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Advances in human neuroimaging has enabled us to study functional connections among various brain regions in pain states. Despite a wealth of studies at high anatomic resolution, the exact neural signals for the timing of pain remain little known. Identifying the onset of pain signals from distributed cortical circuits may reveal the temporal dynamics of pain responses and subsequently provide important feedback for closed-loop neuromodulation for pain.

Here we developed an unsupervised learning method for sequential detection of acute pain signals based on multichannel human EEG recordings. Following EEG source localization, we used a state-space model (SSM) to detect the onset of acute pain signals based on the localized regions of interest (ROIs).

We validated the SSM-based detection strategy using two human EEG datasets, including one public EEG recordings of 50 subjects. We found that the detection accuracy varied across tested subjects and detection methods. We also demonstrated the feasibility for cross-subject and cross-modality prediction of detecting the acute pain signals.

In contrast to the batch supervised learning analysis based on a support vector machine (SVM) classifier, the unsupervised learning method requires fewer number of training trials in the online experiment, and shows comparable or improved performance than the supervised method.

Our unsupervised SSM-based method combined with EEG source localization showed robust performance in detecting the onset of acute pain signals.

Our unsupervised SSM-based method combined with EEG source localization showed robust performance in detecting the onset of acute pain signals.Hepatic involvement by a T-cell neoplasm is rare and often challenging to diagnose in liver biopsies. We collected 40 cases of T-cell neoplasms diagnosed in the liver from five large academic institutions to assess the clinicopathologic features. The patients included 11 women and 29 men, with a median age of 54 (range 2-75) years and a high mortality rate (31/37, 83.8%). Fourteen (35%) patients were diagnosed with hepatosplenic T-cell lymphoma (HSTCL), 13 (32.5%) peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 (32.5%) other types of T-cell neoplasms. Patients with HSTCL were much younger and had worse survival than PTCL-NOS and other T-cell neoplasms (P less then 0.05). On imaging studies, 20 cases (50%) showed abnormalities, including 10 with mass lesions that correlated with normal or cholestatic pattern enzyme elevation. Histomorphological analysis revealed four main patterns; with the exception of mass forming lesions (pattern 4; n = 8), cases with sinusoidal predominant (pattern 1; n = 12), portal predominant with sinusoidal infiltrates (pattern 2; n = 13) or lobular aggregates (pattern 3; n = 5) demonstrated small to medium lymphocytes resembling a reactive/inflammatory process. In addition, we described two cases of T-cell large granular lymphocytic leukemia that mimicked HSTCL, and a case of aggressive post-transplant lymphoproliferative disorder that developed after chronic Epstein-barr virus (EBV) infection, suggesting the importance of EBV testing in some lymphoma cases. As the largest cohort of T-cell neoplasms in liver, our study provides critical data on disease frequency, distribution, and clinicopathologic features that are essential for accurate diagnosis.Lead (Pb) is a neurotoxic heavy metal pollutant. Despite the efforts to reduce Pb environmental exposure and to prevent Pb poisoning, exposure in human populations persists. Studies of adults with history of childhood lead exposure have consistently demonstrated cognitive impairments that have been associated with sustained glutamate signaling. Additionally, some clinical studies have also found correlations between Pb exposure and increased proclivity to drug addiction. Thus, here we sought to investigate if developmental Pb exposure can increase propensity to alcohol consumption and relapse using an alcohol self-administration paradigm. Because Pb exposure is associated with increased glutamatergic tone, we also studied the effects on the expression of synaptic and non-synaptic glutamate transporters in brain regions associated with drug addiction such as the nucleus accumbens (NAc), dorsomedial striatum (DMS), dorsolateral striatum (DLS), and medial prefrontal cortex (mPFC). buy ML141 found that while developmental Pb exposure did not increase risk for alcohol self-administration, it did play a role in relapsing to alcohol. The effects were associated with differential expression of the glutamate transporter 1 (GLT1) and the glutamate/cystine antiporter (xCT). In the NAc and DLS the expression of GLT1 was found to be significantly reduced, while no changes were found in DMS or mPFC. Contrastingly, xCT was found to be upregulated in NAc but downregulated in DLS, with no changes in DMS or mPFC. Our data suggest that lead exposure is involved in relapse to alcohol seeking, an effect that could be associated with downregulation of GLT1 and xCT in the DLS.Kunitz-type proteins that interfere with neuronal transmission have been thus far exclusively detected in venoms of elapid snakes. Here, we report for the first time that such proteins are also present in the venom of a viperid snake. From the venom of the nose-horned viper (Vipera ammodytes ammodytes; Vaa), we isolated Kunitz-type chymotrypsin inhibitors (VaaChi) and demonstrated that these molecules also significantly increase the amplitudes of an indirectly evoked simple muscle contraction of the mouse hemidiaphragm, the end-plate potential and the miniature end-plate potential. By facilitating neuromuscular transmission, these proteins resemble structurally homologous dendrotoxins from mamba (Dendroaspis spp.) venoms, which are blockers of voltage-dependent K+ channels at the presynaptic site of the neuromuscular junction. What is the mechanism behind facilitation of neuromuscular transmission by VaaChi has not been established yet, however, blocking of K+ channels does not seem to be the most probable option.Cellular senescence is important for the maintenance of tissue homeostasis during normal development. In this study, we aimed to investigate the effect of renin angiotensin system (RAS) blockade on renal cell senescence in the developing rat kidney. Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for seven days after birth. We investigated the intrarenal expressions of cell cycle regulators p21 and p16 with immunoblots and immunohistochemistry at postnatal day 8. For the determination of renal cellular senescence, immunostaining for senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) was also performed. Enalapril treatment showed significant alterations in cellular senescence in neonatal rat kidneys. #link# In the enalapril-treated group, intrarenal p16 and p21 protein expressions decreased compared to controls. The expressions of both p21 and p16 were reduced throughout the renal cortex and medulla of enalapril-treated rats. The immunoreactivity of TERT in enalapril-treated kidneys was also weaker than that in control kidneys.