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.     

补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

Psychosocial mechanisms of a behavioral treatment for urinary incontinence of prostate cancer survivors

Abstract

Purpose: We examined underlying psychosocial processes of a behavioral treatment for urinary incontinence (UI) of prostate cancer survivors.

Design: Secondary analysis of data collected from a clinical trial.

Sample: Two hundred forty-four prostate cancer survivors who participated in a clinical trial of behavioral intervention to UI as intervention or control subjects.

Methods: The participants had a 3-month behavioral intervention or usual care and were followed up for an additional 3?months. They were assessed at baseline, 3, and 6?months. Latent growth curve models were performed to examine trajectories of each study variable and relationships among the variables.

Findings: Increasing self-efficacy and social support were significantly and independently associated with more reduction of urinary leakage frequency over time.

Implications for psychosocial oncology: Providing problem-solving skills and social support, including peer support, are essential for empowering patients to reduce UI.     

医院离退休干部参与社会治理现状

通过文献研究、问卷调查、专家访谈、现地调研等方法,分析医院离退休干部参与社会治理的现状及影响因素,探讨社区对离退休干部参与社会治理的需求,提出通过党建引领医院离退休干部参与社会治理的“1235”模式,并给出具体的操作路径,以期为推动医院离退休干部积极参与社会治理提供参考。     

Per‐oral transgastric abdominal surgery

Laparoscopic surgery has several advantages over traditional surgery because it has been shown to be less invasive. The next logical step in the evolution of minimally invasive surgery may be to eliminate all abdominal incisions. The natural orifices provide a port of entry via the gastrointestinal tract to the peritoneal cavity. This approach would require the creation of a perforation, which is considered to be a major complication of endoscopy with significant morbidity and mortality. However, there are several recent studies that have described the technical feasibility and safety of a per‐oral transgastric approach to the peritoneal cavity using conventional endoscopes. Theoretically, this approach could reduce postoperative abdominal wall pain, wound infection, hernia formation, and adhesions. This article aims to summarize the current status of transgastric surgery, currently referred to as natural orifice transluminal endoscopic surgery (NOTES), and to address some of its future challenges.     

Sex‐related Disparity in Surgical Mortality among Pediatric Patients

Background. It has been reported that gender differences in cardiovascular outcomes found in adults also are present in children who undergo surgical repair for congenital heart disease. Methods. California statewide hospital discharge data 1989–99 were used to study outcomes in children <18 years undergoing cardiac surgery. Hospital discharge data were linked to death registry data to study postdischarge death within 30 days of discharge. We used logistic regression to evaluate the effect of gender on mortality controlling for age, race and ethnicity, type of insurance, household income, date and month of surgery, type of admission, hospital case volume, and various types of procedures. Results. There were 25 402 cardiac surgery cases with 1505 in‐hospital deaths (mortality rate of 5.92%). An additional 37 deaths occurred within 30 days after hospital discharge. Crude mortality rates for males (5.99%) and females (5.84%) were not significantly different. However, fewer neonates were female and females underwent a higher proportion of low‐risk procedures than males. Logistic regression revealed that females, compared with males, had a significantly higher odds ratio (OR) for in‐hospital mortality (OR = 1.18, P < .01) and overall (up to 30 days post discharge) mortality (OR = 1.18, P < .01). The risk‐adjusted length of hospital stay was similar between females and males while charges per hospital day were slightly higher in females than males. The prevalence of Down syndrome, pulmonary hypertension, and failure to thrive were higher in females. Conclusions. Female gender is associated with an 18% higher in‐hospital and 30‐day postdischarge mortality as compared with male gender. There was no difference in length of hospital stay between males and females. The mechanism by which female gender acts as a risk factor requires further investigation.     

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.     

羽毛球运动中发生手腕和肩袖损伤的相关因素调查

目的：通过对羽毛球爱好者的问卷调查，结合羽毛球项目的运动特点，分析常见的运动损伤部位及其发病原因、处理方法以及预防措施. 方法：调查于2005—03／11在成都医学院体育教研室羽毛球俱乐部完成，对156名羽毛球爱好者进行运动损伤情况凋查，均自愿参加调查。采用问卷调查和专家访谈相结合的方法，主要结合羽毛球项目的运动特点，调查运动损伤的患病率、损伤类型及其受伤原因，分析其常用的处理方法及预防措施。 结果：共发放问卷156份，收回内容详实问卷156份。（1）损伤患病率：运动损伤患病率为78，84％。（2）损伤类型：156名羽毛球爱好者中急性损伤占52、56％，慢性损伤占26，28％。最容易受伤的手腕处受伤患病率为37．39％，其次是肩袖受伤患病率为30．89％。（3）受伤原因：技术动作不规范是运动损伤最主要的原因，占72，35％，而准备活动不充分和身体疲劳分别占63、41％和22．76％. 结论：为有效预防手腕和肩袖损伤，应加强局部肌肉力量训练等防治措施；注意学习和掌握正确的动作技术要领，做好充分的准备活动是十分必要的.