Macro- and micro-structural white matter differences correlate with cognitive performance in healthy aging

Studies have shown that white matter (WM) volumetric reductions and overall degradation occur with aging. Nonetheless little is known about the WM alterations that may underlie different cognitive status in older individuals. The main goal of the present work was to identify and characterize possible macro and microstructural WM alterations that could distinguish between older healthy individuals with contrasting cognitive profiles (i.e., “poor” vs “good” cognitive performers). Structural and diffusion magnetic resonance imaging was performed in order to quantify local WM volumes, white matter signal abnormalities (WMSA) volume (a measure of lesion burden) and diffusion tensor imaging scalar maps known to probe WM microstructure. A battery of neurocognitive/psychological tests was administered to assess the cognitive performance. Poor performers showed a higher slope for the positive association between WMSA volume and age compared to good performers. Even when controlling for WMSA volume, poor performers also evidenced lower fractional anisotropy, as well as positive associations with age with higher slopes of regression parameters in radial and axial diffusivity. Altogether results suggest that cognitive performance is related to differences in WM, with poor cognitive performers displaying signs of faster aging in WM.     

Revisiting colorectal cancer animal model – An improved metastatic model for distal rectosigmoid colon carcinoma

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model.We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1?×?10⁷ cells/animal) in RNU rats (n?=?55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (^99mTc-MIBI).Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake.With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.     

Evaluation of Gamma Interferon Immune Response Elicited by the Newly Constructed PstS-1(285-374):CFP10 Fusion Protein To Detect Mycobacterium tuberculosis Infection

The PstS1 antigen is highly immunogenic, principally when combined with CFP10 during both latent and active TB infection. In the present study, a selected pstS1 gene fragment was cloned, fused with CFP10, and expressed in Escherichia coli. The product [PstS-1(285-374):CFP10] was compared to the recombinant fused RD1 (region of deletion 1) protein (ESAT-6:CFP10) in detecting Mycobacterium tuberculosis infection in 108 recent contacts of pulmonary tuberculosis (TB) cases, considering a positive tuberculin skin test (TST) to be the baseline. The release of gamma interferon (IFN-γ) in 22-h whole-blood and 5-day lymphocyte stimulation assays primed with each antigen was determined. All contacts were clinically followed for up to 1 year, and 87% of the tuberculin skin test-positive (TST^positive) patients accepted preventative treatment. Concerning the IFN-γ response to PstS-1(285-374):CFP10 in the 22-h and 5-day assays, a slight increase in contact-TST^positive detection was observed (23/54 and 26/54) compared to the level seen with the RD1 protein (18/54 and 24/54) whereas in the TST^negative group, similarly lower numbers (≤5/48) of responders were achieved for both antigens, except for RD1 in the 5-day assay (8/48). By combining the IFN-γ responders to both antigens in the 5-day assays, slightly higher increases in positivity were found in the TST^positive (32/54) and TST^negative (10/48) groups. Two of 12 untreated TST^positive contacts progressed to active TB and were concordantly positive in all assays, except for one contact who lacked positivity in the RD1 5-day assay. We demonstrated for the first time that PstS-1(285-374):CFP10 slightly increased contact positivity and detection of active disease progression, suggesting its potential application as a TB infection marker.