MRI Study on the Functional and Spatial Consistency of Resting State-Related Independent Components of the Brain Network

Objective

Resting-state networks (RSNs), including the default mode network (DMN), have been considered as markers of brain status such as consciousness, developmental change, and treatment effects. The consistency of functional connectivity among RSNs has not been fully explored, especially among resting-state-related independent components (RSICs).

Materials and Methods

This resting-state fMRI study addressed the consistency of functional connectivity among RSICs as well as their spatial consistency between ''at day 1'' and ''after 4 weeks'' in 13 healthy volunteers.

Results

We found that most RSICs, especially the DMN, are reproducible across time, whereas some RSICs were variable in either their spatial characteristics or their functional connectivity. Relatively low spatial consistency was found in the basal ganglia, a parietal region of left frontoparietal network, and the supplementary motor area. The functional connectivity between two independent components, the bilateral angular/supramarginal gyri/intraparietal lobule and bilateral middle temporal/occipital gyri, was decreased across time regardless of the correlation analysis method employed, (Pearson''s or partial correlation).

Conclusion

RSICs showing variable consistency are different between spatial characteristics and functional connectivity. To understand the brain as a dynamic network, we recommend further investigation of both changes in the activation of specific regions and the modulation of functional connectivity in the brain network.     

Role of nucleus accumbens in neuropathic pain: Linked multi-scale evidence in the rat transitioning to neuropathic pain

Despite recent evidence implicating the nucleus accumbens (NAc) as causally involved in the transition to chronic pain in humans, underlying mechanisms of this involvement remain entirely unknown. Here we elucidate mechanisms of NAc reorganizational properties (longitudinally and cross-sectionally), in an animal model of neuropathic pain (spared nerve injury [SNI]). We observed interrelated changes: (1) In resting-state functional magnetic resonance imaging (fMRI), functional connectivity of the NAc to dorsal striatum and cortex was reduced 28 days (but not 5 days) after SNI; (2) Contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28 days after SNI; (3) In SNI (but not sham), covariance of gene expression was upregulated at 5 days and settled to a new state at 28 days; and (4) NAc functional connectivity correlated with dopamine receptor gene expression and with tactile allodynia. Moreover, interruption of NAc activity (via lidocaine infusion) reversibly alleviated neuropathic pain in SNI animals. Together, these results demonstrate macroscopic (fMRI) and molecular reorganization of NAc and indicate that NAc neuronal activity is necessary for full expression of neuropathic pain-like behavior.     

脑卒中后认知障碍患者静息态脑网络特征的功能性近红外光谱研究

目的 探讨脑卒中后认知障碍(PSCI)患者静息态脑网络的连接特征。方法 2020年1月至2021年1月,PSCI患者24例根据简易精神状态检查和蒙特利尔认知评估量表评分分为轻度组(n=12)和中度组(n=12),纳入健康人10例(对照组)。三组被试采用全脑64通道功能性近红外光谱静息态采集6 min。采用NirSpark 1.6.12和SPSS 26.0软件进行处理。结果 中度组基于脱氧血红蛋白的半球间功能连接低于对照组(t=-2.763, P=0.024),主要位于感觉运动皮质间(F=12.674, P=0.031)。结论 PSCI患者主要表现为左右半球间功能连接水平降低,特别是左右感觉运动皮质间连接水平降低。     

Recovery from severe persistent COVID-19 without evidence of an anti-SARS-CoV-2 antibody response in a man with mantle cell lymphoma treated with rituximab

Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome.     

TCTAP 2011: connecting East and West for interventional societies

The Angioplasty Summit TCTAP is an international conference held annually at the end of April in Seoul, Korea that focuses on interventional cardiology. Over the past two decades, this meeting has played an integral part in the Asia–Pacific region on educating physicians and other healthcare professionals who are interested in this field. It has become a very useful opportunity for them to catch up with cutting-edge techniques, overviews and clinical investigations from all over the world.     

Folding of a large protein at high structural resolution

Kinetic folding of the large two-domain maltose binding protein (MBP; 370 residues) was studied at high structural resolution by an advanced hydrogen-exchange pulse-labeling mass-spectrometry method (HX MS). Dilution into folding conditions initiates a fast molecular collapse into a polyglobular conformation (<20 ms), determined by various methods including small angle X-ray scattering. The compaction produces a structurally heterogeneous state with widespread low-level HX protection and spectroscopic signals that match the equilibrium melting posttransition-state baseline. In a much slower step (7-s time constant), all of the MBP molecules, although initially heterogeneously structured, form the same distinct helix plus sheet folding intermediate with the same time constant. The intermediate is composed of segments that are distant in the MBP sequence but adjacent in the native protein where they close the longest residue-to-residue contact. Segments that are most HX protected in the early molecular collapse do not contribute to the initial intermediate, whereas the segments that do participate are among the less protected. The 7-s intermediate persists through the rest of the folding process. It contains the sites of three previously reported destabilizing mutations that greatly slow folding. These results indicate that the intermediate is an obligatory step on the MBP folding pathway. MBP then folds to the native state on a longer time scale (∼100 s), suggestively in more than one step, the first of which forms structure adjacent to the 7-s intermediate. These results add a large protein to the list of proteins known to fold through distinct native-like intermediates in distinct pathways.Fifty years after Anfinsen’s seminal demonstration that an unfolded protein can refold spontaneously when placed under native conditions, major questions concerning the folding process remain unanswered (1, 2). What is the unfolded state like, its degree of compaction, the reality and character of residual structure before folding begins, and its possible role in guiding the folding process (3–7)? Analogous questions relate to folding intermediates and the folding pathway itself. Do proteins fold through many alternative independent pathways as earlier theoretical investigations have suggested (8–12), or do they fold through necessary intermediates in a distinct pathway (13), as a growing list of experimental observations indicate (14, 15)? To answer these questions, it will be necessary to define experimentally the intermediate forms that proteins move through on their way to the native state. The problem has been that these transient states are beyond the reach of the usual high-resolution crystallographic and NMR structural methods. Most experimental folding studies have therefore relied on low-resolution optical methods that can follow folding in real time but rarely provide the structural information necessary to resolve the basic mechanistic questions.Recent work has demonstrated an advanced hydrogen-exchange pulse-labeling mass-spectrometry technology (HX MS) that is able to detect and characterize local structure, even when it is only transiently present during the course of kinetic folding (15, 16). The HX pulse-labeling approach provides a snapshot of main chain amide sites that are protected against HX labeling by H bonds present at the time of the labeling pulse (17, 18). HX MS measurements can determine the position, stability, and dynamic behavior of native and nonnative H-bonded structure and whether it persists or dissipates in subsequent folding. In a recent application, the method was able to describe the structure and time-dependent formation of three sequential native-like folding intermediates in the 155-residue ribonuclease H protein (15).Protein folding studies, whether theoretical or experimental, have been limited to relatively small proteins, with few exceptions. However, biological proteomes and the considerations they raise are dominated by large proteins (19). Here we extend the powerful HX MS technology to the two-domain, 370-residue, maltose binding protein (MBP). MBP is synthesized in the Escherichia coli cytoplasm and transported to the periplasm where it serves as a soluble receptor for the high-affinity capture and import of maltose and maltodextrins (20). The protein folds in vivo after deletion of a signal sequence (21); we study here the mature protein with the signal sequence deleted.When unfolded MBP is placed into native conditions, we find that it rapidly adopts a dynamic collapsed state, which can lead to aggregation in vitro when the concentration is >1 μM and to inclusion body formation in vivo (22). Folding to the native state occurs much more slowly even in the absence of aggregation, with all molecules moving through one or more intermediate states to the native state. The HX MS experiment provides incisive information on the nature of the initially collapsed state, the slow formation and identity of at least one on-pathway native-like intermediate, and the even slower emergence of native structure.     

Mediterranean diet habits in older individuals: Associations with cognitive functioning and brain volumes

To examine the association between dietary habits, cognitive functioning and brain volumes in older individuals, data from 194 cognitively healthy individuals who participated in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were used. At age 70, participants kept diaries of their food intake for 1 week. These records were used to calculate a Mediterranean diet (MeDi) score (comprising dietary habits traditionally found in Mediterranean countries, e.g. high intake of fruits and low intake of meat), with higher scores indicating more pronounced MeDi-like dietary habits. Five years later, participants' cognitive capabilities were examined by the seven minute screening (7MS) (a cognitive test battery used by clinicians to screen for dementia), and their brain volumes were measured by volumetric magnetic resonance imaging. Multivariate linear regression analyses were constructed to examine the association between the total MeDi score and cognitive functioning and brain volumes. In addition, possible associations between MeDi's eight dietary features and cognitive functioning and brain volumes were investigated. From the eight dietary features included in the MeDi score, pertaining to a low consumption of meat and meat products was linked to a better performance on the 7MS test (P = 0.001) and greater total brain volume (i.e. the sum of white and gray matter, P = 0.03) when controlling for potential confounders (e.g. BMI) in the analysis. Integrating all dietary features into the total MeDi score explained less variance in cognitive functioning and brain volumes than its single dietary component meat intake. These observational findings suggest that keeping to a low meat intake could prove to be an impact-driven public health policy to support healthy cognitive aging, when confirmed by longitudinal studies. Further, they suggest that the MeDi score is a construct that may mask possible associations of single MeDi features with brain health domains in elderly populations.     

持续性姿势-感知性头晕患者脑功能网络度中心度研究

目的:应用基于体素的度中心度(DC)方法,探讨持续性姿势-感知性头晕(PPPD)患者脑功能网络的改变。方法:纳入PPPD患者12例及健康受试者12例,均进行静息态功能核磁成像(f MRI),采用基于体素的DC方法分析f MRI数据,比较PPPD患者与健康受试者的差异。进一步进行相关分析,探讨DC改变与PPPD患者临床特征的相关性。结果:与健康受试者相比,PPPD患者右侧楔叶、楔前叶(X=12,Y=-84,Z=21,k=126,P=0.011, FWE校正)DC值显著降低。DC值与DHI(r=-0.677,P=0.016)、DHI-F(r=-0.581,P=0.048)、DHI-E(r=-0.690,P=0.013)均呈负相关。结论:PPPD患者楔叶、楔前叶网络节点属性减弱,可能与患者的持续性头晕不稳及复杂视觉刺激导致症状加重有关。     

抑郁症静息态大脑双侧杏仁核的功能连接

目的：探讨静息态下抑郁症患者大脑半球双侧杏仁核的功能连接特点,了解杏仁核及其功能相关脑区在抑郁症病理机制中的作用。方法：11例首次发作的重性抑郁症患者与11例性别、年龄、受教育程度均与患者相匹配的正常人完成静息态功能性磁共振成像（fMRI）扫描。利用Pearson相关分析方法分析受试者大脑双侧的杏仁核功能连接强度,并利用双样本t检验做组间对比,设P〈0．05为差异具有显著性。结果：静息态下,两组双侧杏仁核均具有明显的功能连接（P〈0．05）,而抑郁症组较对照组的功能连接明显减低（P=0．025）。结论：静息态下抑郁症组双侧杏仁核功能连接存在异常,这可能与抑郁症患者杏仁核异常及杏仁核与其他情感调节相关脑区的协调异常有关。     

孕中期孕妇凝血功能检测的临床意义

目的探讨孕中期孕妇凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、抗血酶Ⅲ(ATⅢ)、蛋白C(PC)、蛋白S(S)、纤维蛋白降解产物(FDP)和D二聚体(DD)检测的临床意义。方法PT、APTT、TT、Fib测定均为凝固法,所有指标均由SYSMEXCA-1500全自动血凝仪进行测定。结果对55例孕中期孕妇(实验组)与55例正常非妊娠妇女(对照组)的凝血功能进行比较分析。孕中期孕妇组PT、APTT、TT、Fib、ATⅢ、PC、PS、FDP和DD值与对照组比较差异有显著性(P<0.01)。结论在妊娠中期孕产妇凝血功能发生了显著变化,表现为妊娠相关的高凝血状态和存在血栓并发症风险,孕产妇需要监测凝血功能。