How to treat subsyndromal anxiety disorder - practical recommendations for implementation in primary care.

BACKGROUND: Anxiety is a common and disabling condition that significantly impacts quality of life. Subsyndromal anxiety (SSA) refers to anxiety symptoms that do not meet the full diagnostic criteria for an anxiety disorder but pose a risk for developing such disorders. We aimed to provide practical recommendations for the treatment of SSA in primary care settings. METHODS: A narrative review was conducted to identify strategies for recognizing and treating patients with SSA. RESULTS: The recommendations for treating SSA include lifestyle modifications such as exercise and stress reduction techniques, psychotherapy, and pharmacological treatments, including natural compounds like the lavender oil extract Silexan. Regular follow-up care is essential to monitor treatment response and address ongoing symptoms. Additionally, the use of the GAD-7 tool is recommended for accurately identifying patients with SSA. CONCLUSION: Implementing these recommendations in primary care can lead to effective treatment of SSA, preventing the development of more severe anxiety disorders. An integrative approach, combining lifestyle modifications, psychotherapy, and pharmacotherapy, including natural compounds, offers significant benefits for managing anxiety.

Anxiety is prevalent and disablingSubsyndromal anxiety is a risk factor for anxiety disordersSubsyndromal anxiety can be assessed with the GAD-7 (Generalised Anxiety Disorder-7 scale)Subsyndromal anxiety can be treated with life-style modification, psychotherapy and pharmacological treatment, including silexan, a natural compound.

The impact of emotional valence on generalization gradients.

Generalization enables individuals to respond to novel stimuli based on previous experiences. The degree to which organisms respond is determined by their physical resemblance to the original conditioned stimulus (CS+), with a stronger response elicited by more similar stimuli, resulting in similarity-based generalization gradients. Recent research showed that cognitive or conceptual dimensions also result in gradients similar to those observed with manipulations of physical dimensions. Such findings suggest that attributes beyond physical similarity play a role in shaping generalization gradients. However, despite its adaptive relevance for survival, there is no study exploring the effectiveness of affective dimensions in shaping generalization gradients. In two experiments (135 Spanish and 150 English participants, respectively), we used an online predictive learning task, in which different stimuli (words and Gabor patches) were paired with the presence - or absence - of a fictitious shock. After training, we assessed whether valence (i.e., hedonic experience) conveyed by words shape generalization gradients. In Experiment 1, the outcome expectancy decreased monotonically with variations in valence of Spanish words, mirroring the gradient obtained with the physical dimension (line orientation). In Experiment 2, conducted with English words, a similar gradient was observed when non-trained (i.e., generalization) words varied along the valence dimension, but not when words were of neutral valence. The consistency of these findings across two different languages strengthens the reliability and validity of the affective dimension as a determinant of generalization gradients. Furthermore, our data highlight the importance of considering the role of affective features in generalization responses, advancing the interplay between emotion, language, and learning.

Further evidence for the role of temporal contiguity as a determinant of overshadowing.

Three experiments explored whether weakening temporal contiguity between auditory cues and an aversive outcome attenuated cue competition in an avoidance learning task with human participants. Overall, with strong temporal contiguity between auditory cues and the outcome during training (the offset of the predictive auditory signals concurred with the onset of the outcome), the target cue trained as part of a compound yielded less avoidance behaviour than the control cue trained alone, an instance of overshadowing. However, weakening temporal contiguity during training (inserting a 5-s trace) attenuated overshadowing, resulting in similar avoidance behaviour in response to the control and target cues. These results provide evidence that, as predicted by a recent modification of Pearce's configural theory, temporal contiguity is critical for determining cue competition.

Category relevance attenuates overshadowing in human predictive learning.

In situations in which multiple predictors anticipate the presence or absence of an outcome, cues compete to anticipate the outcome, resulting in a loss of associative strength compared to control conditions without additional cues. Critically, there are multiple factors modulating the magnitude and direction of such competition, although in some scenarios the effect of these factors remains unexplored. We sought to assess whether the relative salience of the elements in a compound of cues modulates the magnitude of the overshadowing effect in human predictive learning. Two separable categories (i.e., colors and symbols) were used in a predictive learning task. In Experiment 1, different groups of participants were granted with different time of exposure to a compound of cues belonging to different categories (color and symbol) to evaluate potential differences in the magnitude of overshadowing. Furthermore, we used posttest questionnaires to assess whether participants used either only one or both categories during training, and assessed if this impacted the magnitude of overshadowing. In general, overshadowing was not modulated by the time of exposition, except in the case of very short time of exposition with prominent learning about the most salient category. In Experiment 2, the relative salience of a category was biased via prior experience either with a biconditional discrimination or attending only the relevant category (either color or symbol). The previously relevant category was less prone to overshadowing, but not the alternative one. Results are discussed in light of attentional and configural theories of associative learning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Conditioned place avoidance in the planaria Schmidtea mediterranea: A pre-clinical invertebrate model of anxiety-related disorders.

The objective of the present study was to develop a model of avoidance learning and its extinction in planarians (Schmidtea mediterranea). Based on previous experiments showing conditioned place preference, we developed a procedure to investigate conditioned place avoidance (CPA) using shock as an unconditioned stimulus (US) and an automated tracking system to record the animals' behaviour. In Experiment 1, we assessed the unconditioned properties of different shock intensities by measuring post shock activity. In two subsequent experiments we investigated CPA using different designs, surfaces as conditioned stimuli (CSs; rough and smooth), and different US intensities (5 V and 10 V). In general, we observed the successful development of CPA. However, CPA was stronger with higher shock intensities, and we found that, in our preparation, a rough surface is best at entering into an association with the shock than a smooth surface. Finally, we also observed extinction of CPA. The evidence of CPA and its extinction in flatworms validates the planaria as a pre-clinical model for the study of avoidance learning, a hallmark of anxiety disorders.

Contiguity and overshadowing interactions in the rapid-streaming procedure.

When multiple cues are associated with the same outcome, organisms tend to select between the cues, with one revealing greater behavioral control at the expense of the others (i.e., cue competition). However, non-human and human studies have not always observed this competition, creating a puzzling scenario in which the interaction between cues can result in competition, no interaction, or facilitation as a function of several learning parameters. In five experiments, we assessed whether temporal contiguity and overshadowing effects are reliably observed in the streamed-trial procedure, and whether there was an interaction between them. We anticipated that weakening temporal contiguity (ranging from 500 to 1,000 ms) should attenuate competition. Using within-subject designs, participants experienced independent series of rapid streams in which they had to learn the relationship between visual cues (presented either alone or with another cue) and an outcome, with the cue-outcome pairings being presented with either a delay or trace relationship. Across experiments, we observed overshadowing (Experiments 1, 2, 4, and 5) and temporal contiguity effects (Experiments 2, 3, and 4). Despite the frequent occurrence of both effects, we did not find that trace conditioning abolished competition between cues. Overall, these results suggest that the extent to which contiguity determines cue interactions depends on multiple variables, some of which we address in the General discussion.

Social and non-social categorisation in investment decisions and learning.

Categorical processes allow us to make sense of the environment effortlessly by grouping stimuli sharing relevant features. Although these processes occur in both social and non-social contexts, motivational, affective, and epistemic factors specific to the social world may motivate individuation over categorisation of social compared with non-social stimuli. In one experiment, we tested this hypothesis by analysing the reliance on categorical versus individuating information when making investment decisions about social and non-social targets. In an adaptation of the iterative trust game, participants from three experimental groups had to predict the economic outcomes associated with either humans (i.e., social stimuli), artificial races (i.e., social-like stimuli), or artworks (i.e., non-social stimuli) to earn economic rewards. We observed that investment decisions with humans were initially biased by categorical information in the form of gender stereotypes, but later improved through an individuating learning approach. In contrast, decisions made with non-social stimuli were initially unbiased by categorical information, but the category-outcomes associations learned through repeated interactions were quickly used to categorise new targets. These results are discussed along with motivational and perceptual mechanisms involved in investment decisions and learning about social and non-social agents.

Social overshadowing: Revisiting cue-competition in social interactions.

In a large variety of contexts, it is essential to use the available information to extract patterns and behave accordingly. When it comes to social interactions for instance, the information gathered about interaction partners across multiple encounters (e.g., trustworthiness) is crucial in guiding one's own behavior (e.g., approach the trustworthy and avoid the untrustworthy), a process akin to trial-by-trial learning. Building on associative learning and social cognition literatures, the present research adopts a domain-general approach to learning and explores whether the principles underlying associative learning also govern learning in social contexts. In particular, we examined whether overshadowing, a well-established cue-competition phenomenon, impacts learning of the cooperative behaviors of unfamiliar interaction partners. Across three experiments using an adaptation of the iterated Trust Game, we consistently observed a 'social overshadowing' effect, that is, a better learning about the cooperative tendencies of partners presented alone compared to those presented in a pair. This robust effect was not modulated by gender stereotypes or beliefs about the internal communication dynamics within a pair of partners. Drawing on these results, we argue that examining domain-general learning processes in social contexts is a useful approach to understanding human social cognition.

Temporal contiguity determines overshadowing and potentiation of human Action-Outcome performance.

Three experiments (n = 81, n = 81, n = 82, respectively) explored how temporal contiguity influences Action-Outcome learning, assessing whether an intervening signal competed, facilitated, or had no effect on performance and causal attribution in undergraduate participants. Across experiments, we observed competition and facilitation as a function of the temporal contiguity between Action and Outcome. When there was a strong temporal relationship between Action and Outcome, the signal competed with the action, hindering instrumental performance but not causal attribution (Experiments 1 and 3). However, with weak temporal contiguity, the same signal facilitated both instrumental performance and causal attribution (Experiments 1 and 2). Finally, the physical intensity of the signal determined the magnitude of competition. As anticipated by associative learning models, a more salient signal attenuated to a greater extent instrumental performance (Experiment 3). These results are discussed by reference to a recent adaptation of the configural theory of learning.

Coincidencia de Rhupus y embarazo. Reporte de caso / Coincidence of Rhupus and pregnancy. Case report

Resumen ANTECEDENTES: Si bien el lupus eritematoso sistémico y la artritis reumatoide son enfermedades suficientemente descritas, no lo es la asociación de estas, que se denomina rhupus, que hace referencia a la manifestación clínica resultante de ambas enfermedades enmascaradas que dificulta el diagnóstico y tratamiento. CASO CLÍNICO: Paciente de 37 años que inició con un cuadro con características de lupus eritematoso sistémico y artritis reumatoide hacía 16 años. Se encontró con alteraciones en los estudios de laboratorio y con hallazgos radiológicos que apoyaron el cuadro de rhupus. Por lo anterior se documenta la evolución de este padecimiento, que coincide con su embarazo y después de éste. CONCLUSIONES: La aparición simultánea de lupus eritematoso sistémico y artritis reumatoide, aun cuando fue reportada desde hace décadas, es una enfermedad rara en frecuencia, por lo que hay escasa información del rhupus solo y más aún en coincidencia con el embarazo.

Abstract BACKGROUND: Although systemic lupus erythematosus and rheumatoid arthritis are sufficiently described diseases, the association of these is not, and is called rhupus, which refers to the clinical manifestation resulting from both diseases masked, making diagnosis and treatment difficult. CLINICAL CASE: 37-year-old patient who started with a clinical picture with features of systemic lupus erythematosus and rheumatoid arthritis 16 years ago. She was found to have alterations in laboratory studies and radiological findings that supported the diagnosis of rheupus. Therefore, the evolution of this condition is documented, which coincides with and after her pregnancy. CONCLUSIONS: The simultaneous occurrence of systemic lupus erythematosus and rheumatoid arthritis, even though it was reported decades ago, is a rare disease in frequency, so there is scarce information on rhupus alone and even more so in coincidence with pregnancy.

Facilitators and Barriers of Medication Adherence Based on Beliefs of Persons with Bipolar Disorder: A Qualitative Study.

One of the big challenges in treating individuals with bipolar disorder (BD) is nonadherence to medication. This is the principal factor associated with a worse prognosis or outcome of the disease. This study aimed to explore and analyze the individual perceptions that people with BD have about the positive and negative aspects when taking medication. A descriptive and interpretative study was carried out using the qualitative research paradigm with the use of the analytical technique of discourse analysis, extracting the data through the completion of focus groups. Participants' speech was digitally audio-recorded in digital format. In order to complete the codification of the participants' speech content, we relied on the qualitative data analysis (using the QRS NVivo 10 computer software). Thirty-six participants diagnosed with bipolar disorder took part in our study. In the participants' speech concerning the main barriers to pharmacological treatment, three key topics were identified. Perceived facilitators were summarized in four factors. The main facilitators regarding the use of pharmacological treatment in individuals with BD were the ones related with the perceived need for treatment in the acute phase, the recognition of the illness, the shared clinical decision, and the causal biological attribution in the chronic phase. In terms of perceived barriers, social control was identified in both phases, adverse effects in the acute phase, and the absence of effective treatment in the chronic state.

Temporal and spatial contiguity are necessary for competition between events.

Over the last 50 years, cue competition phenomena have shaped theoretical developments in animal and human learning. However, recent failures to observe competition effects in standard conditioning procedures, as well as the lengthy and ongoing debate surrounding cue competition in the spatial learning literature, have cast doubts on the generality of these phenomena. In the present study, we manipulated temporal contiguity between simultaneously trained predictors and outcomes (Experiments 1-4), and spatial contiguity between landmarks and goals in spatial learning (Supplemental Experiments 1 and 2; Experiment 5). Across different parametric variations, we observed overshadowing when temporal and spatial contiguity were strong, but no overshadowing when contiguity was weak. Thus, across temporal and spatial domains, we observed that contiguity is necessary for competition to occur, and that competition between cues presented simultaneously during learning is absent when these cues were either spatially or temporally discontiguous from the outcome. Consequently, we advance a model in which the contiguity between events is accounted for and which explains these results and reconciles the previously contradictory findings observed in spatial learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Probability of high-risk genetic matching with oocyte and semen donors: complete gene analysis or genotyping test?

PURPOSE: To estimate the probability of high-risk genetic matching when assisted reproductive techniques (ART) are applied with double gamete donation, following an NGS carrier test based on a complete study of the genes concerned. We then determine the results that would have been obtained if the genotyping tests most widely used in Spanish gamete banks had been applied. METHODS: In this descriptive observational study, 1818 gamete donors were characterised by NGS. The pathogenic variants detected were analysed to estimate the probability of high-risk genetic matching and to determine the results that would have been obtained if the three most commonly used genotyping tests in ART had been applied. RESULTS: The probability of high-risk genetic matching with gamete donation, screened by NGS and complete gene analysis, was 5.5%, versus the 0.6-2.7% that would have been obtained with the genotyping test. A total of 1741 variants were detected, including 607 different variants, of which only 22.6% would have been detected by all three genotyping tests considered and 44.7% of which would not have been detected by any of these tests. CONCLUSION: Our study highlights the considerable heterogeneity of the genotyping tests, which present significant differences in their ability to detect pathogenic variants. The complete study of the genes by NGS considerably reduces reproductive risks when genetic matching is performed with gamete donors. Accordingly, we recommend that carrier screening in gamete donors be carried out using NGS and a complete study with nontargeted analysis of the variants of the screened genes.

Relapse after incentivized choice treatment in humans: A laboratory model for studying behavior change.

Behavior change interventions that incentivize desired behavior are highly effective for improving personal health, but difficult to maintain long term. Relapse is common and examining the mechanisms that contribute to relapse in experimental settings can identify processes relevant to substance abuse treatment. We developed a laboratory task that parallels a recent operant model of relapse after incentivized choice reported in the rodent laboratory. In two experiments, undergraduate participants first learned to make an operant response (keyboard button; R1) to earn a reinforcer consisting of an image of a preferred snack food (O1). In a second phase (Phase 2), R1 was still reinforced, but a new response (R2) was introduced and reinforced with a different reinforcer (a coin; O2). In a test phase, contingent incentives for R2 were removed (extinction) and relapse of R1 was assessed. Experiment 1 found that the O2 contingency suppressed R1 during Phase 2, and R1 relapsed rapidly in the test. Neither effect was consistently related to O2 value. Experiment 2 examined whether noncontingent presentations of O1 or O2 during the test could weaken relapse. Here, we found that noncontingent reinforcers did little to reduce or slow the increase in R1 responding. The present experiments highlight a laboratory approach to studying variables that may influence relapse after incentivized treatment. We identify and discuss areas for development to address differences between the present results and prior observations from animal and clinical studies. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Reversing the relationship between a nontarget cue and the outcome facilitates subsequent human predictive learning.

Two experiments were conducted to test the effect of experiencing associative interference on later learning. A predictive learning task was used in which human participants had to evaluate whether plants would grow or not (Outcome) after being watered with different fertilizers (Cues). Experiment 1 found that the increase in the prediction error produced by following a pre-exposed nontarget cue by the outcome, facilitated subsequent acquisition of the relationship between the pre-exposed target cue and the outcome. Experiment 2 compared whether learning about the target cue was differentially affected by experiencing two types of associative interference with the nontarget cue: Pairing the pre-exposed cue with the outcome and presenting the cue without outcome after being paired with it. The experience of associative interference with nontarget cues similarly facilitated subsequent learning about the target cue, regardless of the direction of the change in the nontarget cue-outcome relationship. It is suggested that the increase in prediction error produced by the experience of associative interference may lead to a general increase in attention that facilitates subsequent learning.

Evolution of the Use of Corticosteroids for the Treatment of Hospitalised COVID-19 Patients in Spain between March and November 2020: SEMI-COVID National Registry.

OBJECTIVES: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. MATERIAL AND METHODS: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID-19 Registry from March to November 2020. RESULTS: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236-996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19.

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continued treatment, and those taking ARB.

Simulation of oxygen transport and estimation of tissue perfusion in extensive microvascular networks: Application to cerebral cortex.

Advanced imaging techniques have made available extensive three-dimensional microvascular network structures. Simulation of oxygen transport by such networks requires information on blood flow rates and oxygen levels in vessels crossing boundaries of the imaged region, which is difficult to obtain experimentally. Here, a computational method is presented for estimating blood flow rates, oxygen levels, tissue perfusion and oxygen extraction, based on incomplete boundary conditions. Flow rates in all segments are estimated using a previously published method. Vessels crossing the region boundary are classified as arterioles, capillaries or venules. Oxygen levels in inflowing capillaries are assigned based on values in outflowing capillaries, and similarly for venules. Convective and diffusive oxygen transport is simulated. Contributions of each vessel to perfusion are computed in proportion to the decline in oxygen concentration along that vessel. For a vascular network in the mouse cerebral cortex, predicted tissue oxygen levels show a broad distribution, with 99% of tissue in the range of 20 to 80 mmHg under reference conditions, and steep gradients near arterioles. Perfusion and extraction estimates are consistent with experimental values. A 30% reduction in perfusion or a 30% increase in oxygen demand, relative to reference levels, is predicted to result in tissue hypoxia.