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Find video protocols related to scientific articles indexed in Pubmed.
Incidence of Tardive Dyskinesia in Older Adult Patients Treated With Olanzapine or Conventional Antipsychotics.
J Geriatr Psychiatry Neurol
PUBLISHED: 07-11-2014
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The risk of persistent tardive dyskinesia (TD) was compared in patients with acute psychosis or agitation aged 55 years or older who were treated with olanzapine (OLZ) or conventional antipsychotic (CNV) drug therapy.
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A comparative assessment and analysis of 20 representative sequence alignment methods for protein structure prediction.
Sci Rep
PUBLISHED: 07-01-2013
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Protein sequence alignment is essential for template-based protein structure prediction and function annotation. We collect 20 sequence alignment algorithms, 10 published and 10 newly developed, which cover all representative sequence- and profile-based alignment approaches. These algorithms are benchmarked on 538 non-redundant proteins for protein fold-recognition on a uniform template library. Results demonstrate dominant advantage of profile-profile based methods, which generate models with average TM-score 26.5% higher than sequence-profile methods and 49.8% higher than sequence-sequence alignment methods. There is no obvious difference in results between methods with profiles generated from PSI-BLAST PSSM matrix and hidden Markov models. Accuracy of profile-profile alignments can be further improved by 9.6% or 21.4% when predicted or native structure features are incorporated. Nevertheless, TM-scores from profile-profile methods including experimental structural features are still 37.1% lower than that from TM-align, demonstrating that the fold-recognition problem cannot be solved solely by improving accuracy of structure feature predictions.
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Evolutionary dynamics and information hierarchies in biological systems.
Ann. N. Y. Acad. Sci.
PUBLISHED: 05-20-2013
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The study of evolution has entered a revolutionary new era, where quantitative and predictive methods are transforming the traditionally qualitative and retrospective approaches of the past. Genomic sequencing and modern computational techniques are permitting quantitative comparisons between variation in the natural world and predictions rooted in neo-Darwinian theory, revealing the shortcomings of current evolutionary theory, particularly with regard to large-scale phenomena like macroevolution. Current research spanning and uniting diverse fields and exploring the physical and chemical nature of organisms across temporal, spatial, and organizational scales is replacing the model of evolution as a passive filter selecting for random changes at the nucleotide level with a paradigm in which evolution is a dynamic process both constrained and driven by the informational architecture of organisms across scales, from DNA and chromatin regulation to interactions within and between species and the environment.
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A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia.
BMC Psychiatry
PUBLISHED: 05-15-2013
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BACKGROUND: We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). METHODS: Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). RESULTS: There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). CONCLUSION: These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics.Trials registration: A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR SchizophreniaClinicalTrials.gov identifier: NCT00845026.
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Recycling of informational units leads to selection of replicators in a prebiotic soup.
Chem. Biol.
PUBLISHED: 01-03-2013
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Prebiotic chemical reactions would have been greatly aided by a process whereby living materials could have been recycled under conditions of limiting resources. Recombination of RNA fragments is a viable means of recycling but has not been demonstrated. Using systems based on the Azoarcus group I intron ribozyme, computational Monte Carlo studies indicate that a moderate level of recycling activity, spontaneous or catalyzed, leads to the most robust selection scenarios. It is interesting that recycling leads to a threshold effect where a dominant species suddenly jumps to fixation. In conjunction, laboratory studies with the Azoarcus ribozyme corroborate these results, showing that mixtures of scrambled and/or deleteriously mutated molecules can recycle their component fragments to generate fully functional recombinase ribozymes. These studies highlight the importance of recombination and recycling jointly in the advent of living systems.
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The relationship, structure and profiles of schizophrenia measurements: a post-hoc analysis of the baseline measures from a randomized clinical trial.
BMC Psychiatry
PUBLISHED: 06-30-2011
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To fully assess the various dimensions affected by schizophrenia, clinical trials often include multiple scales measuring various symptom profiles, cognition, quality of life, subjective well-being, and functional impairment. In this exploratory study, we characterized the relationships among six clinical, functional, cognitive, and quality-of-life measures, identifying a parsimonious set of measurements.
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Auditory memory decrements, without dissimulation, among patients with major depressive disorder.
Arch Clin Neuropsychol
PUBLISHED: 05-18-2011
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Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.
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A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia.
J Clin Psychopharmacol
PUBLISHED: 04-22-2011
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The primary objective of this study was to test the hypothesis that 1 or more dose levels of LY2140023 monohydrate, an oral prodrug of the potent metabotropic glutamate (mGlu) 2/3 receptor agonist LY404039, given to patients with schizophrenia for 4 weeks would demonstrate significantly greater efficacy than placebo. The HBBI study was a multicenter, randomized, double-blind, parallel, placebo- and active-controlled trial. Male and female patients aged 18 to 65 years who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia were randomized in a 2:2:2:2:2:1 ratio to receive 5-, 20-, 40-, or 80-mg LY2140023 monohydrate twice daily, placebo twice daily, or placebo (am) and 15 mg of olanzapine (pm) daily. Efficacy was defined as the change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score assessed at 4 weeks. The primary analysis did not show that any of the 4 LY2140023 monohydrate doses were more efficacious than placebo as measured by the PANSS total score. Similarly, olanzapine did not significantly separate from placebo. A higher-than-anticipated treatment effect (14.6-point improvement) in the placebo group was observed on PANSS total score. LY2140023 monohydrate was generally well tolerated, although 4 patients reported the serious adverse event of convulsion. LY2140023 monohydrate-treated patients showed little change in dopamine-related adverse events and weight. The results of the HBBI study are considered to be inconclusive because LY2140023 monohydrate and the active control olanzapine did not separate from placebo in the treatment of patients with acutely exacerbated schizophrenia. Additional efficacy, safety, and tolerability testing are needed.
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Cost-effectiveness of early responders versus early nonresponders to atypical antipsychotic therapy.
Clinicoecon Outcomes Res
PUBLISHED: 04-19-2011
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To compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone) and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine.
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Trajectories of response to treatment with atypical antipsychotic medication in patients with schizophrenia pooled from 6 double-blind, randomized clinical trials.
Schizophr. Res.
PUBLISHED: 03-07-2011
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Research has identified distinct trajectories of antipsychotic response in patients with chronic schizophrenia in short-duration trials (~12 weeks). This post-hoc analysis identified trajectories in patients with chronic schizophrenia treated for ?24 weeks. We pooled data from 1990 patients with chronic schizophrenia from 6 randomized, double-blind, olanzapine-comparator trials of atypical antipsychotics. Trajectory analysis identified homogeneous subpopulations within the larger heterogeneous population. Baseline demographics were compared between the identified latent classes. Five distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) Total score were identified: Dramatic Responders (n=47/1990, 2.4%), severely-ill patients (PANSS=124) with rapid and sustained improvement (51%) by Week 3; Partial Responders (n=1802/1990, 90.6%), moderately-ill (PANSS=90) with minimal improvement (21%) by Week 4, and little further improvement; Partial Responders-Unsustained (Late) (n=32/1990, 1.6%), markedly-ill (PANSS=95) with minimal initial improvement followed by worsening after Week 12; Partial Responders-Unsustained (Early) (n=28/1990, 1.4%), markedly-ill (PANSS=102) with minimal initial improvement followed by worsening after Week 8; and Delayed Responders (n=81/1990, 4.1%), markedly-to-severely-ill (PANSS=113) with minimal (11%) improvement at Week 8, but noticeable improvement thereafter (49%). Significant differences were noted for several baseline characteristics (p<.05) and discontinuation rates (46%-72%). Dramatic Responders were younger and more likely to be female and Hispanic with higher baseline illness severity. Analysis of antipsychotic response over 24 weeks in a large, pooled, heterogeneous population treated for schizophrenia revealed 5 distinct trajectories. Most patients had modest and sustained improvements during atypical antipsychotic treatment, regardless of their baseline illness severity, representing a partial response to currently available treatments.
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Identification of early changes in specific symptoms that predict longer-term response to atypical antipsychotics in the treatment of patients with schizophrenia.
BMC Psychiatry
PUBLISHED: 02-09-2011
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To identify a simple decision tree using early symptom change to predict response to atypical antipsychotic therapy in patients with (Diagnostic and Statistical Manual, Fourth Edition, Text Revised) chronic schizophrenia.
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Impact of race on efficacy and safety during treatment with olanzapine in schizophrenia, schizophreniform or schizoaffective disorder.
BMC Psychiatry
PUBLISHED: 11-03-2010
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To examine potential differences in efficacy and safety of treatment with olanzapine in patients with schizophrenia of white and black descent.
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Self-reported cognitive symptoms following mild traumatic brain injury are poorly associated with neuropsychological performance in OIF/OEF veterans.
J Rehabil Res Dev
PUBLISHED: 09-18-2010
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Mild traumatic brain injury (mTBI) is not uncommon among Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans, and many individuals within this group report lingering cognitive difficulties following their injury. For Department of Veterans Affairs clinicians, an accurate assessment of cognitive symptoms is important in providing appropriate clinical care. Although self-assessment is commonly employed to screen for difficulties in cognitive functioning, little is known about the accuracy of self-report in this population. This study collected cognitive, psychiatric, and self-report data from 105 OIF/OEF veterans with mTBI to examine the relationship between self-reported cognitive functioning and objective neuropsychological test performance. Additionally, clinicians who frequently work with OIF/OEF veterans were asked to predict the magnitude of these associations. Self-reported cognitive functioning was not significantly correlated with objective cognitive abilities, suggesting that objective neuropsychological testing should be used when cognitive weakness is suspected. Perceived cognitive deficits were associated with depression, anxiety, and posttraumatic stress disorder, illustrating the additional importance of adequate assessment and treatment of psychiatric symptoms. Clinicians tended to overestimate the association between self-report and test performance.
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Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials.
J Clin Psychopharmacol
PUBLISHED: 05-18-2010
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Extended placebo-controlled clinical trials in schizophrenia research pose an ethical challenge. This study examines factors that have implications for the design and duration of placebo-controlled acute efficacy trials: Does early response discriminate active drug (AD) from placebo, and are the early differences sustained over time? A post hoc pooled analysis of 2 randomized 6-week double-blind clinical trials was performed comparing patients with schizophrenia treated with placebo or low-dose olanzapine (1 mg/d; placebo/low dose [PBO] group, n = 170) to patients treated with a 10- to 20-mg/d dose of haloperidol or medium- to high-dose olanzapine (7.5 to 17.5 mg/d; AD group, n = 252). Mixed-model repeated-measure analysis tested for group differences. Power analysis was undertaken to compare study designs with shorter durations. At 2 weeks, the mean reduction in the Brief Psychiatric Rating Scale total score was significantly greater for the AD group (-10.1) compared with the PBO group (-4.1; P < 0.001); this difference was sustained until the study ended (6 weeks). A higher proportion of early treatment responders were observed for the AD group (52%) compared with the PBO group (29%; P < 0.001). Early nonresponse to placebo or drug was predictive of subsequent nonresponse (negative predictive value: PBO = 95%, AD = 84%). Power analysis indicates that the placebo-drug differences are robust at 2 weeks. Treatment responders from the AD and the PBO groups followed a similar response path. Early response to antipsychotic treatment discriminated AD from placebo. Reducing placebo-controlled clinical trials from 6 weeks to 2 to 4 weeks was found to be a viable option for efficacy identification in acutely ill patients.
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Consumers perspectives on successful and unsuccessful experiences in a drug treatment court.
Subst Use Misuse
PUBLISHED: 05-06-2010
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This study focused on the program experiences of 190 men and women who chose to participate in a drug treatment court in lieu of incarceration in California. Participants had committed non-violent criminal offenses related to drug abuse. The program required 18 months of community-based treatment in conjunction with court supervision including frequent drug testing and 6 months of abstinence for successful program completion. Interviews were conducted in 2007/2008 with 94 participants who had successfully completed treatment and 96 who had not. Open-ended questions addressed reasons for entering and remaining in treatment and supports and obstacles to program completion. Responses were coded using ethnographic content analysis. Factors associated with successful program completion are discussed.
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Early response to antipsychotic therapy as a clinical marker of subsequent response in the treatment of patients with first-episode psychosis.
Psychiatry Res
PUBLISHED: 02-11-2010
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Early response to antipsychotic medication has been shown to accurately predict later response to continued use of the same treatment in patients with chronic schizophrenia. This study examines whether this predictive pattern exists for patients with first-episode psychosis. We used a data-driven threshold for early response of ? 26.2% improvement from baseline on the Positive and Negative Syndrome Scale (PANSS(0-6)) Total score to determine whether response at Week 2 of treatment may predict response at Week 12 in a randomized, double-blind trial of olanzapine versus haloperidol for treatment of patients with first-episode psychosis (N=225). Later response was defined as a ? 40% and ? 50% improvement in PANSS Total(0-6) score and as remission. At Week 2, 43% (97/225) of patients were identified as early responders. At a threshold for later response of ? 50% improvement in PANSS(0-6) Total score, early non-response most strongly predicted later non-response, demonstrating high specificity (74%) and high negative predictive value (80%). As had been seen in the treatment of patients with chronic schizophrenia, early non-response was a robust predictor of subsequent non-response in the treatment of patients with first-episode psychosis.
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Challenging the assumption that improvement in functional outcomes is delayed relative to improvement in symptoms in the treatment of schizophrenia.
Schizophr. Res.
PUBLISHED: 01-15-2010
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Functional improvement is generally thought to be distal to improvement in psychiatric symptoms in patients with schizophrenia. In this study, we assessed the effects of early response/non-response to an atypical antipsychotic across multiple outcome measures.
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Defining "good" and "poor" outcomes in patients with schizophrenia or schizoaffective disorder: a multidimensional data-driven approach.
Psychiatry Res
PUBLISHED: 11-08-2009
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The studys goal was to characterize the typology of patient outcomes based on social and occupational functioning and psychiatric symptoms following antipsychotic drug treatment, and to explore predictors of group membership representing the best/worst outcomes. A hierarchical cluster analysis was used to define groups of patients (n=1449) based on endpoint values for psychiatric symptoms, social functioning, and useful work measured up to 30 weeks of treatment. Stepwise logistic regression was used to construct predictive models of cluster membership for baseline predictors, and with 2/4/8 weeks of treatment. Five distinct clusters of patients were identified at endpoint (Clusters A-E). Patients in Cluster A (25.6%, best outcome) had minimal psychiatric symptoms and mild functional impairment, while patients in Cluster D (14.3%) and E (14.8%) (worst outcome) had moderate-to-severe symptoms and severe functional impairment. Occupational functioning, disorganized thinking, and positive symptoms were sufficient to describe the clusters. Membership in the best/worst clusters was predicted by baseline scores for functioning and symptom severity, and by early changes in symptoms with treatment. Psychiatric symptoms and functioning provided complementary information to describe treatment outcomes. Early symptom response significantly improved the prediction of outcome, suggesting that early monitoring of treatment response may be useful in clinical practice.
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Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy.
BMC Psychiatry
PUBLISHED: 07-14-2009
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Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs.
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Optimal thresholds of early response to atypical antipsychotics: application of signal detection methods.
Schizophr. Res.
PUBLISHED: 05-26-2009
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Identify the optimal magnitude of response to antipsychotic medication at various early time points that best predicts subsequent non-response at 8 weeks.
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Toward homochiral protocells in noncatalytic peptide systems.
Orig Life Evol Biosph
PUBLISHED: 03-20-2009
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The activation-polymerization-epimerization-depolymerization (APED) model of Plasson et al. has recently been proposed as a mechanism for the evolution of homochirality on prebiotic Earth. The dynamics of the APED model in two-dimensional spatially-extended systems is investigated for various realistic reaction parameters. It is found that the APED system allows for the formation of isolated homochiral proto-domains surrounded by a racemate. A diffusive slowdown of the APED network induced, for example, through tidal motion or evaporating pools and lagoons leads to the stabilization of homochiral bounded structures as expected in the first self-assembled protocells.
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The algorithmic origins of life.
J R Soc Interface
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Although it has been notoriously difficult to pin down precisely what is it that makes life so distinctive and remarkable, there is general agreement that its informational aspect is one key property, perhaps the key property. The unique informational narrative of living systems suggests that life may be characterized by context-dependent causal influences, and, in particular, that top-down (or downward) causation-where higher levels influence and constrain the dynamics of lower levels in organizational hierarchies-may be a major contributor to the hierarchal structure of living systems. Here, we propose that the emergence of life may correspond to a physical transition associated with a shift in the causal structure, where information gains direct and context-dependent causal efficacy over the matter in which it is instantiated. Such a transition may be akin to more traditional physical transitions (e.g. thermodynamic phase transitions), with the crucial distinction that determining which phase (non-life or life) a given system is in requires dynamical information and therefore can only be inferred by identifying causal architecture. We discuss some novel research directions based on this hypothesis, including potential measures of such a transition that may be amenable to laboratory study, and how the proposed mechanism corresponds to the onset of the unique mode of (algorithmic) information processing characteristic of living systems.
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Autocatalytic replication and homochirality in biopolymers: is homochirality a requirement of life or a result of it?
Astrobiology
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A key step in the origin of life is the establishment of autocatalytic cycles controlled by biopolymer catalysts. These catalysts (either ribozymes or proteins) are composed of homochiral monomers. Homochirality in living systems is maintained because biopolymers are asymmetric in their catalysis and synthesize molecules of their own handedness. Asymmetric autocatalysis is also possible with small molecules, as demonstrated by the Soai reaction, but it is rare. As far as we know, single nucleotides and amino acids are not autocatalytic. The observation that organic molecules in meteorites can have an enantiomeric excess of a few percent suggests that the prebiotic mixture may have had a partial chiral bias that was caused by external physical influences. Here, we consider the way that such a partial prebiotic bias would influence the origin of ribozymes in an RNA world scenario. We have previously shown how a transition to a living state can occur in a model for RNA polymerization. Here, we add chirality to the problem by considering simultaneous synthesis and polymerization of left- and right-handed monomers. The two chemical synthesis rates may be equal or unequal, due to physical or chemical effects prior to the origin of life. We determine the stationary states of this reaction system. The nonliving state is racemic, or slightly biased. There are two living states that are almost completely homochiral, whether or not the nonliving state is biased. It is a feature of our model that, for some regions of parameter space, living and nonliving states are both found to be stable under the same conditions. The origin of life therefore involves a stochastic transition between the nonliving and living states. Our model extends previous theories by treating the origin of life and the origin of chirality as aspects of the same model.
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Greater executive and visual memory dysfunction in comorbid bipolar disorder and substance use disorder.
Psychiatry Res
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Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. Future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for, and effects of, these illnesses.
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Chiral polymerization in open systems from chiral-selective reaction rates.
Orig Life Evol Biosph
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We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.
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Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension.
Pulm Circ
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We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation.
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Universal sequence replication, reversible polymerization and early functional biopolymers: a model for the initiation of prebiotic sequence evolution.
PLoS ONE
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Many models for the origin of life have focused on understanding how evolution can drive the refinement of a preexisting enzyme, such as the evolution of efficient replicase activity. Here we present a model for what was, arguably, an even earlier stage of chemical evolution, when polymer sequence diversity was generated and sustained before, and during, the onset of functional selection. The model includes regular environmental cycles (e.g. hydration-dehydration cycles) that drive polymers between times of replication and functional activity, which coincide with times of different monomer and polymer diffusivity. Template-directed replication of informational polymers, which takes place during the dehydration stage of each cycle, is considered to be sequence-independent. New sequences are generated by spontaneous polymer formation, and all sequences compete for a finite monomer resource that is recycled via reversible polymerization. Kinetic Monte Carlo simulations demonstrate that this proposed prebiotic scenario provides a robust mechanism for the exploration of sequence space. Introduction of a polymer sequence with monomer synthetase activity illustrates that functional sequences can become established in a preexisting pool of otherwise non-functional sequences. Functional selection does not dominate system dynamics and sequence diversity remains high, permitting the emergence and spread of more than one functional sequence. It is also observed that polymers spontaneously form clusters in simulations where polymers diffuse more slowly than monomers, a feature that is reminiscent of a previous proposal that the earliest stages of life could have been defined by the collective evolution of a system-wide cooperation of polymer aggregates. Overall, the results presented demonstrate the merits of considering plausible prebiotic polymer chemistries and environments that would have allowed for the rapid turnover of monomer resources and for regularly varying monomer/polymer diffusivities.
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The contributions of self-reported injury characteristics and psychiatric symptoms to cognitive functioning in OEF/OIF veterans with mild traumatic brain injury.
J Int Neuropsychol Soc
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Mild traumatic brain injury (mTBI) affects a significant number of combat veterans returning from Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF). Although resolution of mTBI symptoms is expected over time, some individuals continue to report lingering cognitive difficulties. This study examined the contributions of self-reported mTBI injury characteristics (e.g., loss of consciousness, post-traumatic amnesia) and psychiatric symptoms to both subjective and objective cognitive functioning in a sample of 167 OEF/OIF veterans seen in a TBI clinic. Injury characteristics were not associated with performance on neuropsychological tests but were variably related to subjective ratings of cognitive functioning. Psychiatric symptoms were highly prevalent and fully mediated most of the relationships between injury characteristics and cognitive ratings. This indicates that mTBI characteristics such as longer time since injury and loss of consciousness or post-traumatic amnesia can lead to increased perceived cognitive deficits despite having no objective effects on cognitive performance. Psychiatric symptoms were associated with both cognitive ratings and neuropsychological performance, illustrating the important role that psychiatric treatment can potentially play in optimizing functioning. Finally, subjective cognitive ratings were not predictive of neuropsychological performance once psychiatric functioning was statistically controlled, suggesting that neuropsychological assessment provides valuable information that cannot be gleaned from self-report alone.
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Early Perception of Medication Benefit Predicts Subsequent Antipsychotic Response in Schizophrenia.
Clin Schizophr Relat Psychoses
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Background: An easy-to-administer tool for predicting response to antipsychotic treatment could improve the acute management of patients with schizophrenia. We assessed whether a patients perception of medication benefit early in treatment could predict subsequent response or non-response to continued use of the same treatment.Method: This post-hoc analysis used data from a randomized, open-label trial of antipsychotics for treatment of schizophrenia in which attitudes about medication adherence was assessed after 2 weeks of antipsychotic treatment using the Rating of Medication Influences (ROMI) scale. The analysis included 439 patients who had Positive and Negative Syndrome Scale (PANSS) and ROMI scale data at Weeks 2 and 8. Scores on the ROMI subscale Perceived Medication Benefit factor were used to predict subsequent antipsychotic response at Week 8, defined as a ?20% reduction from baseline on the PANSS. Logistic regression was used to identify a cut-off score for the Perceived Medication Benefits factor that could accurately identify antipsychotic responders vs. nonresponders at Week 8.Results: A score of ?2.75 (equal to a mean subscale score of ?11.00) on the ROMI scale Perceived Medication Benefit factor at Week 2 predicted response at Week 8 with high specificity (72%) and negative predictive value (70%), moderate sensitivity (44%) and positive predictive value (47%), and with a 38% misclassification rate.Conclusion: A brief assessment of the patients perception of medication benefit at 2 weeks into treatment appears to be a good predictor of subsequent response and non-response after 8 weeks of treatment with the same antipsychotic.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.