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Young Ninja Group (ages 3-5)

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Ethan Murphy
Ethan Murphy

Midd 922.wmv |TOP|

Release Date: Nov. 08, 2012Runtime: 152min. (HD: 152min.)Director: TAKE-DStudio: MOODYZLabel: MOODYZ DIVASubtitles:----Channel:MOODYZ, PRIMEContent ID: midd00922DVD ID: MIDD-922Series: Cumming 10 times In One Day Can't S...Languages:JapaneseActress(es): Yuria SatomiCategories: Older SisterFeatured ActressHandjobDigital MosaicHi-DefFREE SERVER 1FREE SERVER 1

Midd 922.wmv

Nowadays, the cognitive tests have been widely used for detection of cognitive impairment. However, the cognitive tests scores could be affected by the subjective judgment and drug intervention. Brain magnetic resonance (MR) imaging provided a good opportunity to explore the diabetic cerebral changes. The MR imaging biomarkers are more objective evidence, which could provide a supplement and clue for early diagnosis of cognitive impairment in T2DM patients. On conventional MR images, brain atrophy in some regions could be found (de Bresser et al., 2010; van Elderen et al., 2010; Espeland et al., 2013; Moran et al., 2019). Recently, lots of attention have been paid on the gray matter changes of T2DM patients. Several studies have shown that regional atrophy patterns of gray matter mainly located in frontal lobe, middle temporal gyrus, and posterior cingulate gyrus (Brundel et al., 2010; Moran et al., 2013; Moulton et al., 2015; Fang et al., 2018; Li et al., 2018). Despite the importance of gray matter atrophy in T2DM, white matter abnormalities played a distinct and irreplaceable role in cognitive impairments induced by T2DM. White matter has a vital role for transferring information between gray matter regions. White matter alterations include both microstructural deficits and morphological abnormalities. On one hand, studies of white matter integrity using MR diffusion tensor imaging (DTI) have demonstrated microstructural alterations in different regions in T2DM patients. These studies observed reduced white matter integrity predominantly in the cingulum, the uncinate fasciculus, the superior and inferior longitudinal fasciculus, corpus callosum, and external and internal capsule (Zhang et al., 2014; Nouwen et al., 2017; Yoon et al., 2017; Sun et al., 2018; Xiong et al., 2019). On the other hand, volumetric measurements are widely used to study morphological changes in both normal aging and in neurodegenerative disorders. Understanding changes in regional brain volumes has the potential to aid prediction of onset and progression of many neurodegenerative disorders. However, few studies have been focused on alterations of white matter volume (WMV) in T2DM patients. The loss of WMV in T2DM patients has been observed in temporal lobe, inferior frontal triangle region, and hippocampus (Korf et al., 2006; Gold et al., 2007; Chen et al., 2012; Moran et al., 2013). The alterations of WMV in previous studies did not show a consistent pattern in T2DM. The reason for the inconsistent results may be that T2DM patients included in these studies were in different stages of diabetes-associated cognitive impairment. To our knowledge, we have not found the report of WMV changes in T2DM patients with MCI at present.

The significant correlations between white matter volume and cognitive performance in T2DM patients. Correlations between MoCA scores and white matter volume of five regions, including left posterior cingulate (A), left precuneus (B), and left insula (C), right rostral middle frontal gyrus (D), and right temporal pole (E).

ROC curves of white matter volume of four single regions for mild cognitive impairments in T2DM patients. No significant difference (Z = 0.597, P = 0.551) was found between minimum AUC (right rostral middle frontal gyrus) and the maximum AUC (left precuneus).

To explore the white matter atrophy due to T2DM and T2DM-associated cognitive impairments, we compared the difference of WMV among T2DM-MCI, T2DM-NC, and HC groups. As expected, the WMV was considerably different in some regions among these three groups with FDR correction. After a post hoc test and Bonferroni correction, T2DM-MCI patients had white matter atrophy in the left insula, posterior cingulate, and precuneus, right lateral orbitofrontal gyrus, pars orbitalis gyrus, rostral middle frontal gyrus, and temporal pole, when compared with T2DM-NC patients without clinically confirmed cognitive impairment. Additionally, the T2DM-NC patients did not show significant atrophy in brain white matter compared with the HC. These results indicated that the observed atrophy in brain white matter is strongly associated with cognitive impairment in T2DM patients. Previous studies reported that T2DM was associated with white matter loss mainly in frontal and temporal white matter, which were partly in line with our findings (Chen et al., 2012; Moran et al., 2013). However, some other studies revealed that individuals with T2DM had reductions in hippocampus volumes but superior temporal gyrus had no volume loss, which were not in accordance with our results (Korf et al., 2006; Gold et al., 2007; Cherbuin et al., 2012). In addition, we found that some limbic structures and precuneus, which have been reported associated with cognitive functions (Cavanna and Trimble, 2006; McCrimmon et al., 2012; Hoogenboom et al., 2014), had obviously reduced WMV. The reason of the inconsistent results may be associated with the cognitive state of the included T2DM patients. T2DM patients included in these previous studies were in different stages of diabetes-associated cognitive impairment, whereas in our study, we enrolled T2DM-MCI, the early stages of cognitive impairment in T2DM patients, and T2DM-NC without clinically confirmed cognitive impairments to provide early signs of cognitive dysfunction, which may help clinicians with the earlier prevention of severe cognitive decline in T2DM patients.

The MoCA scores, which served as an index of the cognitive status of the patients, are known to distinguish patients with MCI form the normal population (Petersen et al., 1999). MoCA has shown higher sensitivity in detecting cognitive decline than the MMSE (Nasreddine et al., 2005). Our results revealed that no significant differences were shown in MMSE scores among these three groups, while MoCA scores were significantly higher in HC when compared with T2DM-MCI and T2DM-NC patients, and T2DM-NC patients performed better than T2DM-MCI patients. Furthermore, WMV of five brain regions significantly correlated with the MoCA scores, mainly located in frontotemporal lobe and limbic system, which have been implicated in memory and learning (McCrimmon et al., 2012). Among them, the correlation coefficient of the left posterior cingulate WMV was higher than others. Cingulate gyrus, as one of the important limbic structures, has been reported to be disrupted in T2DM patients (Yau et al., 2010; Hoogenboom et al., 2014; Tan et al., 2016; Nouwen et al., 2017; Groeneveld et al., 2018; Yu et al., 2019). More importantly, its disruption was associated with impairments in cognitive functions including memory, psychomotor speed performance, and executive function in T2DM patients (Hoogenboom et al., 2014). Previous studies have discovered reduced functional connectivity in the default mode network between posterior cingulate gyrus and left medial frontal gyrus in middle-aged T2DM patients. Moreover, reduced FA in the cingulum was correlated with lower functional connectivity between cingulate and medial frontal gyrus (Hoogenboom et al., 2014). Moreover, the white matter loss was also reported in cingulate gyrus attributed to T2DM (Chen et al., 2012). More interestingly, our study also showed that the WMV of left posterior cingulate had a high discriminative ability for T2DM patients with MCI. Thus, the white matter disruption of cingulate gyrus has a possible relationship with cognitive impairments at the early stage in T2DM patients.

On May 2, 2004, a shell containing mustard gas was found in the middle of a street west of Baghdad. The Iraq Survey Group investigation reported that it had been previously "stored improperly", and thus the gas was "ineffective" as a useful chemical agent. Officials from the Defense Department commented that they were not certain if use was to be made of the device as a bomb.[111]

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Even though it's a time travel comedy with the same goofball sense of humor as Executive Producer Seth Rogen's movies, "Future Man" is surprisingly in-the-know about time travel. It's also hilarious, particularly when it hits its stride toward the middle, jumping around to the 1950s, the 1980s, and the futuristic home of "The Terminator" Director James Cameron. Plus, it has one of the best, most intelligent "Back to the Future" parodies ever.


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