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This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. This manuscript was originally published in 1989 as part of an edited book on the therapeutic relation. In this chapter, Paul Eelen takes a critical position against the dominance of the client-centered approach. He presents the therapeutic relation as a behavioural interaction between the patient and his therapist which is subject to laws of learning. This is exemplified by an in-depth analysis of the therapist as a conditioned stimulus. First published as: Eelen, P., Depreeuw, E., & Van den Bergh, O. (1989). De therapeut als geconditioneerde stimulus. In H. Vertommen, G. Cluckers, & G. Lietaer (Eds.), 'De relatie in therapie' (pp. 147–165). Leuven: Universitaire Pers Leuven.1

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. This manuscript was originally published in 1992 and discusses functional analysis as the Achilles heel of cognitive-behavioural therapy (CBT). Functional analysis is that part of CBT where insight in learning principles feeds into clinical case conceptualisation. Even though functional analysis was self-evident for first generation behaviour therapists, its importance has been overlooked since long. It is striking to see how modern CBT-approaches again incorporate functional assessment. First published as: Eelen, P., & Van den Bergh, O. (1992). De gebroken achillespees van de gedragstherapie: enkele bedenkingen bij de functieanalyse. 'Psychotherapeutisch Paspoort', 2, 25–34.1

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. The present manuscript was originally published as part of a Liber Amicorum for Paul Eelen’s own supervisor, prof. Joseph Nuttin. In this chapter, Paul Eelen presents a modern view on Pavlovian learning. It appeared in 1980, at the heyday of cognitive psychology which initially dismissed conditioning. Paul Eelen’s perseverance in presenting learning principles as key to study human behaviour has proven correct and ahead of time. First published as: Eelen, P. (1980). Klassieke conditionering: Klassiek en toch modern. In Liber Amicorum, Prof. J. R. Nuttin, 'Gedrag, dynamische relatie en betekeniswereld' (pp. 321–343). Leuven: Universitaire Pers Leuven.

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. The present manuscript presents a translation of an interview with Paul Eelen by the University of Leuven student magazine Veto. First published as: 'Wetenschap en maatschappij deel vijf: de psycholoog Paul Eelen. “Geen enkele voetballer zal geloven dat hij gedetermineerd is door de bal”'. Interview in Veto Magazine, April 3 2000, 26, pp. 8–9. Interviewed by: Diederik Vandendriessche and Yves Dejaegere.1

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. This manuscript is a transcription of a lecture that was published in 1980. It was Paul Eelen’s first public presentation after a two-year study in the United States, which has inspired much of his later thinking. The text can be viewed as a manifesto for behaviour therapy as it was then advancing in Belgium and the Netherlands. This presentation was given as the introduction to the L.A.P.P. seminar day held October 27, 1980, which was themed: 'Behaviour modification'. The lecture was published as: Eelen, P. (1980). Gedragstherapie en gedragsmodificatie: Achtergronden. 'Leuvens Bulletin L. A. P. P.', 39, 1–19.

This paper outlines a theoretical account of musical self-enhancement. I claim that listening to music serves as a resource for actively manipulating affective states so that a positive self-view is maintained and a sense of optimism is provided. Self-enhancement—the process by which individuals modify their self-worth and gain self-esteem—typically takes place in social interactions. I argue that experiencing music may serve as a unique aesthetic surrogate for interaction, which equally enables self-enhancement. This ability relies on three main characteristics of the musical experience, namely, its capacity to (a) evoke empathetic feelings, (b) elicit social cohesion and affiliation, and (c) elicit feelings of reward. I outline how these characteristics relate to theories of music cognition and empirical findings in psychology and neuroscience research. I also explain the specifics of musical self-enhancement and how it differs from music’s other regulatory functions such as mood- and emotion regulation. My aim in introducing the notion of musical self-enhancement is to broaden our understanding of how music functions as an environmental resource entailing access to unique affective states and how musical experiences are co-constituted by both the agent and the sonic environment. This specific use of music for self-enhancement can be regarded as a form of affective niche construction, providing the external conditions in which people can experience themselves more positively and maintain high self-esteem.

Background & Aims:Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC).Methods:Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results:Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P=0.097 or P=0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P=0.039) independent of whether diarrhea (n=12), constipation (n=5) or bloating (n=5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P=0.019) when compared to incubation with HC supernatant.Conclusion:We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

Background: Apathy, the major manifestation of impaired goal-directed behavior (GDB), is the most common neuropsychiatric syndrome associated with behavioral variant frontotemporal degeneration (bvFTD). The behavioral and biological mechanisms of apathy, however, are not well understood. We hypothesized that GDB has multiple components – including at least initiation, planning and motivation – and that GDB is supported by a network of multiple frontal brain regions. In this study, we examined this hypothesis by evaluating the selective breakdown of GDB in bvFTD, and relating these deficits to grey matter (GM) atrophy and white matter (WM) integrity. Methods: Eighteen apathetic bvFTD participants and 17 healthy controls completed the Philadelphia Apathy Computerized Test (PACT). This test quantifies each of three components of GDB hypothesized to contribute to apathy. We then used regression analyses to relate PACT scores to GM atrophy and reduced white matter (WM) fractional anisotropy (FA) in bvFTD. Results: Compared to controls, bvFTD participants demonstrated significant impairments in each of the three hypothesized components of GDB that contribute to apathy. Regression analyses related each component to disease in specific GM structures and associated WM tracts. Poor initiation thus was related to GM atrophy in anterior cingulate and reduced FA in the cingulum. Planning impairment was related to GM atrophy in dorsolateral prefrontal cortex and reduced FA in superior longitudinal fasciculus. Poor motivation was related to GM atrophy in orbitofrontal cortex and reduced FA in uncinate fasciculus. Conclusions: bvFTD patients have difficulty with initiation, planning and motivation components of GDB. These findings are consistent with the hypotheses that GDB encompasses at least three processes, that these are supported by a large-scale neural network within specific portions of the frontal lobe, and that degradation of any one of these prefrontal regions in bvFTD may contribute to apathy.

The current study examined the musical taste of musicology students as compared to a control student group. Participants (n=1003) completed an online survey regarding the frequency with which they listened to 22 musical styles. A factor analysis revealed six underlying dimensions of musical taste. A hierarchical cluster analysis then grouped all participants, regardless of their status, according to their similarity on these dimensions. The employed exploratory approach was expected to reveal potential differences between musicology students and controls. A three-cluster solution was obtained. Comparisons of the clusters in terms of musical taste revealed differences in the listening frequency and variety of appreciated music styles: The first cluster (51% musicology students / 27% controls) showed the greatest musical engagement across all dimensions although with a tendency towards »sophisticated« musical styles. The second cluster (36% musicology students / 46% controls) exhibited an interest in »conventional« music, while the third cluster (13% musicology students / 27% controls) showed a strong liking of rock music. The results provide some support for the notion of specific tendencies in the musical taste of musicology students and the contribution of familiarity and knowledge towards musical omnivorousness.

From distinct research traditions rumination and overgeneral autobiographical memory retrieval (OGM) have emerged as two vulnerability markers for depression and depressive relapse (Nolen-Hoeksema, 2004; Williams, 2004). Recent research further suggests a causal relation between rumination and OGM (e.g., Watkins & Teasdale, 2001). The present study investigated the inverse relationship, that is, OGM causally influencing ruminative thinking. A scrambled sentences procedure was used to assess the extent to which 112 student participants were engaged in a mental mode consistent with ruminative thinking following either a specific or overgeneral memory retrieval style manipulation. Trait rumination was also assessed prior to the experimental retrieval manipulation, using a self-report scale. It was found that high ruminators, following an overgeneral (as compared to a specific) retrieval style, unscrambled sentences relatively more into sentences with a ruminative meaning. In non or low ruminators this retrieval style manipulation had no such effect. Alongside the findings of Watkins and colleagues (e.g., Watkins & Teasdale, 2001), the present results are consistent with the view of rumination and OGM as two mutually reinforcing vulnerability factors for depression (Williams, 1996, 2004).

Calreticulin is a pleiotropic molecule that normally resides in the lumen of the endoplasmatic reticulum (ER). Here it has various functions, ranging from regulation of calcium homeostasis to ensuring proper protein folding. More recently, calreticulin gained especial interest for its extracellular functions, where it has direct immunomodulatory activity. In this respect, calreticulin activates dendritic cells (DCs) and macrophages. In addition, certain anti-cancer therapies induce the translocation of calreticulin from the ER to the cell surface of dying cancer cells, where calreticulin dictates the immunogenicity of these cells. Interestingly, treatment with Tumor Necrosis Factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL) also induces membrane calreticulin exposure on cancer cells. As shown here, calreticulin directly interacts with TRAIL and its receptor (TRAILR)-signaling complex, as well as with other TNF family members. Of note, TRAIL is a well known immunomodulatory molecule, and is expressed on the surface of natural killer T-cells (NK T-cells). Therefore, calreticulin may have an as yet unrecognized wide(r) impact on immunity, with the TNF ligand family modulating virtually all aspects of the immune response.

Endoplasmic reticulum (ER) chaperones (e.g. calreticulin, heat shock proteins and isomerases) perform a multitude of functions within the ER. However, many of these chaperones can translocate to the cytosol and eventually the surface of cells, particularly during ER stress induced by e.g. drugs, UV irradiation and microbial stimuli. Once on the cell surface or in the extracellular space, the ER chaperones can take on immunogenic characteristics, as mostly described in the context of cancer, appearing as damage-associated molecular patterns recognized by the immune system. How ER chaperones relocate to the cell surface and interact with other intracellular proteins appears to influence whether a tumor cell is targeted for cell death. The relocation of ER proteins to the cell surface can be exploited to target cancer cells for elimination by immune mechanism. Here we evaluate the evidence for the different mechanisms of ER protein translocation and binding to the cell surface and how ER protein translocation can act as a signal for cancer cells to undergo killing by immunogenic cell death and other cell death pathways. The release of chaperones can also exacerbate underlying autoimmune conditions, such as rheumatoid arthritis and multiple sclerosis, and the immunomodulatory role of extracellular chaperones as potential cancer immunotherapies requires cautious monitoring, particularly in cancer patients with underlying autoimmune disease.

In multiple sclerosis (MS) patients, fatigue is rated as one of the most common and disabling symptoms. However, the pathophysiology underlying this fatigue is not yet clear. Several lines of evidence suggest that immunological factors, such as elevated levels of proinflammatory cytokines, may contribute to subjective fatigue in MS patients. Proinflammatory cytokines represent primary mediators of immune-to-brain-communication, modulating changes in the neurophysiology of the central nervous system. Recently, we proposed a model arguing that fatigue in MS patients is a subjective feeling which is related to inflammation. Moreover, it implies that fatigue can be measured behaviorally only by applying specific cognitive tasks related to alertness and vigilance. In the present review we focus on the subjective feeling of MS-related fatigue. We examine the hypothesis that the subjective feeling of MS-related fatigue may be a variant of inflammation-induced sickness behavior, resulting from cytokine-mediated activity changes within brain areas involved in interoception and homeostasis including the insula, the anterior cingulate and the hypothalamus. We first present studies demonstrating a relationship between proinflammatory cytokines and subjective fatigue in healthy individuals, in people with inflammatory disorders, and particularly in MS patients. Subsequently, we discuss studies analyzing the impact of anti-inflammatory treatment on fatigue. In the next part of this review we present studies on the transmission and neural representation of inflammatory signals, with a special focus on possible neural concomitants of inflammation-induced fatigue. We also present two of our studies on the relationship between local gray and white matter atrophy and fatigue in MS patients. Finally, we discuss some implications of our findings and future perspectives.

Objective: Predicting who responds to placebo treatment – and under which circumstances – has been a question of interest and investigation for generations. However, the literature is disparate and inconclusive. This review aims to identify publications that provide high quality data on the topic of placebo response (PR) prediction. Methods: To identify studies concerned with PR prediction, independent searches were performed in an expert database (for all symptom modalities) and in PubMed (for pain only). Articles were selected when a) they assessed putative predictors prior to placebo treatment and b) an adequate control group was included when the association of predictors and PRs were analyzed. Results: Twenty-one studies were identified, most with pain as dependent variable. Most predictors of PRs were psychological constructs related to actions, expected outcomes and the emotional valence attached to these events (goal-seeking, self-efficacy/-esteem, locus of control, optimism). Other predictors involved behavioural control (desire for control, eating restraint), personality variables (fun seeking, sensation seeking, neuroticism), biological markers (sex, a single nucleotide polymorphism related to dopamine metabolism). Finally, suggestibility and beliefs in expectation biases, body consciousness and baseline symptom severity were found to be predictive. Conclusions: While results are heterogeneous, some congruence of predictors can be identified. PRs mainly appear to be moderated by expectations of how the symptom might change after treatment, or the expectation of how symptom repetition can be coped with. It is suggested to include the listed constructs in future research. Furthermore, a closer look at variables moderating symptom change in control groups seems warranted.

Many contemporary neuroscientific investigations face significant challenges in terms of data management, computational processing, data mining and results interpretation. These four pillars define the core infrastructure necessary to plan, organize, orchestrate, validate and disseminate novel scientific methods, computational resources and translational healthcare findings. Data management includes protocols for data acquisition, archival, query, transfer, retrieval and aggregation. Computational processing involves the necessary software, hardware and networking infrastructure required to handle large amounts of heterogeneous neuroimaging, genetics, clinical and phenotypic data and meta-data. In this manuscript we describe the novel high-throughput neuroimaging-genetics computational infrastructure available at the Institute for Neuroimaging and Informatics (INI) and the Laboratory of Neuro Imaging (LONI) at University of Southern California (USC). INI and LONI include ultra-high-field and standard-field MRI brain scanners along with an imaging-genetics database for storing the complete provenance of the raw and derived data and meta-data. A unique feature of this architecture is the Pipeline environment, which integrates the data management, processing, transfer and visualization. Through its client-server architecture, the Pipeline environment provides a graphical user interface for designing, executing, monitoring validating, and disseminating of complex protocols that utilize diverse suites of software tools and web-services. These pipeline workflows are represented as portable XML objects which transfer the execution instructions and user specifications from the client user machine to remote pipeline servers for distributed computing. Using Alzheimer’s and Parkinson’s data, we provide several examples of translational applications using this infrastructure.

Body motion is a rich source of information for social cognition. However, gender effects in body language reading are largely unknown. Here we investigated whether, and, if so, how recognition of emotional expressions revealed by body motion is gender dependent. To this end, females and males were presented with point-light displays portraying knocking at a door performed with different emotional expressions. The findings show that gender affects accuracy rather than speed of body language reading. This effect, however, is modulated by emotional content of actions: males surpass in recognition accuracy of happy actions, whereas females tend to excel in recognition of hostile angry knocking. Advantage of women in recognition accuracy of neutral actions suggests that females are better tuned to the lack of emotional content in body actions. The study provides novel insights into understanding of gender effects in body language reading, and helps to shed light on gender vulnerability to neuropsychiatric impairments in visual social cognition.

Introduction: In December 2022, California (CA) enforced a voter-approved regulation restricting the retail sale of flavoured tobacco products, including menthol cigarettes. Shortly after, new products emerged on the market containing similar blue and green package colours yet with 'non-menthol' descriptors. Using chemical analyses, we measured the content of menthol and 15 other cooling chemicals in Californian cigarettes with 'non-menthol' descriptors and compared concentrations to similar 'menthol'-labelled counterparts available in New York State (NY)., Methods: A convenience sample of 10 brands and types of cigarettes in CA were purchased based on package colours suggesting a cooling effect and/or 'non-menthol' descriptors. The exact brand and type of cigarettes (with menthol descriptors) were purchased in NY. Cigarettes from CA were compared with equivalent cigarettes from NY on package design and colours, cigarette physical characteristics and the presence of cooling additives., Results: Menthol was not detected in any CA cigarette, except for Maverick-green box type, while its presence was confirmed in most NY counterpart products. A synthetic cooling chemical WS-3 was not detected in any NY cigarettes but was detected in four CA brands and types with implied cooling effect, ranging from 1.24±0.04 to 1.97±0.05 mg/cigarette., Conclusion: While manufacturers have removed menthol descriptors from CA packaging and the menthol ingredient from cigarettes, synthetic cooling chemicals detected in several CA brands suggest that cooling sensory effects may still be sustained. Policymakers must consider both the chemical ingredients themselves and sensory effects in future regulatory approaches., Competing Interests: Competing interests: MLG received a research grant from and served as an advisory board member to pharmaceutical companies that manufacture smoking cessation drugs., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Translation initiation in eukaryotes relies on a complex network of interactions that are continuously reorganized throughout the process. As more information becomes available about the structure of the ribosomal preinitiation complex (PIC) at various points in translation initiation, new questions arise about which interactions occur when, their roles, and regulation. The eukaryotic translation factor (eIF) 5 is the GTPase-activating protein (GAP) for the GTPase eIF2, which brings the initiator Met-tRNA i to the PIC. eIF5 also plays a central role in PIC assembly and remodeling through interactions with other proteins, including eIFs 1, 1A, and 3c. Phosphorylation by casein kinase 2 (CK2) significantly increases the eIF5 affinity for eIF2. The interaction between eIF5 and eIF1A was reported to be mediated by the eIF5 C-terminal domain (CTD) and the eIF1A N-terminal tail. Here, we report a new contact interface, between eIF5-CTD and the oligonucleotide/oligosaccharide-binding fold (OB) domain of eIF1A, which contributes to the overall affinity between the two proteins. We also show that the interaction is modulated by dynamic intramolecular interactions within both eIF5 and eIF1A. CK2 phosphorylation of eIF5 increases its affinity for eIF1A, offering new insights into the mechanisms by which CK2 stimulates protein synthesis and cell proliferation., 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., (© 2022 The Authors.)

The HEAT domains are a family of helical hairpin repeat domains, composed of four or more hairpins. HEAT is derived from the names of four family members: huntingtin, eukaryotic translation elongation factor 3 (eEF3), protein phosphatase 2 regulatory A subunit (PP2A), and mechanistic target of rapamycin (mTOR). HEAT domain-containing proteins play roles in a wide range of cellular processes, such as protein synthesis, nuclear transport and metabolism, and cell signaling. The PCI domains are a related group of helical hairpin domains, with a "winged-helix" (WH) subdomain at their C-terminus, which is responsible for multi-subunit complex formation with other PCI domains. The name is derived from the complexes, where these domains are found: the 26S Proteasome "lid" regulatory subcomplex, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). We noted that in structure similarity searches using HEAT domains, sometimes PCI domains appeared in the search results ahead of other HEAT domains, which indicated that the PCI domains could be members of the HEAT domain family, and not a related but separate group, as currently thought. Here, we report extensive structure similarity analysis of HEAT and PCI domains, both within and between the two groups of proteins. We present evidence that the PCI domains as a group have greater structural similarity with individual groups of HEAT domains than some of the HEAT domain groups have among each other. Therefore, our results indicate that the PCI domains have evolved from a HEAT domain that acquired a WH subdomain. The WH subdomain in turn mediated self-association into a multi-subunit complex, which eventually evolved into the common ancestor of the Proteasome lid/CSN/eIF3., Competing Interests: The authors have declared that no competing interests exist.

Translation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met-tRNA i to the PIC. Upon start codon selection and GTP hydrolysis, promoted by eIF5, eIF2-GDP is released in complex with eIF5. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C-terminal tail (CTT) dynamically contact the folded C-terminal domain (CTD) and compete with each other. The eIF5-CTD•CTT interaction favors eIF2β binding to eIF5-CTD, whereas the eIF5-CTD•DWEAR interaction favors eIF1A binding, which suggests how intramolecular contact rearrangement could play a role in PIC remodeling. We show that eIF5 phosphorylation by CK2, which is known to stimulate translation and cell proliferation, significantly increases the eIF5 affinity for eIF2. Our results also indicate that the eIF2β subunit has at least two, and likely three eIF5-binding sites., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the acute blood pressure (BP) and hemodynamic effects of sodium chloride (3% intravenous solution). Although many studies link a change in dietary sodium to a change in BP, few consider the effects of sodium concentration in the blood on BP. We hypothesized that an intravenous sodium load would increase BP, and we quantified alterations in cardiac output (Qc) and peripheral vascular resistance (PVR). Thirteen subjects (age 27 +/- 2 yr) underwent a 60-min 3% saline infusion (0.15 ml.kg(-1).min(-1)). BP was assessed on a beat-to-beat basis with a Finometer, Qc was assessed via the CO(2) rebreathing technique, and PVR was derived. Serum sodium and osmolality increased, and hematocrit declined during the infusion (ANOVA, P < 0.01). Mean arterial pressure (MAP) increased continuously during the infusion from 81.8 +/- 3.4 to 91.6 +/- 3.6 mmHg (ANOVA, P < 0.01). BP responsiveness to sodium was expressed as the slope of the serum sodium-MAP relationship and averaged 1.75 +/- 0.34 mmHg.mmol(-1).l(-1). BP responsiveness to the volume change was expressed as the slope of the hematocrit-MAP relationship and averaged -2.2 +/- 0.35 mmHg/%. The early change in MAP was mediated by an increase in Qc and the late change by an increase in PVR (P < 0.05), corresponding to a 30% increase in plasma norepinephrine. In conclusion, an acute infusion of hypertonic saline was effective in increasing BP, and both sodium and volume appear to be involved in this increase; acute BP responsiveness to serum sodium can be quantified using a MAP-sodium plot.