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Hawkmoth flight follows from a complex interplay between sensory input and motor output. In these, and many other flying insects, their wings, abdomen and legs, all play critical roles in regulating the flight trajectory. To explore how each of these contributes to flight control we used a programmable system on a chip (PSOC) that can both record and stimulate motor pathways. In this study, we are particularly interested in the extent to which abdominal ruddering controls flight trajectory. To explore this issue, we displayed vertically moving visual stimuli to tethered moths and recorded the activation pattern of abdominal flexors. We found that up/down abdominal flexion is driven by a pattern of motor output whose frequency is positively correlated with the speed of the vertical stimulus. There is a strong coupling, therefore, between the abdominal rudder motion and the visual input. We further found that we could stimulate such ruddering motions with a pattern of digital 3 volt pulses that draw very little current (< 100 uA). This stimulus, applied to the ventral nerve chord just caudal to the abdominal ganglia controlling flexion, could be programmed to get a variety of abdominal motions. We also show that we can use the PSOC in this manner to alter the forces (and path) of an insect in tethered and nearly free flight.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody responses in children remain poorly characterized. Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike immunoglobulin G (IgG) titers compared with those with severe coronavirus disease 2019, likely reflecting a longer time since the onset of infection in MIS-C patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C)., Methods: A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion., Results: The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized., Conclusions: Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We present a series of 6 critically ill children with multisystem inflammatory syndrome in children. Key findings of this syndrome include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Adipose tissue is an important site for extragonadal steroid hormone biosynthesis through the expression and activity of P450 aromatase, 11β-hydroxysteroid dehydrogenase (HSD) 1, and 17β-HSDs. The contribution of steroid hormones produced by adjacent adipose tissue for the progression and survival of breast tumors is unknown., Objective: To quantify estrogens (estradiol, estrone) and glucocorticoids (cortisol, cortisone) in breast adipose tissue from both healthy and diseased women and their relationships with adiposity indices and breast cancer prognostic markers., Design and Setting: Breast adipose tissue was collected at time of surgery., Patients: Pre- and postmenopausal women undergoing partial mastectomy for treatment of breast cancer (n = 17) or reduction mammoplasty (n = 6) were studied., Interventions: Relative estrogen and glucocorticoid amounts were determined by liquid chromatography tandem mass spectrometry., Results: The targeted steroids were reliably detected and quantified in mammary adipose tissues. Women with ER+/PR+ tumor had higher relative estradiol amount than women with ER-/PR- tumor (P < .05). The ratio of estradiol-to-estrone was higher in lean women than in women with a body mass index (BMI) ≥ 25 kg/m2 (P < .05). Mixed-model analyses showed that estradiol, cortisone, and cortisol were negatively associated with tumor size (P < .05). Relationships between glucocorticoids and tumor size remained significant after adjustment for BMI. The cortisol-to-cortisone ratio was negatively associated with tumor stage (P < .05) independently of BMI., Conclusions: We reliably quantified estrogens and glucocorticoids in breast adipose tissue from healthy women and women suffering from breast cancer. Our findings suggest that smaller breast tumors are associated with higher relative amounts of estradiol and cortisol in adipose tissue., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes. Both precursor and cleaved forms of IL-37 are secreted. They bind IL-18Rα chain (also used by IL-18 as a receptor subunit) and recruit Toll/IL-1R (TIR)-8 for transducing intracellular signaling. TIR-8 is a member of the IL-1 receptor family (IL-1RF) and was previously known as an orphan receptor. IL-37 suppresses activation of NF-κB and MAPK and activates Mer-PTEN-DOK pathway. It negatively regulates signaling mediated by TLR agonists, proinflammatory cytokines, and IL-1RF ligands. It also affects cell metabolism by inhibiting mTOR, GSK-3α/β, and activating AMPK. Despite having the ability to dampen host's immune responses, the cytokine has been shown to exert antitumor effects, and it has been suggested that it may act as a prognostic marker in a variety of human cancers. Recent studies have suggested that IL-37 may represent a novel therapeutic tool in patients with cancer. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its anti-cancer effects, and suggest guidelines for future research., (© Society for Leukocyte Biology.)

Objectives: Human epidermal growth factor receptor 2 (HER2) plays a central role as a prognostic and predictive marker in breast cancer specimens. Reliable HER2 evaluation is central to determine the eligibility of patients with breast cancer to targeted anti-HER2 therapies such as trastuzumab and lapatinib. Presently, several methods exist for the determination of HER2 status at different levels (protein, RNA, and DNA level)., Methods: In this review, we discuss the main advantages and disadvantages of the techniques developed so far for the evaluation of HER2 status in breast cancer specimens., Results: Each technique has its own advantages and disadvantages. It is therefore not surprising that no consensus has been reached so far on which technique is the best for the determination of HER2 status., Conclusions: Currently, emphasis must be put on standardization of procedures, internal and external quality control assessment, and competency evaluation of already existing methods to ensure accurate, reliable, and clinically meaningful test results. Development of new robust and accurate diagnostic assays should also be encouraged. In addition, large clinical trials are warranted to identify the technique that most reliably predicts a positive response to anti-HER2 drugs., (Copyright© by the American Society for Clinical Pathology.)