Recent insights into the characteristics and role of peritoneal macrophages from ascites of cirrhotic patients

Macrophages are a diverse myeloid cell population involved in innate and adaptive immune responses, embryonic development, wound repair, and regulation of tissue homeostasis. These cells link the innate and adaptive immunities and are crucial in the development and sustainment of various inflammatory diseases. Macrophages are tissue-resident cells in steady-state conditions; however, they are also recruited from blood monocytes after local pathogen invasion or tissue injury. Peritoneal macrophages vary based on their cell complexity, phenotype, and functional capabilities. These cells regulate inflammation and control bacterial infections in the ascites of decompensated cirrhotic patients. Our recent work reported several phenotypic and functional characteristics of these cells under both healthy and pathological conditions. A direct association between cell size, CD14/CD16 expression, intracellular level of GATA-6, and expression of CD206 and HLA-DR activation/maturation markers, indicate that the large peritoneal macrophage CD14^highCD16^high subset constitutes the mature phenotype of human resident peritoneal macrophages during homeostasis. Moreover, elevated expression of CD14/CD16 is related to the phagocytic capacity. The novel large CD14^highCD16^high peritoneal subpopulation is increased in the ascites of cirrhotic patients and is highly sensitive to lipopolysaccharide (LPS)-induced activation, thereby exhibiting features of inflammatory priming. Thus, phosphorylation of ERK1/2, PKB/Akt, and c-Jun is remarkably increased in response to LPS in vitro, whereas that of p38 MAPK is reduced compared with the monocyte-derived macrophages from the blood of healthy controls. Furthermore, in vitro activated monocyte-derived macrophages from ascites of cirrhotic patients secreted significantly higher levels of IL-6, IL-10, and TNF-α and lower amounts of IL-1β and IL-12 than the corresponding cells from healthy donor’s blood. Based on these results, other authors have recently reported that the surface expression level of CD206 can be used to identify mature, resident, inflammatory peritoneal macrophages in patients with cirrhosis. Soluble CD206 is released from activated large peritoneal macrophages, and increased concentrations in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) indicate reduced odds of survival for 90 d. Hence, the level of soluble CD206 in ascites might be used to identify patients with SBP at risk of death. In conclusion, peritoneal macrophages present in ascites of cirrhotic patients display multiple phenotypic modifications characterized by reduced ratio of cells expressing several membrane markers, together with an increase in the ratios of complex and intermediate subpopulations and a decrease in the classic-like subset. These modifications may lead to the identification of novel pharmaceutical targets for prevention and treatment of hepatic damage.     

Evaluating optimized temporal patterns of spinal cord stimulation (SCS)

BackgroundTemporal patterns of stimulation represent a novel dimension for improving the efficacy of spinal cord stimulation to treat chronic neuropathic pain.ObjectiveWe hypothesized that nonregular temporal patterns of stimulation designed using a computational model would be superior to conventional stimulation at constant frequencies or completely random patterns of stimulation.MethodsUsing a computational model of the dorsal horn network and an optimization algorithm based on biological evolution, we designed an optimized pattern of spinal cord stimulation with comparable efficacy and increased efficiency relative to constant frequency (CF) stimulation. We evaluated the effect of different temporal patterns on individual neurons recorded in the dorsal horn of urethane-anesthetized rats.ResultsThe optimized pattern and 50 Hz CF stimulation produced greater inhibition of spontaneously firing neurons recorded in vivo than random 50 Hz stimulation or a pattern designed intentionally with poor fitness. Spinal Cord Stimulation (SCS) led to significant changes in the firing patterns of recorded units, and stimulation patterns that generated significant inhibition also tended to reduce entropy and regularize the firing patterns of units, suggesting that patterns of dorsal horn neuron activity may be important for pain perception in addition to the firing rate.ConclusionsThese results demonstrate that the computational model can be used as a tool for optimizing stimulation parameters and suggest that optimized temporal patterns may increase the efficacy of spinal cord stimulation.     

Investigation of age-related differences in an adapted Hayling task

The Hayling task is traditionally used to assess activation and inhibitory processes efficiency among various populations, such as elderly adults. However, the classical design of the task may also involve the influence of strategy use and efficiency of sentence processing in the possible differences between individuals. Therefore, the present study investigated activation and inhibitory processes in aging with two formats of an adapted Hayling task designed to reduce the involvement of these alternative factors. Thirty young adults (M = 20.7 years) and 31 older adults (M = 69.6 years) performed an adapted Hayling task including a switching block (i.e., unblocked design) in addition to the classical task (i.e., blocked design), and the selection of the response between two propositions. The results obtained with the classical blocked design showed age-related deficits in the suppression sections of the task but also in the initiation ones. These findings can be explained by a co-impairment of both inhibition and activation processes in aging. The results of the unblocked Hayling task, in which strategy use would be reduced, confirmed this age-related decline in both activation and inhibition processes. Moreover, significant correlations between the unblocked design and the Trail Making Test revealed that flexibility is equally involved in the completion of both sections of this design. Finally, the use of a forced-response choice offers a format that is easy to administer to people with normal or pathological aging. This seems particularly relevant for these populations in whom the production of an unrelated word often poses problems.     

Distinct profiles of behavioral inhibition and activation system sensitivity in unipolar vs. bipolar mood disorders

Psychiatric outpatients with mood disorders (n=275) and community controls (n=733) completed a measure of Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS) sensitivity; psychiatric outpatients also completed measures of mood symptom severity. All patients scored higher on BIS compared to controls; patients with bipolar disorders scored higher on BAS scales compared to patients with depressive disorders. BIS and BAS demonstrated unique patterns of association with mood symptoms. Results support the clinical utility of the BIS/BAS.     

The contribution of active and passive mechanisms of 5mC and 5hmC removal in human T lymphocytes is differentiation‐ and activation‐dependent

In mammals, the 5’‐methylcytosine (5mC) modification in the genomic DNA contributes to the dynamic control of gene expression. 5mC erasure is required for the activation of developmental programs and occurs either by passive dilution through DNA replication, or by enzymatic oxidation of the methyl mark to 5‐hydroxymethylcytosine (5hmC), which can persist as such or undergo further oxidation and enzymatic removal. The relative contribution of each mechanism to epigenetic control in dynamic biological systems still remains a compelling question. To explore this critical issue, we used primary human T lymphocytes, in which two cellular states can be clearly identified, namely quiescent naïve T cells, which are slowly or rarely proliferating, and rapidly proliferating activated T cells. We found that active mechanisms of methylation removal were selectively at work in naïve T cells, while memory T lymphocytes entirely relied on passive, replication‐dependent dilution, suggesting that proliferative capacity influences the choice of the preferential demethylation mechanism. Active processes of demethylation appear to be critical in quiescent naïve T lymphocytes for the maintenance of regulatory regions poised for rapid responses to physiological stimuli.     

Fidelity or flexibility: An ethnographic study of the implementation and use of the Patient Activation Measure

Objective

To evaluate the use of the PAM in the English National Health service. The PAM is a validated scale that measures ‘activation’ (people’s knowledge, skills, and confidence in managing their health) and assigns patients to four categories of activation (low-to-high). Some evidence suggests that higher activation levels correlate to better clinical outcomes and patient experiences, and lower healthcare costs. Empirical studies of implementing the PAM are scarce.

结核性腹膜炎和肝癌患者的腹水与血清趋化因子测定及其意义

目的研究结核性腹膜炎，肝癌所引起的腹水和腹水中趋化因子-调节活化正常T细胞表达和分泌因子（RANTEs）和基质细胞衍生因子（SDF-1），以及它们的受体CCR3和CXCR4的表达水平及临床意义。方法用酶联免疫吸附法（ELISA）和流式细胞仪（FCM）测定16例结核性腹膜炎，39例肝癌患者以及正常对照20例血清和／或腹水中RANTES、SDF-1和受体CCR3、CXCR4的水平。结果结核性腹膜炎血清及腹水中SDF-1以及CXCR4升高，而肝癌患者血清及腹水中RANTES以及受体CCR3水平上升。结论趋化因子在腹部结核和肿瘤时会出现不同性质T细胞免疫应答，为以后的应用奠定实验基础。     

A Modular Activation/Coherence Approach to Evaluating Clinical/QEEG Correlations and for Guiding Neurofeedback Training: Modular Insufficiencies,Modular Excesses,Disconnections, and Hyperconnections

ABSTRACT

Current approaches to QEEG-guided neurofeedback involve efforts to normalize the abnormalities seen, without reference to the functional localization of the cortical areas involved. Recent advances in cortical neurophysiology indicate that specific brain areas are developed to perform certain functions (cortical modules). Complex brain functions require cooperation between modules, particularly during a learning situation. For example, the left prefrontal “activation module” must cooperate with one or both occipital “visual modules” to attend and see something on a chalkboard. To remember what has been seen, both temporal “memory modules” must cooperate with the visual modules for the image to be retained in short-term memory. If the connections between these modules are not functioning optimally, visual learning will be impaired. Decreased coherence (hypocoherence) indicates a decrease in functional connectivity between these modules, and increased coherence (hypercoherence) indicates an increase in functional connectivity between the modules. Neurofeedback can be used to normalize coherence between these modules, thereby improving the efficiency of their cooperation in the learning process. If coherence is less than normal, it is trained up. If coherence is more than normal, it is trained down. Three cases are presented where this approach has succeeded in remediating the client's symptoms.