Feature selection for structure-activity correlation using binary particle swarms

We present a new feature selection algorithm for structure-activity and structure-property correlation based on particle swarms. Particle swarms explore the search space through a population of individuals that adapt by returning stochastically toward previously successful regions, influenced by the success of their neighbors. This method, which was originally intended for searching multidimensional continuous spaces, is adapted to the problem of feature selection by viewing the location vectors of the particles as probabilities and employing roulette wheel selection to construct candidate subsets. The algorithm is applied in the construction of parsimonious quantitative structure-activity relationship (QSAR) models based on feed-forward neural networks and is tested on three classical data sets from the QSAR literature. It is shown that the method compares favorably with simulated annealing and is able to identify a better and more diverse set of solutions given the same amount of simulation time.     

A peroxyoxalate chemiluminescence-based assay for the evaluation of hydrogen peroxide scavenging activity employing 9,10-diphenylanthracene as the fluorophore

INTRODUCTION: A simple, rapid, sensitive, and enzyme-free analytical method for estimating scavenging of hydrogen peroxide (H2O2) was developed. METHODS: Peroxyoxalate chemiluminescence (POCL) was measured, using 9,10-diphenylanthracene as fluorophore. RESULTS: The chemiluminescence signal was found to be linear in response to increasing amounts of H2O2 in ethyl acetate/acetonitrile (9:1) (r2 = .9990), within a range of concentrations varying from 9.0 to 72.0 microM. In contrast, acetonitrile was highly unsuitable because of poor linearity (r2 = .3736) and poor signal stability. The linearity of POCL inhibition, as a measure of H2O2 scavenging, was tested employing well-known, lipid-soluble antioxidants, including beta-carotene, butylated hydroxytoluene (BHT) and alpha-tocopherol, and also the more polar flavonol quercetin, and the water-soluble L-ascorbic acid (AA). Under the experimental conditions, the corresponding values of H2O2 scavenging activity (SA(HP)) for quercetin, beta-carotene, alpha-tocopherol, and L-AA were 19.1 +/- 0.4, 70.9 +/- 20.1, 8.4 +/- 0.4, and 44.8 +/- 5.6 x 10(-3) microM(-1) DISCUSSION: The data establish the assay as a method for assessing the H2O2 quenching activity of lipid-soluble antioxidants.     

Roles of the two active sites of somatic angiotensin-converting enzyme in the cleavage of angiotensin I and bradykinin: insights from selective inhibitors

Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each bearing a functional active site. The in vivo contribution of each active site to the release of angiotensin II (Ang II) and the inactivation of bradykinin (BK) is still unknown. To gain insights into the functional roles of these two active sites, the in vitro and in vivo effects of compounds able to selectively inhibit only one active site of ACE were determined, using radiolabeled Ang I or BK, as physiological substrates of ACE. In vitro studies indicated that a full inhibition of the Ang I and BK cleavage requires a blockade of the two ACE active sites. In contrast, in vivo experiments in mice demonstrated that the selective inhibition of either the N-domain or the C-domain of ACE by these inhibitors prevents the conversion of Ang I to Ang II, while BK protection requires the inhibition of the two ACE active sites. Thus, in vivo, the cleavage of Ang I and BK by ACE appears to obey to different mechanisms. Remarkably, in vivo the conversion of Ang I seems to involve the two active sites of ACE, free of inhibitor. Based on these findings, it might be suggested that the gene duplication of ACE in vertebrates may represent a means for regulating the cleavage of Ang I differently from that of BK.     

The diagnostic validity of the Athens Insomnia Scale

OBJECTIVE: To provide documentation for the diagnostic validity of the Athens Insomnia Scale (AIS), a self-assessment psychometric tool which has previously shown high consistency, reliability and external validity for the evaluation of the intensity of sleep difficulty. METHODS: The AIS was administered to a total of 299 subjects (105 primary insomniacs, 100 psychiatric outpatients, 44 psychiatric inpatients and 50 nonpatient controls) who were also assessed for the ICD-10 diagnosis of "nonorganic insomnia" blindly in terms of the AIS scores. RESULTS: 176 subjects were identified as insomniacs and 123 as noninsomniacs. Logistic regression of AIS total score against the ICD-10 diagnosis of insomnia demonstrated that a score of 6 is the optimum cutoff based on the balance between sensitivity and specificity. When diagnosing individuals with a score of 6 or higher as insomniacs, the scale presents with 93% sensitivity and 85% specificity (90% overall correct case identification). For this cutoff score, in the general population, the scale has a positive predictive value (PPV) of 41% and a negative predictive value (NPV) of 99%. For the same cutoff score, among unselected psychiatric patients, the PPV was found to be 86% and the NPV 92%. Other cutoff scores can be also considered, however, depending on the importance of avoiding false positive or false negative results; for example, for a cutoff score of 10, the PPV in the general population reaches about 90% without the NPV becoming lower than 94%. CONCLUSION: The AIS can be utilized in clinical practice and research, not only as an instrument to measure the intensity of sleep-related problems, but also as a screening tool in reliably establishing the diagnosis of insomnia.     

Total and corrected antioxidant capacity in hemodialyzed patients

Background  

Oxidative stress may play a critical role in the vascular disease of end stage renal failure and hemodialysis patients. Studies, analyzing either discrete analytes and antioxidant substances, or the integrated total antioxidant activity of human plasma during hemodialysis, give contradictory results.     

Clinical presentation of the "depression-executive dysfunction syndrome" of late life.

It has been proposed that a "depression-executive dysfunction (DED) syndrome" occurs in late life. This assertion was based on clinical, neuropathological, and neuroimaging findings suggesting that frontostriatal dysfunctions contribute to the development of both depression and executive dysfunction and influence the course of depression. The authors describe the clinical presentation of DED and its relationship to disability, studying 126 elderly subjects with major depression and evaluating depressive symptoms, cognitive functioning, disability, and personality dimensions. Patients with the DED syndrome had reduced fluency, impaired visual naming, paranoia, loss of interest in activities, and psychomotor retardation, but showed a rather mild vegetative syndrome. Depressive symptomatology, and especially psychomotor retardation and loss of interest in activities, contributed to disability in DED patients, whereas paranoia was associated with disability independently of executive dysfunction. These findings may aid clinicians in identifying patients needing vigilant follow-up, because depression with executive dysfunction was found to be associated with disability, poor treatment response, relapse, and recurrence.     

A dose-escalation study of irinotecan (CPT-11) in combination with gemcitabine in patients with advanced non-small cell lung cancer previously treated with a cisplatin-based front line chemotherapy

PURPOSE: CPT-11 and gemcitabine are both active agents against non-small cell lung cancer (NSCLC). We conducted a phase I study to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of their combination in patients with previously treated advanced NSCLC. PATIENTS AND METHODS: Twenty-seven patients with histologically confirmed NSCLC, who had failed cisplatin-based front-line chemotherapy, were enrolled. The patients' median age was 56 years, 24 were male and 22 had a performance status (WHO) 0-1. Gemcitabine was administered on days 1 and 8, as a 30-minute i.v. infusion, at escalated doses ranging from 900 to 1200 mg/m2. CPT-11 was given over a 60-minute i.v. infusion on day 8 at escalated doses ranging from 200 to 350 mg/m2, following gemcitabine administration. The treatment was repeated every three weeks. RESULTS: The MTD was exceeded at dose-level 7 with CPT-11 350 mg/m2 and gemcitabine 1200 mg/m2, where all three enrolled patients presented DLTs (one patient grade 4 thrombocytopenia, one grade 3 diarrhea and one grade 3 asthenia). The recommended doses for future phase II studies are CPT-11 300 mg/m2 on day 8 and gemcitabine 1200 mg/m2 on days 1 and 8. A total of 107 treatment cycles were administered. Grade 3/4 neutropenia was observed in 13 (13%) cycles, febrile neutropenia in 3 (3%) and grade 3/4 thrombocytopenia in 2 (2%). Grade 2/3 diarrhea was seen in 6 (6%) cycles, grade 2/3 nausea and vomiting in 13 (13%) and grade 2/3 asthenia in 8 (8%). Other toxicities were mild. Among 23 patients evaluable for response, PR was achieved in one (4.5%), SD in 12 (52.5%) and PD in 10 (43%). CONCLUSION: The results of this phase I study clearly demonstrate that gemcitabine and CPT-11 can be efficiently combined in a low-toxicity regimen with doses equal or near monotherapy levels. Further studies are needed to evaluate the efficacy of this combination in both chemotherapy-naive and pre-treated patients with advanced NSCLC.     

Predictors of early recovery from major depression among persons admitted to community-based clinics: an observational study

BACKGROUND: Twenty years have elapsed since the National Institute of Mental Health Collaborative Depression Study reported on the early course and treatment of major depression within the mental health sector. Using similar methods, an observational study was conducted to assess relationships between initial depression severity, personality dysfunction and other baseline characteristics, subsequent treatment, and 3-month outcomes among persons admitted to public and voluntary sector outpatient clinics, including 1 academic program. METHODS: A 2-stage sampling technique was used to recruit subjects (N = 165) diagnosed by the Structured Clinical Interview for DSM-IV, Patient Version, as having a major depression episode. Sociodemographic and clinical characteristics were assessed at admission. Data on treatment and outcome were obtained at 3 months using structured instruments from the Longitudinal Interview Follow-up Evaluation. Logistic regression was used to assess hypothesized predictors of early recovery. Analyses were carried out in the total sample and after dichotomizing subjects by baseline depression severity. RESULTS: Fifty (30.3%) of the 165 subjects met recovery criteria. Less than half of the subjects (45%) met criteria for adequate pharmacotherapy. Less severe depression, having received adequate antidepressant treatment, female sex, and being married independently predicted early recovery. In the more depressed subgroup, early recovery was associated with female sex. Among less severely depressed subjects, high personality dysfunction scores and being married were significant predictors. CONCLUSIONS: Initial depression severity and receiving adequate pharmacotherapy predict early recovery in individuals with major depression seeking outpatient treatment. A minority of persons receive intensive antidepressant treatment. Less severe personality dysfunction and being married predicts early recovery among persons with less severe depression.     

Strongyloides stercoralis infection as a cause of acute granulomatous appendicitis in an HIV-positive patient in Athens,Greece

A case of acute granulomatous appendicitis due to Strongyloides stercoralis infection in an HIV-positive patient is described. To our knowledge this is the first case presented in the literature.