Brain functional specialization and cooperation in Alzheimer's disease.

BACKGROUND: Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. OBJECTIVE: This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty-four clinically diagnosed AD patients and 52 age- and sex-matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). RESULTS: In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging-cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine-based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave-one-out cross-validation. CONCLUSION: This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD.

Sex differences in functional connectivity and the predictive role of the connectome-based predictive model in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline. Sex differences in the progression of AD exist, but the neural mechanisms are not well understood. The purpose of the current study was to explore sex differences in brain functional connectivity (FC) at different stages of AD and their predictive ability on Montreal Cognitive Assessment (MoCA) scores using connectome-based predictive modeling (CPM). Resting-state functional magnetic resonance imaging was collected from 81 AD patients (44 females), 78 amnestic mild cognitive impairment patients (44 females), and 92 healthy controls (50 females). The FC analysis was conducted and the interaction effect between sex and group was investigated using two-factor variance analysis. The CPM was used to predict MoCA scores. There were sex-by-group interaction effects on FC between the left dorsolateral superior frontal gyrus and left middle temporal gyrus, left precuneus and right calcarine fissure surrounding cortex, left precuneus and left middle occipital gyrus, left middle temporal gyrus and left precentral gyrus, and between the left middle temporal gyrus and right cuneus. In the CPM, the positive network predictive model significantly predicted MoCA scores in both males and females. There were significant sex-by-group interaction effects on FC between the left precuneus and left middle occipital gyrus, and between the left middle temporal gyrus and right cuneus could predict MoCA scores in female patients. Our results suggest that there are sex differences in FC at different stages of AD. The sex-specific FC can further predict MoCA scores at individual level.

Periodontitis is associated with altered brain structure and function in normal cognition middle-aged and elderly individuals.

BACKGROUND: Numerous studies have proposed that periodontitis is a potential risk factor for Alzheimer's disease. However, the association between periodontitis and brain normal cognition in aged and elderly individuals (NCs) is unclear. Such a link could provide clues to Alzheimer's disease development and strategies for early prevention. OBJECTIVE: To explore the associations between periodontal condition and metrics of both brain structure and function among NCs with the help of multimodal magnetic resonance imaging (MRI). METHODS: High-resolution T1-weighted structural data, resting-state functional-MRI data, and measures of periodontal condition were collected from 40 NCs. Cortical volume, thickness, and area as well as regional homogeneity were calculated with the aid of DPABISurf software. Correlation analyses were then conducted between each imaging metric and periodontal index. RESULTS: Consistent negative correlations were observed between severity of periodontitis (mild, moderate, severe) and cortical volume, area, and thickness, not only in brain regions that took charge of primary function but also in brain regions associated with advanced cognition behavior. Among participants with mild attachment loss (AL) and a shallow periodontal pocket depth (PPD), periodontal index was positively correlated with most measures of brain structure and function, while among participants with severe AL and deep PPD, periodontal index was negatively correlated with measures of brain structure and function (all p < .005 for each hemisphere). CONCLUSIONS: Our results demonstrate that periodontitis is associated with widespread changes in brain structure and function among middle-aged and elderly adults without signs of cognitive decline, which might be a potential risk factor for brain damage.

Education reduces cognitive dysfunction in Alzheimer's disease by changing regional cerebral perfusion: An in-vivo arterial spin labeling study.

OBJECTIVE: Formal education and other cognitive challenges influence brain structure and improve function. It is believed that cognitive activities create a cognitive reserve (CR) that can slow the decline due to aging and neurodegenerative diseases. This study investigated alterations of regional cerebral blood flow (rCBF) associated with high and low CR in different stages of Alzheimer's disease (AD) and examined whether rCBF alteration mediates the relationship between education and cognitive performance. METHODS: Patients with AD or amnestic mild cognitive impairment (aMCI) and healthy controls were divided into low cognitive reserve (LCR) and high cognitive reserve (HCR) subgroups according to median of education years (≤ 9 vs. > 9 years). The final study population included 89 AD patients (67 LCR, 22 HCR), 74 aMCI patients (44 LCR, 30 HCR), and 66 healthy controls (29 LCR, 37 HCR). All subjects were examined by arterial spin labeling magnetic resonance imaging and a neurocognitive test battery. rCBF was compared among groups by two-way analysis of variance. Mediation analyses were used to explore the relationships among education, rCBF, and cognitive test scores. RESULTS: There were significant interaction effects of disease state (AD, aMCI, HC) and education level (LCR, HCR) on CBF in right hippocampus, posterior cingulate cortex, and right inferior parietal cortex (R_IPC). Education regulated episodic memory score by influencing right hippocampal CBF in HC_HCR and aMCI_HCR subgroups. CONCLUSION: Our results indicate that the protective effect of education against cognitive dysfunction in early-stage AD is mediated at least partially by altered CBF in right hippocampus.

Sex Difference in General Cognition Associated with Coupling of Whole-brain Functional Connectivity Strength to Cerebral Blood Flow Changes During Alzheimer's Disease Progression.

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder that results in irreversible cognitive impairments. Nonetheless, there are numerous sex-dependent differences in clinical course. We examined potential contributions of neurovascular coupling deficits to sex differences in AD progression. T1-weighted three-dimensional structural magnetic resonance images, functional blood oxygen level dependent and arterial spin labeling images were acquired from 50 AD patients (28 females), 52 amnesic mild cognitive impairment patients (31 females), and 59 healthy controls (36 females). Short- and long-range functional connectivity strength (FCS) and cerebral blood flow (CBF) values were calculated for all participants. Then, the CBF/FCS coupling ratio, which represented the amount of blood supply per unit of connectivity strength, was calculated for each voxel. Two-way ANOVA was performed to identify group × sex interactions and main effects of group. Correlation analysis was used to assess associations between CBF/FCS ratios and Mini-Mental State Examination (MMSE). There were significant group × sex interaction effects on short-range coupling ratios of right middle temporal gyrus, left angular gyrus, left inferior orbital frontal gyrus, and left superior frontal gyrus as well as on the long-range coupling ratios of right middle temporal gyrus, left precuneus, left posterior cingulate cortex, and left angular gyrus. There were significant negative correlations between MMSE scores and CBF/FCS ratios for all regions with significant group × sex interactions among female patients, while positive correlations were found among male patients. Our results demonstrate significant sex differences in neurovascular coupling mechanisms associated with cognitive function during the course of AD.

Sex-dependent changes in emotional memory associated with cerebral blood flow alterations during Alzheimer's disease progression.

PURPOSE: Sex differences in Alzheimer's disease (AD) progression provide clues to pathogenesis and better patient management. We examined sex differences in emotional memory among AD patients, amnestic mild cognitive impairment (aMCI) patients, and healthy controls (HCs) as well as potential associations with altered regional cerebral blood flow (rCBF). METHODS: The recognition memory task with emotional pictures was applied to evaluate enhancement of emotional memory (EEM) and 3D pseudo-continuous arterial spin labeling MRI was performed to measure the rCBF in 74 AD patients (41 females), 74 aMCI patients (45 females), and 74 HCs (43 females). Group differences in EEM were tested by two-way analysis of covariance (ANCOVA) with repeated measures. The main effects of clinical group and sex as well as group × sex interactions on rCBF were assessed by two-way ANCOVA. Correlation analyses were conducted to investigate associations between EEM and rCBF. RESULTS: With disease progression, EEM gradually disappeared. Among aMCI patients, females exhibited a greater index of recollection (Pr) for positive/high-arousal and negative/low-arousal pictures versus neutral pictures (P = 0.005, P = 0.003), while males exhibited a greater Pr for negative/high-arousal versus neutral pictures (P = 0.001). There were significant sex × group effects on rCBF in left inferior parietal, supramarginal, superior temporal and middle temporal gyri, and rCBF of left inferior parietal gyrus was correlated with Pr for positive/high-arousal pictures among female aMCI patients (r = 0.584, q = 0.005). CONCLUSION: Males and females exhibit distinct changes in EEM associated with altered rCBF, which should be considered in future neuroimaging studies.

The contribution of the left precuneus to emotion memory in migraine without aura patients.

Background: The impact of migraine without aura (MWoA) on cognitive function remains controversial, especially given the sparse literature on emotional memory. Methods: Twenty seven MWoA patients and 25 healthy controls (HCs) were enrolled in this cross-sectional study. Emotional memory behavior was evaluated by combining incidental encoding with intentional encoding of five emotional categories of visual stimulus [positive valence + high arousal (PH), negative valence + high arousal (NH), positive valence + low arousal (PL), negative valence + low arousal (NL), and neutral (N)]. The recollection performance (Pr) was measured and compared. Then, the neural relevance was explored by correlating the Pr with gray matter volume (GMV) and resting-state functional connectivity (rs-FC) based on structural and functional magnetic resonance imaging. Results: No significant differences in recollection performance or emotional enhancement of memory effect were observed. However, MWoA patients were more sensitive to the valence and arousal of emotional stimuli under incidental encoding. Significantly, the Pr-PH under incidental encoding and Pr-PL under intentional encoding were negatively correlated with the GMV of the left precuneus, and the rs-FC between the left precuneus and putamen was positively correlated with Pr-PL under intentional encoding in MWoA patients. Conclusion: Our study demonstrated the tendency for the influence of migraine on emotional memory and revealed the left precuneus as a critical contributor to recollection performance, providing novel insights for understanding emotional memory and its neural mechanisms in MWoA patients.

Abnormal Functional Connectivity of Thalamic Subdivisions in Alzheimer's Disease: A Functional Magnetic Resonance Imaging Study.

Alzheimer's disease (AD) is characterized by global cognitive impairment in multiple cognitive domains. Thalamic dysfunction during AD progression has been reported. However, there are limited studies regarding dysfunction in the functional connectivity (FC) of thalamic subdivisions and the relationship between such dysfunction and clinical assessments. This study examined dysfunction in the FC of thalamic subdivisions and determined the relationship between such dysfunction and clinical assessments. Forty-eight patients with AD and 47 matched healthy controls were recruited and assessed with scales for multiple cognitive domains. Group-wise comparisons of FC with thalamic subdivisions as seed points were conducted to identify abnormal cerebral regions. Moreover, correlation analysis was conducted to evaluate the relationship between abnormal FC and cognitive performance. Decreased FC of the intralaminar and medial nuclei with the left precuneus was observed in patients but not in heathy controls. The abnormal FC of the medial nuclei with the left precuneus was correlated with the Mini Mental State Examination score in the patient group. Using the FC values showing between-group differences, the linear support vector machine classifier achieved quite good in accuracy, sensitivity, specificity and area under the curve. Dysfunction in the FC of the intralaminar and medial thalamus with the precuneus may comprise a potential neural substrate for cognitive impairment during AD progression, which in turn may provide new treatment targets.

The protective impact of education on brain structure and function in Alzheimer's disease.

BACKGROUND: The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. METHODS: Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. RESULTS: In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. CONCLUSIONS: Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

Sex Difference in Network Topology and Education Correlated With Sex Difference in Cognition During the Disease Process of Alzheimer.

Background: Alzheimer's disease (AD) manifests differently in males and females. However, the neuro-mechanism and influence factors are still unknown. Objective: To explore sex differences in brain network topology during AD disease progression and its association with cognition and possible influencing factors. Methods: Resting-state functional magnetic resonance imaging (MRI) data and cognitive scores were collected from 82 AD patients (50 females), 56 amnestic mildly cognitive impaired patients (29 females), and 63 healthy controls (38 females). Global and regional topological network metrics and modular architecture were calculated. Two-way ANOVA was performed to explore group and sex interactions and their main effects. Mediation analysis was used to explore the relationship among education, inter/intra-network connectivity, and the Mini-Mental State Examination (MMSE) score. Results: Lower levels of education, lower MMSE scores, and a positive correlation between the level of education and MMSE scores were found in female AD patients (p = 0.024, r = 0.319). Significantly lower connectivity strength within the sensorimotor network, dorsal attention network, ventral attention network (VAN), and between the sensorimotor and VAN were observed in male AD patients (p = 0.006, 0.028, 0.046, and 0.013, respectively). Group and sex interactions were also found in nodal properties, mainly in the frontal lobe, temporal lobe, middle cingulum, precuneus, and postcentral gyrus. Several of the altered brain network properties were associated with cognitive behavior in male AD patients. Education regulated the MMSE score through the mediation of connection strength between the default mode and limbic networks (LN) in the patient group (aMCI and AD combined). Conclusion: Our results demonstrate that sex differences exist at the brain network level in AD. Sex differences in network topology and education are correlated with sex differences in cognition during AD progression.

Effect of Nrf2 signaling pathway on the improvement of intestinal epithelial barrier dysfunction by hyperbaric oxygen treatment after spinal cord injury.

Disruption of the intestinal epithelial barrier following spinal cord injury (SCI) seriously affect long-term quality of life. Oxidative stress-induced epithelial cells' injury contributes to the epithelial barrier dysfunction. Hyperbaric oxygen (HBO) treatment has been proved to alleviate SCI. However, it is unclear whether or not HBO treatment affects intestinal barrier function following SCI. In this study, our purpose was to explore the impact of HBO treatment on intestinal epithelial barrier function and underlying mechanisms following SCI. An SCI model was established in rats, and the rats received HBO treatment. Intestinal injury, mucosal permeability, intercellular junction proteins, and oxidative stress indicators were evaluated in our study. We found that HBO treatment significantly alleviated intestinal histological damage, reduced mucosal permeability, and markedly prevented bacterial translocation. Furthermore, HBO treatment significantly increased the expression of Claudin-1 and E-cadherin, inhibited intestinal tissue oxidative stress as demonstrated by upregulation of superoxide dismutase and glutathione, and HBO downregulated malondialdehyde. Mechanically, we demonstrated that HBO treatment ameliorated intestinal oxidative stress possibly through upregulating nuclear factor E2-related factor 2 (Nrf2) and its downstream targets, Heme oxygenase-1(HO-1), NADH-quinone oxidoreductase-1(NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC). These results suggested that HBO treatment triggered antioxidative effects against intestinal epithelial barrier dysfunction by promoting Nrf2 signaling pathway after SCI.

Crossed cerebellar diaschisis after stroke detected noninvasively by arterial spin-labeling MR imaging.

BACKGROUND: As a noninvasive perfusion-weighted MRI technique, arterial spin-labeling (ASL) was becoming increasingly used to evaluate cerebral hemodynamics in many studies. The relation between ASL-MRI and crossed cerebellar diaschisis (CCD) was rarely discussed. In this study, the aim of our study was to assess the performance of ASL-MRI in the detection of crossed cerebellar diaschisis after stroke in compared with single-photon emission CT (SPECT). RESULTS: 17 of 51(33.3%) patients revealed CCD phenomenon by the SPECT method. In CCD-positive group, CBFASL of ipsilateral cerebellar were significantly increased compared with contralateral cerebellar (p < 0.0001) while no significant differences (p = 0.063, > 0.001) in the CCD-negative group. Positive correlation was detected between admission National institute of health stroke scale (NIHSS) and asymmetry index of SPECT (AISPECT) (r = 0.351, p = 0.011), AIASL (r = 0.372, p = 0.007); infract volume and AISPECT (r = 0.443, p = 0.001), AIASL (r = 0.426, p = 0.002). Significant correlation was also found between cerebral blood flow of SPECT (CBFSPECT) and CBFASL, AISPECT and AIASL (r = 0.204, p = 0.04; r = 0.467, p = 0.001, respectively). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AIASL was 0.829. CONCLUSIONS: CBF derived from ASL-MRI could be valuable for assessment of CCD in supratentorial stroke patients. Additionally, CCD was significantly associated with larger ischemic volume and higher initial NIHSS score.

The effect of different atmosphere absolute hyperbaric oxygen on the expression of extracellular histones after traumatic brain injury in rats.

By observing the dynamic changes of extracellular histones H1, H2A, H4, and NF-κB expression in brain tissues after brain injury in rats, we explore the association among the expression of extracellular histones H1, H2A, H4, and NF-κB following traumatic brain injury (TBI), as well as the effect of different atmospheres absolute hyperbaric oxygen (HBO) intervention on the expression and possible mechanisms. A total of 120 SD rats were randomly divided into 4 groups: Sham-operated (SH), TBI (traumatic brain injury) group, traumatic brain injury and hyperbaric oxygen treatment 1.6ATA (TBI + HBO1) group, and traumatic brain injury and hyperbaric oxygen treatment2.2ATA (TBI + HBO2) group, with 30 rats in each group. The rats in each group were then randomly divided into five smaller time-specific sub-groups: 3 h, 6 h, 12 h, 24 h, and 48 h after surgery. TBI models were established, and the brain tissue around the lesion was taken at different time points. On the one hand,we detected the level of local histones H1, H2A, H4, and NF-κB by RT-PCR and Western Blot. On the other hand, we used immunohistochemical methods to detect the expression of NF-κB, while using the TUNEL method to observe the cell apoptosis in experimental groups after brain injury. Extracellular histones H1, H2A, H4, and NF-κB proteins were highly expressed at 3 h, then with a slight fluctuation, reached to peak at 48 h after the injury. HBO can affect the expression of histones H1, H2A, H4, and NF-κB. The decline of each indicator in the 1.6ATA group was significantly lower than that in the 2.2ATA group, especially within 6 h (P < 0. 05). In addition, NF-κB expression was consistent with the pathological changes of apoptosis in experimental groups. Hyperbaric oxygen therapy with relatively low pressure (1.6ATA) at the early stage can significantly inhibit the expression of extracellular histones H1, H2A, H4, and NF-κB around the lesion, reduce the apoptosis of nerve cells, and thus play an important role in alleviating secondary brain injury.

Endoplasmic reticulum stress may be involved in insulin resistance and lipid metabolism disorders of the white adipose tissues induced by high-fat diet containing industrial trans-fatty acids.

BACKGROUND: Consumption of industrially produced trans-fatty acids (iTFAs) can result in alteration to lipid profile and glucose metabolism. Moreover, a diet high in iTFAs could increase the risk of obesity, cardiovascular diseases (CVDs) and type 2 diabetes mellitus. Glucose and lipid metabolism are closely linked in white adipose tissue (WAT), yet the underlying mechanisms of the effect of iTFAs in WAT are poorly understood. MATERIALS AND METHODS: Parameters of glucose homeostasis, lipid profiles and markers of endoplasmic reticulum (ER) stress of WAT were measured in rats maintained on a high-fat diet containing margarine (HFD-M) (n=10) compared to controls maintained on standard chow (n=10) over 16 weeks. RESULTS: Fat mass and body weight was significantly increased in rats maintained on the HFD-M compared to controls (P<0.01). HFD-M rats had increased levels of insulin (INS), homeostasis model assessment of insulin resistance and serum lipid profile was significantly altered. The expression of glucose-regulated protein 78 (GRP78) and the phosphorylation of inositol-requiring enzyme 1-alpha and c-Jun N-terminal kinase (JNK) were significantly increased in subcutaneous and retroperitoneal adipose depots of HFD-M-fed rats. In vitro, wider ER lumens were observed in 100µmol/L elaidic acid (EA)-treated human mature adipocytes. We observed activation of ER stress markers, impaired INS receptor signaling and increased lipogenesis in adipocytes after EA exposure. These effects could be alleviated by inhibiting ER stress in adipocytes in vitro. CONCLUSION: Collectively these data suggest that ER stress may be involved in INS resistance and lipid metabolism disorders induced by high-fat diet containing iTFAs. These findings suggest that WAT could be regarded as a key target organ for inhibiting ER stress to reverse the impaired INS receptor signaling, alleviate lipid metabolism disorders, and provide a novel approach to prevent and treat INS resistance and dyslipidemia-related chronic diseases such as T2MD and CVDs.

Brain Structural Correlates of Odor Identification in Mild Cognitive Impairment and Alzheimer's Disease Revealed by Magnetic Resonance Imaging and a Chinese Olfactory Identification Test.

Alzheimer's disease (AD) is a common memory-impairment disorder frequently accompanied by olfactory identification (OI) impairments. In fact, OI is a valuable marker for distinguishing AD from normal age-related cognitive impairment and may predict the risk of mild cognitive impairment (MCI)-to-AD transition. However, current olfactory tests were developed based on Western social and cultural conditions, and are not very suitable for Chinese patients. Moreover, the neural substrate of OI in AD is still unknown. The present study investigated the utility of a newly developed Chinese smell identification test (CSIT) for OI assessment in Chinese AD and MCI patients. We then performed a correlation analysis of gray matter volume (GMV) at the voxel and region-of-interest (ROI) levels to reveal the neural substrates of OI in AD. Thirty-seven AD, 27 MCI, and 30 normal controls (NCs) completed the CSIT and MRI scans. Patients (combined AD plus MCI) scored significantly lower on the CSIT compared to NCs [F(2,91) = 62.597, p < 0.001)]. Voxel-level GMV analysis revealed strong relationships between CSIT score and volumes of the left precentral gyrus and left inferior frontal gyrus (L-IFG). In addition, ROI-level GMV analysis revealed associations between CSIT score and left amygdala volumes. Our results suggest the following: (1) OI, as measured by the CSIT, is impaired in AD and MCI patients compared with healthy controls in the Chinese population; (2) the severity of OI dysfunction can distinguish patients with cognitive impairment from controls and AD from MCI patients; and (3) the left-precentral cortex and L-IFG may be involved in the processing of olfactory cues.

Detection of Crossed Cerebellar Diaschisis by Intravoxel Incoherent Motion MR Imaging in Subacute Ischemic Stroke.

Intravoxel incoherent motion has received extensive attention in brain studies for its potential as a non-invasive magnetic resonance perfusion method. However, studies on intravoxel incoherent motion imaging and crossed cerebellar diaschisis detection are relatively scarce. The aim of our study was to evaluate the feasibility of using intravoxel incoherent motion imaging in crossed cerebellar diaschisis diagnosis in subacute ischemic stroke patients by comparing results from intravoxel incoherent motion imaging, single-photon emission computed tomography, and arterial spin-labeling perfusion methods. In total, 39 patients with subacute ischemic stroke who underwent intravoxel incoherent motion, arterial spin-labeling, and single-photon emission computed tomography scanning were enrolled. Intravoxel incoherent motion-derived perfusion-related parameters including fast diffusion coefficient, vascular volume fraction, arterial spin-labeling-derived cerebral blood flow as well as single-photon emission computed tomography-derived cerebral blood flow of bilateral cerebellum were measured. A crossed cerebellar diaschisis-positive result was considered present with an asymmetry index ≥10% of single-photon emission computed tomography. In the crossed cerebellar diaschisis-positive group, fast diffusion coefficient, arterial spin-labeling-derived cerebral blood flow, and computed tomography-derived cerebral blood flow of the contralateral cerebellum decreased compared with those of the ipsilesional cerebellum; whereas vascular volume fraction significantly increased. The National Institutes of Health Stroke Scale score and infarct volume in the crossed cerebellar diaschisis-positive group were significantly higher than those in the crossed cerebellar diaschisis-negative group. A positive correlation was detected between the fast diffusion coefficient-based asymmetry index and the single-photon emission computed tomography-based asymmetry index, fast diffusion coefficient-based asymmetry, and arterial spin-labeling based asymmetry index; whereas the vascular volume fraction-based asymmetry index value had a negative correlation with the single-photon emission computed tomography-based asymmetry index and arterial spin-labeling based asymmetry index. Furthermore, the area under the receiver operating characteristic curve value of the arterial spin-labeling-based asymmetry index was 0.923. The fast diffusion coefficient derived from the intravoxel incoherent motion could be valuable for the assessment of crossed cerebellar diaschisis in supratentorial stroke patients.

Infrared induced repeatable self-healing and removability of mechanically enhanced graphene-epoxy flexible materials.

A repeatable self-healing epoxy composite mechanically enhanced by graphene nanosheets (GNS) was prepared from an epoxy monomer with Diels-Alder (DA) bonds, octanediol glycidyl ether (OGE) and polyether amine (D230). The GNS/epoxy composites, with a maximum tensile modulus of 14.52 ± 0.45 MPa and elongation at break more than 100%, could be healed several times under Infrared (IR) light with the healing efficiency as high as 90% through the molecule chain mobility and the rebonding of reversible DA bonds between furan and maleimide. Also, they displayed excellent recyclable ability by transforming into a soluble polymer, which offers a wide range of possibilities to produce epoxy flexible materials with healing and removable abilities.

Peripheral Blood Lymphocyte-to-Monocyte Ratio as a Useful Prognostic Factor in Newly Diagnosed Multiple Myeloma.

The survival of individuals with tumors may be predicted by the peripheral blood lymphocyte-to-monocyte ratio (LMR) upon diagnosis in recent studies. For patients with multiple myeloma (MM) in the era of novel agents, the prognostic significance of LMR remains unclear. In this study, the prognostic impact of LMR is evaluated by 285 patients with MM who are treated with proteasome inhibitor and/or immunomodulatory drug. LMR is a proven predictor of survival using the receiver operating characteristic curve, with 4.2 as the cutoff point. Patients with LMR ≤ 4.2 at diagnosis had poorer overall survival (OS) and progression-free survival (PFS) than those with LMR > 4.2. In addition, multivariate analysis showed that LMR less than 4.2 is an independent predictor for the OS (hazard ratio [HR]: 1.703; 95% confidence interval [CI]: 1.020-2.842; P = 0.042) and PFS (HR: 1.831; 95% CI: 1.098-3.053; P = 0.021). According to the test, the LMR at diagnosis, which functions as a simple index reflecting host systemic immunity, can predict clinical outcomes in patients with MM who are treated with new agents.

Multiple Isoforms of Nesprin1 Are Integral Components of Ciliary Rootlets.

SYNE1 (synaptic nuclear envelope 1) encodes multiple isoforms of Nesprin1 (nuclear envelope spectrin 1) that associate with the nuclear envelope (NE) through a C-terminal KASH (Klarsicht/Anc1/Syne homology) domain (Figure 1A) [1-4]. This domain interacts directly with the SUN (Sad1/Unc84) domain of Sun proteins [5-7], a family of transmembrane proteins of the inner nuclear membrane (INM) [8, 9], to form the so-called LINC complexes (linkers of the nucleoskeleton and cytoskeleton) that span the entire NE and mediate nuclear positioning [10-12]. In a stark departure from this classical depiction of Nesprin1 in the context of the NE, we report here that rootletin recruits Nesprin1α at the ciliary rootlets of photoreceptors and identify asymmetric NE aggregates of Nesprin1α and Sun2 that dock filaments of rootletin at the nuclear surface. In NIH 3T3 cells, we show that recombinant rootletin filaments also dock to the NE through the specific recruitment of an ∼600-kDa endogenous isoform of Nesprin1 (Nes1600kDa) and of Sun2. In agreement with the association of Nesprin1α with photoreceptor ciliary rootlets and the functional interaction between rootletin and Nesprin1 in fibroblasts, we demonstrate that multiple isoforms of Nesprin1 are integral components of ciliary rootlets of multiciliated ependymal and tracheal cells. Together, these data provide a novel functional paradigm for Nesprin1 at ciliary rootlets and suggest that the wide spectrum of human pathologies linked to truncating mutations of SYNE1 [13-15] may originate in part from ciliary defects.

Bortezomib-based treatment for multiple myeloma patients with renal impairment: A systematic review and meta-analysis of observational studies.

BACKGROUND: Renal insufficiency is a common and severe complication of patients with multiple myeloma. The aim of this study was to evaluate bortezomib-based treatment for multiple myeloma patients with renal insufficiency. METHODS: The Cochrane Library, Embase, PubMed, ISI, China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Chongqing VIP Database, and Wan Fang Data were systematically searched to identify observational studies from January 1, 2001, to December 31, 2015. Myeloma response rate and renal remission rate were pooled by using risk ratio and 95% confidence interval (CI). The Cochran Q and I statistics were used to assess heterogeneity. Sensitivity analysis was performed to test the feasibility of pooled results. Publication bias was conducted when included studies were ≥9. Furthermore, grades of evidence were performed to evaluate study quality. RESULTS: Eleven retrospective cohort studies were included in the final analysis. The number of available studies and risk ratios (95% CI) were, respectively, 10 and 1.48 (95% CI: 1.28-1.71) for myeloma overall response, 6 and 3.69 (95% CI: 2.22-6.13) for myeloma complete response, 9 and 1.47 (95% CI: 1.28-1.69) for renal overall remission, and 8 and 1.49 (95% CI: 1.26-1.75) for renal complete remission. No significant publication bias was observed and sensitivity analysis confirmed the stability of results. The overall qualities of evidence were high for myeloma complete response and medium for the other 3 outcomes based on the Grading of Recommendations, Assessment, Development and Evaluation system. CONCLUSION: Current evidence indicated that bortezomib-based treatment could improve myeloma overall response (especially myeloma complete response) and renal overall remission (including renal complete remission).