A signal-detection theory based perspective on design of warning

The effects of warnings are analyzed using a distributed signal-detection theory model. It is established that selectivity always increases effectiveness. The implications to optimal warning design for intermittent versus continuous hazards are discussed. The changes in the behavior of the 6 human subjects in response to changes in the warning levels are consistent with the predictions of the model.     

Treatment of large cold benign thyroid nodules not eligible for surgery with percutaneous ethanol injection

We studied the effect of percutaneous ethanol injection (PEI) in the treatment of cold, cytologically benign, large (>10 mL) thyroid nodules (CBNs) in 41 patients. The end-point of our study was to evaluate the efficacy of PEI on: 1) local symptomatology, assessed by an arbitrary symptom score; and 2) nodule volume and tracheal displacement (at ultrasonography). Follow-up ranged from 12-36 (21 +/- 9) months. Symptom score was significantly reduced (P < 0.01) after 6 months and at the end of the follow-up (2.1 +/- 0.3 vs. 0.2 +/- 0.5 and vs. 0.2 +/- 0.4). A significant (P < 0.01) nodule volume reduction was observed, without differences between solid or mixed CBNs; the reduction was 50% or more in 92.7% of patients. Neither clinical parameters nor pretreatment nodule ultrasonographic features were related to nodule reduction. Disappearance or significant reduction (>0.5 cm) of tracheal displacement was obtained in 61% and in 39% of patients, respectively. One patient experienced prethyroid region edema, pain, and mild fewer, which reversed within 1 week; and one patient had dysphonia, caused by vocal cord palsy, which reversed spontaneously within 1 month. At the end of the follow-up, nodules with just necrotic material at cytology showed a greater (P < 0.05) volume reduction than nodules with residual benign thyroid cells. Our data suggest that PEI is a safe and effective treatment of large CBNs, although sometimes serious side effects do occur.     

A conserved TN8TCCT motif in the octapeptide-encoding region of Pax genes which has the potential to direct cytosine methylation

Our previous findings have shown that the developmental genes Pax7 and Pax3 are differentially methylated; the gene region that encodes the paired domain is hypomethylated, whereas the region that encodes the homeodomain is hypermethylated. For this reason, the known DNA sequence between the paired and homeoboxes was analysed for the presence of a conserved DNA motif to which a modifying protein could bind in order to direct the methylation or demethylation of surrounding gene sequences. The octapeptide-encoding region was found to contain several nucleotides that were highly conserved throughout the Pax gene family from phylogenetically distant species. The most conserved nucleotides are thought to comprise a motif TN8TCCT where N8=any combination of eight nucleotides. A conserved octapeptide-like-encoding sequence containing the TN8TCCT motif was also found in non-Pax genes of higher eukaryotes and in the non-coding strand of plants. Moreover, differential methylation seems to be associated with the presence of the TN8TCCT motif in p53 and the human oestrogen receptor genes. The presence of the TN8TCCT motif within an octapeptide-like-encoding sequence in human T-cell leukaemia virus type 1 might suggest that the putative recognition motif may have been introduced into various host genomes via some form of retroviral agent.     

The success of locoregional, low-dose recombinant interleukin-2 therapy in tumor-bearing mice is dependent on the time of rIL-2 administration

The most common chromosomal aberrations in myelodysplastic syndromes (MDS) are complete or partial loss of chromosomes 5 and 7, and trisomy 8. To identify genes important in the pathogenesis of this disease that could be associated with these gross chromosomal defects, we have employed the differential display PCR (DDPCR) procedure developed by Liang and Pardee. This method allows simultaneous comparison of several cDNA sources for the presence of differentially expressed genes. Polymorphonuclear cells (PMNs) from two MDS patients, containing a 5q deletion or a trisomy 8, and three healthy controls were used. Initial screening resulted in the identification of five and three partial cDNA sequences, respectively that were either differentially expressed in both patient samples or in individual patients, as compared with the controls. The authenticity of aberrant expression was verified by reanalyzing the same primer combinations on newly prepared cDNA. Differential expression of the three remaining fragments was subsequently checked on a larger panel of MDS patients, using amplicon-specific primer sets. These were obtained by cloning and sequencing of the fragments. For one partial cDNA (DC3), the original expression pattern, i.e., decreased expression in individual MDS patients, was confirmed. These results demonstrate the utility of the DDPCR procedure to isolate differentially expressed sequences in primary patient samples where the availability of cells is a limiting factor.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

The psychosomatic network: foundations of mind-body medicine

Research in the 1980s uncovered ubiquitous neuropeptide-receptor distribution in brain structures associated with emotional processing, and throughout many organ systems. This finding supported neuropeptides as biochemical substrates of emotion, and the neuropeptide-receptor network as a parasynaptic system crossing traditional brain-body boundaries. The medical relevance of these findings was affirmed by psychoneuroimmunology research: neuropeptides help to regulate immunocyte trafficking, there is bidirectional communication between nervous and immune system components, immunocytes produce neuropeptides, and nerve cells produce immune-associated cytokines. In the past decade, the concept of a unified psychosomatic network has been strengthened by animal and human research demonstrating relationships between behavior and neuropeptide-mediated regulation of immune functions. Research on emotional expression or disclosure in healthy human subjects as well as in cancer and HIV-positive patients has shown significant positive correlations with clinically relevant immune functions and/or positive health outcomes. Psychosocial interventions emphasizing emotional expression or active coping have evidenced survival benefits in breast cancer and melanoma. These findings suggest that emotional expression generates balance in the neuropeptide-receptor network and a functional healing system. Emotional expression is also a marker for psychospiritual vitalization, and further research should evaluate links between energy-based models of health and neuropeptide-receptor-based models under the rubric of an informational paradigm.     

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), a novel bis-naphthalimide with potent nonselective tumoricidal activity in vitro

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.     

Dynamic proteome in enigmatic preeclampsia: an account of molecular mechanisms and biomarker discovery

The coevolution of genomics and proteomics has led to advancements in the field of diagnosis and molecular mechanisms of disease. Proteomics is now stepping into the field of obstetrics, where early diagnosis of pregnancy complication such as preeclampsia (PE) is imperative. PE is a multifactorial disease characterized by hypertension with proteinuria, which is a leading cause of maternal and neonatal morbidity and mortality occurring in 5-7% of pregnancies worldwide. This review discusses the probable molecular mechanisms that lead to PE and summarizes the proteomics research carried out in understanding the pathogenicity of PE, and for identifying the candidate biomarker for diagnosis of the disease.     

Sustainable Synthesis of Biaryls Using Silica Supported Ferrocene Appended N-Heterocyclic Carbene-Palladium Complex

Catalysis Letters - A novel silica supported ferrocene appended N-heterocyclic carbene-palladium complex (SilFemBenzNHC@Pd) has been prepared and characterized by using fourier transform infrared...     

Analysis of sub-anatomic diffusion tensor imaging indices in white matter regions of Alzheimer with MMSE score

In this study, an attempt has been made to find the correlation between diffusion tensor imaging (DTI) indices of white matter (WM) regions and mini mental state examination (MMSE) score of Alzheimer patients. Diffusion weighted images are obtained from the ADNI database. These are preprocessed for eddy current correction and removal of non-brain tissue. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (DA) indices are computed over significant regions (Fornix left, Splenium of corpus callosum left, Splenium of corpus callosum right, bilateral genu of the corpus callosum) affected by Alzheimer disease (AD) pathology. The correlation is computed between diffusion indices of the significant regions and MMSE score using linear fit technique so as to find the relation between clinical parameters and the image features. Binary classification has been employed using support vector machine, decision stumps and simple logistic classifiers on the extracted DTI indices along with MMSE score to classify Alzheimer patients from healthy controls. It is observed that distinct values of DTI indices exist for the range of MMSE score. However, there is no strong correlation (Pearson's correlation coefficient ‘r’ varies from 0.0383 to −0.1924) between the MMSE score and the diffusion indices over the significant regions. Further, the performance evaluation of classifiers shows 94% accuracy using SVM in differentiating AD and control. In isolation clinical and image features can be used for prescreening and diagnosis of AD but no sub anatomic region correlation exist between these features set. The discussion on the correlation of diffusion indices of WM with MMSE score is presented in this study.