Maternal stress is a key risk factor for neurodevelopmental disorders, including schizophrenia and autism, which often exhibit a sex bias in rates of presentation, age of onset, and symptom severity. The placenta is an endocrine tissue that functions as an important mediator in responding to perturbations in the intrauterine environment and is accessible for diagnostic purposes, potentially providing biomarkers predictive of disease. Therefore, we have used a genome-wide array approach to screen placental expression across pregnancy for gene candidates that are sex-biased and stress-responsive in mice and translate to human tissue. We identifed O-linked- N -acetylglucosamine (O-GlcNAc) transferase (OGT), an X-linked gene important in regulating proteins involved in chromatin remodeling, as fitting these criteria. Levels of both OGT and its biochemical mark, O - GlcNAcylation, were significantly lower in males and further reduced by prenatal stress. Examination of human placental tissue found similar patterns related to X chromosome dosage. As a demonstration of the importance of placental OGT in neurodevelopment, we found that hypothalamic gene expression and the broad epigenetic microRNA environment in the neonatal brain of placental-specific hemizygous OGT mice was substantially altered. These studies identified OGT as a promising placental biomarker of maternal stress exposure that may relate to sex-biased outcomes in neurodevelopment.

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness.

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Background: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice.Objective: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. Materials and methods:Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. Results:The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'A multidisciplinary team comprised of experts from a diversity of fields was assembled, including allergists and other healthcare professional...

It has been recently demonstrated that pain behavior in the mouse can be modulated by the presence of a conspecific, but what remains unclear is whether such pain behavior can serve the function of soliciting social approach. Using a novel social approach paradigm, we tested mice in various dyadic or triadic conditions, including "jailed" mice-some in pain via intraperitoneal injection of 0.9% acetic acid-and test mice free to approach or avoid the jailed mice. We observed a sex-specific effect whereby female, but not male, test mice approached a familiar same-sex conspecific in pain more frequently than an unaffected familiar or unfamiliar, but affected, conspecific. Despite a substantial literature emphasizing oxytocin's role in affiliative and pair-bonding behavior, this effect was also observed in female mice lacking the oxytocin receptor, suggesting that pain-related social approach may not be mediated by oxytocin. Furthermore, we found that the frequency of contact by the test mouse was negatively correlated with the pain behavior of the jailed mouse, suggesting that proximity of a familiar unaffected conspecific may have analgesic properties.

The heterogeneous nature of asthma has been understood for decades, but the precise categorization of asthma has taken on new clinical importance in the era of specific biologic therapy. The simple categories of allergic and non-allergic asthma have given way to more precise phenotypes that hint at underlying biologic mechanisms of variable airflow limitation and airways inflammation. Understanding these mechanisms is of particular importance for the approximately 10% of patients with severe asthma. Biomarkers that aid in phenotyping allow physicians to “personalize” treatment with targeted biologic agents. Unfortunately, testing for these biomarkers is not routine in patients whose asthma is refractory to standard therapy. Scientific advances in the recognition of sensitive and specific biomarkers are steadily outpacing the clinical availability of reliable and non-invasive assessment methods designed for the prompt and specific diagnosis, classification, treatment, and monitoring of severe asthma patients. This article provides a practical overview of current biomarkers and testing methods for prompt, effective management of patients with severe asthma that is refractory to standard therapy.

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness.

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