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Depression and heart failure in patients with a new myocardial infarction.

BACKGROUND: Heart failure (HF) is a disabling chronic illness that is increasing in prevalence. Despite advances in its medical treatment, little is known about its psychosocial correlates. This investigation compared the prevalence of depression in patients with and without HF who were hospitalized with myocardial infarction (MI) and also at high psychosocial risk. METHODS: Baseline data from the 2444 participants in the ENRICHD clinical trial were used. Within 28 days of the MI, all patients were assessed for depression using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, for HF based upon left ventricular dysfunction or history of HF and for demographic and medical confounders. RESULTS: Eight hundred forty-seven patients (34.7%) met the criteria for HF. Major depression was observed in 43% in the HF group compared with 36% in the non-HF group (P < .001). Multivariate modeling showed a 38% increase in odds of HF for patients with major depression, after adjustment for sociodemographic factors and medical comorbidities (adjusted OR 1.38, 95% CI 1.09-1.76). CONCLUSIONS: These findings suggest that in patients with new MI who are at psychosocial risk, major depression is more prevalent in those who also have HF. Because major depression undermines adherence and lowers quality of life, special efforts to diagnose and treat it in post-MI patients with HF appear warranted.

Aged↗

Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial.

Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.

Adult↗

Chemotactic sensing of extracellular antibiotic resistance genes enables their efficient removal by Stutzerimonas stutzeri.

The dissemination of antibiotic resistance genes (ARGs) in wastewater environments poses a severe threat to public health. Extracellular ARGs (eARGs) persist as free DNA fragments that are refractory to efficient removal by conventional physicochemical treatment technologies. Here, we isolated Stutzerimonas stutzeri CHY07 from municipal sewage and demonstrated that extracellular DNA fragments, including eARGs, can serve as chemoattractants for environmental bacteria. Through genomic mining, molecular docking, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and protein-ligand interaction profiling, we identified the chemoreceptor Mcp16 as the primary sensor of extracellular DNA and revealed that it achieves sequence-independent recognition of the DNA phosphate backbone. We further established the endogenous pentapeptide VRSVR as a methylation substrate for CheR and constructed the engineered strain CHY07-2 (mcp16::VRSVR) using an SSB/CRISPR-Cas9 ribonucleoprotein (RNP) system. This strain exhibited significantly enhanced chemotactic responsiveness, achieving 72-h removal efficiencies of 96.56% and 91.60% for low- and high-molecular-weight eARGs in non-sterile WWTP secondary effluent; conversely, mcp16 deletion markedly attenuated both chemotaxis and removal, whereas in situ complementation restored them. These findings reveal a "chemotaxis-contact-removal" cascade - with a proposed self-reinforcing loop - in eARG-removing bacteria, providing both a theoretical framework and a technical paradigm for enhancing pollutant removal through targeted amplification of microbial chemotaxis.

Chemotaxis↗

Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial.

Depression is a major worldwide health problem. Indeed, by 2020, depressive disorders are estimated to represent the second largest disease burden worldwide. Although a variety of pharmaceutical agents are available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. Our objective was to assess the efficacy of petal of Crocus sativus in the treatment of mild-to-moderate depression in a 6-week double-blind, placebo-controlled and randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM IV participated in the trial. In this double-blind, placebo-controlled and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 30 mg/day (BD) (Group 1) and capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, petal of C. sativus produced a significantly better outcome on Hamilton Depression Rating Scale than placebo (d.f.=1, F=16.87, p<0.001). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of petal of C. sativus in the treatment of mild-to-moderate depression. A large-scale trial is justified.

Adult↗

Structure and specific RNA binding of ADAR2 double-stranded RNA binding motifs.

Adenosine deaminases that act on RNA (ADARs) site-selectively modify adenosines to inosines within RNA transcripts, thereby recoding genomic information. How ADARs select specific adenosine moieties for deamination is poorly understood. Here, we report NMR structures of the two double-stranded RNA binding motifs (dsRBMs) of rat ADAR2 and an NMR chemical shift perturbation study of the interaction of the two dsRBMs with a 71 nucleotide RNA encoding the R/G site of the GluR-B. We have identified the protein and the RNA surfaces involved in complex formation, allowing us to present an NMR-based model of the complex. We have found that dsRBM1 recognizes a conserved pentaloop, whereas dsRBM2 recognizes two bulged bases adjacent to the editing site, demonstrating RNA structure-dependent recognition by the ADAR2 dsRBMs. In vitro mutagenesis studies with both the protein and the RNA further support our structural findings.

Adenosine Deaminase↗

Legal aspects and international assistance related to the deliberate use of chemicals to cause harm.

National and international law is an essential component of the array of measures serving to protect against the hostile release of biological or chemical agents, and to help to mitigate the consequences should such a release nevertheless take place. These includes the Geneva Protocol of 1925, the Chemical Weapons Convention of 1993, for which the Organization for the Prohibition of Chemical Weapons (OPCW) has been established in 1997. In addition to the OPCW, the international community has made preparations through the United Nations (e.g. United Nations Office for the Coordination of Humanitarian Affairs, World Health Organization) for assistance to governments against which biological and chemical weapons might be used. This paper provides an overview of the international mechanisms for assistance and is based on the Second Edition of the Public Health Response to Biological and Chemical Weapons: WHO Guidance (). Toxicologists throughout the world should know these regulations and act accordingly.

Chemical Warfare↗

[Escitalopram for treatment of major depressive disorder in adults].

Escitalopram is a selective serotonin reuptake inhibitor (SSRI); it is the therapeutically active S-enantiomer of the racemic mixture, citalopram. This review aimed to compare the efficacy and tolerability of escitalopram versus citalopram and several other SSRIs (citalopram, fluoxetine, paroxetine, sertraline), and a selective reuptake inhibitor of noradrenaline and serotonin, venlafaxine XR, for treatment of DSM IV (Diagnostic and Statistical Manual of mental disorders - fourth edition) major depressive disorder, based on the studies evaluated by the Commission de la Transparence de la R6publique Frangaise, and data from a pooled analysis presented in 2005 at the 158th annual congress of the American Psychiatric Association. Change from baseline to end-point on total MADRS (Montgomery-Asberg Depression Rating Scale--10 items, score range: 0-60) was the primary efficacy parameter; changes on HAM-D17 (Hamilton rating scale for depression--17 items), CGI-S and CGI-I (Clinical global Impression-Severity and-Improvement), and response rates (> or = 50% MADRS score reduction) and remissions (< 12 MADRS score) were the secondary efficacy parameters. Tolerability assessment was based on the numbers and rates of adverse events observed with treatment, and the DESS (Discontinuation Emergent Signs and Symptoms-43 items) scale was used for assessment of adverse events observed with treatment withdrawal. Analyses were based on intention to treat using the LOCF (last observation carried forward) method. Efficacy of escitalopram appeared to be at least equivalent to that of the active comparators in all cases. The difference between active compounds was more marked when depressive symptoms were more severe. From the point of view of tolerability, frequency of adverse effects occurring on treatment and the frequency of treatment discontinuations due to adverse effects were comparable with both escitalopram and the active comparators; however, the comparisons were mostly favourable to escitalopram, though differences were generally not statistically significant. In both studies of escitalopram versus venlafaxine XR, treatment discontinuations due to adverse events were less frequent on escitalopram than on venlafaxine XR (7.5% vs 11.2%, and 4.1% vs 16.0% respectively). With regard to adverse events associated with the withdrawal period, the signs and symptoms occurring on treatment discontinuation assessed after 1 week using the DESS scale were less frequent on escitalopram than on venlafaxine XR at 8 weeks and paroxetine at 24 weeks. Concerning suicide risk, a review of clinical trials involving 2277 patients on escitalopram and 1814 patients on placebo showed that this risk was minimal, and similar in both groups; moreover, no evidence was found suggesting that escitalopram might promote suicidal behaviour compared with placebo. These results suggest that escitalopram is suitable to be considered as a first-line drug treatment for major depressive disorder.

Adult↗

Learning about DNA polymerase function by studying antimutator DNA polymerases.

Mutant bacteriophage T4 DNA polymerases exist that appear primarily to reduce the frequency of AT-to-GC transitions when this [antimutator' phenotype is assessed by genetic methods. This observation disagrees with in vitro studies, which indicate that T4 antimutator DNA polymerases have increased proofreading abilities and effectively edit all types of base substitution errors. One explanation that reconciles the apparent in vivo mutational specificity of antimutator DNA polymerases with their biochemical properties is that the in vivo mutational specificity identifies mismatched primer-termini that are corrected less efficiently by the wild-type level of proofreading activity, but are corrected if proofreading is increased.

Bacteriophage T4↗

The reduced graph descriptor in virtual screening and data-driven clustering of high-throughput screening data.

Virtual screening and high-throughput screening are two major components of lead discovery within the pharmaceutical industry. In this paper we describe improvements to previously published methods for similarity searching with reduced graphs, with a particular focus on ligand-based virtual screening, and describe a novel use of reduced graphs in the clustering of high-throughput screening data. Literature methods for reduced graph similarity searching encode the reduced graphs as binary fingerprints, which has a number of issues. In this paper we extend the definition of the reduced graph to include positively and negatively ionizable groups and introduce a new method for measuring the similarity of reduced graphs based on a weighted edit distance. Moving beyond simple similarity searching, we show how more flexible queries can be built using reduced graphs and describe a database system that allows iterative querying with multiple representations. Reduced graphs capture many important features of ligand-receptor interactions and, in conjunction with other whole molecule descriptors, provide an informative way to review HTS data. We describe a novel use of reduced graphs in this context, introducing a method we have termed data-driven clustering, that identifies clusters of molecules represented by a particular whole molecule descriptor and enriched in active compounds.

Journal Article↗

The reliability and validity of the panic disorder self-report: a new diagnostic screening measure of panic disorder.

This study examined the Panic Disorder Self-Report (PDSR), a new self-report diagnostic measure of panic disorder based on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994). PDSR diagnoses were compared with structured interview diagnoses of individuals with generalized anxiety disorder, social phobia, and panic disorder and nonanxious controls. Receiver operating characteristic analyses revealed that the PDSR showed 100% specificity and 89% sensitivity. The PDSR also demonstrated retest reliability, convergent and discriminant validity, and kappa agreement of .93 with a structured interview. Finally, the PDSR demonstrated clinical validity. Students who were identified as having panic disorder using the PDSR did not have significantly different scores on the Panic Disorder Severity Scale--Self-Report form (P. R. Houck, D. A. Speigel, M. K. Shear, & P. Rucci, 2002) than a panic disordered community sample. However, both groups had significantly higher scores than students identified as not meeting criteria for panic disorder.

Adult↗

Rewiring the keyboard: evolvability of the genetic code.

The genetic code evolved in two distinct phases. First, the 'canonical' code emerged before the last universal ancestor; subsequently, this code diverged in numerous nuclear and organelle lineages. Here, we examine the distribution and causes of these secondary deviations from the canonical genetic code. The majority of non-standard codes arise from alterations in the tRNA, with most occurring by post-transcriptional modifications, such as base modification or RNA editing, rather than by substitutions within tRNA anticodons.

Animals↗

Natural killer cells and dendritic cells: rendezvous in abused tissues.

Natural killer (NK) cells and dendritic cells (DCs) are two types of specialized cell of the innate immune system, the reciprocal interaction of which results in a potent, activating cross-talk. For example, DCs can prime resting NK cells, which, in turn, after activation, might induce DC maturation. However, NK cells negatively regulate the function of DCs also by killing immature DCs in peripheral tissues. Moreover, a subset of NK cells, after migration to secondary lymphoid tissues, might have a role in the editing of mature DCs based on the selective killing of mature DCs that do not express optimal surface densities of MHC class I molecules. So, cognate interactions between NK cells and DCs provide a coordinated mechanism that is involved not only in the regulation of innate immunity, but also in the promotion of appropriate downstream adaptive responses for defence against pathogens.

Animals↗

Sample size effects on temporal reliability of language sample measures of preschool children.

The present study examined the temporal reliability of four quantitative measurements of operationally defined linguistic behaviors observed in a naturalistic setting. The measures of language production were computed using the Systematic Analysis of Language Transcripts (SALT) software from two 20-minute language samples obtained 3 to 14 days apart for each of 20 preschool-aged children. Samples were edited to different sizes based either on duration (12 or 20 minutes) or on limits of the total number of complete and intelligible utterances (from 25 to 175 in increments of 25). Inadequate reliability was found for the language sample measure, total number of words; hence, the validity of this measure is questionable. In contrast, very high temporal reliability coefficients (r > .92) were obtained for the language sample measures of number of different words, mean length of utterance in morphemes, and mean sentence length in morphemes when derived from a large number (> or = 175) of complete and intelligible utterances. The temporal reliability of these measures reached acceptable levels, not only for research purposes, but for diagnostic purposes as well.

Child, Preschool↗

Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression.

BACKGROUND: Depression is an international public health problem. Impairment in social and occupational functioning, increased comorbidity with other psychiatric and medical conditions, and an increased risk of mortality are a few of its consequences. Some psychiatrists have the impression that selective serotonin re-uptake inhibitors may not work as well as tricyclic anti-depressants in severe depression and/or melancholia. On the contrary, there is a general belief that selective serotonin re-uptake inhibitors are superior to the tricyclic anti-depressants in having fewer side-effects, particularly cardiovascular effects. The objective of this double-blind study was to compare the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe major depression. METHODS: A total of 48 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), forth edition for major depression, based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton Rating Scale for Depression score of at least 20. In this double-blind, single-center trial, patients were randomly assigned to receive nortriptyline 150 mg/day (group 1) or fluoxetine 60 mg/day (group 2) for 6-weeks. The outcome of the two groups was assessed using Hamilton Depression Rating Scale, a side-effect checklist and a regular ECG assessment. RESULTS: The results suggest that the efficacy of nortriptyline is superior to fluoxetine in this group of major depressed patients. No significant differences were observed between dropout rates in the two groups but anti-cholinergic side-effects were significantly more frequent with nortriptyline than with fluoxetine but there was no significant difference in cardiovascular effects in particular QTc prolongation. CONCLUSION: The results of the current study suggest that nortriptyline was more effective than fluoxetine in the treatment of moderate to severe depression. A larger study is warranted.

Adult↗

Amphetamine withdrawal: I. Reliability, validity and factor structure of a measure.

OBJECTIVE: The aim of this study was to create a short, reliable and valid questionnaire for the evaluation of amphetamine withdrawal, which we shall call the Amphetamine Withdrawal Questionnaire (AWQ). METHOD: Items of the AWQ included in this study were based on the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) and a comprehensive review. A field trial for assessing the reliability, validity and factor structure was conducted in outpatients and inpatients with amphetamine withdrawal. RESULTS: Thirty and 102 patients' data were included in the reliability-validity tests and the factor study, respectively. Due to the very low mean score of insomnia item, this item was excluded from subsequent analyses. The AWQ internal consistency was satisfactory with a Cronbach's alpha of 0.77. For test-retest reliability, a Spearman rank order correlation coefficient of the AWQ total score was 0.79. The AWQ total score for criterion validity was moderately correlated with the other two accepted measures. Principal component analysis, eigenvalue-one test and a varimax rotation performed to elicit the factors of AWQ yielded a three-factor model of AWQ: namely hyperarousal, reversed vegetative and anxiety factors. CONCLUSIONS: The AWQ is a short, reliable and valid measure for assessing amphetamine withdrawal symptoms. Further studies with a larger number of patients should be conducted to confirm the results of this factor analysis.

Adolescent↗

Correspondence between adolescent report, parent report, and teacher report of manic symptoms.

OBJECTIVE: To examine differences between source-specific manic symptoms. METHODS: In total, 104 consecutive adolescent outpatient referrals were evaluated for their psychiatric status using a questionnaire based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders that was completed by parents, teachers, and youths. RESULTS: Approximately one third of the youths met symptom criteria for mania by at least one informant; however, only 38% of these met such criteria by at least two informants. Youths who had manic symptoms according to two informants were significantly more symptomatic both on mental status exam and in other dimensions of psychopathology than youths who did not have corroborated manic symptoms. Cross-informant agreement was generally poor when symptoms were scored dimensionally. CONCLUSIONS: Manic symptoms are relatively nonspecific in outpatient samples. Using more than one informant increases the likelihood of selecting subjects with serious and possibly manic disorders.

Adolescent↗

Effects of combined treatment on Turkish children diagnosed with attention-deficit/hyperactivity disorder: a preliminary report.

OBJECTIVE: The main aim of this study was to investigate the effects of combined treatment on children diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHOD: After careful screening, 47 children (57%) diagnosed with ADHD + oppositional defiant disorder (ODD) and 36 children (43%) diagnosed with ADHD + conduct disorder (CD) were included in the study. Treatment consisted of ongoing medication (methylphenidate) management and a parent-training program that continued for 5 months. Children were assessed in multiple domains by multiple sources of information at baseline and at the end of the 1st, 3rd, and 6th months by parent- and teacher-completed the Turgay Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S), Conners Parent Rating Scale (CPRS), and Conners Teacher Rating Scale (CTRS). Mother-child relationship was assessed by the Parental Acceptance and Rejection Questionnaire (PARQ). RESULTS: Combined treatment was effective in reducing the ADHD, ODD, and CD symptoms. Analyses of the data revealed that medication, rather than parent training, was responsible for the improvements both in the symptoms and in the mother-child relationship. CONCLUSIONS: The results of the study, in line with the Multimodal Treatment Study of Children with ADHD (MTA) findings, highlighted the role of stimulant medication in the treatment of ADHD.

Adolescent↗

Ridom TraceEdit: a DNA trace editor and viewer.

Ridom TraceEdit is a cross-platform graphical DNA trace viewer and editor. TraceEdit displays the chromatogram files from Applied Biosystems automated sequencers and files in the Staden SCF format. Incorrect base calls can be edited and saved.

Algorithms↗