1,2-Dichloroethane causes anxiety and cognitive dysfunction in mice by disturbing GABA metabolism and inhibiting the cAMP-PKA-CREB signaling pathway.

1,2-Dichloroethane (1,2-DCE) is a powerfully toxic neurotoxin, which is a common environmental pollutant. Studies have indicated that 1,2-DCE long-term exposure can result in adverse effects. Nevertheless, the precise mechanism remains unknown. In this study, behavioral results revealed that 1,2-DCE long-term exposure could cause anxiety and learning and memory ability impairment in mice. The contents of γ-aminobutyric acid (GABA) and glutamine (Gln) in mice's prefrontal cortex decreased, whereas that of glutamate (Glu) increased. With the increase in dose, the activities of glutamate decarboxylase (GAD) decreased and those of GABA transaminase (GABA-T) increased. The protein and mRNA expressions of GABA transporter-3 (GAT-3), vesicular GABA transporter (VGAT), GABA A receptor α2 (GABAARα2), GABAARγ2, K-Cl cotransporter isoform 2 (KCC2), GABA B receptor 1 (GABABR1), GABABR2, protein kinase A (PKA), cAMP-response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), c-fos, c-Jun and the protein of glutamate dehydrogenase (GDH) and PKA-C were decreased, while the expression levels of GABA transporter-1 (GAT-1) and Na-K-2Cl cotransporter isoform 1 (NKCC1) were increased. However, there was no significant change in the protein content of succinic semialdehyde dehydrogenase (SSADH). The expressions of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) contents were also reduced. In conclusion, the results of this study show that exposure to 1,2-DCE could lead to anxiety and cognitive impairment in mice, which may be related to the disturbance of GABA metabolism and its receptors along with the cAMP-PKA-CREB pathway.

Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses.

AIM: To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses (IOLs). METHODS: This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June 2020. All patients underwent comprehensive preoperative and postoperative ophthalmologic examination, and data were collected including age, sex, surgical indications, best-corrected visual acuity, refractive error, intraocular pressure. Presence of intraoperative and postoperative surgical complications was documented. RESULTS: A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±5.3mo. Visual acuity improved from a mean of 0.35 (0.46±0.32 logMAR) preoperatively to 0.61 (0.21±0.18 logMAR) at the 3-month follow-up (P=0.002). The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was -1.24±0.80 diopters (D) and -1.42±0.97 D, respectively. There was no statistically significant difference between preoperative and postoperative astigmatism (P=0.156). The mean IOL-induced astigmatism was -0.23±0.53 D. The mean spherical equivalent at the 3-month follow-up was -0.1±0.94 D. No major complications were noted during the follow-up period. CONCLUSION: Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

Is moderate resistance training adequate for older adults with sarcopenia? A systematic review and network meta-analysis of RCTs.

BACKGROUND: Resistance training (RT) and nutritional supplementation are recommended for the management of sarcopenia in older adults. However, optimal RT intensity for the treatment of sarcopenia has not been well investigated. METHODS: This network meta-analysis aims to determine the comparative effectiveness of interventions for sarcopenia, taking RT intensity into consideration. RT intensity was classified into light-to-moderate intensity RT(LMRT), moderate intensity RT(MRT), and moderate-to-vigorous intensity RT(MVRT) based on percentage of one repetition maximum (%1RM) and/or rating of perceived exertion. RESULTS: A total of 50 RCTs (N = 4,085) were included after screening 3,485 articles. The results confirmed that RT with or without nutrition was positively associated with improved measures of muscle strength and physical performance. Regarding RT intensity, LMRT only demonstrated positive effects on hand grip (aerobic training + LMRT + nutrition: mean difference [MD] = 2.88; 95% credential intervals [CrI] = 0.43,5.32). MRT provided benefits on improvement in the 30-s chair stand test (repetitions) (MRT: MD = 2.98, 95% CrI = 0.35,5.59), timed up and go test (MRT: MD = -1.74, 95% CrI: = -3.34,-0.56), hand grip (MRT: MD = 2.44; 95% CrI = 0.03,5.70), and leg press (MRT: MD = 8.36; 95% CrI = 1.87,13.4). MVRT also improved chair stand test repetitions (MVRT: MD = 5.64, 95% CrI = 0.14,11.4), gait speed (MVRT + nutrition: MD = 0.21, 95% CrI = 0.003,0.48), appendicular skeletal muscle index (MVRT + nutrition: MD = 0.25, 95% CrI = 0.01,0.5), and leg press (MVRT: MD = 14.7, 95% CrI: 5.96,22.4; MVRT + nutrition: MD = 17.8, 95% CrI: 7.55,28.6). CONCLUSION: MVRT had greater benefits on muscle mass, lower extremity strength, and physical performance compared to MRT. Increasing RT intensity may be recommended for sarcopenic older adults.

G-CSF-mobilized peripheral blood mononuclear cells combined with platelet-rich plasma restored the ovarian function of aged rats.

BACKGROUND: Regenerative medicine with peripheral blood mononuclear cell (PBMC) transplantation sheds light on the issue of premature ovarian insufficiency (POI). However, the efficiency of PBMC treatment in natural ovarian aging (NOA) remains unclear. METHODS: Thirteen-month-old female Sprague-Dawley (SD) rats were used to verify the NOA model. Seventy-two NOA rats were randomly divided into three groups: the NOA control group, PBMC group, and PBMC+platelet-rich plasma (PRP) group. PBMCs and PRP were transplanted by intraovarian injection. The effects on ovarian function and fertility were measured after transplantation. RESULTS: Transplantation of PBMCs could restore the normal estrous cycle, consistent with the recovery of serum sex hormone levels, increased follicle numbers at all stages, and restoration of fertility by facilitating pregnancy and live birth. Moreover, when combined with PRP injection, these effects were more significant. The male-specific SRY gene was detected in the ovary at all four time points, suggesting that PBMCs continuously survived and functioned in NOA rats. In addition, after PBMC treatment, the expression of angiogenesis-related and glycolysis-related markers in the ovaries was upregulated, which indicated that these effects were associated with angiogenesis and glycolysis. CONCLUSIONS: PBMC transplantation restores the ovarian functions and fertility of NOA rats, and PRP could enhance the efficiency. Increased ovarian vascularization, follicle production, and glycolysis are likely the major mechanisms.

Patient and Provider Perspectives on Symptom Monitoring During Outpatient Chemotherapy: Interview Study.

BACKGROUND: Fluctuating symptoms and side effects are common during outpatient cancer treatment, and approaches to monitoring symptoms vary widely across providers, patients, and clinical settings. To design a remote symptom monitoring system that patients and providers find to be useful, it may be helpful to understand current clinical approaches to monitoring and managing chemotherapy-related symptoms among patients and providers and assess how more frequent and systematic assessment and sharing of data could improve patient and provider experiences. OBJECTIVE: The goals of this study were to learn about patient and provider perspectives on monitoring symptoms during chemotherapy, understand barriers and challenges to effective symptom monitoring at one institution, and explore the potential value of remote symptom monitoring between provider visits. METHODS: A total of 15 patients who were currently undergoing or had recently completed chemotherapy and 7 oncology providers participated in semistructured interviews. Interviews were transcribed and coded using an iterative thematic analysis approach. The study was conducted at a National Cancer Institute-Designated Comprehensive Cancer Center. RESULTS: Four main themes were discussed by patients and providers: (1) asynchronous nature of current methods for tracking and managing symptoms, (2) variability in reported symptoms due to patient factors, (3) limitations of existing communication channels, and (4) potential value of real-time remote symptom monitoring during chemotherapy. Current asynchronous methods and existing communication channels resulted in a disconnect between when symptoms are most severe and when conversations about symptoms happen, a situation further complicated by memory impairments during chemotherapy. Patients and providers both highlighted improvements in patient-provider communication as a potential benefit of remote real-time symptom monitoring. Providers also emphasized the value of temporal data regarding when symptoms first emerge and how they progress over time, as well as the potential value of concurrent activity or other data about daily activities and functioning. Patients noted that symptom monitoring could result in better preparation for subsequent treatment cycles. CONCLUSIONS: Both patients and providers highlighted significant challenges of asynchronous, patient-initiated, phone-dependent symptom monitoring and management. Oncology patients and providers reported that more routine remote monitoring of symptoms between visits could improve patient-provider communication, prepare patients for subsequent chemotherapy cycles, and facilitate provider insight and clinical decision-making with regard to symptom management.

Identification and validation of a signature based on macrophage cell marker genes to predict recurrent miscarriage by integrated analysis of single-cell and bulk RNA-sequencing.

Recurrent miscarriage (RM) is a chronic, heterogeneous autoimmune disease that has serious social and personal consequences. No valid and reliable diagnostic markers or therapeutic targets for RM have been identified. Macrophages impact the innate immune system and can be used as diagnostic and prognostic markers for many diseases. We first collected 16 decidua and villi tissue samples from 5 normal patients and 3 RM patients for single-cell RNA sequencing data analysis and identified 1293 macrophage marker genes. We then screened a recurrent miscarriage cohort (GSE165004) for 186 macrophage-associated marker genes that were significantly differentially expressed between RM patients and the normal pregnancy endometrial tissues, and performed a functional enrichment analysis of differentially expressed genes. We then identified seven core genes (ACTR2, CD2AP, MBNL2, NCSTN, PUM1, RPN2, and TBC1D12) from the above differentially expressed gene group that are closely related to RM using the LASSO, Random Forest and SVM-RFE algorithms. We also used GSE26787 and our own collection of clinical specimens to further evaluate the diagnostic value of the target genes. A nomogram was constructed of the expression levels of these seven target genes to predict RM, and the ROC and calibration curves showed that our nomogram had a high diagnostic value for RM. These results suggest that ACTR2 and NCSTN may be potential targets for preventative RM treatments.

The probability and possible influence factors of intermittent ovarian function recovery in patients with premature ovarian insufficiency.

RESEARCH QUESTION: What are the probability and underlying influence factors of intermittent ovarian function recovery in patients with idiopathic premature ovarian insufficiency (POI)? DESIGN: This was a retrospective cohort study conducted in tertiary hospitals recruiting 162 patients diagnosed with POI based on European Society of Human Reproduction and Embryology criteria from June 2015 to March 2022. The incidence of intermittent ovarian function recovery was evaluated, and the possible influence factors were investigated by univariate and multivariate analysis. RESULTS: Among 162 POI patients, 48 (29.63%) presented intermittent ovarian function recovery, and 11 (6.79%) were natural pregnancies; 114 (70.37%) patients failed to show ovarian function recovery. No association was found between initial clinical features and intermittent ovarian function recovery. In contrast, the variables of FSH, LH, oestradiol, anti-Müllerian hormone (AMH), ovarian volume, passive smoking and weekly exercise time after diagnosis were correlated with intermittent ovarian function recovery in patients with POI and further analysis indicated that FSH concentration at diagnosis (odds ratio [OR] 0.964, 95% confidence interval [CI] 0.934-0.995, P = 0.023), passive smoking (OR 0.369, 95% CI 0.141-0.963, P = 0.042) and weekly exercise time after diagnosis (OR 5.592, 95% CI 1.83-17.088, P = 0.003) were influence factors of intermittent ovarian function recovery in POI patients. CONCLUSIONS: The incidence of intermittent ovarian function recovery in patients with idiopathic POI was 29.63%, and the natural pregnancy rate was 6.79%. Lower FSH concentration at diagnosis, no passive smoking and a weekly exercise time ≥1.5 h after the diagnosis may be beneficial for intermittent ovarian function recovery in POI patients.

Disturbance of glutamate metabolism and inhibition of CaM-CaMKII-CREB signaling pathway in the hippocampus of mice induced by 1,2-dichloroethane exposure.

1,2-Dichloroethane (1,2-DCE) is a highly toxic neurotoxicity, and the brain tissue is the main target organ. At present, long-term exposure to 1,2-DCE has been shown to cause cognitive dysfunction in some studies, but the mechanism is not clear. The results of this study showed that long-term 1,2-DCE exposure decreased learning and memory abilities in mice and impaired the structure and morphology of neurons in the hippocampal region. Moreover, except for the mRNA level of PAG, the enzymatic activities and protein levels of GS and PAG, as well as the mRNA level of GS were inhibited. With increasing dose of exposure, the protein and mRNA expression of GLAST and GLT-1 also decreased. Contrarily, there were protein and mRNA expression upregulation of GluN1, GluN2A and GluN2B in the hippocampus, as well as increased levels of extracellular Glu and intracellular Ca2+. In addition, 1,2-DCE exposure also downregulated the protein expression levels of CaM, CaMKII and CREB. Taken together, our results suggest that long-term 1,2-DCE exposure impairs the learning and memory capacity in mice, which may be attributed to the disruption of Glu metabolism and the inhibition of CaM- CaMKII-CREB signaling pathway in the hippocampus.

Dual-Graph Attention Convolution Network for 3-D Point Cloud Classification.

Three-dimensional point cloud classification is fundamental but still challenging in 3-D vision. Existing graph-based deep learning methods fail to learn both low-level extrinsic and high-level intrinsic features together. These two levels of features are critical to improving classification accuracy. To this end, we propose a dual-graph attention convolution network (DGACN). The idea of DGACN is to use two types of graph attention convolution operations with a feedback graph feature fusion mechanism. Specifically, we exploit graph geometric attention convolution to capture low-level extrinsic features in 3-D space. Furthermore, we apply graph embedding attention convolution to learn multiscale low-level extrinsic and high-level intrinsic fused graph features together. Moreover, the points belonging to different parts in real-world 3-D point cloud objects are distinguished, which results in more robust performance for 3-D point cloud classification tasks than other competitive methods, in practice. Our extensive experimental results show that the proposed network achieves state-of-the-art performance on both the synthetic ModelNet40 and real-world ScanObjectNN datasets.

HOXA10 improves endometrial receptivity by upregulating E-cadherin†.

In the endometrium of women with recurrent implantation failure and unexplained recurrent miscarriage, the expression levels of homeobox A10 and E-cadherin were positively correlated. To explore whether homeobox A10 regulates E-cadherin during endometrial receptivity establishment, Ishikawa and RL95-2 cells were transfected with target-specific small interfering RNA (siRNA) and overexpression plasmid of homeobox A10. The expression levels of homeobox A10 and E-cadherin were measured by western blot and quantitative Real-time Polymerase Chain Reaction (qRT-PCR). Attachment assay of JEG-3 spheroids to endometrial cells were conducted to explore the adhesive functions after homeobox A10 interfered. Chromatin immunoprecipitation assays and dual luciferase reporter were used to investigate the regulatory mechanism of homeobox A10. The CD1 mice were transfected with si-homeobox A10 to confirm these results in vivo. In Ishikawa and RL95-2 cells, the expression of E-cadherin was positively correlated with homeobox A10 when it was silenced/overexpressed. Consistently, the adhesion of endometrial epithelium cells and trophoblast cells was inhibited after homeobox A10 was silenced, and exogenous restoration of E-cadherin expression reversed this effect to some extent. Homeobox A10 regulates the expression of E-cadherin by directly binding to a conserved motif (TGTACTAAAAA) located in the E-cadherin promoter region. In addition, after knockdown of homeobox A10 in CD1 mice, both the implantation and live birth rates were decreased. In conclusion, homeobox A10 can bind to the E-cadherin promoter region and directly regulate its expression, thereby improving endometrial receptivity and subsequently increasing the embryo adhesion and implantation.

Changes in retinal sensitivity following inverted internal limiting membrane flap technique for large macular holes.

PURPOSE: The aim of this study was to evaluate the effect of inverted internal limiting membrane (ILM) flap technique and measure the retinal sensitivity using microperimetry-1 (MP-1) test in patients with large macular hole (MH). MATERIALS AND METHODS: We enrolled patients undergoing surgery for idiopathic MHs from January 2016 to October 2019. Only patients having a minimum diameter of idiopathic MH exceeding 500 µm were included in this study. All patients underwent complete preoperative ophthalmologic examinations, optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) measurements. Postoperative OCT and BCVA were evaluated at least 3 months postoperatively. In addition, these patients also received MP-1 pre- and postoperatively for retinal sensitivity measurement. RESULTS: Totally ten patients (ten eyes) were included for analysis. The mean retinal sensitivity within central 12° and 40° was statistically improved after surgery (P < 0.05). The number of absolute or relative scotoma (stimulus values ≤4 dB) within central 4° showed a significant reduction postoperatively. There was also a significant increase in visual acuity postoperatively. CONCLUSION: Patients with large MH have a great successful rate by receiving inverted ILM flap technique. In our study, all MHs of ten eyes were closed postoperatively. The results also demonstrated that ILM flap technique improves both the functional and anatomic outcomes.

The function of metformin in endometrial receptivity (ER) of patients with polycyclic ovary syndrome (PCOS): a systematic review and meta-analysis.

BACKGROUND: This meta-analysis summarizes evidence from studies using metformin (Met) to improve endometrial receptivity (ER) in women with PCOS. METHODS: Following the PRISMA protocol, we conducted a comprehensive search of academic literature from various databases, including PubMed, EMbase and Cochrane libraries. Studies published in English before Jan 27, 2021, were recruited for primary screening. Data on endometrial thickness (EMT), endometrial artery resistance index (RI), clinical pregnancy rate (CPR) and miscarriage rate (MR) were extracted and analyzed. RESULTS: Sixty-two eligible studies that included 6571 patients were evaluated in this meta-analysis. Primary indicators are EMT and endometrial aetery RI; secondary indicators include the clinical pregnancy rate and miscarriage rate. Metformin significantly increased EMT (SMD = 2.04, 95% CI (0.96,3.12),P = 0.0002) and reduced endometrial artery RI compared to the non-Met group (SMD = - 2.83, 95% CI: (- 5.06, - 0.59), P = 0.01). As expected, metformin also improved CPR and reduced MR in PCOS patients as a result, clinical pregnancy rate (risk ratio [RR] = 1.26, 95% CI: 1.11-1.43, P = 0.0003), and miscarriage rate (RR = 0.73, 95% CI:0.58-0.91, P = 0.006). CONCLUSION: Metformin may improve endometrial receptivity (ER) in PCOS patients by increasing EMT and reducing endometrial artery RI. However, the level of most original studies was low, with small sample sizes. More large-scale, long-term RCTs with rigorous methodologies are needed.

Talin1 regulates endometrial adhesive capacity through the Ras signaling pathway.

AIMS: Blastocyst implantation is mainly depended on the adhesion between cells and cell matrix. Endometrial adhesion plays an important role in establishing embryo implantation, but the underlying mechanisms are remains unclear. Talin1 is a local adhesion complex protein that is necessary for cell adhesion and movement. However, the role and mechanisms of Talin1 in embryo implantation are still unclear. MAIN METHODS: The expression of Talin1 and Integrin αvß3 was measured in the receptive endometrium from the RIF (Recurrent implantation failure) cohort and NC (normal fertile control group) cohort. A JEG-3 trophoblast and endometrial epithelial cell adhesion model and pregnant mouse model were established. The molecular mechanism of Talin1-mediated cell adhesion was explored by RNA sequencing, RT-qPCR, as well as western blotting assays. KEY FINDINGS: Talin1 enhances endometrial cell adhesion by regulating the Ras signaling pathway, and ultimately facilitates embryo implantation. SIGNIFICANCE: This study revealed the molecular mechanisms of regarding the pathogenesis of RIF caused by endometrial receptivity insufficiency. Further pharmacological research on the Ras signaling pathway would be valuable and might provide new therapeutic targets for RIF patients.

Effects of Environment and Lifestyle Factors on Premature Ovarian Failure.

Premature ovarian insufficiency (POI) or primary ovarian failure is defined as a cessation of the menstrual cycle in women younger than 40 years old. It is strictly defined as more than 4 months of oligomenorrhea or amenorrhea in a woman <40 years old, associated with at least two follicle-stimulating hormone (FSH) levels >25 U/L in the menopausal range, detected more than 4 weeks apart. It is estimated that POI was affected 1 and 2% of women. Although 80% of POI cases are of unknown etiology, it is suggested that genetic disorder, autoimmune origin, toxins, and environmental factors, as well as personal lifestyles, may be risk factors of developing POI. In this section, we will discuss the influences of environmental and lifestyle factors on POI. Moreover updated basic research findings regarding how these environmental factors affect female ovarian function via epigenetic regulations will also be discussed.

LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3.

BACKGROUND: Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. METHODS: QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study. RESULTS: We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K. CONCLUSION: LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.

Variation of diagnostic criteria in women with chronic endometritis and its effect on reproductive outcomes: A systematic review and meta-analysis.

This meta-analysis aimed to evaluate the variation in the diagnostic criteria for chronic endometritis (CE) and its effect on reproductive outcomes. A search of the academic literature was conducted in various databases including PubMed, Embase, Cochrane Library, and Chinese National Knowledge Internet. Studies published in English or Chinese prior to October 1, 2019, were included in the primary screen. Data on the CE incidence rate, cure rate after antibiotic therapy, clinical pregnancy rate, miscarriage rate, and live birth rate were extracted and analyzed. Twelve eligible studies involving 1879 patients were included in this meta-analysis. Compared with strict diagnostic criteria, studies that used broad diagnostic criteria to identify CE reported a higher incidence rate (odds radio [OR] = 2.96, 95% confidence interval [CI]: 1.13-6.44), clinical pregnancy rate (OR = 1.83, 95 % CI: 1.18-2.8), and live birth rate (OR = 2.08, 95 % CI: 1.43-3.02). Compared with a short treatment course, a longer course of antibiotic treatment significantly improved the cure rate of CE (OR = 0.29, 95% CI: 0.18-0.47). Based on these findings, variation in the diagnostic criteria may alter the incidence rate, clinical pregnancy rate, and live birth rate of women with CE. A consensus on the diagnostic criteria must be established to obtain a better understanding of and additional information about CE.

Functional Alignment with Anatomical Networks is Associated with Cognitive Flexibility.

Cognitive flexibility describes the human ability to switch between modes of mental function to achieve goals. Mental switching is accompanied by transient changes in brain activity, which must occur atop an anatomical architecture that bridges disparate cortical and subcortical regions by underlying white matter tracts. However, an integrated perspective regarding how white matter networks might constrain brain dynamics during cognitive processes requiring flexibility has remained elusive. To address this challenge, we applied emerging tools from graph signal processing to examine whether BOLD signals measured at each point in time correspond to complex underlying anatomical networks in 28 individuals performing a perceptual task that probed cognitive flexibility. We found that the alignment between functional signals and the architecture of the underlying white matter network was associated with greater cognitive flexibility across subjects. By computing a concise measure using multi-modal neuroimaging data, we uncovered an integrated structure-function correlate of human behavior.

Brain network efficiency is influenced by the pathologic source of corticobasal syndrome.

OBJECTIVE: To apply network-based statistics to diffusion-weighted imaging tractography data and detect Alzheimer disease vs non-Alzheimer degeneration in the context of corticobasal syndrome. METHODS: In a cross-sectional design, pathology was confirmed by autopsy or a pathologically validated CSF total tau-to-ß-amyloid ratio (T-tau/Aß). Using structural MRI data, we identify association areas in fronto-temporo-parietal cortex with reduced gray matter density in corticobasal syndrome (n = 40) relative to age-matched controls (n = 40). Using these fronto-temporo-parietal regions of interest, we construct structural brain networks in clinically similar subgroups of individuals with Alzheimer disease (n = 21) or non-Alzheimer pathology (n = 19) by linking these regions by the number of white matter streamlines identified in a deterministic tractography analysis of diffusion tensor imaging data. We characterize these structural networks using 5 graph-based statistics, and assess their relative utility in classifying underlying pathology with leave-one-out cross-validation using a supervised support vector machine. RESULTS: Gray matter density poorly discriminates between Alzheimer disease and non-Alzheimer pathology subgroups with low sensitivity (57%) and specificity (52%). In contrast, a statistic of local network efficiency demonstrates very good discriminatory power, with 85% sensitivity and 84% specificity. CONCLUSIONS: Our results indicate that the underlying pathologic sources of corticobasal syndrome can be classified more accurately using graph theoretical statistics derived from patterns of white matter network organization in association cortex than by regional gray matter density alone. These results highlight the importance of a multimodal neuroimaging approach to diagnostic analyses of corticobasal syndrome.

Graph Frequency Analysis of Brain Signals.

This paper presents methods to analyze functional brain networks and signals from graph spectral perspectives. The notion of frequency and filters traditionally defined for signals supported on regular domains such as discrete time and image grids has been recently generalized to irregular graph domains, and defines brain graph frequencies associated with different levels of spatial smoothness across the brain regions. Brain network frequency also enables the decomposition of brain signals into pieces corresponding to smooth or rapid variations. We relate graph frequency with principal component analysis when the networks of interest denote functional connectivity. The methods are utilized to analyze brain networks and signals as subjects master a simple motor skill. We observe that brain signals corresponding to different graph frequencies exhibit different levels of adaptability throughout learning. Further, we notice a strong association between graph spectral properties of brain networks and the level of exposure to tasks performed, and recognize the most contributing and important frequency signatures at different levels of task familiarity.

Acidosis Mediates the Switching of Gs-PKA and Gi-PKCε Dependence in Prolonged Hyperalgesia Induced by Inflammation.

Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Previous studies suggested that in male Sprague Dawley rats, prostaglandin E2 (PGE2)-induced short-term hyperalgesia depends on protein kinase A (PKA) activity, whereas long-lasting hyperalgesia induced by PGE2 with carrageenan pre-injection, requires protein kinase Cε (PKCε). However, the mechanism underlying the kinase switch with short- to long-term hyperalgesia remains unclear. In this study, we used the inflammatory agents carrageenan or complete Freund's adjuvant (CFA) to induce long-term hyperalgesia, and examined PKA and PKCε dependence and switching time. Hyperalgesia induced by both agents depended on PKA/PKCε and Gs/Gi-proteins, and the switching time from PKA to PKCε and from Gs to Gi was about 3 to 4 h after inflammation induction. Among the single inflammatory mediators tested, PGE2 and 5-HT induced transient hyperalgesia, which depended on PKA and PKCε, respectively. Only acidic solution-induced hyperalgesia required Gs-PKA and Gi-PKCε, and the switch time for kinase dependency matched inflammatory hyperalgesia, in approximately 2 to 4 h. Thus, acidosis in inflamed tissues may be a decisive factor to regulate switching of PKA and PKCε dependence via proton-sensing G-protein-coupled receptors.