Glioma-Induced Disruption of Resting-State Functional Connectivity and Amplitude of Low-Frequency Fluctuations in the Salience Network

BACKGROUND AND PURPOSE:Cognitive challenges are prevalent in survivors of glioma, but their neurobiology is incompletely understood. The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on resting-state functional connectivity and amplitude of low-frequency fluctuations of the salience network, a key neural network associated with cognition.MATERIALS AND METHODS:Sixty-nine patients with glioma (mean age, 48.74 [SD, 14.32] years) who underwent resting-state fMRI were compared with 31 healthy controls (mean age, 49.68 [SD, 15.54] years). We identified 4 salience network ROIs: left/right dorsal anterior cingulate cortex and left/right anterior insula. Average salience network resting-state functional connectivity and amplitude of low-frequency fluctuations within the 4 salience network ROIs were computed.RESULTS:Patients with gliomas showed decreased overall salience network resting-state functional connectivity (P = .001) and increased amplitude of low-frequency fluctuations in all salience network ROIs (P < .01) except in the left dorsal anterior cingulate cortex. Compared with controls, patients with left-sided gliomas showed increased amplitude of low-frequency fluctuations in the right dorsal anterior cingulate cortex (P = .002) and right anterior insula (P < .001), and patients with right-sided gliomas showed increased amplitude of low-frequency fluctuations in the left anterior insula (P = .002). Anterior tumors were associated with decreased salience network resting-state functional connectivity (P < .001) and increased amplitude of low-frequency fluctuations in the right anterior insula, left anterior insula, and right dorsal anterior cingulate cortex. Patients with high-grade gliomas had decreased salience network resting-state functional connectivity compared with healthy controls (P < .05). The right anterior insula showed increased amplitude of low-frequency fluctuations in patients with grade II and IV gliomas compared with controls (P < .01).CONCLUSIONS:By demonstrating decreased resting-state functional connectivity and an increased amplitude of low-frequency fluctuations related to the salience network in patients with glioma, this study adds to our understanding of the neurobiology underpinning observable cognitive deficits in these patients. In addition to more conventional functional connectivity, amplitude of low-frequency fluctuations is a promising functional-imaging biomarker of tumor-induced vascular and neural pathology.

Detrimental effects of cancer on cognitive function and, consequently, on the quality of life are emerging as a key focus of cancer survivorship both in research and clinical practice.^1,2 Brain tumors have been shown to affect memory, processing, and attention in patients; however, their underlying neurobiology is incompletely understood.³ Using resting-state functional MR imaging (rsfMRI) to evaluate changes in cognitive resting-state networks may provide a better understanding of the pathology underlying the observable cognitive disruptions in gliomas, the most common primary brain tumor in adults.A “triple network model” of neurocognitive pathology has been proposed, which encompasses the default mode network, involved in mind wandering; the central executive network, involved in decision-making; and the salience network (SN), implicated in modulating activation of the default mode network and central executive network by detecting the presence of salient stimuli.^4-8 While previous rsfMRI research has largely focused on tumor-induced changes in the default mode network,^9,10 our study examined the less-studied SN, a network rooted in the anterior insula and the dorsal anterior cingulate cortex.⁶Prior studies evaluating gliomas and SN resting-state functional connectivity (RSFC) provided conflicting results in small patient samples: Maesawa et al¹⁰ found no significant differences in the SN in 12 patients, while Liu et al¹¹ more recently found decreased SN connectivity in 13 patients. Gliomas impact the integrity of the neurovascular unit to varying degrees, resulting in neurovascular uncoupling that has been reported to confound fMRI interpretations in patients with brain tumors.^12-14 Additionally, research has reported neuronal plasticity manifested by structural reorganization and functional remodeling of neural networks in patients with gliomas with possible alterations in clinically observable cognitive manifestations.^15-17 An rsfMRI metric, the amplitude of low-frequency fluctuations (ALFF), has recently shown promise as a biomarker for brain plasticity and hemodynamic characterization, including neurovascular uncoupling in patients with gliomas.^15-19The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on overall RSFC and regional normalized ALFF within the SN in a large patient population. We hypothesized that there would be decreased average SN RSFC and altered ALFF in patients with gliomas compared with healthy controls. Recent studies have acknowledged that gliomas have variable effects on network integrity based on lesion location and proximity to network ROIs,^20-22 and unilateral gliomas can be associated with plasticity in both the ipsilateral and contralateral hemispheres.^11,17 Research also supports differences in resting-state network reorganization in aggressive high-grade gliomas compared with slower-growing low-grade gliomas.^20,23 Therefore, we also hypothesized that there would be differences in average SN RSFC and regional ALFF in patients based on the anterior-versus-posterior location, hemispheric side, and grade of glioma.     

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Knowledge of the Brain Death Concept in Dominican Immigration Residents in Spain and Florida

The Latin American population has a double way of immigration, one toward the United States by proximity and another toward Spain by sociocultural affinity. This population increase is affecting organ donation and transplantation in receiving countries.

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

软组织损伤引起慢性疼痛的治疗

目的：综述运动系统软组织损伤引起慢性疼痛的各种治疗方法的研究进展。资料来源：应用计算机检索Medline1980—01／2006—04与运动系统软组织损伤引起慢性疼痛的治疗相关文章，检索词“Soft tissue injury，pain．chronic，comprehensive therapy”，并限定文章语言种类为“English”；同时计算机检索中国期刊全文数据库1994—01／2006-04期间的相关文章，检索词“软组织损伤、慢性疼痛、治疗方法”，并限定语言种类为中文。同时手工查阅相关书籍。资料选择：对资料进行初审，所选文献内容符合：①软组织损伤引起的慢性疼痛药物治疗的研究。②软组织损伤引起的慢性疼痛微创治疗的研究。③软组织损伤引起的慢性疼痛运动疗法的研究。④软组织损伤引起的慢性疼痛心理治疗的研究。⑤软组织损伤引起的慢性疼痛其他疗法的研究。排除重复性研究的文献。资料提炼：共收集到40篇关于软组织损伤引起的慢性疼痛治疗方法的文献，均为全文，23篇符合纳入标准，排除17篇重复性研究。同时录入书籍3本。资料综合：软组织损伤引起的慢性疼痛的产生是生理、心理及社会因素复杂结合的结果，个体表现差异较大，目前尚无特效治疗方法，常用的治疗方法有：药物治疗、微创治疗、运动疗法、心理治疗、物理疗法及其他疗法。结论：对于软组织损伤引起的慢性疼痛的治疗必须以整体的观点对其进行合理的评估和个体化治疗，才能收到良好的效果。     

Short-term prognosis of patients with acute coronary syndromes through the evaluation of physical activity status, the adoption of Mediterranean diet and smoking habits: the Greek Acute Coronary Syndromes (GREECS) study.

PURPOSE: Our aim was to evaluate whether healthy dietary habits, physical activity and non-smoking are associated with less severe acute coronary syndromes and better short-term prognosis. SUBJECTS AND METHODS: From October 2003 to September 2004, 2172 patients (1649 males), hospitalized for severe acute coronary syndromes in six major hospitals in Greece were included in the study. The severity of severe acute coronary syndromes was assessed through troponin-I and maximum creatinine kinase MB levels, while 30-day recurrent event rate (death or rehospitalization for cardiovascular disease, angioplasty or coronary artery bypass surgery) was used to evaluate the prognosis of the patients. A 'healthy index' that assessed adherence to the Mediterranean diet, moderate alcohol intake, physical activity and abstinence from smoking was developed (range 0-4). RESULTS: One unit increment in the healthy index was associated with -12.4+/-2.4 ng/ml decrease in troponin I levels (P=0.001) and -9.7+/-2.5 ng/ml decrease in maximum creatinine kinase MB levels (P=0.001). The in-hospital mortality rate was 3.2% in males and 5.7% in females (i.e. overall 82 deaths, P=0.009); during the first 30 days following hospitalization the event rate was 15.7% in males and 16.3% in females (P=0.001). Values of the healthy index above one (i.e. presence of two or more protective factors) seemed to be associated with 44-84% lower risk of having recurrent events (P<0.001), even after various adjustments were made. CONCLUSION: Among patients who had had severe acute coronary syndromes, a healthy lifestyle seemed to be associated with less severe cardiac events and lower risk of death or rehospitalization 30 days after the event.     

Chronische Transplantatdysfunktion

Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen.     

Littoral‐cell angioma as a rare cause of splenomegaly

We report the case of a littoral‐cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.