Psychosocial and symbolic dimensions of the breast explored through a Visual Matrix

This article explores knowledge about the breast in the psychosocial interplay of lived experience, addressing a gap in empirical research on this highly gendered cultural trope and embodied organ. We present findings from a study that used a free-associative psychosocial method – the Visual Matrix – in order to stimulate, and capture expressions of, tacit aspects of the breast that have evaded discursive representation, as well as to generate understanding of relations between embodied and enculturated experience. Little research has been conducted on women’s affirmative experience of breasts, possibly because their bio-psycho-sociocultural complexity affords an onto-epistemological and empirical challenge. Our data revealed how an aesthetic of the grotesque in one matrix allowed the mainly female group to use humour as a “creative psychic defence” against culturally normative and idealised aspects of the breast. This was expressed through sensual symbolisations of breasted experience, affectively delivered with exuberance and joy. There was an emphasis on the breast’s potency and its potential for both abundant nurturance and potent “weaponisation”. By establishing this feminine poetic mode, Visual Matrix imagery symbolised life and death as tolerable, inseparable yet ambiguous dimensions of breasts, thereby resisting anxious splitting. The breast’s life-affirming qualities included the sensual, the visceral and the joyful – a materialsemiotic knowing. This was in marked contrast to a second matrix where associations were weighted towards the spectacular breast of an ocular-centric culture that privileges heteromasculine looking. This matrix reflected a more ambivalent and sometimes troubled response among participants. Reasons for the difference between the two matrices are discussed in terms of how they responded to the tension between embodied and enculturated experiences

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

To which world regions does the valence–dominance model of social perception apply?

Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007); L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from CONICET, Argentina; L.K., F.K. and Á. Putz were supported by the European Social Fund (EFOP-3.6.1.-16-2016-00004; ‘Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs’). K.U. and E. Vergauwe were supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E. Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported by a French National Research Agency ‘Investissements d’Avenir’ programme grant (ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research Training Program Scholarship. The Raipur Group is thankful to: (1) the University Grants Commission, New Delhi, India for the research grants received through its SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science; and (2) the Center for Translational Chronobiology at the School of Studies in Life Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was supported by grants from the Beijing Natural Science Foundation (5184035) and CAS Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported by the National Science Foundation Graduate Research Fellowship (R010138018). We acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E. Tolomeo (Magna Græcia University of Catanzaro); E. De Stefano (University of Padova); S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R. C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New Zealand), A. Ateş, E. Güneş and S. Can Özdemir (Boğaziçi University); I. Pedersen and T. Roos (Åbo Akademi University); N. Paetz (Escuela de Comunicación Mónica Herrera); J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B. Todorova (University of Vienna, Austria). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

REDUCED ACETYLCHOLINE RECEPTOR DENSITY, MORPHOLOGICAL REMODELING, AND BUTYRYLCHOLINESTERASE ACTIVITY CAN SUSTAIN MUSCLE FUNCTION IN ACETYLCHOLINESTERASE KNOCKOUT MICE

The vertebrate neuromuscular junction is designed for rapid transmission of excitatory signals for initiation of muscle contraction.5 Among the features responsible for the high throughput of this synapse are the close proximity of the presynaptic and postsynaptic membranes,10 the direct coupling of acetylcholine (ACh) binding to the opening of the ion channel associated with the nicotinic acetylcholine receptor (nAChR),27 the brief open time of this channel,21,27 and the presence of cholinesterase (ChE) for hydrolysis of ACh.21,30 At the endplate, there are two distinct ChEs for transmitter hydrolysis: acetylcholinesterase (EC 3.1.1.7, AChE) and butyrylcholinesterase (EC 3.1.1.8, BChE).33 Both enzymes can exist in a multisubunit, collagen-tailed form with selective localization at the endplate basallamina.33 Because of its superior catalytic activity for ACh hydrolysis, AChE is the dominant enzyme, whereas the role of BChE is generally evident only after AChE is inhibited.3,4 Inhibition of ChE results in a progressive accumulation of ACh, especially during periods of repetitive stimulation, leading to desensitization of nAChRs and consequent muscle weakness.12,17 Under this condition, transmitter persists beyond its normal lifetime and is slowly removed from the endplate region by diffusion.21,30 Diffusion is impeded in part by morphological barriers, such as the apposition of the nerve terminal to the postjunctional membrane,5,10 and by the high density of postjunctional nAChRs.21,22,25 If ChE is inhibited pharmacologically or removed by collagenase treatment, repeated binding to nAChR makes diffusional loss of ACh slow and inefficient.21,22,30 The influence of nAChRs on retention of transmitter was termed “buffered diffusion” by Katz and Miledi21 and accounts for findings that elimination of ACh is considerably slower than that expected for free diffusion. 30 Inhibitors of ChE are highly toxic, producing incapacitation and death within minutes.28 The cause of death is complex, involving loss of central respiratory drive,6,29 bronchospasm,1,2 and the inability of the diaphragm muscle to sustain tetanic tension. 19 Because most ChE inhibitors show little selectivity between AChE and BChE, and may have direct actions unrelated to ChE inhibition, it is difficult to establish the role of AChE activity in neuromuscular transmission. To overcome this difficulty, we studied twitch and tetanic tensions in diaphragm muscles from AChE knockout (AChE-/-) mice that fail to express AChE but do contain normal levels of BChE.7,24,36 Stimulation of the phrenic nerve in isolated diaphragm preparations from AChE-/- mice revealed large single twitches and sustained tetanic tensions at 70 and 100 Hz. These findings suggest that, over a limited frequency range, diaphragm muscles from AChE-/- mice are able to compensate for the loss of AChE activity. An understanding of these adaptive mechanisms is expected to provide insight on protection strategies that may be effective against the toxic actions of ChE inhibitors such as the highly lethal nerve agents

Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma

Abstract Background Chemotherapeutic options for the treatment of canine lymphoma have not changed in several decades necessitating the identification of new therapeutics to improve patient outcome. KPT-335 (verdinexor) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) that exhibited anti-tumor activity against non-Hodgkin lymphoma in a prior phase I study. The objective of this phase II study was to expand upon the initial findings and assess the activity and safety in a larger population of dogs with lymphoma. Results Fifty-eight dogs with naïve or progressive B-cell and T-cell lymphoma were enrolled in this clinical trial. KPT-335 was administered orally in one of three dosing groups, based on the previously established biologically active dose of 1.5 mg/kg three times weekly. Treatment with single-agent, orally administered KPT-335 resulted in an objective response rate (ORR) of 37%, of which dogs with T-cell lymphoma had an ORR of 71%. KPT-335 was well tolerated in all dose groups with grade 1–2 anorexia being the most common adverse event. Anorexia was responsive to symptomatic and supportive medications, including prednisone. Conclusions These data demonstrate that KPT-335 has biologic activity in canine lymphoma, and support continued evaluation of SINE compounds such as KPT-335 in combination with standard chemotherapeutics in canine lymphoma

REDUCED ACETYLCHOLINE RECEPTOR DENSITY, MORPHOLOGICAL REMODELING, AND BUTYRYLCHOLINESTERASE ACTIVITY CAN SUSTAIN MUSCLE FUNCTION IN ACETYLCHOLINESTERASE KNOCKOUT MICE

The vertebrate neuromuscular junction is designed for rapid transmission of excitatory signals for initiation of muscle contraction.5 Among the features responsible for the high throughput of this synapse are the close proximity of the presynaptic and postsynaptic membranes,10 the direct coupling of acetylcholine (ACh) binding to the opening of the ion channel associated with the nicotinic acetylcholine receptor (nAChR),27 the brief open time of this channel,21,27 and the presence of cholinesterase (ChE) for hydrolysis of ACh.21,30 At the endplate, there are two distinct ChEs for transmitter hydrolysis: acetylcholinesterase (EC 3.1.1.7, AChE) and butyrylcholinesterase (EC 3.1.1.8, BChE).33 Both enzymes can exist in a multisubunit, collagen-tailed form with selective localization at the endplate basallamina.33 Because of its superior catalytic activity for ACh hydrolysis, AChE is the dominant enzyme, whereas the role of BChE is generally evident only after AChE is inhibited.3,4 Inhibition of ChE results in a progressive accumulation of ACh, especially during periods of repetitive stimulation, leading to desensitization of nAChRs and consequent muscle weakness.12,17 Under this condition, transmitter persists beyond its normal lifetime and is slowly removed from the endplate region by diffusion.21,30 Diffusion is impeded in part by morphological barriers, such as the apposition of the nerve terminal to the postjunctional membrane,5,10 and by the high density of postjunctional nAChRs.21,22,25 If ChE is inhibited pharmacologically or removed by collagenase treatment, repeated binding to nAChR makes diffusional loss of ACh slow and inefficient.21,22,30 The influence of nAChRs on retention of transmitter was termed “buffered diffusion” by Katz and Miledi21 and accounts for findings that elimination of ACh is considerably slower than that expected for free diffusion. 30 Inhibitors of ChE are highly toxic, producing incapacitation and death within minutes.28 The cause of death is complex, involving loss of central respiratory drive,6,29 bronchospasm,1,2 and the inability of the diaphragm muscle to sustain tetanic tension. 19 Because most ChE inhibitors show little selectivity between AChE and BChE, and may have direct actions unrelated to ChE inhibition, it is difficult to establish the role of AChE activity in neuromuscular transmission. To overcome this difficulty, we studied twitch and tetanic tensions in diaphragm muscles from AChE knockout (AChE-/-) mice that fail to express AChE but do contain normal levels of BChE.7,24,36 Stimulation of the phrenic nerve in isolated diaphragm preparations from AChE-/- mice revealed large single twitches and sustained tetanic tensions at 70 and 100 Hz. These findings suggest that, over a limited frequency range, diaphragm muscles from AChE-/- mice are able to compensate for the loss of AChE activity. An understanding of these adaptive mechanisms is expected to provide insight on protection strategies that may be effective against the toxic actions of ChE inhibitors such as the highly lethal nerve agents

Low-temperature and circadian signals are integrated by the sigma factor SIG5

Chloroplasts are a common feature of plant cells and aspects of their metabolism, including photosynthesis, are influenced by low-temperature conditions. Chloroplasts contain a small circular genome that encodes essential components of the photosynthetic apparatus and chloroplast transcription/translation machinery. Here, we show that in Arabidopsis, a nuclear-encoded sigma factor that controls chloroplast transcription (SIGMA FACTOR5) contributes to adaptation to low-temperature conditions. This process involves the regulation of SIGMA FACTOR5 expression in response to cold by the bZIP transcription factors ELONGATED HYPOCOTYL5 and ELONGATED HYPOCOTYL5 HOMOLOG. The response of this pathway to cold is gated by the circadian clock, and it enhances photosynthetic efficiency during long-term cold and freezing exposure. We identify a process that integrates low-temperature and circadian signals, and modulates the response of chloroplasts to low-temperature conditions