Search

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.

[This corrects the article DOI: 10.3389/fimmu.2021.633297.].

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.

Abstract Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate’s concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

BackgroundThe activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.MethodsThe effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.ResultsTumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.ConclusionWe propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.

(1) Background: The pandemic led to significant healthcare disruptions, resulting in postponed surgeries and extended waiting times for non-urgent treatments, including hysteroscopies essential for diagnosing endometrial cancer. This study aims to formulate a risk stratification model to enhance the prioritization of hysteroscopy procedures in Brazil; (2) Methods: A case-control study was conducted at Vila Santa Catarina Hospital in São Paulo, analyzing the medical records of 2103 women who underwent hysteroscopy between March 2019 and March 2022. We used bivariate analysis and multivariate linear regression to identify risk factors associated with endometrial cancer and formulate a nomogram; (3) Results: The findings revealed a 5.5% incidence of pre-invasive and invasive endometrial disease in the study population, with an average waiting time of 120 days for hysteroscopy procedures. The main risk factors identified were hypertension, diabetes, postmenopausal bleeding, and obesity; (4) Conclusions: This research highlights the urgent need for efficient prioritization of hysteroscopy procedures in the wake of the pandemic. The developed nomogram is an innovative tool for identifying patients at higher risk of endometrial cancer, thus facilitating timely diagnosis and treatment and improving overall patient outcomes in a strained healthcare system.

Herbivores often grapple with structural defences in their host plants, which may pose especially difficult challenges for juveniles due to their underdeveloped feeding morphology. The degree to which juvenile herbivore survival is limited by structural defences as well as the strategies used to overcome them are not well understood. We hypothesized that juveniles benefit from feeding near adults because adults pierce through physical barriers while feeding, enabling juveniles to access nutrients that they otherwise could not. We tested this feeding facilitation hypothesis in the leaf-footed bug Leptoglossus zonatus (Hemiptera: Coreidae). Bugs were raised with an adult or a juvenile conspecific and fed a diet of pecans with or without shells. As predicted, we found that juveniles suffered greater mortality when fed nuts with shells than when fed nuts without shells. Contrary to our expectations, the presence of an adult feeding on the same nut did not lessen this effect. Therefore, the presence of an adult does not ameliorate the feeding difficulties faced by juvenile L. zonatus, despite evidence for feeding facilitation in related insect species. This study adds to our understanding of how host plant defences can limit the survival of even highly generalist herbivores.

The allocation of critical care resources and triaging patients garnered a great deal of attention during the COVID-19 pandemic, but there is a paucity of guidance regarding the ethical aspects of resource allocation and patient prioritization in ‘normal’ circumstances for Canadian healthcare systems. One context where allocation and prioritization decisions are required are surgical waitlists, which have been globally exacerbated due to the COVID-19 pandemic. In this paper, we detail the process used to develop an ethics framework to support prioritization for elective surgery at The Hospital for Sick Children, Toronto, a tertiary pediatric hospital. Our goal was to provide guidance for the more value-laden aspects of prioritization, particularly when clinical urgency alone is insufficient to dictate priority. With this goal in mind, we worked to capture familial, relational, and equity considerations. As part of our institution’s concerted efforts to ethically and effectively address our surgical backlog, an ethics working group was formed comprising clinicians from surgery, anesthesiology, intensive care, a hospital bioethicist, a parent advisor, and an academic bioethics researcher. A reflective equilibrium process was used to develop an ethics framework. To this end, the same methodology was used to create a support for patient prioritization that identifies clinically and morally relevant factors for prioritization among medically similar surgical cases, with a substantive goal being to identify and redress health inequities in surgical prioritization, inasmuch as this is possible. While further steps are needed to validate several aspects of the framework, our research suggests that an ethics framework grounded in the practical realities of hospital operations provides consistency, transparency, and needed support for decisions that are often left to individual clinicians, as well as an opportunity to reflect upon the presence of health inequities in all domains of healthcare delivery.

Abstract Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats’ depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.

Traumatic brain injury (TBI) has a profound impact on cognitive and mental functioning, leading to lifelong impairment and significantly diminishing the quality of life for affected individuals. A healthy blood–brain barrier (BBB) plays a crucial role in guarding the brain against elevated levels of blood glutamate, making its permeability a vital aspect of glutamate regulation within the brain. Studies have shown the efficacy of reducing excess glutamate in the brain as a treatment for post-TBI depression, anxiety, and aggression. The purpose of this article is to evaluate the involvement of dietary glutamate in the development of depression after TBI. We performed a literature search to examine the effects of diets abundant in glutamate, which are common in Asian populations, when compared to diets low in glutamate, which are prevalent in Europe and America. We specifically explored these effects in the context of chronic BBB damage after TBI, which may initiate neurodegeneration and subsequently have an impact on depression through the mechanism of chronic glutamate neurotoxicity. A glutamate-rich diet leads to increased blood glutamate levels when contrasted with a glutamate-poor diet. Within the context of chronic BBB disruption, elevated blood glutamate levels translate to heightened brain glutamate concentrations, thereby intensifying neurodegeneration due to glutamate neurotoxicity.

Immunotherapy has revolutionized the treatment of several cancers, including melanoma and lung cancer. However, for colorectal cancer, it is ineffective for 95% of patients with microsatellite-stable disease. Recent evidence suggests that the liver’s immune microenvironment plays a pivotal role in limiting the effectiveness of immunotherapy. There is also evidence to show that targeting liver metastases with locoregional therapies, such as surgery or irradiation, could potentiate immunotherapy for these patients. This review presents evidence from preclinical studies regarding the underlying mechanisms and from clinical studies that support this approach. Furthermore, we outline potential directions for future clinical trials. This innovative strategy could potentially establish immunotherapy as an effective treatment for MS-stable colorectal cancer patients, which are currently considered resistant.