Hippocampus-specific fMRI group activation analysis using the continuous medial representation

We present a new shape-based approach for regional group activation analysis in fMRI studies. The method restricts anatomical normalization, spatial smoothing and random effects statistical analysis to the space inside and around a structure of interest. Normalization involves finding intersubject correspondences between manually outlined masks, and it leverages the continuous medial representation, which makes it possible to extend surface-based shape correspondences to the space inside and outside of structures. Our approach is an alternative to whole-brain normalization in cases where the latter may fail due to anatomical variability or pathology. It also provides an opportunity to analyze the shape and thickness of structures concurrently with functional activation. We apply the technique to the hippocampus and evaluate it using data from a visual scene encoding fMRI study, where activation in the hippocampus is expected. We produce detailed statistical maps of hippocampal activation, as well as maps comparing activation inside and outside of the hippocampus. We find that random effects statistics computed by the new approach are more significant than those produced using the Statistical Parametric Mapping framework (Friston, K.J., Holmes, A.P., Worsley, K.J., Poline, J.-P., Firth, C.D., Frackowiak, R.S.J. 1994, Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping, 2(4): 189-210) at low levels of smoothing, suggesting that greater specificity can be achieved by the new method without a severe tradeoff in sensitivity.     

Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones under metal-free and solvent-free conditions for minimizing waste generation

Brønsted acidic ionic liquid was found to be an efficient and recyclable catalyst for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones. The reactions proceeded smoothly with a broad scope of substrates providing the expected products in good to excellent yields under an atom-economical pathway. The low-cost recyclable catalyst, metal- and solvent-free conditions, and the ease of product isolation are the highlighted advantages in solving the issue of trace metal contamination in synthesized pharmaceuticals.

A facile, efficient, and atom-economic method for preparing benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones under metal- and solvent-free condition has been developed.     

Rotational thromboelastometry parameters as predicting factors for bleeding in immune thrombocytopenic purpura

Objective/BackgroundPatients with immune thrombocytopenic purpura (ITP) often present with a severe reduction in platelet counts and suffer from an increased risk of bleeding. However, platelet counts do not accurately predict bleeding risk in these patients.MethodsWe thereby conducted a case series prospective study to compare the ability to predict hemorrhage in ITP patients between platelet counts and various rotational thromboelastometry (ROTEM) parameters.ResultsThe inclusion criteria for patients diagnosed with acute, persistent, and chronic ITP were platelet counts of <30 × 10⁹/L and no clinically significant bleeding (grade ≥ 2 according to the WHO Bleeding Scale) at the beginning of the study. After 24 hours of follow-up, of the 45 enrolled patients, 14 (31.1%) experienced clinically significant bleeding. The mean platelet counts of patients with and without clinically significant bleeding were not statistically different (p = .09). However, the mean EXTEM maximum clot firmness (MCF), EXTEM A10, EXTEM area under the curve (AUC), and platelet maximum clot elasticity (MCE) values of the two groups were statistically different (p < .05). There was also a significant difference in IPF values between these two groups (p < .05.)ConclusionResults obtained from this preliminary study demonstrate that ROTEM parameters might be useful in predicting factors for hemorrhage in ITP patients. Future studies with a larger sample size is warranted to confirm our findings, which will allow prompt and effective bleeding management in ITP patients.     

Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.     

Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced inhibition of factor VIIa/tissue factor activity

Recent studies have shown that antithrombin III (AT III)/heparin is capable of inhibiting the catalytic activity of factor VIIa bound either to relipidated tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report studies of the mechanism of which by AT III inhibits factor VIIa bound to cell surface TF and compare this inhibitory mechanism with that of tissue factor pathway inhibitor (TFPI)-induced inhibition of factor VIIa/TF. AT III alone and AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF. Our data show that the decrease in the amount of factor VIIa associated with cell surface TF in the presence of AT III was the result of (1) accelerated dissociation of factor VIIa from cell surface TF after the binding of AT III to factor VIIa/TF complexes and (2) the inability of the resultant free factor VIIa-AT III complexes to bind effectively to a new cell surface TF site. Binding of TFPI/factor Xa to cell surface factor VIIa/TF complexes markedly decreased the dissociation of factor VIIa from the resultant quaternary complex of factor VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could reverse the AT III-induced inhibition of cell surface factor VIIa/TF activity but not TFPI/factor Xa-induced inhibition of factor VIIa/TF activity.     

AIDS-related cholangiopathy

Several types of biliary tract abnormality of undertermined origin have been described among AIDS patients. The aims of this study are (1) to evaluate whether biliary tree involvement is in fact one or several homogeneous morphological entities, (2) to specify the role of CMV orCryptosporidium sp. infection, and (3) to evaluate the possible efficacy of treatment. Since ultrasound had revealed abnormality in the biliary tree, 26 consecutive AIDS patients underwent cholangiography. Cholangiograms enabled us to distinguish between two types of biliary tract involvement: (1) gradual and regular stenosis of the terminal portion of the common bile duct associated with dilation but without irregularity of the intrahepatic biliary ducts was present in 27% of our cases, and (2) distal stenosis of the extrahepatic biliary ducts combined with diffuse irregularity of the caliber of the intrahepatic bile ducts was present in 73% of our cases. Concomitant infection by CMV orCryptosporidium sp. was significantly more frequent when intrahepatic duct irregularities were present (94%) than when absent (14%,P<0.001). Anti-CMV treatment and sphincterotomy were unsuccessful in treating anomalies of the intrahepatic biliary tract. Conversely, sphincterotomy caused rapid and lasting disappearance of pain in all our patients. In conclusion, biliary tract involvement in AIDS patients is of two types. CMV infection and infection byCryptosporidium sp. are most frequent when the large intrahepatic ducts are implicated.     

Identification of Possible Virulence Marker from Campylobacter jejuni Isolates

A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.     

Treatment practice in the elderly patient with chronic lymphocytic leukemia—analysis of the combined SEER and Medicare database

The median age at diagnosis of chronic lymphocytic leukemia (CLL) is 72, but patients enrolled in randomized trials are often a decade younger. Therapy selection and outcomes in the older, comorbid population are less understood. We evaluated treatment patterns and outcomes among 2,985 first primary CLL patients from the linked Surveillance, Epidemiology, and End Results–Medicare database. There were 151 chlorambucil (CLB), 594 rituximab monotherapy (R-mono), 696 rituximab?+?intravenous chemotherapy (R?+?IV Chemo), and 1,544 IV chemo-only patients. Patients administered CLB and R-mono were the oldest and had the highest comorbidity burden while patients receiving R?+?IV Chemo were the youngest and had the lowest comorbidity burden (p?<?0.0001). In the multivariate survival analysis, receipt of R?+?IV Chemo was associated with significantly lower mortality risk vs. IV Chemo-only (hazard ratio (HR)?=?0.73; 95 % confidence interval (CI) 0.62–0.87) and a non-significant mortality risk reduction with R-mono vs. CLB (HR?=?0.47; 95 % CI: 0.21-1.05). Older age and increasing comorbidity score were significantly associated with higher mortality. These findings suggest that chemoimmunotherapy is more effective than chemotherapy in an elderly population with a high prevalence of comorbidity, and this extends the conclusions from clinical trials in younger, medically fit patients.