indicates that categorical choices in human vibrotactile comparisons are represented in a response modality-dependent manner.

Intraparietal sulcus maintains working memory representations of somatosensory categories in an adaptive, context-dependent manner.

Working memory (WM) representations are generally known to be influenced by task demands, but it is not clear whether this extends to the somatosensory domain. One way to investigate the influence of task demands is with categorization paradigms, wherein either a single stimulus or an associated category is maintained in WM. In the somatosensory modality, category representations have been identified in the premotor cortex (PMC) and the intraparietal sulcus (IPS). In this study we used multivariate-pattern-analysis with human fMRI data to investigate whether the WM representations in the PMC, IPS or other regions are influenced by changing task demands. We ensured the task-dependent, categorical WM information was decorrelated from stimulus features by (1) teaching participants arbitrary, non-rule based stimulus groupings and (2) contrasting identical pairs of stimuli across experimental conditions, where either a single stimulus or the associated group was maintained in WM. Importantly, we also decoupled the decision and motor output from the WM representations. With these experimental manipulations, we were able to pinpoint stimulus-specific WM information to the left frontal and parietal cortices and context-dependent, group-specific WM information to the left IPS. By showing that grouped stimuli are represented more similarly in the Group condition than in the Stimulus condition, free from stimulus and motor output confounds, we provide novel evidence for the adaptive nature of somatosensory WM representations in the IPS with changing task-demands.

Decoding vibrotactile choice independent of stimulus order and saccade selection during sequential comparisons.

Decision-making in the somatosensory domain has been intensively studied using vibrotactile frequency discrimination tasks. Results from human and monkey electrophysiological studies from this line of research suggest that perceptual choices are encoded within a sensorimotor network. These findings, however, rely on experimental settings in which perceptual choices are inextricably linked to sensory and motor components of the task. Here, we devised a novel version of the vibrotactile frequency discrimination task with saccade responses which has the crucial advantage of decoupling perceptual choices from sensory and motor processes. We recorded human fMRI data from 32 participants while they performed the task. Using a whole-brain searchlight multivariate classification technique, we identify the left lateral prefrontal cortex and the oculomotor system, including the bilateral frontal eye fields (FEF) and intraparietal sulci, as representing vibrotactile choices. Moreover, we show that the decoding accuracy of choice information in the right FEF correlates with behavioral performance. Not only are these findings in remarkable agreement with previous work, they also provide novel fMRI evidence for choice coding in human oculomotor regions, which is not limited to saccadic decisions, but pertains to contexts where choices are made in a more abstract form.

Content-Specific Codes of Parametric Vibrotactile Working Memory in Humans.

To understand how the brain handles mentally represented information flexibly in the absence of sensory stimulation, working memory (WM) studies have been essential. A seminal finding in monkey research is that neurons in the prefrontal cortex (PFC) retain stimulus-specific information when vibrotactile frequencies were memorized. A direct mapping between monkey studies and human research is still controversial. Although oscillatory signatures, in terms of frequency-dependent parametric beta-band modulation, have been observed recently in human EEG studies, the content specificity of these representations in terms of multivariate pattern analysis has not yet been shown. Here, we used fMRI in combination with multivariate classification techniques to determine which brain regions retain information during WM. In a retro-cue delayed-match-to-sample task, human subjects memorized the frequency of vibrotactile stimulation over a 12 s delay phase. Using an assumption-free whole-brain searchlight approach, we tested with support vector regression which brain regions exhibited multivariate parametric WM codes of the maintained frequencies during the WM delay. Interestingly, our analysis revealed an overlap with regions previously identified in monkeys composed of bilateral premotor cortices, supplementary motor area, and the right inferior frontal gyrus as part of the PFC. Therefore, our results establish a link between the WM codes found in monkeys and those in humans and emphasize the importance of the PFC for information maintenance during WM also in humans.SIGNIFICANCE STATEMENT Working memory (WM) research in monkeys has identified a network of regions, including prefrontal regions, to code stimulus-specific information when vibrotactile frequencies are memorized. Here, we performed an fMRI study during which human subjects had to memorize vibratory frequencies in parallel to previous monkey research. Using an assumption-free, whole-brain searchlight decoding approach, we identified for the first time regions in the human brain that exhibit multivariate patterns of activity to code the vibratory frequency parametrically during WM. Our results parallel previous monkey findings and show that the supplementary motor area, premotor, and the right prefrontal cortex are involved in vibrotactile WM coding in humans.

Content-specific codes of parametric auditory working memory in humans.

Brain activity in frontal regions has been found to represent frequency information with a parametric code during working memory delay phases. The mental representation of frequencies has furthermore been shown to be modality independent in non-human primate electrophysiology and human EEG studies, suggesting frontal regions encoding quantitative information in a supramodal manner. A recent fMRI study using multivariate pattern analysis (MVPA) supports an overlapping multimodal network for the maintenance of visual and tactile frequency information over frontal and parietal brain regions. The present study extends the investigation of working memory representation of frequency information to the auditory domain. To this aim, we used MVPA on fMRI data recorded during an auditory frequency maintenance task. A support vector regression analysis revealed working memory information in auditory association areas and, consistent with earlier findings of parametric working memory, in a frontoparietal network. A direct comparison to an analogous dataset of vibrotactile parametric working memory revealed an overlap of information coding in prefrontal regions, particularly in the right inferior frontal gyrus. Therefore, our findings indicate that the prefrontal cortex represents frequency-specific working memory content irrespective of the modality as has been now also revealed for the auditory modality.

Overlapping frontoparietal networks for tactile and visual parametric working memory representations.

Previous working memory (WM) research based on non-human primate electrophysiology and human EEG has shown that frontal brain regions maintain frequencies of flutter stimulation across different sensory modalities by means of a supramodal parametric WM code. These findings imply that frontal regions encode the memorized frequencies in a sensory-unspecific, quantitative format. Here, we explored which brain regions maintain information about frequencies provided by different sensory modalities at the level of activity pattern across fMRI voxel populations. Moreover, we sought evidence for a supramodal multivariate WM representation. Participants maintained the same set of frequencies of tactile vibration and visual flicker for a 6 s WM delay in a frequency discrimination task. A support vector regression model for multivariate pattern analysis was applied. We observed that sensory cortices were only selective for memoranda of their corresponding modalities, while frontoparietal regions exhibited distinguishable activity patterns to memorized frequencies regardless of sensory modality. A common multivariate code was not evident in our data. Collectively, we show that mnemonic representations for stimulus frequencies are maintained throughout the cortical hierarchy, in line with the suggested transformation of information across different representational formats. Although evidence for a supramodal multivariate code is absent, our findings underpin the generalized role of the frontoparietal cortex for maintaining quantitative information across sensory modalities.

Effects of microRNA-24 targeting C-myc on apoptosis, proliferation, and cytokine expressions in chondrocytes of rats with osteoarthritis via MAPK signaling pathway.

To investigate whether microRNA-24 (miR-24) targeting C-myc affects chondrocytes of rats with osteoarthritis (OA) via the MAPK signaling pathway. Thirty rats were assigned as a sham group and an OA group (established as OA rat models by cutting the anterior cruciate ligaments and removing 1/3 medial meniscus). TUNEL staining and immunohistochemistry were conducted for cell apoptosis index (AI) and positive expression rate of C-myc protein. Enzyme-linked immuno sorbent assay (ELISA) was carried out for serum level of IL-1ß and TNF-α. Primary chondrocytes were assigned into the blank, negative control (NC), miR-24 mimics, miR-24 inhibitors, siRNA-C-myc, and miR-24 inhibitors+siRNA-C-myc groups. The expressions of miR-24, C-myc, p38, ERK, JNK, IL-1ß, and TNF-α in tissues and cells were detected using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting. CCK8 assay and flow cytometry were performed for cell proliferation and apoptosis. The OA group showed higher IL-1ß, TNF-α, AI, and C-myc than the sham group. C-myc is a target gene of miR-24. Compared with the blank group, the miR-24 mimics and siRNA-C-myc groups showed reduced expression of C-myc, IL-1ß, TNF-α, p38, p-p38, ERK, p-ERK, JNK, and p-JNK, apoptosis rate yet increased cell proliferation; however, the miR-24 inhibitors group exhibited an opposite trend. The miR-24 inhibitors+siRNA-C-myc group presented a same tendency compared to the siRNA-C-myc group. Upregulated miR-24 downregulates C-myc could suppress apoptosis and promote proliferation of chondrocytes to prevent the occurrence and subsequent progression of OA via inactivating the MAPK signaling pathway.

[Efficacy Observation for Treating Ankylosing Spondylitis by Chinese Herbs and Recombinant Hu- man Tumor Necrosis Factor Receptor II-Antibody Fusion Protein].

OBJECTIVE: To observe the clinical effect of Chinese medical (CM) syndrome differentiation based Chinese herbs and recombinant human tumor necrosis factor receptor II-antibody fusion protein (etanercept) for treating ankylosing spondylitis (AS) patients. METHODS: Totally 35 AS patients were treated with syndrome differentiation based Chinese herbs and etanercept. Reinforcing Shen and strengthening Du channel, activating meridians to stop pain was principle used in syndrome differentiation based treatment. Etanercept was subcutaneously injected, 25 mg each time; twice per week for the first three months and once a week for the latter three months. The clinical efficacy was evaluated after 3 and 6 months of treatment. Meanwhile, ASAS20 and ASAS50 standards arriving rates were also observed. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), visual analog score (VAS) for spine pain, VAS for night pain, patient global assessment (PGA), VAS for physician global assessment, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, cervical rotation, Schober improved test, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were observed before treatment, 3 and 6 months after treatment. RESULTS: Compared with before treatment, BASDAI, BASFI, VAS for spine pain, night pain, physician global assessment, PGA, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, Schober improved test, ESR, and CRP all decreased after 3 and 6 months of treatment, with statistical difference (P < 0.05). Cervical rotation also decreased after 6 months of treatment, with statistical difference (P < 0.05). Compared with 3 months of treatment, total effective rate of CM syndrome, ASAS20 and ASAS50 standards arriving rates increased after 6 months of treatment, with statistical difference (P < 0.05). There were statistical differences in all indices mentioned above between after 3 months of treatment and after 6 months of treatment (P < 0.05). CONCLUSION: Syndrome differentiation based Chinese herbs combined etanercept could alleviate inflammatory reaction favorably, control the progression of active AS, and improve joint functions.

Network mechanisms of ongoing brain activity's influence on conscious visual perception.

Sensory inputs enter a constantly active brain, whose state is always changing from one moment to the next. Currently, little is known about how ongoing, spontaneous brain activity participates in online task processing. We employed 7 Tesla fMRI and a threshold-level visual perception task to probe the effects of prestimulus ongoing brain activity on perceptual decision-making and conscious recognition. Prestimulus activity originating from distributed brain regions, including visual cortices and regions of the default-mode and cingulo-opercular networks, exerted a diverse set of effects on the sensitivity and criterion of conscious recognition, and categorization performance. We further elucidate the mechanisms underlying these behavioral effects, revealing how prestimulus activity modulates multiple aspects of stimulus processing in highly specific and network-dependent manners. These findings reveal heretofore unknown network mechanisms underlying ongoing brain activity's influence on conscious perception, and may hold implications for understanding the precise roles of spontaneous activity in other brain functions.

Isoindoline-based fluorogenic probes bearing a self-immolative linker for the sensitive and selective detection of O-GlcNAcase activity.

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

Spatiotemporal neural dynamics of object recognition under uncertainty in humans.

While there is a wealth of knowledge about core object recognition-our ability to recognize clear, high-contrast object images-how the brain accomplishes object recognition tasks under increased uncertainty remains poorly understood. We investigated the spatiotemporal neural dynamics underlying object recognition under increased uncertainty by combining MEG and 7 Tesla (7T) fMRI in humans during a threshold-level object recognition task. We observed an early, parallel rise of recognition-related signals across ventral visual and frontoparietal regions that preceded the emergence of category-related information. Recognition-related signals in ventral visual regions were best explained by a two-state representational format whereby brain activity bifurcated for recognized and unrecognized images. By contrast, recognition-related signals in frontoparietal regions exhibited a reduced representational space for recognized images, yet with sharper category information. These results provide a spatiotemporally resolved view of neural activity supporting object recognition under uncertainty, revealing a pattern distinct from that underlying core object recognition.

Differences in oscillometric blood pressure readings between unsupported and supported back conditions.

Appropriate body posture is important for accurate blood pressure (BP) measurement. However, the impact of an unsupported back on BP readings is currently controversial. This study included 224 subjects (18-86 years old, 54.5 ± 15.5 years old, 105 males). BP was measured with an oscillometric BP device randomly following one of two protocols for back support conditions: (1) supported-unsupported-supported-unsupported, or (2) unsupported-supported-unsupported-supported. The average of the two systolic BP (SBP) and diastolic BP (DBP) readings in the same position was recorded as the final BP value. The differences in BP between the unsupported and supported back conditions were calculated as delta BP. Moreover, the percentage variation in BP (PV) was calculated with the formula delta BP/BP with an unsupported back. Multivariable regression analysis evaluated the impact of age, sex, hypertension history and supported BP level on PV. The SBP/DBP levels measured with an unsupported back were slightly higher than those when the back was supported (132.7 ± 19.5/79.6 ± 12.9 mmHg vs. 130.3 ± 20.0/78.5 ± 14.3 mmHg), and the delta SBP (2.3 mmHg) was statistically significant. The multivariable regression analysis showed that age was a positive factor but supported SBP level as a negative factor for systolic PV, while age and supported DBP level were positive factors, but hypertension history was a negative factor for diastolic PV. For a group participant, the mean difference in oscillometric SBP/DBP in the unsupported back position was 2.3/1.0 mmHg higher than that in the supported back position.

Effect of integrated Traditional Chinese and Western Medicine on gout.

OBJECTIVE: To evaluate the curative effect of integrated Traditional Chinese and Western Medicine on gout, and to investigate the therapy timing and exact treatment options of integrated medicine. METHODS: Totally 860 patients were enrolled, including 460 patients with intermittent gout, 200 patients with active Traditional Chinese Medicine (TCM) syndrome (TCM syndrome score ≥ 6) and 200 patients with stable TCM syndrome (score < 6). They were randomly divided into intervention and control groups. The control group was treated according to Western Medicine guidelines. The intervention group was treated with integrated Traditional Chinese and Western Medicine. The efficacy of TCM syndrome, joint pain score, joint swelling score, ESR, C-reactive protein, serum uric acid, liver and kidney function, and the duration of remission of TCM syndrome were compared between the two groups before and after treatments. RESULTS: For the patients with stable TCM syndrome, there was no significant difference in the effective rate and inefficiency between the intervention group and the control group. For the active type, the effective rate of the intervention group is better than the control group significantly. For the stable type, there was no significant difference between the intervention group and the control group in improving the scores of joint pain and swelling, reducing the level of ESR, C-reactive protein, serum uric acid and improving liver and kidney function. For the active type, the differences between the two groups were significant. The stable stage of gout in the intervention group was longer than the control group. CONCLUSION: For the gout patients with stable TCM syndrome in the acute stage of gout, we can use TCM treatment or Western Medicine alternatively; for the patients with active TCM syndrome, the scheme of combination of Traditional Chinese and Western Medicine can be applied, with the better curative effect than any medicine alone.

Study on the differentially expressed genes and signaling pathways in dermatomyositis using integrated bioinformatics method.

Dermatomyositis is a common connective tissue disease. The occurrence and development of dermatomyositis is a result of multiple factors, but its exact pathogenesis has not been fully elucidated. Here, we used biological information method to explore and predict the major disease related genes of dermatomyositis and to find the underlying pathogenic molecular mechanism.The gene expression data of GDS1956, GDS2153, GDS2855, and GDS3417 including 94 specimens, 66 cases of dermatomyositis specimens and 28 cases of normal specimens, were obtained from the Gene Expression Omnibus database. The 4 microarray gene data groups were combined to get differentially expressed genes (DEGs). The gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were operated by the database for annotation, visualization and integrated discovery and KEGG orthology based annotation system databases, separately. The protein-protein interaction networks of the DEGs were built from the STRING website. A total of 4097 DEGs were extracted from the 4 Gene Expression Omnibus datasets, of which 2213 genes were upregulated, and 1884 genes were downregulated. Gene ontology analysis indicated that the biological functions of DEGs focused primarily on response to virus, type I interferon signaling pathway and negative regulation of viral genome replication. The main cellular components include extracellular space, cytoplasm, and blood microparticle. The molecular functions include protein binding, double-stranded RNA binding and MHC class I protein binding. KEGG pathway analysis showed that these DEGs were mainly involved in the toll-like receptor signaling pathway, cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, complement and coagulation cascades, arginine and proline metabolism, phagosome signaling pathway. The following 13 closely related genes, XAF1, NT5E, UGCG, GBP2, TLR3, DDX58, STAT1, GBP1, PLSCR1, OAS3, SP100, IGK, and RSAD2, were key nodes from the protein-protein interaction network.This research suggests that exploring for DEGs and pathways in dermatomyositis using integrated bioinformatics methods could help us realize the molecular mechanism underlying the development of dermatomyositis, be of actual implication for the early detection and prophylaxis of dermatomyositis and afford reliable goals for the curing of dermatomyositis.

Effects of lentivirus-mediated ornithine decarboxylase gene on the proliferation and apoptosis of fibroblast-like synoviocytes in rats with arthritis.

OBJECTIVE: This study aimed to explore the effects of lentivirus-mediated ornithine decarboxylase (ODC) gene on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) in rats with rheumatoid arthritis (RA). METHODS: Twenty Lewis rats were randomized into control group (ten rats without processing) and RA group (ten rats of adjuvant-induced arthritis). The third-generation FLSs were randomized into test, control and blank groups. MTT assay and flow cytometry were employed to detect cell proliferation and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), and interleukin-2 (IL-2). RESULTS: Lewis rats in the RA group became ill from 11days on and got seriously ill 18days after modeling. However, rats in the control group had no obvious change. MTT assay showed that the test group had higher cell proliferation than the blank and control groups (P1<0.001; P2<0.001). Flow cytometry revealed that the apoptosis of FLSs in the test group was significantly lower than that in the blank and control groups (P1<0.001; P2<0.001). ELISA showed that the test group had higher TNF-α, IFN-γ and IL-2 level than the control and blank groups (all P<0.001), but no significant difference was found between the control and blank groups (all P>0.05). CONCLUSION: The results indicated that overexpression of ODC gene promotes the proliferation while suppressing apoptosis of FLSs in rats with RA.

MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling.

This study investigated whether microRNA-146a (miR-146a) mediating TLR4/NF-κB pathway affected proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes from 12 RA patients (RA-FLSs). FLSs in the logarithmic growth phase were assigned into the control, miR-146a mimic miR-146a inhibitor, Tak-242 (treated with TLR4/NF-κB pathway inhibitor) and mimic + lipopolysaccharide (LPS) groups. Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry. The expression of miR-146a, TLR4/NF-κB pathway-related proteins and cytokines were determined by RT-qPCR, western blotting and ELISA, and the release of NO by Greiss reaction. RA rat models were constructed and the primary cells were classified into the control, negative control (NC), miR-146a mimic, miR-146a inhibitor, Tak-242, mimic + LPS, and TLR4 groups. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen (PCNA) and intercellular adhesion molecular-1 (ICAM-1). The results showed that miR-146a levels were lower in RA-FLSs than control fibroblasts. miR-146a mimic and Tak-242 decreased RA-FLS proliferation and increased RA-FLS apoptosis, while miR-146a inhibitor had an opposite trend. miR-146a mimic and Tak-242 also decreased expression of TLR4, NF-κB, IL-1ß, IL-6, IL-8, IL-17, COX-2, MMP-3, Seprase, and iNOS, as well as reduced NO level in RA-FLSs while miR-146a inhibitor and TLR4 increased them. TLR4 and NF-κB levels and the positive rates of PCNA and ICAM-1 expressions were lower in RA-FLSs from RA rats given miR-146a mimic from control or miR-146a inhibitor-treated rats. These results suggest that miR-146a inhibits the proliferation and inflammatory response of RA-FLSs by down-regulating TLR4/NF-κB pathway.

Seeing Double: Exploring the Phenomenology of Self-Reported Absence of Rivalry in Bistable Pictures.

Ambiguous images such as Rubin's vase-face can be interpreted in at least two different ways. These interpretations are typically taken to be mutually exclusive, and ambiguous images have thus served as models of perceptual competition. Here, we present data that challenges this view. In an online survey, we found that a large proportion of people within the general population reported that the two percepts were not competing but could be perceived simultaneously. Of those who reported that they could see both percepts simultaneously, we invited 17 participants to take part in a functional magnetic resonance imaging (fMRI) experiment. In the scanner, participants saw images that could be interpreted as either a landscape or a face and reported at every point in time whether they perceived predominantly the face, the landscape, or both simultaneously. We explored behavioral and neurophysiological (with fMRI) correlates of the reported subjective experience of entertaining two percepts simultaneously by comparing them to those of the simple percepts (i.e., face or landscape). First, by comparing percept durations, we found that the simultaneous state was as stable as the two other percepts. Second, by measuring blood-oxygen-level-dependent (BOLD) signal levels within the fusiform face area (FFA), occipital face area (OFA) and parahippocampal place area (PPA), we found evidence from objective data that confirmed the subjective reports. While the results in FFA and OFA were not conclusive, in PPA, BOLD signal levels during subjective reports of perceiving both a landscape and a face were lower than the BOLD signal levels associated with reports of perceiving a landscape (and, in turn, reports of seeing a landscape were associated with greater BOLD signal levels than reports of seeing a face, thus suggesting that BOLD signal levels in PPA are a valid correlate of subjective experience in this task). In sum, the objective measures suggest that entertaining two percepts simultaneously in mind can be regarded as a distinct (mixed) perceptual state. We argue with these results that a more central role of subjective report in cognitive neuroscience is sometimes warranted.

Efficacy and safety of TNF-α inhibitors for active ankylosing spondylitis patients: Multiple treatment comparisons in a network meta-analysis.

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with impact on axial skeleton, peripheral joints and enthuses, and it may result in severe disabilities of those parts. Tumor necrosis factor-α (TNF-α) inhibitors are considered as an effective treatment for patients with active AS. In this study, we conducted a network meta-analysis to compare the clinical outcomes of active AS patients treated with TNF-α inhibitors. Randomized controlled trials (RCTs) evaluating the efficacy and safety of TNF-α inhibitors were retrieved in literature search and selected for meta-analysis. Changes in ASAS20 response, ASAS40 response and BASDAI 50% response were regarded as efficacy outcomes; serious adverse events (SAE) and all cause withdrawals were regarded as safety outcomes. Both traditional pairwise meta-analysis and network meta-analysis were performed. The results showed that adalimumab and infliximab had better clinical outcomes. Infliximab consistently appeared to be the most effective TNF-α inhibitors with a high risk of adverse events for patients with active AS; meanwhile, adalimumab ranked highest with respect to adverse effects with efficacy secondary to infliximab. As a result, we were unable to conclude the optimal TNF-α inhibitor and this issue should be solved by future researchers.

Upregulated Expression of microRNA-16 Correlates with Th17/Treg Cell Imbalance in Patients with Rheumatoid Arthritis.

To explore the correlation between miR-16 expression in T cells of peripheral blood mononuclear cells (PBMCs) and Th17/Treg imbalance in rheumatoid arthritis (RA) patients. Forty RA patients were recruited as the case group and further grouped as active RA and inactive RA groups; 21 healthy individuals were selected as the control group. Th17 and Treg were measured by flow cytometry, and their related cytokines were measured by FlowCytomix. RORγt, FoxP3 mRNA, and miR-16 expression in T cells was determined by real-time quantitative polymerase chain reaction. Western blotting was performed to measure RORγt and FoxP3 protein expression. RA patients showed upregulated Th17 and RORγt mRNA and protein expression compared with the controls (all p < 0.05); active RA patients showed lower Treg and FoxP3 mRNA and protein expression compared with inactive RA patients and controls (all p < 0.05). Secretion levels of Th17-related cytokines were higher in active RA patients than in inactive RA patients and controls (all p < 0.05); whereas those of Treg-related cytokines were lower in active RA patients than in controls (all p < 0.05). Active RA patients showed increased miR-16 expression in Th17 cells and decreased miR-16 expression in Treg cells of PBMCs (both p < 0.05). Pearson's test showed that in the PBMCs of the RA patients, miR-16 expression in the Th17 cells was positively related with RORγt mRNA expression, and miR-16 expression in the Treg cells was positively related with FoxP3 mRNA expression (both p < 0.05). The expression of miR-16 in Th17 and Treg cells of PBMCs in RA patients was closely associated with the expression of RORγt and FoxP3. MiR-16 may be involved in Th17/Treg imbalance of RA patients by affecting the expression of RORγt and FoxP3.