The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Personality and Augmenting/Reducing (A/R) in auditory event-related potentials (ERPs) during emotional visual stimulation

An auditory augmenting/reducing ERP paradigm recorded for 5 intensity tones with emotional visual stimulation was used, for the first time, to test predictions derived from the revised Reinforcement Sensitivity Theory (rRST) of personality with respect to two major factors: behavioral inhibition system (BIS), fight/flight/freeze system (FFFS). Higher BIS and FFFS scores were negatively correlated with N1/P2 slopes at central sites (C3, Cz, C4). Conditional process analysis revealed that the BIS was a mediator of the association between the N1/P2 slope and the FFFS scores. An analysis of covariance showed that lower BIS scorers exhibited larger N1/P2 amplitudes across all tone intensities while watching negative, positive and neutral pictures. Additionally, lower FFFS scorers compared to higher FFFS scorers disclosed larger N1/P2 amplitudes to the highest tone intensities and these differences were even more pronounced while watching positive emotional pictures. Findings were explained assuming the operation of two different, but related processes: transmarginal inhibition for the BIS; the attention/emotional gating mechanism regulating cortical sensory input for the FFFS trait. These findings appear consistent with predictions derived from the rRST, which traced fear and anxiety to separate but interacting neurobehavioural systems

Pilot study evaluating a brief mindfulness intervention for those with chronic pain: study protocol for a randomized controlled trial.

BACKGROUND: The burden of chronic pain is a major challenge, impacting the quality of life of patients. Intensive programmes of mindfulness-based therapy can help patients to cope with chronic pain but can be time consuming and require a trained specialist to implement. The self-management model of care is now integral to the care of patients with chronic pain; home-based interventions can be very acceptable, making a compelling argument for investigating brief, self-management interventions. The aim of this study is two-fold: to assess the immediate effects of a brief self-help mindfulness intervention for coping with chronic pain and to assess the feasibility of conducting a definitive randomized controlled trial to determine the effectiveness of such an intervention. METHODS/DESIGN: A randomized controlled pilot study will be conducted to evaluate a brief mindfulness intervention for those with chronic pain. Ninety chronic pain patients who attend hospital outpatient clinics will be recruited and allocated randomly to either the control or treatment group on a 1:1 basis using the computer-generated list of random numbers. The treatment group receives mindfulness audios and the control group receives audios of readings from a non-fiction book, all of which are 15 minutes in length. Immediate effects of the intervention are assessed with brief psychological measures immediately before and after audio use. Mindfulness, mood, health-related quality of life, pain catastrophizing and experience of the intervention are assessed with standardized measures, brief ratings and brief telephone follow-ups, at baseline and after one week and one month. Feasibility is assessed by estimation of effect sizes for outcomes, patient adherence and experience, and appraisal of resource allocation in provision of the intervention. DISCUSSION: This trial will assess whether a brief mindfulness-based intervention is effective for immediately reducing perceived distress and pain with the side effect of increasing relaxation in chronic pain patients and will determine the feasibility of conducting a definitive randomized controlled trial. Patient recruitment began in January 2015 and is due to be completed in June 2016. TRIAL REGISTRATION: ISRCTN61538090 Registered 20 April 2015

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

Osteoprotegerin in Exosome-Like Vesicles from Human Cultured Tubular Cells and Urine

Urinary exosomes have been proposed as potential diagnostic tools. TNF superfamily cytokines and receptors may be present in exosomes and are expressed by proximal tubular cells. We have now studied the expression of selected TNF superfamily proteins in exosome-like vesicles from cultured human proximal tubular cells and human urine and have identified additional proteins in these vesicles by LC-MS/MS proteomics. Human proximal tubular cells constitutively released exosome-like vesicles that did not contain the TNF superfamily cytokines TRAIL or TWEAK. However, exosome-like vesicles contained osteoprotegerin (OPG), a TNF receptor superfamily protein, as assessed by Western blot, ELISA or selected reaction monitoring by nLC-(QQQ)MS/MS. Twenty-one additional proteins were identified in tubular cell exosomelike vesicles, including one (vitamin D binding protein) that had not been previously reported in exosome-like vesicles. Twelve were extracellular matrix proteins, including the basement membrane proteins type IV collagen, nidogen-1, agrin and fibulin-1. Urine from chronic kidney disease patients contained a higher amount of exosomal protein and exosomal OPG than urine from healthy volunteers. Specifically OPG was increased in autosomal dominant polycystic kidney disease urinary exosome-like vesicles and expressed by cystic epithelium in vivo. In conclusion, OPG is present in exosome-like vesicles secreted by proximal tubular epithelial cells and isolated from Chronic Kidney Disease urine.This work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDINREN RD06/0016, RD12/0021, PI11/01854, PI10/00072 PI09/ 00641 and PS09/00447); Comunidad de Madrid (Fibroteam S2010/BMD-2321, S2010/BMD-2378); Sociedad Española de NefrologÍa; European Network (HEALTH F2-2008-200647); DIALOK European project LSHB-CT-2007-036644; Fundacion Lilly and IRSIN/FRIAT to JE; Programa Intensificación Actividad Investigadora (ISCIII/ Agencia Laín-Entralgo/CM) to AO; Instituto de Salud Carlos III (FIS PI11/01401, CP09/00229); and Fundación Conchita Rábago de Jiménez DÍaz to GAL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

oA novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology

<p>Abstract</p> <p>Background</p> <p>Epidemiological and clinical studies, often including anthropometric measures, have established obesity as a major risk factor for the development of type 2 diabetes. Appropriate cut-off values for anthropometric parameters are necessary for prediction or decision purposes. The cut-off corresponding to the Youden-Index is often applied in epidemiology and biomedical literature for dichotomizing a continuous risk indicator.</p> <p>Methods</p> <p>Using data from a representative large multistage longitudinal epidemiological study in a primary care setting in Germany, this paper explores a novel approach for estimating optimal cut-offs of anthropomorphic parameters for predicting type 2 diabetes based on a discontinuity of a regression function in a nonparametric regression framework.</p> <p>Results</p> <p>The resulting cut-off corresponded to values obtained by the Youden Index (maximum of the sum of sensitivity and specificity, minus one), often considered the optimal cut-off in epidemiological and biomedical research. The nonparametric regression based estimator was compared to results obtained by the established methods of the Receiver Operating Characteristic plot in various simulation scenarios and based on bias and root mean square error, yielded excellent finite sample properties.</p> <p>Conclusion</p> <p>It is thus recommended that this nonparametric regression approach be considered as valuable alternative when a continuous indicator has to be dichotomized at the Youden Index for prediction or decision purposes.</p

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial) A Multicenter, Randomized, Controlled Clinical Trial

Copyright \ua9 2023 by the American Thoracic Society. Rationale: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)–related acute respiratory distress syndrome (ARDS). Objectives: We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]–enriched, umbilical cord–derived MSCs) in COVID-19–related ARDS. Methods: In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT 03042143), patients with moderate to severe COVID-19–related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148). The primary safety and efficacy outcomes were the incidence of serious adverse events and oxygenation index at Day 7, respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2:FIO2 ratio, and Sequential Organ Failure Assessment score. Clinical outcomes relating to duration of ventilation, lengths of ICU and hospital stays, and mortality were collected. Long-term follow-up included diagnosis of interstitial lung disease at 1 year and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at Days 0, 4, and 7. Measurements and Main Results: Sixty participants were recruited (final analysis: n = 30 received ORBCEL-C, n = 29 received placebo; 1 participant in the placebo group withdrew consent). Six serious adverse events occurred in the ORBCEL-C group and three in the placebo group (risk ratio, 2.9 [95% confidence interval, 0.6–13.2]; P = 0.25). Day 7 mean (SD) oxygenation index did not differ (ORBCEL-C, 98.3 [57.2] cm H2O/kPa; placebo, 96.6 [67.3] cm H2O/kPa). There were no differences in secondary surrogate outcomes or in mortality at Day 28, Day 90, 1 year, or 2 years. There was no difference in the prevalence of interstitial lung disease at 1 year or significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome. Conclusion: ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19–related ARDS but did not improve surrogates of pulmonary organ dysfunction

The EDKB: an established knowledge base for endocrine disrupting chemicals

<p>Abstract</p> <p>Background</p> <p>Endocrine disruptors (EDs) and their broad range of potential adverse effects in humans and other animals have been a concern for nearly two decades. Many putative EDs are widely used in commercial products regulated by the Food and Drug Administration (FDA) such as food packaging materials, ingredients of cosmetics, medical and dental devices, and drugs. The Endocrine Disruptor Knowledge Base (EDKB) project was initiated in the mid 1990’s by the FDA as a resource for the study of EDs. The EDKB database, a component of the project, contains data across multiple assay types for chemicals across a broad structural diversity. This paper demonstrates the utility of EDKB database, an integral part of the EDKB project, for understanding and prioritizing EDs for testing.</p> <p>Results</p> <p>The EDKB database currently contains 3,257 records of over 1,800 EDs from different assays including estrogen receptor binding, androgen receptor binding, uterotropic activity, cell proliferation, and reporter gene assays. Information for each compound such as chemical structure, assay type, potency, etc. is organized to enable efficient searching. A user-friendly interface provides rapid navigation, Boolean searches on EDs, and both spreadsheet and graphical displays for viewing results. The search engine implemented in the EDKB database enables searching by one or more of the following fields: chemical structure (including exact search and similarity search), name, molecular formula, CAS registration number, experiment source, molecular weight, etc. The data can be cross-linked to other publicly available and related databases including TOXNET, Cactus, ChemIDplus, ChemACX, Chem Finder, and NCI DTP. </p> <p>Conclusion</p> <p>The EDKB database enables scientists and regulatory reviewers to quickly access ED data from multiple assays for specific or similar compounds. The data have been used to categorize chemicals according to potential risks for endocrine activity, thus providing a basis for prioritizing chemicals for more definitive but expensive testing. The EDKB database is publicly available and can be found online at <url>http://edkb.fda.gov/webstart/edkb/index.html</url>.</p> <p><b>Disclaimer:</b><it>The views presented in this article do not necessarily reflect those of the US Food and Drug Administration.</it></p