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Background: Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs.Methods: We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI.Results: We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs.Conclusion: Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs.Trial Registration: No. NCT02425696 ; registered on April 21, 2015. [ABSTRACT FROM AUTHOR]

Background: Red blood cells are the most abundant cells in the blood that deliver oxygen to the whole body. Erythropoietin (EPO), a positive regulator of erythropoiesis, is currently the major treatment for chronic anemia. Granulocyte colony-stimulating factor (G-CSF) is a multifunctional cytokine and a well-known regulator of hematopoietic stem cell proliferation, differentiation, and mobilization. The use of EPO in combination with G-CSF has been reported to synergistically improve erythroid responses in a group of patients with myelodysplastic syndromes who did not respond to EPO treatment alone; however, the mechanism remains unclear. Methods: C57BL/6 J mice injected with G-CSF or EPO were used to compare the erythropoiesis status and the efficiency of erythroid mobilization by flow cytometry. Results: In this study, we found that G-CSF induced more orthochromatophilic erythroblast production than did EPO in the bone marrow and spleen. In addition, in contrast to EPO treatments, G-CSF treatments enhanced the efficiency of the mobilization of newly synthesized reticulocytes into peripheral blood. Our results demonstrated that the effects of G-CSF on erythropoiesis and erythrocytic mobilization were independent of EPO secretion and, in contrast to EPO, G-CSF promoted progression of erythropoiesis through transition of early stage R2 (basophilic erythroblasts) to late stage R4 (orthochromatophilic erythroblasts). Conclusions: We demonstrate for the first time that G-CSF treatments induce a faster erythropoiesis-enhancing response than that of EPO. These findings suggest an alternative approach to treating acute anemia, especially when patients are experiencing a clinical emergency in remote areas without proper blood bank supplies. [ABSTRACT FROM AUTHOR]

Background: Long-term potentiation (LTP) is well recognized as a cellular-correlated synaptic plasticity of learning and memory. However, its reversal forms of synaptic plasticity, depotentiation, is less studied and its association with behaviors is also far from clear. Previously, we have shown that nanomolar orexin A can prevent the depotentiation induced by low frequency stimulation (LFS) following theta burst stimulation-induced LTP, namely inducing re-potentiation, at hippocampal CA1 synapses in vitro. Here, we explored the functional correlate of this orexin-mediated hippocampal re-potentiation. Methods and results: We found that intraperitoneal ( i.p.) injection process-paired contextual exposures during the conditioned place preference (CPP) task in mice resulted in re-potentiation at CA1 synapses of hippocampal slices, regardless of whether the CPP behavior is expressed or not. Simply exposing the mouse in the CPP apparatus, or giving the mouse consecutive i.p. injections of saline in its home cage or a novel cage did not lead to hippocampal re-potentiation. Besides, this CPP training process-induced hippocampal re-potentiation was prevented when mice were pretreated with TCS1102, a dual orexin receptor antagonist. These results suggest that the expression of hippocampal re-potentiation is orexin-dependent and requires the association of differential spatial contexts and i.p. injections in the CPP apparatus. Conclusions: Together, we reveal an unprecedentedly orexin-mediated modulation on hippocampal depotentiation by the training process in the CPP paradigm. [ABSTRACT FROM AUTHOR]

Background: Association studies have been employed to investigate the relationships between host single nucleotide polymorphisms (SNPs) and susceptibility to pulmonary Tuberculosis (PTB). However, such candidate genetic markers have not been widely studied in Chinese population, especially with respect to the disease development from latent M. tuberculosis infection (LTBI).Methods: In this case-control study, 44 candidate SNPs were examined in a total of 600 participants (PTB patients, LTBI controls and healthy controls without M. tuberculosis infection) from Zhengzhou, China. The two groups of controls were frequency matched on gender and age with PTB patients. Genotyping was carried out by the Illumina Golden Gate assay.Results: When comparing PTB patients with LTBI controls but not healthy controls without M. tuberculosis infection, significant associations with disease development were observed for TLR9 1174 A/G, TLR9 1635 A/G and IFNG 2109G/A. The two loci in TLR9 were in LD in our study population (r(2)=0.96, D'=1.00). A combined effect of the genotypes associated with increased risk of PTB (i.e. TLR9 1174G/G and IFNG 2109 A/A) was found when comparing PTB patients with LTBI controls (p=0.004) but not with healthy controls without infection (p=0.433).Conclusions: Potential associations between TLR9 and IFN-γ genetic polymorphisms and PTB were observed in a Chinese population which supports further study of the roles played by TLR9/IFN-γ pathway during the development of PTB. [ABSTRACT FROM AUTHOR]