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Objective: The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing that may be generated in the insula and dorsal anterior cingulate cortex (dACC). Low-intensity focused ultrasound (LIFU) can selectively modulate sub-regions of the insula and dACC to better understand their contributions to the HEP., Methods: Healthy participants (n = 16) received stereotaxically targeted LIFU to the anterior insula (AI), posterior insula (PI), dACC, or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was HEP amplitudes. Relationships between LIFU pressure and HEP changes and effects of LIFU on heart rate and heart rate variability (HRV) were also explored., Results: Relative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; PI effects were partially explained by increased LIFU pressure. LIFU did not affect heart rate or HRV., Conclusions: These results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions., Significance: Our findings have implications for the causal role of these areas in bottom-up heart-brain communication that could guide future work investigating the HEP as a marker of interoceptive processing in healthy and clinical populations., Competing Interests: Declaration of interest The authors declare no conflicts of interest., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The regulation of virulence in plant-pathogenic fungi has emerged as a key area of importance underlying host infections. Recent work has highlighted individual transcription factors (TFs) that serve important roles. A prominent example is PnPf2, a member of the Zn2Cys6 family of fungal TFs, which controls the expression of effectors and other virulence-associated genes in Parastagonospora nodorum during infection of wheat. PnPf2 orthologues are similarly important for other major fungal pathogens during infection of their respective host plants, and have also been shown to control polysaccharide metabolism in model saprophytes. In each case, the direct genomic targets and associated regulatory mechanisms were unknown. Significant insight was made here by investigating PnPf2 through chromatin-immunoprecipitation (ChIP) and mutagenesis approaches in P. nodorum. Two distinct binding motifs were characterised as positive regulatory elements and direct PnPf2 targets identified. These encompass known effectors and other components associated with the P. nodorum pathogenic lifestyle, such as carbohydrate-active enzymes and nutrient assimilators. The results support a direct involvement of PnPf2 in coordinating virulence on wheat. Other prominent PnPf2 targets included TF-encoding genes. While novel functions were observed for the TFs PnPro1, PnAda1, PnEbr1 and the carbon-catabolite repressor PnCreA, our investigation upheld PnPf2 as the predominant transcriptional regulator characterised in terms of direct and specific coordination of virulence on wheat, and provides important mechanistic insights that may be conserved for homologous TFs in other fungi., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 John et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The fungus Parastagonospora nodorum causes septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA in P. nodorum development and virulence was investigated here. Deletion of the P. nodorum VeA ortholog, PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion of PnVeA also decoupled the expression of major necrotrophic effector genes. In addition, the deletion of PnVeA resulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation., (© 2024. The Author(s).)

Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat-evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, μg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 μg isoproterenol infusion, the GAD group (n = 24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the healthy comparison (HC) group (n = 24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than the HC group during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 μg isoproterenol infusion. Using analyzable blood oxygenation level-dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing in prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Interoception-the perception of internal bodily signals-has emerged as an area of interest due to its implications in emotion and the prevalence of dysfunctional interoceptive processes across psychopathological conditions. Despite the importance of interoception in cognitive neuroscience and psychiatry, its experimental manipulation remains technically challenging. This is due to the invasive nature of existing methods, the limitation of self-report and unimodal measures of interoception, and the absence of standardized approaches across disparate fields. This article integrates diverse research efforts from psychology, physiology, psychiatry, and engineering to address this oversight. Following a general introduction to the neurophysiology of interoception as hierarchical predictive processing, we review the existing paradigms for manipulating interoception (e.g., interoceptive modulation), their underlying mechanisms (e.g., interoceptive conditioning), and clinical applications (e.g., interoceptive exposure). We suggest a classification for interoceptive technologies and discuss their potential for diagnosing and treating mental health disorders. Despite promising results, considerable work is still needed to develop standardized, validated measures of interoceptive function across domains and before these technologies can translate safely and effectively to clinical settings., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Injuries induced by falls represent the main cause of failure in the French Navy Special Forces selection course. In the present study, we made the assumption that probing the posture might contribute to predicting the risk of fall-related injury at the individual level., Methods: Before the start of the selection course, the postural signals of 99 male soldiers were recorded using static posturography while they were instructed to maintain balance with their eyes closed. The event to be predicted was a fall-related injury during the selection course that resulted in the definitive termination of participation. Following a machine learning methodology, we designed an artificial neural network model to predict the risk of fall-related injury from the descriptors of postural signal., Results: The neural network model successfully predicted with 69.9% accuracy (95% CI 69.3-70.5) the occurrence of a fall-related injury event during the selection course from the selected descriptors of the posture. The area under the curve value was 0.731 (95% CI 0.725-0.738), the sensitivity was 56.8% (95% CI 55.2-58.4) and the specificity was 77.7% (95% CI 76.8-0.78.6)., Conclusion: If confirmed with a larger sample, these findings suggest that probing the posture using static posturography and machine learning-based analysis might contribute to inform risk assessment of fall-related injury during military training, and could ultimately lead to the development of novel programmes for personalised injury prevention in military population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Military Physical and Sports Training program was developed by the French Army in order to train, optimize, and maintain individual readiness. Although the health benefits of sport practice do not need to be demonstrated, such activities can cause acute musculoskeletal injuries that need to be addressed. The prevalence of lower limb injury is rather high in the French military population and, in particular, ranges from 15 to 45% during Special Forces selection courses. Thus, this project aims to investigate the efficiency of a body-centered program designed to enhance body awareness. The program seeks to train the mind to actively pay attention to body information, while the latter is viewed as a protective factor against fall injuries. We assume: (i) that postural control can be improved by enhancing the level of body awareness; and (ii) that greater postural awareness could be beneficial in reducing the risk of fall injuries. The body-centered prevention program is based on the Optimization of the Resources of the Armed Forces (ORAF) intervention, which focuses on mental preparation and recovery, and has been deployed in the French Army for many years., Method and Analyses: The study focuses on five French Special Forces selection courses (400 soldiers/ participants). It is divided into two stages (year 1, year 2). The first year is dedicated to data collection from the control group (200 participants), while in the second year the ORAF intervention will be deployed. In both year, participants will be subjected to the same enrollment schedule (Fig 3). The main objective is to evaluate the effectiveness of the ORAF intervention in reducing the rate of fall injuries during military selection, based on a multidisciplinary method that captures demographic, biological, biometric, clinical, and para-clinical measures., Trial Registration: Registration number: IDRCB number 2021-A02108-33, Clinical Trial: NCT05451394., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Obligi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Significant bone loss occurs after heart transplantation, predominantly in the first year, with increased risk of incident fractures. The goal of this study was to evaluate the prevalence of fragility fractures in a population of heart transplantation patients and to identify the independent risk factors for fractures., Methods: This was a prospective monocentric study that included patients with heart transplantation occurring < 10 years who were undergoing heart transplantation monitoring. All patients underwent bone mineral density evaluation by dual-energy X-ray absorptiometry and radiographies to establish the presence of vertebral fractures., Results: We included 79 patients (61 men); the mean age was 56.8 ± 10.8 years. The mean time between transplantation and inclusion was 32.3 ± 35.0 months. Incident fractures were diagnosed in 21 (27%) patients after heart transplantation. Vertebral fractures were the most frequent (30 vertebral fractures for 15 patients). Osteoporosis was confirmed in 22 (28%) patients. Mean bone mineral density at the femoral neck and total hip was lower with than without fracture (femoral neck: 0.777 ± 0.125 vs 0.892 ± 0.174 g/cm 2 , p<0.01; total hip: 0.892 ± 0.165 vs 0.748 ± 0.07 g/cm 2 , p<0.001), with a significant result on multivariate analysis. The mean time from transplantation to the first fracture was 8.0 ± 7.6 months., Discussion: Our study confirmed a high vertebral fracture risk in heart transplant patients, especially during the first year after transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Forien, Coralli, Verdonk, Ottaviani, Ebstein, Demaria, Palazzo, Dorent and Dieudé.)

SARS-CoV-2 Omicron variant was first detected in France mid-November 2021 in wastewater treatment plants while cases started to increase at the beginning of December. The maximum incidence occurred in mid-January 2022. The Omicron wave spread rapidly throughout France in general population with lower case-fatality rate compared with previous waves. Little is known about infection with Omicron variant in heart transplant (HT) recipients. In this study, we examined incidence and mortality rate of COVID-19 in the general population and among 1,263 HT recipients during the period from June, 2021 to February, 2022, described characteristics of HT recipients infected with SARS-CoV-2 during Omicron (December 1st, 2021-February 7, 2022) and Delta (June 1st- November 30, 2021) periods, and compared hospital course of HT recipients with Omicron and Delta variant infection. Our findings contrast with the reported lower severity for Omicron variant infection compared with Delta variant infection in immunocompetent individuals., Competing Interests: Disclosure statement The authors have no disclosure regarding the present study., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

While the coronavirus disease 2019 (COVID-19) pandemic placed a heavy burden on healthcare systems worldwide, it also induced urgent mobilisation of research teams to develop treatments preventing or curing the disease and its consequences. It has, therefore, challenged critical care research to rapidly focus on specific fields while forcing critical care physicians to make difficult ethical decisions. This narrative review aims to summarise critical care research -from organisation to research fields- in this pandemic setting and to highlight opportunities to improve research efficiency in the future, based on what is learned from COVID-19. This pressure on research revealed, i.e., (i) the need to harmonise regulatory processes between countries, allowing simplified organisation of international research networks to improve their efficiency in answering large-scale questions; (ii) the importance of developing translational research from which therapeutic innovations can emerge; (iii) the need for improved triage and predictive scores to rationalise admission to the intensive care unit. In this context, key areas for future critical care research and better pandemic preparedness are artificial intelligence applied to healthcare, characterisation of long-term symptoms, and ethical considerations. Such collaborative research efforts should involve groups from both high and low-to-middle income countries to propose worldwide solutions. As a conclusion, stress tests on healthcare organisations should be viewed as opportunities to design new research frameworks and strategies. Worldwide availability of research networks ready to operate is essential to be prepared for next pandemics. Importantly, researchers and physicians should prioritise realistic and ethical goals for both clinical care and research., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)