Comparison of the Impact of Ga-68-DOTATATE and F-18-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors

This study aimed to assess the clinical impact of 68Ga-DOTATATE and 18F-fluorodeoxyglucose with respect to the management plan and to evaluate the prognostic value of both tracers. Methods: A total of 104 patients (55 males, 49 females; median age 58 years, range 20–90) with histopathologically proven neuroendocrine tumors (NETs) underwent both 68Ga-DOTATATE and 18F-FDG PET/CT. Twenty-eight patients (26.9%) had poorly differentiated (PD) and 76 (73.1%), well-differentiated tumors. PET/CT results and SUVs were compared with prognostic factors such as pathologic grading (G1, G2, G3), chromogranin A, and proliferation index (Ki67). Results: 68Ga-DOTATATE and 18F-FDG PET/CT findings were discordant in 65 (62.5%) and concordant in 39 (37.5%) pts. PET/CT results changed the therapeutic plan in 84 (80.8%) pts. In 22 (21.1%) pts decision making was based on 18F-FDG findings, in 32 (30.8%) on findings with both radiotracers, and in 50 (48.1%) on 68Ga-DOTATATE findings. The most frequent management decision based on 18F-FDG was initiation of chemotherapy (10 pts, 47.6%). The most common treatment decision due to 68Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 pts, 27.4%). In 11/28 (39.2%) pts with PD NETs the management decision was based only on 18F-FDG results. For 68Ga-DOTATATE, SUVmax was higher for G1 and lower for G3 tumors (p=0.012). However, no significant differences in 18F-FDG-derived SUVs were observed between different tumor grades (p=0.38). Mann-Whitney test showed significant differences in 68Ga-DOTATATE SUVmax between tumors with Ki<5% and tumors with Ki>5% (p=0.004), without significance differences in 18F-FDG SUVmax. Log-rank analysis showed statistically significant differences in survival for patients with bone vs soft tissue or no metastasis for both 18F-FDG (p=0.037) and 68Ga-DOTATATE (p=0.047). Overall survival was found to decline rapidly with increasing histological grade (p=0.001), with estimated survival of 91 months for G1, 59 months for G2, and 48 months for G3. Conclusion: 18F-FDG PET/CT had no clinical impact in G1 NETs and moderate impact in G2 NETs. However in PD NETs, 18F-FDG PET/CT plays a significant clinical role in combination with 68Ga-DOTATATE. 68Ga DOTATATE SUVmax values relate to tumor grade and Ki67 index and can be used prognostically

The influence of early aging on eye movements during motor simulation

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging

Aging Affects the Mental Rotation of Left and Right Hands

BACKGROUND:Normal aging significantly influences motor and cognitive performance. Little is known about age-related changes in action simulation. Here, we investigated the influence of aging on implicit motor imagery. METHODOLOGY/PRINCIPAL FINDINGS:Twenty young (mean age: 23.9+/-2.8 years) and nineteen elderly (mean age: 78.3+/-4.5 years) subjects, all right-handed, were required to determine the laterality of hands presented in various positions. To do so, they mentally rotated their hands to match them with the hand-stimuli. We showed that: (1) elderly subjects were affected in their ability to implicitly simulate movements of the upper limbs, especially those requiring the largest amplitude of displacement and/or with strong biomechanical constraints; (2) this decline was greater for movements of the non-dominant arm than of the dominant arm. CONCLUSIONS/SIGNIFICANCE:These results extend recent findings showing age-related alterations of the explicit side of motor imagery. They suggest that a general decline in action simulation occurs with normal aging, in particular for the non-dominant side of the body

Smooth Muscle miRNAs Are Critical for Post-Natal Regulation of Blood Pressure and Vascular Function

Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation

Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers

Selective ablation of follicular dendritic cells in mice results in disorganization of primary follicles and dispersal of B cells out of splenic germinal centers

The role of motor simulation in action perception: a neuropsychological case study

Research on embodied cognition stresses that bodily and motor processes constrain how we perceive others. Regarding action perception the most prominent hypothesis is that observed actions are matched to the observer’s own motor representations. Previous findings demonstrate that the motor laws that constrain one’s performance also constrain one’s perception of others’ actions. The present neuropsychological case study asked whether neurological impairments affect a person’s performance and action perception in the same way. The results showed that patient DS, who suffers from a frontal brain lesion, not only ignored target size when performing movements but also when asked to judge whether others can perform the same movements. In other words DS showed the same violation of Fitts’s law when performing and observing actions. These results further support the assumption of close perception action links and the assumption that these links recruit predictive mechanisms residing in the motor system

Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P(1) receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility

Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers

Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. We report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared with T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses