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Background: Sleep apnea (SA), a modifiable risk factor in - atrial fibrillation (AF), is associated with worse outcomes in AF. We aimed to assess the prevalence and severity of SA in patients with AF, and, subsequently, to assess the positive predictive value (PPV) of moderate to severe SA by a home-monitoring device in comparison to cardio-respiratory monitoring (CRM) in consecutive patients with AF., Methods: This cross-sectional study recruited unselected patients with AF without known SA from an out-patient clinic at Department of Cardiology, Herlev-Gentofte University Hospital. Participants underwent four consecutive nights of sleep-recording with the home-monitoring device NightOwl™ (NO). Moderate SA was defined as an Apnea-Hypopnea Index (AHI) of 15-29 and severe SA as ≥ 30 AHI. Participants with moderate to severe SA was offered CRM for validation of the diagnosis., Results: We included 126 patients with AF with a median age of 68 (interquartile range: 60-75) years, 42 (33 %) women, 70 (56 %) hypertension, 61 (48 %) hyperlipidemia and 49 (39 %) heart failure. NO detected severe SA in 36 (29 %) of patients with AF, moderate SA in 35 (28 %), mild SA in 45 (36 %) and no SA in 10 (8 %). Of 71 patients with moderate to severe SA by NO, 38 patients underwent CRM and the PPV of NO was 0.82 (31/38) to diagnose moderate SA and 0.92 (22/24) to diagnose severe SA by CRM., Conclusion: Moderate to severe SA by NO was highly prevalent in patients with AF without known SA. A home-monitoring device such as NO could be an easy and feasible SA screening tool in patients with AF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Binding theories assume that features of stimuli and executed responses can be integrated together in one event file (Hommel, Visual Cognition, 5, 183-216, 1998; Hommel, Cognitive Sciences, 8, 494-500, 2004). Every reencounter with one or more of the stored features leads to an automatic retrieval of the previously constructed event file and hence of the response-even the repetition of a task-irrelevant distractor stimulus can retrieve a previously encoded response. This so-called distractor-response binding effect is typically investigated using a sequential prime-probe design that allows the orthogonal variation of response relation (response repetition vs. resporrevertnse change) and distractor relation (distractor repetition vs. distractor change), while probe response times and error rates are measured as dependent variable. Previous research has shown that task-relevant stimuli can be represented at different levels (e.g., perceptual and conceptual; see Henson et al., Trends in Cognitive Sciences, 18, 376-384, 2014), yet it is not clear at which level of representation distractor stimuli are processed. In the present study, we focused on the level of representation of response-irrelevant distractor stimuli. To this end, a crossmodal distractor-response binding paradigm was used that enables the differentiation between the perceptual and conceptual representation of the distractor by allowing the systematic repetition and change of conceptual distractor features independent of perceptual repetitions. The results suggest that the repetition of perceptual distractor features is indispensable for the initiation of the retrieval process while the sole repetition of conceptual distractor features is not sufficient to start the retrieval process.

The intensity of a stimulus has been found to have a distinct impact upon response processes (e.g., response speed, response force, & response selection). For instance, reaction times are faster to bright than to dim stimuli (e.g., Kohfeld, 1971). In the present study, we investigated the possible influence of stimulus intensity on binding processes. According to binding theories, stimulus and response features are integrated together in short-lived memory traces, called event files (Hommel, 1998). Any re-encounter with one of these integrated features leads to the automatic retrieval of the previously constructed event file and thus of the response. Thereby bindings between stimuli (relevant and irrelevant) and responses have a direct impact on behavior. In the present experiment, we presented distractors with increasing stimulus intensity and found that intensity did exert an influence on binding processes. However, our results suggest that distractor intensity per se has no direct influence on the binding effect (the more intense a distractor is, the larger the binding effect), but that distractor intensity has an indirect effect on binding via grouping due to similarity between target and distractor intensity., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

If a target stimulus is presented together with a response irrelevant distractor stimulus, both stimuli can be encoded together with the response in an event file [see Hommel (Trends Cogn Sci 8:494-500, 2004)]. The repetition of the distractor can retrieve the encoded response. This kind of distractor-based retrieval is an important mechanism in action control. In the present experiment, we investigate whether and how distractor-based retrieval of event files is influenced by encoding specificity-a retrieval principle that has been suggested to affect retrieval in short-term and long-term memory. Using a prime-probe design, the number of identical distractors on each display was varied. The results showed that the distractor-based retrieval process is modulated by encoding specificity, in that only high (low) number of distractors retrieves former event files with high (low) number of distractors. Taken together, distractor-based retrieval in action control follows principles known from short-term memory and long-term memory retrieval.

If a target stimulus is presented together with a response-irrelevant distractor stimulus, both stimuli can be encoded together with the response in an event file (see Hommel, 2004). The repetition of any feature of such an event-file can then retrieve the previously encoded response. This kind of feature-based retrieval is an important mechanism in action control. Typically, a direct link between perception and action is assumed, whereas the possible role of semantics is unspecified so far. Only a couple of previous studies analyzed whether the repetition of semantic features can elicit event-file retrieval. Yet, in these studies, semantic repetition often included perceptual repetition as well; even more problematic is trying to analyze perceptual repetitions while excluding semantic repetitions. Thus, here we used a different approach by repeating perceptual features but contrasted semantic and perceptual repetitions. In particular, in 2 experiments we found evidence that perceptual features of a distractor (the letters of an irrelevant word) are integrated with the response and can later retrieve the response, even if only some of these features are repeated thus forming a semantically different concept (i.e., presenting Buch [book] retrieves the response made to Bach [brook]). Our result shed new light on the relation between perception, action, and semantics in action control. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

In selection tasks, target and distractor features can be encoded together with the response into the same short-lived memory trace, or event file (see Hommel, 2004), leading to bindings between stimulus and response features. The repetition of a stored target or distractor feature can lead to the retrieval of the entire episode, including the response-so-called "binding effects." Binding effects due to distractor repetition are stronger for grouped than for nongrouped target and distractor stimulus configurations. Modulation of either of two mechanisms that lead to the observed binding effects might be responsible here: Grouping may influence either stimulus-response integration or stimulus-response retrieval. In the present study we investigated the influences of grouping on both mechanisms independently. In two experiments, target and distractor letters were grouped (or nongrouped) via color (dis)similarity separately during integration and retrieval. Grouping by color similarity affected integration and retrieval mechanisms independently and in different ways. Color dissimilarity enhanced distractor-based retrieval, whereas color similarity enhanced distractor integration. We concluded that stimulus grouping is relevant for binding effects, but that the mechanisms that contribute to binding effects should be carefully separated.

Selective attention refers to the ability to selectively act upon relevant information at the expense of irrelevant information. Yet, in many experimental tasks, what happens to the representation of the irrelevant information is still debated. Typically, 2 approaches to distractor processing have been suggested, namely distractor inhibition and distractor-based retrieval. However, it is also typical that both processes are hard to disentangle. For instance, in the negative priming literature (for a review Frings, Schneider, & Fox, 2015) this has been a continuous debate since the early 1980s. In the present study, we attempted to prove that both processes exist, but that they reflect distractor processing at different levels of representation. Distractor inhibition impacts stimulus representation, whereas distractor-based retrieval impacts mainly motor processes. We investigated both processes in a distractor-priming task, which enables an independent measurement of both processes. For our argument that both processes impact different levels of distractor representation, we estimated the exponential parameter (τ) and Gaussian components (μ, σ) of the exponential Gaussian reaction-time (RT) distribution, which have previously been used to independently test the effects of cognitive and motor processes (e.g., Moutsopoulou & Waszak, 2012). The distractor-based retrieval effect was evident for the Gaussian component, which is typically discussed as reflecting motor processes, but not for the exponential parameter, whereas the inhibition component was evident for the exponential parameter, which is typically discussed as reflecting cognitive processes, but not for the Gaussian parameter. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Purpose: T-cell-located CD4 antigen represents one of the therapeutic targets in rheumatoid arthritis (RA). However, up to now there is no established imaging tool to visualize this target in vivo. The aim of our study was to assess the safety and tolerability of a technetium-99m labelled murine anti-human CD4 IgG1-Fab fragment ([(99m)Tc]-anti-CD4-Fab, [(99m)Tc]-EP1645) in patients with active synovitis due to RA, and to evaluate its potential as a marker of disease activity., Methods: In the present phase I proof of principle study five patients with RA were examined. Planar scans of the whole body, hands, and feet were taken 30 min up to 24h after application of 550 ± 150 MBq [(99m)Tc]-anti-CD4-Fab, followed by visual analyses, comparison with clinical data in 68 joints per patient and semiquantitative analysis of hand and wrist joints., Results: Neither infusion related adverse events nor adverse events during follow up were observed. No increase in human anti-murine antibody titres was seen. All patients had positive scans in almost 70% of clinically affected joints. Positive scans were also found in 8% of joints without evidence of swelling or tenderness., Conclusion: Scintigraphy with [(99m)Tc]-anti-CD4-Fab is a promising technique for evaluation of inflammatory activity in patients with RA, pre-therapeutical evaluation of CD4 status and therapy control. Tracer uptake in clinically inconspicuous joints strongly indicates diagnostic potential of [(99m)Tc]-anti-CD4-Fab. Whether this technique is eligible as a prognostic factor in RA needs to be analysed in further studies as well as the pathophysiological background of clinically affected joints lacking tracer uptake., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To optimize patient treatment and rational use of antimicrobials, it is important to provide fast information on findings in blood-cultures (BCs). The purpose of this study was to evaluate the impact of using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) on positive BCs containing Gram-positive cocci in clusters to differentiate between Staphylococcus aureus (SA) and coagulase negative staphylococci (CoNS) on the prescribed antimicrobial therapy and on the number of contacts between microbiologist and clinician. All cases of positive BCs in our laboratory with SA or CoNS in the year 2011 were identified and the charts were reviewed retrospectively. The group of patients with BCs tested with PNA-FISH was compared to the group of patients with untested BCs. A total of 200 patients with SA and 725 patients with CoNS were included. The mean number of contacts was 0.82 when PNA-FISH showed CoNS and 1.39 when PNA-FISH was not done (p < 0.0001). More patients were recommended appropriate antimicrobial therapy for SA bacteraemia in the PNA-FISH group (98.0%) than in the non-PNA-FISH group (89.4 %) (p = 0.025). The percentage treated with dicloxacillin was 29.6 in the PNA-FISH group, and 8.2 in the non-PNA-FISH group (p = 0.0003). The use of PNA-FISH on BCs in this study was associated with more appropriate and narrow spectrum antimicrobial therapy for patients with SA in an area with low prevalence of methicillin-resistant SA, and a lower number of contacts between clinical microbiologist and clinician about BCs with CoNS as contaminants.

Objectives: Clinical data are lacking on optimal levels of specific antipneumococcal antibodies (PnPsAbs) in patients with primary immunodeficiency (PID) receiving intravenous immunoglobulin (IVIG) replacement. Objectives were to conduct a prospective multicenter study providing data on total immunoglobulin G (IgG) and peak/trough levels of PnPsAbs specifically targeting the 16 most prevalent pneumococcal serotypes in IVIG-treated children with PID; to compare trough PnPsAb levels with those measured in healthy adults and the IVIG product; and to evaluate PnPsAb protection correlates with thresholds based on World Health Organization., Methods: Patients received 7 consecutive IVIG infusions. Total IgG and PnPsAb levels were determined on plasma samples obtained before and after infusion., Results: Twenty-two children with PID were treated with IVIG (mean weekly dose: 0.10 g/kg). The mean trough and peak levels of total IgG were 7.77 and 13.93 g/L, respectively. Trough and peak geometric mean concentrations and distribution curves differed between serotypes and showed wide dispersion (0.17-7.96 µg/mL). In patients (89%-100%), antibodies against most serotypes reached trough levels ≥ 0.2 µg/mL, a threshold considered protective against invasive pneumococcal infection. For several serotypes, trough levels reached ≥ 1.0 to 1.3 µg/mL, the level found in adults. Trough geometric mean concentrations correlated well with the PnPsAb contents of the IVIG product., Conclusions: In IVIG-treated children with PID, protective PnPsAb levels for most pathogenic serotypes were obtained. A correlation was observed between PnPsAb levels in patients and in the IVIG product. This offers the potential to improve infection prevention by adapting the IVIG product and dose according to epidemiology.

Mounting evidence suggests beneficial effects of albumin dialysis-based liver support in patients suffering from acute-on-chronic liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological liver support device, based on the exchange of albumin-bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion-exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin-associated esterase-like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (B(max)) increased about twofold. For albumin obtained from CAF-DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase-like activities associated with these albumins were either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following 7-h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human albumin. However, in vitro incubations of these albumins for several hours resulted in supplier-specific changes in warfarin binding, suggesting an influence of stabilizers on the stability of binding properties. Further preclinical and clinical studies are required to elucidate the clinical relevance of these in vitro results, that is, to what extent these changes in albumin binding properties result in altered performance of albumins in the secondary circuit during the MARS procedure., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background and Objectives: Plasma pools for the production of human plasma medicinal products are distinguished according to the collection method (recovered or apheresis plasma) and the donor remuneration status. National regulations and the physical status of the donor determine the donation frequency and plasma volume per session. Relevant protein contents of different types of pools have not fully been compared., Materials and Methods: We compared the levels of total protein, 15 main relevant plasma protein markers, and anti-B19 and anti-Streptococcus pneumoniae IgG in single-type pools of donations from different countries (Belgium, Finland, France, the Netherlands, Germany, United States). Both recovered plasma from non-remunerated donors and apheresis plasma from remunerated and non-remunerated donors were studied., Results: Pools from paid US high-frequency, high-volume plasmapheresis donors showed significantly lower total protein (-9%), albumin (-15%), total IgG (-24%), IgM (-28%), hemopexin (-11%) and retinol-binding protein (-10%) but higher C1-inhibitor, pre-albumin and C-reactive protein contents than pools from unpaid European Union (EU) or US whole-blood or plasmapheresis donors. In contrast to pools from compensated EU plasmapheresis donors, pools from unpaid whole-blood or plasmapheresis donors showed no significant differences, whatever the collection method or country. Reductions in specific protein contents correlated well with protein half-life., Conclusion: These results should be taken into account with regard to donor health management and protein recovery., (© 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.)

CD4(+) T cells specific for the acetylcholine receptor (AChR) are assumed to play an important role in pathogenesis of myasthenia gravis (MG). A large and diverse number of potential T cell epitopes have been reported for different experimental setups aiming at the identification of disease-relevant T cells in MG. Investigating the T cell response to the epsilon subunit of human AChR, we explore complementary in vitro and in vivo approaches (PBMC from MG patients and mice transgenic for HLA-DR3 and human CD4) to address the possibilities and limitations of different strategies for elucidating natural autoimmune T cell epitopes.

IL-1Ra prevents IL-1 induced inflammatory signalling, a mechanism potentially important for several pathological conditions characterized by inflammation. When administered as a drug in the recombinant form, it displays a protective effect towards them. We postulated that this action could also be achieved by pharmacological activation of endogenous IL-1Ra production. We previously showed that photochemotherapy and UV-light increased monocyte/macrophages IL-1Ra secretion. A similar effect has been shown for IVIg. The aim of this study was to define optimal in vitro conditions for induction of IL-1Ra secretion. As both agents induce lymphocytes apoptosis, we focused our analysis on the influence of IVIg on UV-induced-IL-1Ra production on this mechanism. After overnight preincubation at 37 degrees C, UV-irradiated PBL mixed with two IVIg concentrations (1 and 25 mg/ml) were cocultured with autologous PBMC. Apoptosis was measured by annexin V/PI. IL-1Ra secretion was evaluated by RT-PCR and Luminex microbead array assay. A significant additive dose-dependent influence of IVIg (+85%; p=0.0005) on UV-induced IL-1Ra secretion, involved both Fc-receptor activation at a low dose (1 mg/ml) and a potent apoptotic action on PBL reinforcing the UV effect at high concentrations (25 mg/ml). We conclude that lymphocyte apoptosis represents an important pathway contributing to enhancement of UV-induced monocyte/macrophages IL-1Ra production by IVIg and that these findings should be considered when evaluating in vivo protocols for photochemotherapy and IVIg treatment, in hope of improving efficacy.

Inhibitory antibodies directed against blood coagulation factor VIII (FVIII) impair FVIII replacement therapy, constituting a serious complication in haemophilic and autoimmune patients. Identifying B-cell FVIII epitopes and mapping them on the molecule remain important challenges. Using a combination of different algorithms, more than 30 hypothetical linear epitopes were predicted on the FVIII molecule surface. We selected several major predicted sequences, spanning all FVIII domains, for specific antibody induction in rabbits. All peptides tested successfully induced production of specific anti-FVIII rabbit antibodies, supporting the relevance of our approach. To investigate the presence of FVIII-reactive antibodies in the healthy donor population, a pooled fraction rich in all IgG subclasses was purified on peptide-Sepharose columns. Substantial amounts of Ig, specific for each FVIII peptide, were purified with yields ranging from 8 to 223 ng/mg immunoglobulins. Our results confirm the diversity of FVIII epitopes recognised by natural human anti-FVIII autoantibodies. All IgG subclasses were found in the affinity-isolated anti-peptide material, with overrepresentation of IgG2 and IgG4. Evidence was also found for new FVIII epitopes. Five human anti-peptide preparations displayed FVIII-neutralising activity, ranging from 1.3 to 5.3 BU/mg. Although the presence of naturally occurring anti-FVIII antibodies in healthy donors has been previously described, our methodology has allowed, for the first time, a fine mapping of several inhibitory and non-inhibitory epitopes. Our observations support the hypothesis that FVIII inhibitors in haemophilia A and autoimmune disease may originate from the proliferation of natural FVIII-specific B-cell clones.