On the timing of overt attention deployment: Eye-movement evidence for the priority accumulation framework.

Most visual-search theories assume that our attention is automatically allocated to the location with the highest priority at any given moment. The Priority Accumulation Framework (PAF) challenges this assumption. It suggests that the priority weight at each location accumulates across sequential events and that evidence for the presence of action-relevant information contributes to determining when attention is deployed to the location with the highest accumulated priority. Here, we tested these hypotheses for overt attention by recording first saccades in a free-viewing spatial-cueing task. We manipulated search difficulty (Experiments 1 and 2) and cue salience (Experiment 2). Standard theories posit that when oculomotor capture by the cue occurs, it is initiated before the search display appears; therefore, these theories predict that the cue's impact on the distribution of first saccades should be independent of search difficulty but influenced by the cue's saliency. By contrast, PAF posits that the cue can bias competition later, after processing of the search display has already started, and therefore predicts that such late impact should increase with both search difficulty and cue salience. The results fully supported PAF's predictions. Our account suggests a distinction between attentional capture and attentional-priority bias that resolves enduring inconsistencies in the attentional-capture literature. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

COVID-19 in Patients Undergoing Hemodialysis: Prevalence and Asymptomatic Screening During a Period of High Community Prevalence in a Large Paris Center.

RATIONALE & OBJECTIVE: Due to extensive comorbid conditions, coronavirus disease 2019 (COVID-19) has a poor prognosis in people receiving maintenance hemodialysis. In this article, we describe our experience with 200 maintenance hemodialysis patients in a hemodialysis center that used universal reverse transcriptase-polymerase chain reaction testing, including 38 COVID-19-positive patients. STUDY DESIGN: Descriptive observational cohort, including the time line of patient diagnoses along with contextual events including precautions, testing, screening algorithms, clinical diagnostics and therapy, and the clinical course of COVID-19-infected patients and their final outcomes. SETTING & PARTICIPANTS: 200 patients within a single hemodialysis center with 2 dialysis clinics in Paris. RESULTS: Among 200 maintenance hemodialysis patients, 38 (19%) had COVID-19 diagnosed; of these, 15 (39.5%) were admitted to the hospital, including 4 who required intensive care unit (ICU) care. There were 8 (21%) deaths. The most common symptom was fever, followed by dry cough, fatigue, and dyspnea. All COVID-19-infected patients had lymphopenia and an increase in C-reactive protein levels. Median time from the onset of respiratory symptoms to ICU admission was 1 to 2 days. Durations of non-ICU hospitalizations and ICU stays were 7 and 13 days, respectively. LIMITATIONS: Retrospective study, single hemodialysis center. CONCLUSIONS: Dialysis patients are a highly susceptible population and hemodialysis centers are a high-risk area in a COVID-19 epidemic. "Unexplained" lymphopenia and/or an increase in C-reactive protein level should lead physicians to the diagnosis of COVID-19 and should, when possible, be followed by diagnostic testing with universal reverse transcriptase-polymerase chain reaction, as well as the reinforcement of contamination barrier measures.

Factors associated with parathyroid hormone control in haemodialysis patients with secondary hyperparathyroidism treated with cinacalcet in real-world clinical practice: Mimosa study.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is frequent in haemodialysis (HD) patients. Oral cinacalcet-hydrochloride (HCl) decreases parathyroid hormone (PTH); however, real-life PTH data, according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, are still lacking. Our goal is to assess the percentage of cinacalcet-HCl-treated HD patients with controlled SHPT (PTH <9× upper limit of the normal range) after 12 months (M12) of treatment. METHODS: This is a retrospective observational study in HD patients with SHPT treated by cinacalcet-HCl between 2005 and 2015 and dialysed in seven French HD centres using the same database (Hemodial™). RESULTS: The study included 1268 patients with a mean (standard deviation) follow-up of 21 ± 12 months. Their mean dialysis vintage was 4.3 ± 5.6 years. PTH values were available and exploitable at M12 in 50% of them (645 patients). Among these patients, 58.9% had controlled (mean PTH of 304 ± 158 pg/mL) and 41.1% uncontrolled SHPT (mean PTH of 1084 ± 543) at M12. At the baseline, patients with controlled SHPT were older (66 ± 15 versus 61 ± 17 years), and had lower PTH (831 ± 346 versus 1057 ± 480 pg/mL) and calcaemia (2.18 ± 0.2 versus 2.22 ± 0.19 mmol/L) than uncontrolled patients. In multivariate analysis, these three factors still remained significantly associated with controlled SHPT. CONCLUSION: In this real-life study, 41.1% of HD patients with SHPT treated with cinacalcet-HCl remained with a PTH above the KDIGO recommended target after 12 months of treatment. Apart from the possibility of non-compliance, the severity of SHPT appears to be a major factor determining the response to cinacalcet-HCl treatment, reinforcing the importance of treating SHPT at earlier stages.

Role of the general practitioner in the care of BRCA1 and BRCA2 mutation carriers: General practitioner and patient perspectives.

BACKGROUND: General practitioners (GPs) have an increasing role in referring patients with putative mutation in BRCA1/2 genes for genetics consultation and for long-term follow-up of mutation carriers. METHODS: We compared the expectations of the GPs' role according to BRCA1/2 mutation carriers and to GPs themselves. RESULTS: Overall, 38% (58/152) of eligible GPs and 70% (176/252) of eligible patients were surveyed. Although 81% of GPs collected the family history, only 24% considered that they know criteria indicating genetics consultation and 39% sufficient knowledge of BRCA1/2 guidelines to answer patients' questions. Twelve% of GPs were aware of the French national guidelines. Among unsatisfied patients, 40% felt that their GP was able to answer (moderately, sufficiently, or completely) specific questions about BRCA1/2 care as compared with 81% in satisfied patients. Only 33% of GPs reported being informed directly by the geneticist about the patients' results. GPs' main expectations for their role in BRCA1/2 carrier care were psychological support and informing relatives about screening (72% and 71%, respectively), which contrasts with the perceptions of patients, who mainly requested medical advice for BRCA1/2-related care (51%). CONCLUSION: There is an important need for GP training and enhancing interactions between GPs and geneticists to improve the GP's role in BRCA1/2 screening and management.

[Common physiological basis for post-traumatic stress disorder and dependence to drugs of abuse: Implications for new therapeutic approaches]. / Bases physiologiques communes pour les troubles de stress post-traumatique et la dépendance aux drogues d'abus : conséquences pour de nouvelles approches thérapeutiques.

Post-traumatic stress disorder (PTSD) and addiction to drugs of abuse are two common diseases, showing high comorbidity rates. This review presents a number of evidence showing similarities between these two pathologies, especially the hyper-responsiveness to environmental cues inducing a reactivation of the target memory leading either to re-experiencing (PTSD), or drug craving. Accordingly, PTSD and addiction to drug of abuse might by considered as memory pathologies, underlined by the same physiological process. We propose that these two pathologies rely on an uncoupling of the monoaminergic systems. According to this hypothesis, exposure to extreme conditions, either negative (trauma) or positive (drugs) induced a loss of the reciprocal control that one system usually exerts on the other monoaminergic system, resulting to an uncoupling between the noradrenergic and the serotonergic systems. Results obtained in our laboratory, using animal models of these pathologies, demonstrate that after a trauma, such as after repeated drug injections, rats developed both a behavioral sensitization (increases of the locomotion in response to a stimulation of the monoaminergic systems) and a pharmacological sensitization (increases of noradrenergic release within the prefrontal cortex). These results support our hypothesis and led us to propose new and innovative therapeutic approaches consisting either to induce a re-coupling of the monoaminergic systems, or to modify the pathological memories by using an emotional memory remodeling. Extremely encouraging results have already been obtained in rats and in humans, opening new and promising therapeutic avenues.

Repeated amphetamine injections alter behavior and induce a delayed behavioral sensitization modulated by reactivity to novelty: Similarities and differences with trauma consequences.

Supporting our hypothesis of common biological bases for post-traumatic stress disorder (PTSD) and addiction, we recently reported that rats exposed to a single prolonged stress (SPS), a PTSD model, develop a delayed behavioral sensitization of the noradrenergic system, similar to that observed in mice after four repeated drug administrations. However, sensitization after trauma was modulated by reactivity to novelty, and this aspect that had not been explored in the addiction model. The first aim of the paper was thus to investigate the influence of reactivity to novelty on delayed behavioral sensitization in rats after four repeated amphetamine injections. Injections were either distributed over 4 days, as conducted in mouse models of addiction, or massed during a single session, reproducing SPS conditions. The second aim was to investigate whether repeated amphetamine injections have similar behavioral consequences to those induced by PTSD. Our results showed that massed amphetamine injections induced more anxiety than distributed injections, and led to avoidance of drug-associated cues avoidance, while distributed injections somewhat reduced the startle response, such as is seen in SPS. In addition, massed amphetamine injections induced a delayed behavioral sensitization clearly affected by the reactivity to novelty, reproducing results observed following exposure to traumatic events. Finally, all rats receiving repeated amphetamine injections exhibited a behavioral sensitization in response to exposure to drug-associated cues. Taken together, these data strengthen the position that drug addiction and PTSD share some common mechanisms that we tried to clarify in this paper.

Integration of New Information with Active Memory Accounts for Retrograde Amnesia: A Challenge to the Consolidation/Reconsolidation Hypothesis?

Active (new and reactivated) memories are considered to be labile and sensitive to treatments disrupting the time-dependent consolidation/reconsolidation processes required for their stabilization. Active memories also allow the integration of new information for updating memories. Here, we investigate the possibility that, when active, the internal state provided by amnesic treatments is represented and integrated within the initial memory and that amnesia results from the absence of this state at testing. We showed in rats that the amnesia resulting from systemic, intracerebroventricular and intrahippocampal injections of the protein synthesis inhibitor cycloheximide, administered after inhibitory avoidance training or reactivation, can be reversed by a reminder, including re-administration of the same drug. Similar results were obtained with lithium chloride (LiCl), which does not affect protein synthesis, when delivered systemically after training or reactivation. However, LiCl can induce memory given that a conditioned taste aversion was obtained for a novel taste, presented just before conditioning or reactivation. These results indicate that memories can be established and maintained without de novo protein synthesis and that experimental amnesia may not result from a disruption of memory consolidation/reconsolidation. The findings more likely support the integration hypothesis: posttraining/postreactivation treatments induce an internal state, which becomes encoded with the memory, and should be present at the time of testing to ensure a successful retrieval. This integration concept includes most of the previous explanations of memory recovery after retrograde amnesia and critically challenges the traditional memory consolidation/reconsolidation hypothesis, providing a more dynamic and flexible view of memory. SIGNIFICANCE STATEMENT: This study provides evidence challenging the traditional consolidation/reconsolidation hypotheses that have dominated the literature over the past 50 years. Based on amnesia studies, that hypothesis states that active (i.e., new and reactivated) memories are similarly labile and (re)established in a time-dependent manner within the brain through processes that require de novo protein synthesis. Our data show that new/reactivated memories can be formed without protein synthesis and that amnesia can be induced by drugs that do not affect protein synthesis. We propose that amnesia results from memory integration of the internal state produced by the drug that is subsequently necessary for retrieval of the memory. This interpretation gives a dynamic view of memory, rapidly stored and easily updated when active.

Diagnosis and management of congenital hypothyroidism associated with pseudohypoparathyroidism.

UNLABELLED: Hypothyroidism is a particular condition observed in pseudohypoparathyroidism (PHP), a rare disorder characterized by parathyroid (PTH) resistance leading to hypocalcemia and hyperphosphatemia associated with a GNAS (guanine nucleotide-binding protein α-subunit) mutation (PHP1A) or epimutation (PHP1B). To determine the presence of hypothyroidism at birth we conducted a retrospective study in our cohort of patients presenting with either PHP1A (n = 116) or PHP1B (n = 99). We also investigated patients presenting at birth with congenital hypothyroidism (CH) and a eutopic thyroid gland for phosphocalcium abnormalities suggesting PTH resistance and PHP. Our study reveals CH as the earliest diagnostic clue for PHP1A, but not for PHP1B. We estimated the frequency of CH at birth to be between 8 and 34% in patients presenting with PHP1A. The elevation of phosphatemia and PTH concentration precedes hypocalcemia in PHP1A. Conversely, the frequency of PHP1A in patients presenting CH is dramatically low. This may be due to the low prevalence of PHP1A which remains unknown. CONCLUSIONS: Subclinical and overt hypothyroidism can occur in PHP1A patients at birth many years before PTH resistance becomes clinically apparent. Although such cases appear to be rare, some pediatric patients with unexplained CH are likely to benefit from measuring calcium, phosphorus, and PTH for extended periods of time.

Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: an effect abolished by a single amphetamine injection.

The present study had two main goals. First, to investigate whether an animal model of post traumatic stress disorder (PTSD), single prolonged stress (SPS) leads to one of the main PTSD symptom: avoidance of trauma-related stimuli. Second, to investigate whether a single amphetamine injection delivered 30 days after SPS can reduce these symptoms. Olfactory and auditory cues were added to the SPS context and reactivity to these cues were tested more than one month later using an odor discrimination test, and freezing to the trauma-related tone. Other PTSD symptoms, such as anxiety (elevated plus maze) and hyperarousal (acoustic startle response), were also investigated in these rats. Some behavioural reactivity to the environmental cues was observed in rats exposed to SPS. However, a subgroup of these rats showed an exaggerated disruption in performance in 3 to 4 of the behavioral tests relative to controls, suggesting that two classes of rats, those that are susceptible and those that are resilient to SPS, can be dissociated. When rats were treated with amphetamine (1mg/kg) injected in the SPS context 30 days after SPS, traumatized rats no longer differed from their corresponding controls and all were identified as resilient. The present data demonstrated that rats exposed to SPS can be either susceptible or resilient and a single amphetamine injection can abolish the associated symptoms. We propose that combining memory reactivation, with an amphetamine-induced positive mood, can modify the emotional valence of the initial memory, inducing long-lasting remodeling of the traumatic memory, thereby opening a novel therapeutic avenue.

Traumatic stress in rats induces noradrenergic-dependent long-term behavioral sensitization: role of individual differences and similarities with dependence on drugs of abuse.

RATIONALE: The aim of this paper is to provide evidence for the hypothesis that posttraumatic stress disorder (PTSD) and drug addiction rely on common processes. OBJECTIVE: Our objective is to show that a noradrenergic-dependent behavioral sensitization occurs after the development of PTSD, in a way similar to that recently demonstrated after repeated drug injections. METHODS: Rats classified into high and low responders to novelty (HR/LR) were subjected to a single prolonged stress (SPS). Cross-sensitization was evaluated after d-amphetamine injection (1.0 mg/kg) in a locomotor activity test given either 4, 15, or 90 days later. To determine the involvement of the noradrenergic system, rats were injected with the α2-receptor agonist, clonidine (20 µg/kg), during the SPS. Subsequently, their auditory startle response (ASR) and cross-sensitization were assessed. RESULTS: SPS affected both the hypothalamic-pituitary-adrenal axis and the ASR, replicating some PTSD-like symptoms. Behavioral sensitization was found after 15, 21, and 90 days after the SPS in LR rats, and a behavioral desensitization in HR rats after 15 days. Clonidine delivered during the SPS prevented the behavioral sensitization in LR rats, as well as the effects on ASR in HR and LR rats. CONCLUSIONS: Exposure to SPS is shown to affect behavior and induce a behavioral sensitization to d-amphetamine that is modulated by individual differences. Both of these effects depend on the noradrenergic system. Altogether, the present results (1) replicate findings obtained after repeated drug exposure and (2) strengthen our hypothesis of a common physiological basis between PTSD and drug addiction.

[Online hemodiafiltration: is it really more expensive?]. / Hémodiafiltration en ligne : y a-t-il réellement un surcoût ?

Online hemodiafiltration has been shown to have many benefits in terms of morbi-mortality and to increase middle weight molecules removal. However, this technique is supposed to have an additional cost which may be an obstacle to increase its development in hemodialysis centers. The aim of the study is to achieve an accurate pharmaco-economic evaluation for determining the real overcost of online hemodiafiltration (OL-HDF) in comparison with high flux hemodialysis (HF-HD) using standard priming. We have identified the additional costs related to the consumables and monitors and the additional costs imposed by the technique itself (water consumption and microbiological analysis). In the center, more than 28,000 sessions per year are performed with 70% in OL-HDF (90% post-dilution). The consumable overcost ranges from -2.55 to +3.35 euros per session depending on the monitor and on the HDF modality. The overcost of microbiological analysis is +1.1 euros per session. The theoretical additional water consumption is calculated from different dialysat flow rates and OL-HDF modality. Its ranges from +50.8L to +74.8L per session increasing the water overcost from +0.15 to +0.23 euros per session. This accurate evaluation shows that the cost difference of OL-HDF depends on monitor used and on the OL-HDF modality. In our center, it ranges from -1.29 to +4.58 euros per session.

Ionic dialysance and determination of Kt/V in on-line hemodiafiltration with simultaneouspre- and post-dilution.

PURPOSE: A direct determination of Kt/V using ionic dialysance for estimating K and bio-impedancemetry for estimating V is compared with the usual indirect estimation based on the second generation Daugirdas equation during a new technique of hemodiafiltration with simultaneous pre- and post-dilution (mixed-HDF).
 METHODS: In 31 informed consented patients, the urea distribution volume (V) is estimated by total body water (VBCM ) measured by the Body Composition Monitor (BCM; Fresenius Medical Care, Bad Homburg, Germany) based on bio-impedance spectroscopy. The value (KOCM t)/VBCM is calculated during 114 mixed-HDF sessions (duration 4 hours) from the measurement of ionic dialysance KOCM by the OCM module, standard on the 5008 dialysis monitor (Fresenius Medical Care, Germany). The single pool (Kt/V)sp is determined from blood urea concentration measurements using the Daugirdas equation. RESULTS: Mixed-HDF is a very high-efficiency hemodialysis with a delivered dialysis dose Kt/V near from 2 per 4-hour session. (KOCM t)/VBCM (1.97 ± 0.28) is consistent with (Kt/V)sp (2.01 ± 0.34) with a correlation coefficient at 0.72. CONCLUSIONS: Direct calculation of Kt/V from estimating K by OCM and V by BCM is consistent with the usual indirect estimation by the second generation Daugirdas equation. Therefore, the regular determination of V by BCM allows the estimation of single-pool Kt/V at each session without the need of blood sampling.

Radial artery graft stenosis treated by percutaneous intervention.

OBJECTIVE: This study aims to evaluate the clinical implications of radial artery graft stenosis and the performance of percutaneous intervention (PCI) of radial artery (RA) grafts. METHODS: Out of 291 patients, 18 (6.2%) underwent PCI of an RA graft. The indications for PCI were acute myocardial infraction (n=1), angina (n=10) and scintigraphic abnormality (n=5). Two patients were asymptomatic and underwent PCI prior to major extracardiac surgery. The location of the RA stenosis was proximal (n=2) or distal anastomosis (n=5) and body of the conduit (n=11). From 1992 to 2001, balloon dilatation alone was performed on nine RA grafts at 1.7 years after surgery. Since 1999, stenting of nine RA grafts was achieved at 9.2 years after surgery. Three bare-metal and six drug-eluting stents were implanted. Stent mean diameter and length were 2.75 mm and 16 mm, respectively. Simultaneous PCI of other coronaries was achieved in five cases. RESULTS: At 5.8 years, clinical follow-up showed heart failure (n=2) and recurrent angina (n=3), all after balloon dilatation. Control angiogram was performed in 14 cases at 4.5 years by conventional angiography (n=8) and 64-slice CT scan (n=6). One RA graft was occluded due to competitive flow from the native coronary vessel. Two RA restenoses following balloon dilatation were treated by stenting with long-term success (n=1) and secondary occlusion (n=1). Intra-stent RA stenosis was noted in one asymptomatic patient. All patients survived at long term except for one non-cardiac death at 5.9 years. CONCLUSION: Focal stenosis of radial artery graft is a rare angiographic finding and its meaning is unequivocal. PCI with balloon alone should be restricted to the early postoperative period during which spasm is difficult to exclude. Stenting offers excellent and durable results and shall be preferred in most cases.

Long-term (5- to 20-year) patency of the radial artery for coronary bypass grafting.

OBJECTIVE: The aim of this study was to assess the angiographic results of the radial artery as a coronary bypass conduit at long term (>5 years). METHODS: Radial artery grafts were controlled in 202 patients at 10.1 years by conventional angiography (n = 79) and computed tomography (n = 123). Clinical or paraclinical evidence of ischemia was noted in 81 patients, whereas 121 patients were asymptomatic. Some 520 conduits were controlled: radial artery (n = 230), left internal thoracic artery (n = 190), right internal thoracic artery (n = 30), and veins (n = 70). Radial arteries were anastomosed to the right coronary (24%), marginal (58%), diagonal (16%), and left anterior descending (<1%) arteries, whereas left internal thoracic arteries were primarily anastomosed to the left anterior descending artery (95%). The mean number of antithrombotic and anti-anginal medications was 1.2 and 1.9 per patient, respectively. RESULTS: The ejection fraction was slightly decreased compared with its preoperative value (54% +/- 11% vs 57% +/- 9%; P = .009). Nine reoperations were required at 10.5 years for valve replacement (n = 8) and isolated bypass (n = 1). Percutaneous intervention was performed in 48 patients (24%) at 7.6 years on a graft (28%) or a native coronary artery (72%). The 10-year patency of radial artery grafts was 83%, which was lower than the patency of left internal thoracic arteries (95%, P < .001) and similar to the patency of right internal thoracic arteries (87%, P = .66) and veins (81%, P = .50). No medication seemed to influence radial artery graft patency (aspirin: P = .26; calcium blockers: P = .36). All graft patency was lower when clinical or paraclinical evidence of ischemia was present than in asymptomatic cases (83% vs 90% P = .02). The patency of left anterior descending grafts was higher than that of non-left anterior descending grafts (96% vs 82% P < .001). CONCLUSION: The radial artery-to-coronary bypass conduit provided a low coronary reoperation rate with an excellent patency (83%) up to 20 years postoperatively.