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Transforming growth factor-beta 1 gene polymorphisms and cardiovascular disease in hemodialysis patients. Background. Atherosclerotic vascular disease is a leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that inhibits the atheromatous process. We studied coding region polymorphisms of the TGF-β1 gene (+869 T → C at codon 10 and +915 G → C at codon 25) as genetic susceptibility factors for prevalent vascular disease and cardiac outcomes in a cohort of HD patients enrolled in the HEMO Study. Methods. Genotyping was carried out using polymerase chain reaction-sequence specific primer (PCR-SSP) methods with a cytokine genotyping tray. Prevalent vascular disease was coded from the Index of Disease Severity (IDS) scores for ischemic heart disease (IHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), and congestive heart failure (CHF), 0 indicating absence, and 1 to 3 increasing grades of severity. The presence of any vascular disease (VD) (i.e., any degree of IHD/PVD/CVD), and the number of coexistent vascular system diseases per patient were derived. Cardiac outcomes, one of the secondary outcomes of the HEMO Study, were expressed as a composite of the first hospitalization for, or death from, cardiac causes. Results. The cohort consisted of 183 patients at enrollment, 56% male, 44% African American (AA), and 40% diabetic. The mean age was 62.4 ± 12.2 years, and median dialysis vintage 2.02 years. The most frequent genotype at codon 10 was T/C (67%), and at codon 25 was G/G (72%). IHD was present in 52% of patients; 65% had at least one vascular system involvement, and 31% had 2 or more. On both univariate and multivariate analysis, the G/C genotype at codon 25 was significantly associated with the presence and extent of vascular disease at enrollment. The median time to cardiac outcome, defined as a composite of the first hospitalization for, or death from, cardiac causes, was 411 days in patients with the G/C genotype compared with 851 days in those with the G/G genotype ( P= 0.03). Patients with the G/C genotype had a 1.6-fold increased hazard for cardiac outcomes after adjustment for baseline covariates ( P= 0.04). Conclusion. The G/C substitution at codon 25 was associated with an increased risk for prevalent vascular disease, new onset cardiac morbidity, and cardiac mortality in HD patients, and may be a genetic susceptibility factor for the development of atherosclerosis. Further studies are required to evaluate the role of TGF-β1 as a candidate gene. [ABSTRACT FROM AUTHOR]

Cytokine gene polymorphisms in hemodialysis patients: Association with comorbidity, functionality, and serum albumin. Background. Cytokine-orchestrated chronic inflammation plays a major role in long-term morbidity and mortality in patients with end-stage renal disease (ESRD) on hemodialysis (HD). In this cross-sectional study, we evaluated the association between specific alleles/genotypes and combinations of genotypes of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 with indices of comorbidity, functional status, and other biological markers in a cohort of 183 ESRD patients recruited to the Hemodialysis (HEMO) Study from two Boston centers. Methods. Genotyping was performed for single nucleotide polymorphisms in the promoter region of IL-6 (–174 G→C), TNF-α (–308 G→A), and IL-10 (−1082 G→A). The relationship of specific genotypes to the index of coexistent disease (ICED) score (an index of comorbidity), Karnofsky Index (a measure of functional status), serum albumin, and nutritional indices (anthropometric measurements, body mass index, normalized protein catabolic ratio) were studied. Plasma IL-6 levels, as well as TNF-α and IL-10 production by endotoxin-stimulated peripheral blood mononuclear cells (PBMC), were also measured by enzyme-linked immunosorbent assay (ELISA). Results. Patients with the high producer genotypes for the proinflammatory cytokines IL-6 (G/G and G/C) and TNF-α (G/A and A/A) had significantly higher comorbidity (ICED scores of ≥2) and lower functional scores (Karnofsky Index) compared with patients with the low producer genotypes for these cytokines (C/C and G/G, respectively). In contrast, patients with the high and intermediate producer genotypes (G/G and G/A) for the anti-inflammatory cytokine IL-10 had a higher Karnofsky Index compared with those with the low producer genotype (A/A). Serum albumin levels were lower in patients with the TNF-α high producer genotype (G/A and A/A) compared with those with the low producer genotype (G/A and A/A). On multivariate analysis, the IL-6 high producer genotypes were associated with an odds ratio (OR) of 4.87 for higher comorbidity (ICED scores ≥2) ( P= 0.02), and 4.9 for lower Karnofsky Index (lower functional status) ( P= 0.04) compared with patients with the low IL-6 producer genotypes. Similarly, the TNF-α high producer genotype was associated with increased odds for a higher ICED score, lower Karnofsky Index, and lower serum albumin compared with patients with the low producer genotype for this cytokine. In contrast, the IL-10 high/intermediate producer genotype was associated with increased odds for a higher Karnofsky Index ( P= 0.05). Cytokine genotype combinations—the TNF-α high producer and IL-6 high producer genotype combination, and the IL-6 high producer and IL-10 low producer genotype combination—were independently associated with a higher ICED score. These genotype combinations, as well as the TNF-α high producer and IL-10 low producer genotype combination, were also associated with a lower Karnofsky Index. Conclusion. In ESRD patients on long-term HD, single nucleotide polymorphisms in the promoter region of the proinflammatory cytokines IL-6 and TNF-α, and the regulatory monokine IL-10, show a strong association with indices of comorbidity and function, and biological and nutritional markers. [ABSTRACT FROM AUTHOR]

Effect of a novel adsorbent on cytokine responsiveness to uremic plasma. Background. Middle molecules such as β2 -microglobulin (β2 M) and advanced glycation end products (AGE)–modified proteins contribute to inflammation in uremia. The BetaSorb™ column is a new adsorptive device, which contains copolymeric beads, suitable for removal of β2 M and other middle molecules. We assessed the effect of this column on the bioreactivity of uremic plasma, as measured by cytokine responsiveness. Methods. Uremic plasma was perfused in vitro through the column (10 mL/min) and samples were collected after 10 to 30 passes. Endotoxin-stimulated tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) production by THP-1–derived monocytes was measured following brief exposure to uremic plasma. β2 M levels were measured. The contribution of AGE-modified proteins to the bioreactivity of uremic plasma was explored. Results. TNF-α and IL-10 production markedly decreased after 30 passes (629 ± 78 vs. 144 ± 62 pg/mL; 207 ± 25 vs. 117 ± 23 pg/mL; P = 0.04). The column removed β2 M efficiently with a marked decline in plasma levels by 99% after 30 passes. Neutralization of AGE receptor (RAGE) resulted in a further reduction in the bioreactivity of uremic plasma. This was observed with nonperfused, as well as perfused, uremic plasma, suggesting that AGE-modified proteins were biologically active and still present after perfusion. Conclusion. The sorbent beads removed uremic solute(s) that prime monocytes to enhanced cytokine production. Removal of β2 M was efficient, and of native and AGE-modified middle molecules likely. [ABSTRACT FROM AUTHOR]

• Distribution of equal states (DES) quantifies the amplitude fluctuations. • Pathological features of epileptic EEGs are detected by the DES. • Ictal EEGs have abnormally low DES while the postictal manifest high DES. • DES is conceptually simple and computationally fast. • DES yields reliable outcomes even in a very short EEG. Slightly different bouts of brain electrical activity may yield equal readings under low-resolution electroencephalogram (EEG) data recordings; however, the underlying information contained in the distribution of equalities has received little attention. In this paper, we elucidated the fundamental reason for the existence of equal states and proposed a novel feature descriptor, i.e., the distribution of equal states (DES), for EEG quantitative amplitude fluctuations. We employed epileptic EEGs from the Bonn public database as well as those from Sprague Dawley rats in a pilocarpine animal model of epilepsy to test the effectiveness of the DES. The test results suggested that the ictal EEG from both groups had abnormally low DES due to neural firing and severe brain activity, whereas smooth postictal EEGs manifested the highest DES. The findings are in line with epileptic pathological conditions and highlight the physiological information contained by the DES. Remarkably, the DES reliably characterizes the amplitude fluctuations even in very short EEGs, and it has high stationarity with respect to the starting point of the data. Overall, with characteristics of simplicity and robustness, the DES is effective for quantifying amplitude fluctuations and serves as a practical biomarker for epileptic EEG recordings. [ABSTRACT FROM AUTHOR]

Visual object tracking, which is primarily based on visible light image sequences, encounters numerous challenges in complicated scenarios, such as low light conditions, high dynamic ranges, and background clutter. To address these challenges, incorporating the advantages of multiple visual modalities is a promising solution for achieving reliable object tracking. However, the existing approaches usually integrate multimodal inputs through adaptive local feature interactions, which cannot leverage the full potential of visual cues, thus resulting in insufficient feature modeling. In this study, we propose a novel multimodal hybrid tracker (MMHT) that utilizes frame-event-based data for reliable single object tracking. The MMHT model employs a hybrid backbone consisting of an artificial neural network (ANN) and a spiking neural network (SNN) to extract dominant features from different visual modalities and then uses a unified encoder to align the features across different domains. Moreover, we propose an enhanced transformer-based module to fuse multimodal features using attention mechanisms. With these methods, the MMHT model can effectively construct a multiscale and multidimensional visual feature space and achieve discriminative feature modeling. Extensive experiments demonstrate that the MMHT model exhibits competitive performance in comparison with that of other state-of-the-art methods. Overall, our results highlight the effectiveness of the MMHT model in terms of addressing the challenges faced in visual object tracking tasks. [ABSTRACT FROM AUTHOR]

Absence epilepsy, characterized by transient loss of awareness and bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) on electroencephalography (EEG) during absence seizures, is generally believed to arise from abnormal interactions between the cerebral cortex (Ctx) and thalamus. Recent animal electrophysiological studies suggested that changing the neural activation level of the external globus pallidus (GPe) neurons can remarkably modify firing rates of the thalamic reticular nucleus (TRN) neurons through the GABAergic GPe–TRN pathway. However, the existing experimental evidence does not provide a clear answer as to whether the GPe–TRN pathway contributes to regulating absence seizures. Here, using a biophysically based mean-field model of the GPe-corticothalamic (GCT) network, we found that both directly decreasing the strength of the GPe–TRN pathway and inactivating GPe neurons can effectively suppress absence seizures. Also, the pallido-cortical pathway and the recurrent connection of GPe neurons facilitate the regulation of absence seizures through the GPe–TRN pathway. Specifically, in the controllable situation, enhancing the coupling strength of either of the two pathways can successfully terminate absence seizures. Moreover, the competition between the GPe–TRN and pallido-cortical pathways may lead to the GPe bidirectionally controlling absence seizures, and this bidirectional control manner can be significantly modulated by the Ctx–TRN pathway. Importantly, when the strength of the Ctx–TRN pathway is relatively strong, the bidirectional control of absence seizures by changing GPe neural activities can be observed at both weak and strong strengths of the pallido-cortical pathway.These findings suggest that the GPe–TRN pathway may have crucial functional roles in regulating absence seizures, which may provide a testable hypothesis for further experimental studies and new perspectives on the treatment of absence epilepsy. [ABSTRACT FROM AUTHOR]

In temporal lobe epilepsy (TLE), the epileptogenic zones, such as the temporal lobe structure, could generate pathological high-frequency oscillations (pHFOs, 250–500 Hz) before the ictal period. These pHFOs have also been observed during the process of seizures in both TLE patients and animals, exhibiting a critical role as promising biomarkers for TLE seizures. TLE seizures could be modulated via regulating the neural excitability in epileptogenic zones, for that TLE is primarily associated with the excitation-inhibition imbalance. However, whether these kinds of modulations could also impact the pHFOs characteristics during TLE seizures is still unclear. For this purpose, we pharmaco-genetically inhibited the principal cells (PCs) in the mouse CA3 region and tracked the difference in the behavioral and electrophysiological features during LiCl-pilocarpine-induced TLE seizure between the hM4Di+CNO (experimental) mice and mCherry+CNO (control) mice. Delayed latency, decreased averaged duration, and reduced counts of the generalized seizure were observed in the experimental mice. Besides, the electrophysiological characteristics, such as the firing rate of PCs and the count of pHFO, exhibited significant decline in the CA3 and CA1 regions. During TLE seizure, there existed strong phase-coupling between pHFO and PCs spike timing in the control mice, while it was abolished in the experimental mice. In addition, we also found that the counts of pHFO were significantly associated with the behavioral features, indicating the close relationships within them. Collectively, our findings suggested that alterations in pHFO and the retardation of seizures may be attributed to disruptions in neuronal excitability, and the variations of electrophysiological features were related to seizure severity during TLE seizures. These results provide valuable insights into the role of pHFOs in TLE and shed light on the underlying mechanisms involved. • Inactivation of CA3 principal cells (PCs) reduces TLE seizures, neuronal spiking activity, and pHFO counts. • Both CA3 and CA1 PCs exhibit a decoupling of discharge timing from pHFO upon inhibition of CA3 pyramidal cells. • pHFO counts are associated with behavioral features in TLE. [ABSTRACT FROM AUTHOR]

Effective frequency recognition algorithms are critical in steady-state visual evoked potential (SSVEP) based brain–computer interfaces (BCIs). In this study, we present a hierarchical feature fusion framework which can be used to design high-performance frequency recognition methods. The proposed framework includes two primary techniques for fusing features: spatial dimension fusion (SD) and frequency dimension fusion (FD). Both SD and FD fusions are obtained using a weighted strategy with a nonlinear function. To assess our novel methods, we used the correlated component analysis (CORRCA) method to investigate the efficiency and effectiveness of the proposed framework. Experimental results were obtained from a benchmark dataset of thirty-five subjects and indicate that the extended CORRCA method used within the framework significantly outperforms the original CORCCA method. Accordingly, the proposed framework holds promise to enhance the performance of frequency recognition methods in SSVEP-based BCIs. [ABSTRACT FROM AUTHOR]

Abstract Our mysterious brain is believed to operate near a non-equilibrium point and generate critical self-organized avalanches in neuronal activity. A central topic in neuroscience is to elucidate the underlying circuitry mechanisms of neuronal avalanches in the brain. Recent experimental evidence has revealed significant heterogeneity in both synaptic input and output connectivity, but whether the structural heterogeneity participates in the regulation of neuronal avalanches remains poorly understood. By computational modeling, we predict that different types of structural heterogeneity contribute distinct effects on avalanche neurodynamics. In particular, neuronal avalanches can be triggered at an intermediate level of input heterogeneity, but heterogeneous output connectivity cannot evoke avalanche dynamics. In the criticality region, the co-emergence of multi-scale cortical activities is observed, and both the avalanche dynamics and neuronal oscillations are modulated by the input heterogeneity. Remarkably, we show similar results can be reproduced in networks with various types of in- and out-degree distributions. Overall, these findings not only provide details on the underlying circuitry mechanisms of nonrandom synaptic connectivity in the regulation of neuronal avalanches, but also inspire testable hypotheses for future experimental studies. [ABSTRACT FROM AUTHOR]

Very high-frequency oscillations (VHFOs, >500 Hz) are considered a highly sensitive biomarker of seizures. We hypothesized that VHFOs may exhibit specificity towards hypersynchronous (HYP) seizures and low-voltage fast (LVF) seizures in temporal lobe epilepsy (TLE). Local field potentials were recorded from the hippocampal network in TLE mice induced by pilocarpine. Subsequently, we analyzed the VHFO features, including their temporal-frequency characteristics and VHFO/theta coupling, during three states: baseline, preictal, and postictal for both HYP- and LVF-seizure groups. Significant changes in most of the VHFO features were observed during the preictal state in both seizure groups. In the postictal state, VHFO features in the HYP-seizure group exhibited inverse alterations and appeared to align with those observed during baseline conditions. However, such phenomena were not observed after TLE seizures in the LVF-seizure group. Our findings highlight distinct patterns of VHFO feature changes across different states of HYP seizures and LVF seizures. These results suggest that VHFOs could serve as indicative biomarkers for seizure alterations specifically associated with HYP-seizure states • The temporal-frequency features of VHFOs are altered in distinctive fashions during different seizure types. • VHFO/theta couplings were associated with the altered states of the HYP seizure type. • VHFOs features have the potential as a biomarker of HYP-seizure type [ABSTRACT FROM AUTHOR]

Previous research has shown that dorsal hippocampus plays an important role in spatial memory process. Music exposure can enhance brain-derived neurotrophic factor (BDNF) expression level in dorsal hippocampus (DH) and thus enhance spatial cognition ability. But whether music experience may affect different subregions of DH in the same degree remains unclear. Here, we studied the effects of exposure to Mozart K.448 on learning behavior in developing rats using the classical Morris water maze task. The results showed that early music exposure could enhance significantly learning performance of the rats in the water maze test. Meanwhile, the BDNF/TrkB level of dorsal hippocampus CA3 (dCA3) and dentate gyrus (dDG) was significantly enhanced in rats exposed to Mozart music as compared to those without music exposure. In contrast, the BDNF/TrkB level of dorsal hippocampus CA1 (dCA1) was not affected. The results suggest that the spatial memory improvement by music exposure in rats may be associated with the enhanced BDNF/TrkB level of dCA3 and dDG. [ABSTRACT FROM AUTHOR]

Abstract: Background: Glucosamine sulfate is used for the treatment of arthrosis, especially osteoarthritis of the knee joint. The available evidence suggests differences in its pharmacokinetics in Chinese subjects compared with non-Chinese subjects. Objective: The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of glucosamine sulfate 500 mg after single oral administration in healthy Chinese volunteers. Methods: This open-label, randomized-sequence, single-dose, 2-way crossover study was performed at the First Hospital of Nanjing Medical University, Nanjing, China. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 500-mg dose of the test or reference capsule formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Glucosamine sulfate was assayed using a liquid-chromatography tandem mass spectrometry method. For analysis of pharmacokinetic properties, including Cmax, AUC0−t, and AUC0−∞), blood samples were obtained at intervals over a 14-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of Cmax and AUC were within the predetermined equivalence range (70%–143% for Cmax and 80%–125% for AUC) as established by the State Food and Drug Administration (SFDA) of China. Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). Results: Twenty–two healthy male Chinese subjects were enrolled (mean [range] age, 24 [22–26] years; weight, 63.9 [58.5–69.3] kg; height, 172 [167–177] cm); all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of Cmax, AUC0−t, and AUC0−∞) were 93.4 to 127.3, 92.4 to 114.5, and 92.7 to 114.6, respectively (all, P = NS). The AUC0−∞ of the test and reference formulations was 1.83 (0.66) and 1.77 ( 0.72) μg/h/mL, respectively. No AEs were observed or reported during the study. Conclusions: In this small study in healthy male Chinese volunteers, a single 500-mg dose of the test formulation met the SFDA''s regulatory definition for bioequivalence to the reference formulation. Both formulations were well tolerated. [Copyright &y& Elsevier]