Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Sleep spindle activity and psychotic experiences: Examining the mediating roles of attentional performance and perceptual distortions in a daytime nap study.

Decreased sleep spindle activity in individuals with psychotic disorders is well studied, but its contribution to psychotic symptom formation is not well understood. This study explored potential underlying mechanisms explaining the association between decreased sleep spindle activity and psychotic symptoms. To this end, we analysed the links between sleep spindle activity and psychotic experiences and probed for the mediating roles of attentional performance and perceptual distortions in a community sample of young adults (N = 70; 26.33 ± 4.84 years). Polysomnography was recorded during a 90-min daytime nap and duration, amplitude, and density from slow (10-13 Hz) and fast (13-16 Hz) spindles were extracted. Attentional performance was assessed via a test battery and with an antisaccadic eye movement task. Psychotic experiences (i.e., paranoid thoughts; hallucinatory experiences) and perceptual distortions (i.e., anomalous perceptions; sensory gating deficits) were assessed via self-report questionnaires. We conducted sequential mediation analyses with spindle activity as predictor, psychotic experiences as dependent variable, and attentional performance and perceptual distortions as mediators. We found reduced right central spindle amplitude to be associated with paranoid thoughts. Increased antisaccadic error rate was associated with anomalous perceptions and perceptual distortions were associated with psychotic experiences. We did not find significant mediation effects. The findings support the notion that reduced sleep spindle activity is involved in the formation of paranoid thoughts and that decreased antisaccadic performance is indicative of perceptual distortions as potential precursors for psychotic experiences. However, further research is needed to corroborate the proposed mediation hypothesis.

A framework for language technologies in behavioral research and clinical applications: Ethical challenges, implications, and solutions.

Technological advances in the assessment and understanding of speech and language within the domains of automatic speech recognition, natural language processing, and machine learning present a remarkable opportunity for psychologists to learn more about human thought and communication, evaluate a variety of clinical conditions, and predict cognitive and psychological states. These innovations can be leveraged to automate traditionally time-intensive assessment tasks (e.g., educational assessment), provide psychological information and care (e.g., chatbots), and when delivered remotely (e.g., by mobile phone or wearable sensors) promise underserved communities greater access to health care. Indeed, the automatic analysis of speech provides a wealth of information that can be used for patient care in a wide range of settings (e.g., mHealth applications) and for diverse purposes (e.g., behavioral and clinical research, medical tools that are implemented into practice) and patient types (e.g., numerous psychological disorders and in psychiatry and neurology). However, automation of speech analysis is a complex task that requires the integration of several different technologies within a large distributed process with numerous stakeholders. Many organizations have raised awareness about the need for robust systems for ensuring transparency, oversight, and regulation of technologies utilizing artificial intelligence. Since there is limited knowledge about the ethical and legal implications of these applications in psychological science, we provide a balanced view of both the optimism that is widely published on and also the challenges and risks of use, including discrimination and exacerbation of structural inequalities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Antigen presentation by B cells enables epitope spreading across an MHC barrier.

Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

Structural Study of Diketopyrrolopyrrole Derivative Thin Films: Influence of Deposition Method, Substrate Surface, and Aging.

We report the morphology and microstructure of n-dialkyl side-chain-substituted thiophene DPP end-capped with phenyl groups (Ph-TDPP-Ph) thin films and compare the influence of deposition method and substrate surface using thermally oxidized Si and graphene substrates as well as monolayer graphene surfaces with an underlying self-assembled octadecyltrichlorosilane monolayer, complemented by an aging study of spin-coated films over a 2 weeks aging period. A distinct difference in morphology was observed between spin-coated and vacuum-deposited thin films, which formed a fiber-like morphology and a continuous layer of terraced grains, respectively. After an initial film evolution, all combinations of deposition method and substrate type result in well-ordered thin films with almost identical crystalline phases with slight variations in crystallinity and mosaicity. These findings point toward strong intermolecular forces dominating during growth, and the templating effect observed for other oligomer films formed on graphene is consequently ineffective for this material type. Upon aging of spin-coated films, a noticeable evolution involving two different morphologies and crystalline phases were observed. After several days, the thin film evolved into a more stable crystal phase and a fiber-like morphology. Moreover, slight variation in optical spectra were elucidated on the basis on density functional theory calculations. These results demonstrate that thin-film properties of DPP derivatives can be tailored by manipulating the film formation process.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Critical reflections on the concept and impact of "scaling up" in Global Mental Health.

The field of Global Mental Health (GMH) aims to address the global burden of mental illness by focusing on closing the "treatment gap" faced by many low- and middle-income countries (LMICs). To increase access to services, GMH prioritizes "scaling up" mental health services, primarily advocating for the export of Western centred and developed biomedical and psychosocial "evidence-based" approaches to the Global South. While this emphasis on scalability has resulted in the increased availability of mental health services in some LMICs, there have been few critical discussions of this strategy. This commentary critically appraises the scalability of GMH by questioning the validity and sustainability of its approach. We argue that the current approach emphasizes the development of mental health services and interventions in "silos," focusing on the treatment of mental illnesses at the exclusion of a holistic and contextualized approach to people's needs. We also question the opportunities that the current approach to GMH offers for the growth of mental health programmes of local NGOs and investigate the potential pitfalls that scalability may have on NGOs' impact and ability to innovate. This commentary argues that any "scaling up" of mental health services must place sustainability at the core of its mission by favouring the growth and development of local solutions and wider forms of support that prioritize social inclusion and long-lasting mental health recovery.

Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance.

Globally, enteropathogenic bacteria are a major cause of morbidity and mortality.1-3 Campylobacter, Salmonella, Shiga-toxin-producing Escherichia coli, and Listeria are among the top five most commonly reported zoonotic pathogens in the European Union.4 However, not all individuals naturally exposed to enteropathogens go on to develop disease. This protection is attributable to colonization resistance (CR) conferred by the gut microbiota, as well as an array of physical, chemical, and immunological barriers that limit infection. Despite their importance for human health, a detailed understanding of gastrointestinal barriers to infection is lacking, and further research is required to investigate the mechanisms that underpin inter-individual differences in resistance to gastrointestinal infection. Here, we discuss the current mouse models available to study infections by non-typhoidal Salmonella strains, Citrobacter rodentium (as a model for enteropathogenic and enterohemorrhagic E. coli), Listeria monocytogenes, and Campylobacter jejuni. Clostridioides difficile is included as another important cause of enteric disease in which resistance is dependent upon CR. We outline which parameters of human infection are recapitulated in these mouse models, including the impact of CR, disease pathology, disease progression, and mucosal immune response. This will showcase common virulence strategies, highlight mechanistic differences, and help researchers from microbiology, infectiology, microbiome research, and mucosal immunology to select the optimal mouse model.

Aberrant adapting of beliefs under stress: a mechanism relevant to the formation of paranoia?

BACKGROUND: Difficulties in the ability to adapt beliefs in the face of new information are associated with psychosis and its central symptom - paranoia. As cognitive processes and psychotic symptoms are both known to be sensitive to stress, the present study investigated the exact associations between stress, adapting of beliefs [reversal learning (RL), bias against disconfirmatory evidence (BADE), and jumping to conclusions (JTC)] and paranoia. We hypothesized that paranoia would increase under stress and that difficulties in adapting of beliefs would mediate or moderate the link between stress and paranoia. Furthermore, we hypothesized that the investigated effects would be strongest in the group of individuals diagnosed with a psychotic disorder. METHODS: We exposed 155 participants (38 diagnosed with a psychotic disorder, 40 individuals with attenuated psychotic symptoms, 39 clinical controls diagnosed with an obsessive-compulsive disorder, and 38 healthy controls) to a control condition and a stress condition, in which we assessed their levels of paranoia and their ability to adapt beliefs. We applied multilevel models to analyze the data. RESULTS: Paranoia was higher in the stress condition than in the control condition, b = 1.142, s.e. = 0.338, t(150) = 3.381, p < 0.001. RL, BADE, and JTC did not differ between conditions and did not mediate or moderate the association between stress and paranoia (all ps > 0.05). CONCLUSIONS: The results support the assumption that stress triggers paranoia. However, the link between stress and paranoia does not seem to be affected by the ability to adapt beliefs.

Ambimodal Bispericyclic [6 + 4]/[4 + 6] Transition State Competes with Diradical Pathways in the Cycloheptatriene Dimerization: Dynamics and Experimental Characterization of Thermal Dimers.

The thermal dimerization of cycloheptatriene is predicted to occur by a concerted [6 + 4] cycloaddition via an ambimodal [6 + 4]/[4 + 6] transition state (TS) and a competing stepwise diradical (6 + 2) cycloaddition; both dimers subsequently undergo intramolecular [4 + 2] cycloadditions to afford thermally stable tetracyclic products. The ambimodal TS is the 10π-electron version of the prototype bispericyclic dimerization of cyclopentadiene discovered by Caramella et al. in 2002. Quantum mechanical studies using several common DFT functionals and post-HF methods, ωB97X-D, M06-2X, DLPNO-CCSD(T), NEVPT2, and PWPB95-D3(BJ), and quasiclassical molecular dynamics simulations provide details of bond timing and bifurcation pathways. By comparing the ambimodal [6 + 4]/[4 + 6] TS for cycloheptatriene dimerization with the ambimodal [4 + 2]/[2 + 4] TS of cyclopentadiene dimerization, we found that the high distortion energy in cycloheptatriene dimerization is the key to its relatively high energy barrier. The computational investigations were coupled with experimental studies of the cycloheptatriene dimerization, which resulted in the isolation of the two tetracyclic dimers. At lower temperature, the product from the predicted exo-[6 + 4]/[4 + 6] cycloaddition, followed by a subsequent intramolecular [4 + 2] cycloaddition, predominantly forms, while at higher temperature, the diradical (6 + 2) cycloadduct is the major product.

Pinpointing affective disturbances in psychosis: A comparison of temporal affect dynamics in individuals with psychotic disorders, individuals with attenuated psychotic symptoms, and clinical and healthy controls.

Affective disturbances in psychosis are well-documented but our understanding of their phenotypic nature in everyday life remains limited. Filling this gap could advance mechanistic models of the affective pathway to psychosis and pave the ground for new research avenues. Therefore, this study focused on temporal affect dynamics in psychosis, i.e., the patterns with which affect fluctuates over time. We applied experience-sampling with nine assessments per day over one week in participants with psychotic disorders (PSY), participants with attenuated psychotic symptoms (AS), clinical controls with obsessive compulsive disorders (OCD) and healthy controls (HC; total N = 139) to assess whether in PSY and AS, dynamics in affective valence and arousal are characterized by higher instability (i.e., extreme and frequent moment-to-moment fluctuations of affect intensities), higher affective variability (i.e., larger range of affect intensities), or lower inertia (i.e., higher frequency of affective changes), compared to the clinical and healthy control samples. Mixed-model ANOVAs revealed higher instability in both PSY and OCD compared to HC, but no significant differences for variability and inertia. AS had an intermediate position and did not differ significantly from any other group. We found evidence for small to medium effect sizes for the influence of mean affect levels on the dynamic indicators. Our findings indicate that individuals with psychotic disorders have increased affective instability and that this could be a transdiagnostic phenomenon. Zooming in on the variability and inertia components did not confer additional benefits. Emotion-focused interventions for psychosis should focus on reducing frequent and extreme affective fluctuations.

Impacts of nutrient loading and fish grazing on the phytoplankton community and cyanotoxin production in a shallow tropical lake: Results from mesocosm experiments.

Given the increasing eutrophication of water bodies in Africa due to increasing anthropogenic pressures, data are needed to better understand the responses of phytoplankton communities to these changes in tropical lakes. These ecosystems are used by local human populations for multiple purposes, including fish and drinking water production, potentially exposing these populations to health threats if, for example, an increase in toxic cyanobacterial blooms is associated with increasing eutrophication. To test the short-term response of the phytoplankton community to the addition of nutrients (phosphorus and nitrogen, alone or in combination) and Nile tilapia, we developed an in situ mesocosm experiment in a freshwater lagoon located near Abidjan (Ivory Coast). We found that phytoplankton growth (estimated by chlorophyll-a quantification) was highly stimulated when both nitrogen and phosphorus were added, while there was no clear evidence for such colimitation by these two nutrients when considering their concentrations in the lagoon. Phytoplankton growth was accompanied by significant changes in the diversity and composition of this community and did not lead to an increase in the proportions of cyanobacteria. However, the addition of fish to some mesocosms resulted in a drastic decrease in phytoplankton biomass and a dominance of chlorophytes in this community. Finally, these experiments showed that the addition of nitrogen, alone or combined with phosphorus, stimulated microcystin production by cyanobacteria. In addition, no evidence of microcystin accumulation in the fish was found. Taken together, these data allow us to discuss strategies for controlling cyanobacterial blooms in this tropical ecosystem.

The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus.

Introduction: Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development. Methods: We blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell intrinsic effects were further investigated in vitro and in autoreactive mixed bone marrow chimeras. Results: GC block failed to curb autoimmune progression in the R848 model based on anti-dsDNA and plasma cell output, superoligomeric DNA complexes, and immune complex deposition in glomeruli. The 564Igi model confirmed this based on anti-dsDNA and plasma cell output. In vitro, loss of Bcl-6 prevented GC B cell expansion and accelerated plasma cell differentiation. In a competitive scenario in vivo, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output. Discussion: We identified the extrafollicular pathway as a key contributor to autoimmune progression. We propose that therapeutic targeting of low quality and poorly controlled extrafollicular responses could be a desirable strategy to curb autoreactivity, as it would leave intact the more stringently controlled and high-quality GC responses providing durable protection against infection.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial.

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions. METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm). ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles. TRIAL REGISTRATION NUMBER: NCT04293146.

Multiple-day high-dose beetroot juice supplementation does not improve pulmonary or muscle deoxygenation kinetics of well-trained cyclists in normoxia and hypoxia.

Dietary nitrate (NO3-) supplementation via beetroot juice (BR) has been reported to lower oxygen cost (i.e., increased exercise efficiency) and speed up oxygen uptake (VO2) kinetics in untrained and moderately trained individuals, particularly during conditions of low oxygen availability (i.e., hypoxia). However, the effects of multiple-day, high dose (12.4 mmol NO3- per day) BR supplementation on exercise efficiency and VO2 kinetics during normoxia and hypoxia in well-trained individuals are not resolved. In a double-blinded, randomized crossover study, 12 well-trained cyclists (66.4 ± 5.3 ml min-1∙kg-1) completed three transitions from rest to moderate-intensity (~70% of gas exchange threshold) cycling in hypoxia and normoxia with supplementation of BR or nitrate-depleted BR as placebo. Continuous measures of VO2 and muscle (vastus lateralis) deoxygenation (ΔHHb, using near-infrared spectroscopy) were acquired during all transitions. Kinetics of VO2 and deoxygenation (ΔHHb) were modeled using mono-exponential functions. Our results showed that BR supplementation did not alter the primary time constant for VO2 or ΔHHb during the transition from rest to moderate-intensity cycling. While BR supplementation lowered the amplitude of the VO2 response (2.1%, p = 0.038), BR did not alter steady state VO2 derived from the fit (p = 0.258), raw VO2 data (p = 0.231), moderate intensity exercise efficiency (p = 0.333) nor steady state ΔHHb (p = 0.224). Altogether, these results demonstrate that multiple-day, high-dose BR supplementation does not alter exercise efficiency or oxygen uptake kinetics during normoxia and hypoxia in well-trained athletes.

Sleep and circadian rhythm disruption predict persecutory symptom severity in day-to-day life: A combined actigraphy and experience sampling study.

Sleep-related problems are prevalent in patients with psychotic disorders, yet their contribution to fluctuations in delusional experiences is less clear. This study combined actigraphy and experience-sampling methodology (ESM) to capture the relation between sleep and next-day persecutory symptoms in patients with psychosis and prevailing delusions. Individuals with current persecutory delusions (PD; n = 67) and healthy controls (HC; n = 39) were assessed over 6 consecutive days. Objective sleep and circadian rhythm measures were assessed using actigraphy. Every morning upon awakening, subjective sleep quality was measured using ESM. Momentary assessments of affect and persecutory symptoms were gathered at 10 random time points each day using ESM. Robust linear mixed modeling was performed to assess the predictive value of sleep measures on affect and daytime persecutory symptoms. PD showed significantly lower scores for subjective quality of sleep but significantly higher actigraphic-measured sleep duration and efficiency compared with HC. Circadian rhythm disruption was associated with more pronounced severity of persecutory symptoms in HC. Low actigraphy-derived sleep efficiency was predictive of next-day persecutory symptoms in the combined sample. Negative affect was partly associated with sleep measures and persecutory symptoms. Our results imply an immediate relationship between disrupted sleep and persecutory symptoms in day-to-day life. They also emphasize the relevance of circadian rhythm disruption for persecutory symptoms. Therapeutic interventions that aim to reduce persecutory symptoms could benefit from including modules aimed at improving sleep efficacy, stabilizing sleep-wake patterns, and reducing negative affect. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The relationship between nightmares and psychotic experiences in young adults.

BACKGROUND: There is indication that frequent nightmares are an early indicator of psychotic disorders in adolescents and young adults. Yet which aspects of nightmares are relevant and how they contribute to psychotic experiences has remained unclear. METHODS: We conducted a cross-sectional online survey in a community sample of young adults between the ages of 18 and 27 (n = 486) to identify aspects of nightmares (nightmare frequency (NF), nightmare distress (ND), nightmare contents), that are related to specific psychotic experiences (paranoid thoughts, hallucinations, negative symptoms) after controlling for sleep quality, and examined factors that potentially mediate this relationship (stress, depression). RESULTS: Nightmare frequency and -distress were significantly associated with paranoid thoughts, hallucinations and negative symptoms (NF: rs = 0.293 - 0.139; ND: rs = 0.411 - 0.166). Nightmares significantly added to explaining paranoid thoughts and hallucinations, over and above sleep quality, but not to explaining negative symptoms. The relations between nightmare distress and psychotic experiences were partially mediated by stress (percentage mediated for paranoid thoughts: 38.20%; for hallucinations: 11.77%) and depression (percentage mediated for paranoid thoughts: 56.61%; for hallucinations: 28.02%). The most commonly reported nightmare contents revolved around being chased, falling and losing a close relative and specific contents were significantly related to the frequency of hallucinations (eg, threatening surroundings, OR = 1.73) or paranoia (eg, workspace bullying, OR = 2.02). CONCLUSIONS: Thorough assessments of nightmares and sleep disturbances in young individuals could facilitate early detection of those at risk and help to target preventive treatments. However, longitudinal studies are needed to test for a causal relationship between nightmares and the development of psychotic symptoms.