BackgroundAlzheimer’s disease (AD) is the most common form of dementia and patients often have visual disorders. Mild cognitive impairment (MCI) is characterized by a memory deficit when compared with those of a similar age and education level which could indicate an earlier onset of AD. The aim of this study is to measure the changes of the retinal nerve fiber layer (RNFL) thickness of AD and MCI patients in comparison with the normal age controls.MethodsThe RNFL thickness was assessed using optical coherence tomography (OCT) in patients with MCI, AD (mild, moderate and severe) and the age matched controls.ResultsThe thickness of RNFL in the superior quadrant and total mean values are gradually and significantly decreased from MCI to severe AD when compared to that in the controls. There is also a significant reduction of the retinal nerve fiber layer in the inferior quadrant in severe AD patients.ConclusionsOur data indicate that the retinal nerve fiber layer degeneration is paralleled with dementia progression. Owing to its non-invasive and cost effective nature, monitoring RNFL thickness may have a value in assessing disease progression and the efficacy of any treatments.

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Treatment of adult Philadelphia chromosome-positive lymphocytic leukemia is rarely successful. We report here the effects of TZD18, a novel dual ligand specific for peroxisome proliferatoractivated receptor ␣ and ␥ (PPAR␣/␥) on Ph ؉ lymphocytic leukemia cell lines BV173, SD1, and SupB-15. Exposure of these cells to TZD18 resulted in growth inhibition in a dose-and time-dependent manner that was associated with G 1 cell cycle arrest. This effect was much stronger than that mediated by the PPAR␥ ligand pioglitazone (PGZ), which also belongs to the thiazolidinediones (TZD) class of ligands. However, it may not be mediated through PPAR␥ or PPAR␣ activation because antagonists of PPAR␥ and PPAR␣ cannot reverse it. Study of the key regulators of cell cycle progression by Western blot analysis showed that the expression of the cyclin-dependent kinase inhibitor (CDKI) p27 kip1 , but not that of p21 cip1 , was enhanced, whereas that of c-Myc, cyclin E, cyclin D2, and cyclindependent kinases 2 and 4 (CDK-2 and CDK-4) was decreased when these cells were treated with TZD18 (10 or 20 M). Therefore, the up-regulation of p27 kip1 and the down-regulation of CDK-2 and CDK-4 may, at least in part, account for the G 1 cell cycle arrest. Furthermore, a remarkable induction of apoptosis was observed in the cells treated with this dual ligand.No obvious alteration of bcl-2 protein level occurred, but bax was up-regulated in these TZD18-treated cells. Activation of caspase 8 and caspase 9 by TZD18 was also observed. Importantly, NF-B DNAbinding activity was markedly decreased by the TZD18 treatment. In addition, TZD18 enhanced the growth inhibitory effect of imatinib, a specific tyrosine kinase inhibitor therapeutically used in the treatment of Ph ؉ leukemia. Overall, our findings strongly suggest that TZD18 may offer a new therapeutic approach to aid in the treatment of Ph ؉ lymphocytic leukemia. IntroductionAlthough significant progress has been made in the treatment of acute lymphocytic leukemia (ALL), the prognosis for patients with Philadelphia chromosome-positive (Ph ϩ )/Bcr-Abl ϩ adult ALL is still very poor. After first remission, allogeneic stem cell transplantation is the treatment of choice. However, most patients are not eligible for this therapy because of advanced age or lack of a suitable stem cell donor (for reviews, see Redaelli et al 1 and Bassan et al 2 ). Imatinib (Gleevec, previously known as STI571 and CGP57148), the selective tyrosine kinase inhibitor, displayed pronounced antileukemic activity in Ph ϩ chronic myeloid leukemia (CML) and ALL. It is used after allogeneic stem cell transplantation and is recommended for relapsed or refractory Ph ϩ ALL as salvage therapy to facilitate subsequent transplantation. 3 However, quick emergence of resistance to this agent is a major problem in the treatment of patients with Ph ϩ leukemia. Another major obstacle to imatinib-based therapies is the persistence of Ph ϩ cells despite the application of imatinib. Based on these arguments, the development of novel therapeutic a...

Considerable evidence suggests that proinflammatory pathways drive self-renewal of cancer stem-like cells (CSC), but the underlying mechanisms remain mainly undefined. Here we report that the let7 repressor LIN28B and its regulator IKBKB (IKKb) sustain cancer cell stemness by interacting with the Wnt/TCF7L2 (TCF4) signaling pathway to promote cancer progression. We found that LIN28B expression correlated with clinical progression and stemness marker expression in breast cancer patients. Functional studies demonstrated that the stemness properties of LIN28B-expressing human breast and lung cancer cells were enhanced by IKKb, whereas loss of LIN28B abolished stemness properties in these settings. These phenomena were driven through interactions with TCF7L2, which enhanced LIN28B expression by direct binding to intron 1 of the LIN28B gene, which in turn promoted TCF7L2 mRNA translation through a positive feedback loop. Notably, RNAimediated silencing of LIN28B or pharmacologic inhibition of IKKb was sufficient to suppress primary and metastatic tumor growth in vivo. Together, our results establish the LIN28B/ TCF7L2 interaction loop as a central mediator of cancer stemness driven by proinflammatory processes during progression and metastasis, possibly offering a new therapeutic target for generalized interventions in advanced cancers.

BackgroundThe correlation between intracranial pressure (ICP) and intraocular pressure (IOP) is still controversial in literature and hence whether IOP can be used as a non-invasive surrogate of ICP remains unknown. The aim of the current study was to further clarify the potential correlation between ICP and IOP.MethodsThe IOP measured with Goldmann applanation tonometer was carried out on 130 patients whose ICP was determined via lumber puncture. The Pearson correlation coefficient between ICP and IOP was calculated, the fisher line discriminated analysis to evaluate the effectivity of using IOP to predict the ICP level.ResultsA significant correlation between ICP and IOP was found. ICP was correlated significantly with IOP of the right eyes (p < 0.001) and IOP of the left eyes (p = 0.001) and mean IOP of both eyes (p < 0.001), respectively. However, using IOP as a measurement to predict ICP, the accuracy rate was found to be 65.4%.ConclusionOur data suggested that although a significant correlation exists between ICP and IOP, caution needs to be taken when using IOP readings by Goldmann applanation tonometer as a surrogate for direct cerebrospinal fluid pressure measurement of ICP.

Various studies have been performed on drought hazard assessment at the national or regional scales, but few studies to date at the global scale, especially on global agriculture. In this paper, we utilized an agricultural drought hazard index (DHI), based on both drought severity and drought occurrence rate, derived from 3‐month scale Standardized Precipitation Index (SPI) and the phenology data of main crops (rice, maize, wheat, barley, sorghum and soybean) to assess the agricultural drought hazard grades of the world during 1980–2008. The results indicated that area percentages of high and very high agricultural drought hazard zones were approximately 23.57 and 27.19% of the total agricultural area in the world. Moreover, those zones mostly were distributed in central United States, southeastern South America, most of Europe, southwestern Russia, both southern Congo and Nigeria, east‐central and southwest China, Southeast Asia and eastern Australia, and most of those areas were also located in semi‐humid or humid climate zones. In addition, some regions above were also found to be the very high agricultural drought hazard zones for the main crops: East‐central and southwest China for wheat, maize, rice and soybean; Europe for wheat, maize and barley; Southeast Asia for rice; both central United States and southeastern South America for wheat, maize, soybean and sorghum.

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BackgroundUltrasonograpic retrobulbar optic nerve sheath diameter (ONSD) measurement is considered to be an alternative noninvasive method to estimate intracranial pressure,but the further validation is urgently needed. The aim of the current study was to investigate the association of the ultrasonographic ONSD and intracranial pressure (ICP) in patients.MethodsOne hundred and ten patients whose intracranial pressure measured via lumbar puncture were enrolled in the study. Their retrobulbar ONSD with B-scan ultrasound was determined just before lumber puncture. The correlation between the ICP and the body mass index (BMI), ONSD or age was established respectively with the Pearson correlation coefficient analysis. The discriminant analysis was used to obtain a discriminant formula for predicting ICP with the ONSD、BMI、gender and age. Another 20 patients were recruited for further validation the efficiency of this discriminant equation.ResultsThe mean ICP was 215.3 ± 81.2 mmH2O. ONSD was 5.70 ± 0.80 mm in the right eye and 5.80 ± 0.77 mm in the left eye. A significant correlation was found between ICP and BMI (r = 0.554, p < 0.001), the mean ONSD (r = 0.61, P < 0.001), but not with age (r = −0.131, p = 0.174) and gender (r = 0.03, p = 0.753). Using receiver operating characteristic (ROC) curve analysis, the critical value for the risk mean-ONSD was 5.6 mm from the ROC curve, with the sensitivity of 86.2% and specificity of 73.1%. With 200 mmH2O as the cutoff point for a high or low ICP, stepwise discriminant was applied, the sensitivity and specificity of ONSD predicting ICP was 84.5%-85.7% and 86.5%-92.3%.ConclusionsOphthalmic ultrasound measurement of ONSD may be a good surrogate of invasive ICP measurement. This non-invasive method may be an alternative approach to predict the ICP value of patients whose ICP measurement via lumbar puncture are in high risk. The discriminant formula, which incorporated the factor of BMI, had similar sensitivity and higher specificity than the ROC curve.