Self-Regulation of Brain Activity in Patients with Postherpetic Neuralgia: A Double-Blind Randomized Study Using Real-Time fMRI Neurofeedback

Background

A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback could be an alternative approach for chronic pain treatment. Considering the relative small sample of patients recruited and not strictly controlled condition, it is desirable to perform a replication as well as a double-blinded randomized study with a different control condition in chronic pain patients. Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients – patients with postherpetic neuralgia (PHN) and used a different sham neurofeedback control. We explored the feasibility of self-regulation of the rostral anterior cingulate cortex (rACC) activation in patients with PHN through rtfMRI neurofeedback and regulation of pain perception.

Methods

Sixteen patients (46–71 years) with PHN were randomly allocated to a experimental group (n = 8) or a control group (n = 8). 2 patients in the control group were excluded for large head motion. The experimental group was given true feedback information from their rACC whereas the control group was given sham feedback information from their posterior cingulate cortex (PCC). All subjects were instructed to perform an imagery task to increase and decrease activation within the target region using rtfMRI neurofeedback.

Results

Online analysis showed 6/8 patients in the experimental group were able to increase and decrease the blood oxygen level dependent (BOLD) fMRI signal magnitude during intermittent feedback training. However, this modulation effect was not observed in the control group. Offline analysis showed that the percentage of BOLD signal change of the target region between the last and first training in the experimental group was significantly different from the control group’s and was also significantly different than 0. The changes of pain perception reflected by numerical rating scale (NRS) in the experimental group were significantly different from the control group. However, there existed no significant correlations between BOLD signal change and NRS change.

Conclusion

Patients with PHN could learn to voluntarily control over activation in rACC through rtfMRI neurofeedback and alter their pain perception level. The present study may provide new evidence that rtfMRI neurofeedback training may be a supplemental approach for chronic clinical pain management.     

Lily Cultivars Have Allelopathic Potential in Controlling Orobanche aegyptiaca Persoon

As a devastating holoparasitic weed, Orobanche aegyptiaca Persoon. (Egyptian broomrape) causes serious damage to agricultural production and threatens economic development, which has raised widespread concern. The present study was conducted to determine whether lilies have the potential to be used as ‘trap crops’ for controlling O. aegyptiaca Persoon. In the experiments, the ability of three popular lily cultivars (Lilium Oriental hybrids ‘Sorbonne’, Lilium LA (Longiflorum hybrids x Asiatic hybrids) hybrids ‘Ceb Dazzle’, and Lilium Longiflorum hybrids (L. formosanum x L. longiflorum) ‘L. formolongo’) to induce O. aegyptiaca Persoon. seed germination was assessed. Parts of the three lily cultivars, including the rhizosphere soil and underground and above-ground organs, all induced “suicidal germination” of parasitic O. aegyptiaca Persoon. seed at four growth stages. Specifically, Sorbonne and Ceb Dazzle behaved with similar allelopathy, and the bulb, scale leaf and aerial stem exhibited stronger allelopathic effects on O. aegyptiaca Pers. germination compared to other organs. Aqueous L. formolongo leaf extracts may contain more stable, effective stimulants given that they induced the highest germination rate at 76.7% even though the extracts were serially diluted. We speculate that these organs may be advantageous in further isolating and purifying economical active substances that can be substitutes for GR24. These results indicate that lilies have the potential to be used as a trap crops or can be processed into green herbicide formulations that can be applied in agriculture production to rapidly deplete the seed bank of O. aegyptiaca Persoon. parasitic weeds in soil.     

Thrombotic Role of Blood and Endothelial Cells in Uremia through Phosphatidylserine Exposure and Microparticle Release

The mechanisms contributing to an increased risk of thrombosis in uremia are complex and require clarification. There is scant morphological evidence of membrane-dependent binding of factor Xa (FXa) and factor Va (FVa) on endothelial cells (EC) in vitro. Our objectives were to confirm that exposed phosphatidylserine (PS) on microparticle (MP), EC, and peripheral blood cell (PBC) has a prothrombotic role in uremic patients and to provide visible and morphological evidence of PS-dependent prothrombinase assembly in vitro. We found that uremic patients had more circulating MP (derived from PBC and EC) than controls. Additionally, patients had more exposed PS on their MPs and PBCs, especially in the hemodialysis group. In vitro, EC exposed more PS in uremic toxins or serum. Moreover, reconstitution experiments showed that at the early stages, PS exposure was partially reversible. Using confocal microscopy, we observed that PS-rich membranes of EC and MP provided binding sites for FVa and FXa. Further, exposure of PS in uremia resulted in increased generation of FXa, thrombin, and fibrin and significantly shortened coagulation time. Lactadherin, a protein that blocks PS, reduced 80% of procoagulant activity on PBC, EC, and MP. Our results suggest that PBC and EC in uremic milieu are easily injured or activated, which exposes PS and causes a release of MP, providing abundant procoagulant membrane surfaces and thus facilitating thrombus formation. Blocking PS binding sites could become a new therapeutic target for preventing thrombosis.     

Mapping and Congenic Dissection of Genetic Loci Contributing to Hyperglycemia and Dyslipidemia in Mice

Background

Patients with dyslipidemia have an increased risk of developing type 2 diabetes, and diabetic patients often have dyslipidemia. Potential genetic connections of fasting plasma glucose with plasma lipid profile were evaluated using hyperlipidemic mice.

Methods

225 male F₂ mice were generated from BALB/cJ (BALB) and SM/J(SM) Apoe-deficient (Apoe^−/−) mice and fed a Western diet for 5 weeks. Fasting plasma glucose and lipid levels of F₂ mice were measured before and after 5 weeks of Western diet and quantitative trait locus (QTL) analysis was performed using data collected from these two time points. 144 SNP(single nucleotide polymorphism) markers across the entire genome were typed.

Results

One major QTL (logarithm of odds ratio (LOD): 6.46) peaked at 12.7 cM on chromosome 9,Bglu16, and 3 suggestive QTLs on chromosomes 15, 18 and X were identified for fasting glucose, and over 10 loci identified for lipid traits. Bglu16 was adjacent to a major QTL, Hdlq17, for high-density lipoprotein (HDL) cholesterol (LOD: 6.31, peak: 19.1 cM). A congenic strain with a donor chromosomal region harboring Bglu16 and Hdlq17 on the Apoe^−/− background showed elevations in plasma glucose and HDL levels. Fasting glucose levels were significantly correlated with non-HDL cholesterol and triglyceride levels, especially on the Western diet, but only marginally correlated with HDL levels in F₂ mice.

Conclusions

We have demonstrated a correlative relationship between fasting glucose and plasma lipids in a segregating F₂ population under hyperlipidemic conditions, and this correlation is partially due to genetic linkage between the two disorders.     

Impaired Autophagy in Adult Bone Marrow CD34+ Cells of Patients with Aplastic Anemia: Possible Pathogenic Significance

Aplastic anemia (AA) is a bone marrow failure syndrome that is caused largely by profound quantitative and qualitative defects of hematopoietic stem and progenitor cells. However, the mechanisms underlying these defects remain unclear. Under conditions of stress, autophagy acts as a protective mechanism for cells. We therefore postulated that autophagy in CD34⁺ hematopoietic progenitor cells (HPCs) from AA patients might be impaired and play a role in the pathogenesis of AA. To test this hypothesis, we tested autophagy in CD34⁺ cells from AA samples and healthy controls and investigated the effect of autophagy on the survival of adult human bone marrow CD34⁺ cells. We found that the level of autophagy in CD34⁺ cells from AA patients was significantly lower than in age/sex-matched healthy controls, and lower in cases of severe AA than in those with non-severe AA. Autophagy in CD34⁺ cells improved upon amelioration of AA but, compared to healthy controls, was still significantly reduced even in AA patients who had achieved a complete, long-term response. We also showed that although the basal autophagy in CD34⁺ cells was low, the autophagic response of CD34⁺ cells to “adversity” was rapid. Finally, impaired autophagy resulted in reduced differentiation and proliferation of CD34⁺ cells and sensitized them to death and apoptosis. Thus, our results confirm that autophagy in CD34⁺ cells from AA patients is impaired, that autophagy is required for the survival of CD34⁺ cells, and that impaired autophagy in CD34⁺ HPCs may play an important role in the pathogenesis of AA.     

Profile and Determinants of Retinal Optical Intensity in Normal Eyes with Spectral Domain Optical Coherence Tomography

Purpose

To investigate the profile and determinants of retinal optical intensity in normal subjects using 3D spectral domain optical coherence tomography (SD OCT).

Methods

A total of 231 eyes from 231 healthy subjects ranging in age from 18 to 80 years were included and underwent a 3D OCT scan. Forty-four eyes were randomly chosen to be scanned by two operators for reproducibility analysis. Distribution of optical intensity of each layer and regions specified by the Early Treatment of Diabetic Retinopathy Study (ETDRS) were investigated by analyzing the OCT raw data with our automatic graph-based algorithm. Univariate and multivariate analyses were performed between retinal optical intensity and sex, age, height, weight, spherical equivalent (SE), axial length, image quality, disc area and rim/disc area ratio (R/D area ratio).

Results

For optical intensity measurements, the intraclass correlation coefficient of each layer ranged from 0.815 to 0.941, indicating good reproducibility. Optical intensity was lowest in the central area of retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and photoreceptor layer, except for the retinal pigment epithelium (RPE). Optical intensity was positively correlated with image quality in all retinal layers (0.553<β<0.851, p<0.01), and negatively correlated with age in most retinal layers (-0.362<β<-0.179, p<0.01), except for the RPE (β = 0.456, p<0.01), outer nuclear layer and photoreceptor layer (p>0.05). There was no relationship between retinal optical intensity and sex, height, weight, SE, axial length, disc area and R/D area ratio.

Conclusions

There was a specific pattern of distribution of retinal optical intensity in different regions. The optical intensity was affected by image quality and age. Image quality can be used as a reference for normalization. The effect of age needs to be taken into consideration when using OCT for diagnosis.     

Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies

Background

The PDE4B single nucleotide polymorphisms (SNPs) have been reported to be associated with schizophrenia risk. However, current findings are ambiguous or even conflicting. To better facilitate the understanding the genetic role played by PDE4B in susceptibility to schizophrenia, we collected currently available data and conducted this meta-analysis.

Methods

A comprehensive electronic literature searching of PubMed, Embase, Web of Science and Cochrane Library was performed. The association between PDE4B SNPs and schizophrenia was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under allelic, dominant and recessive genetic models. The random effects model was utilized when high between-study heterogeneity (I² > 50%) existed, otherwise the fixed effects model was used.

Results

Five studies comprising 2376 schizophrenia patients and 3093 controls were finally included for meta-analysis. The rs1040716 was statistically significantly associated with schizophrenia risk in Asian and Caucasian populations under dominant model (OR = 0.87, 95% CI: 0.76–0.99, P = 0.04). The rs2180335 was significantly related with schizophrenia risk in Asian populations under allelic (OR = 0.82, 95% CI: 0.72–0.93, P = 0.003) and dominant (OR = 0.75, 95% CI: 0.64–0.88, P < 0.001) models. A significant association was also observed between rs4320761 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.75–1.00, P = 0.048). In addition, a strong association tendency was found between rs6588190 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.76–1.00, P = 0.055).

Conclusion

This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia. However, due to limited sample size, more large-scale, multi-racial association studies are needed to further clarify the genetic association between various PDE4B variants and schizophrenia.