scholarly journals Physiological microbial exposure has a temporally limited inhibitory effect on lung ILC2 responses to allergens in mice

2021 ◽  
Author(s):  
Stephen Jameson ◽  
Katharine Block ◽  
Koji Iijima ◽  
Mark Pierson ◽  
Daniel Walsh ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inhibitory Effect ◽  
Poly I:C ◽  
Acute Type ◽  
Laboratory Mice ◽  
Cell Responses ◽  
Fungal Allergen ◽  
The Impact

Abstract The impact of microbes on restraining the immune response to allergens has been extensively studied and is a key element of the hygiene hypothesis. Lung type 2 innate lymphoid cell responses to airway allergens can be inhibited by administration of a number of microbial products; however, it is unclear whether such an effect would be observed with natural infections and how sustained any observed inhibitory effects would be. To answer these questions, we used a murine model of physiological microbial exposures through cohousing SPF laboratory mice with pet store mice and examined the acute type 2 response to intranasally delivered fungal allergen extract Alternaria alternata. We found laboratory mice cohoused with pet store mice for two weeks display a suppressed ILC2 response to A. alternata which resulted in reduced eosinophilia. By comparison, mice cohoused for at least two months had ILC2 and eosinophil responses similar to SPF mice despite dramatic changes to the composition of the immune cell populations in the lungs. Lung ILC2 in two-month cohoused mice were still sensitive to subsequent inflammatory cues, as administration of poly(I:C) was able to suppress ILC2 activation and eosinophilia equally well in SPF and two-month cohoused animals. These findings suggest ILC2 dynamically respond to their environment and are not easily desensitized long-term. 

scholarly journals The Causes and Long-Term Consequences of Viral Encephalitis

2021 ◽  
Vol 15 ◽  
Author(s):  
Karen Bohmwald ◽  
Catalina A. Andrade ◽  
Nicolás M. S. Gálvez ◽  
Valentina P. Mora ◽  
José T. Muñoz ◽  
...  
Keyword(s):  
Viral Encephalitis ◽  
Viral Infections ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Brain Inflammation ◽  
High Morbidity ◽  
Stiff Neck ◽  
The Impact ◽  
The Brain

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

scholarly journals Imaginary Worlds: The Status of Simulation Modeling in Claims for Cost-Effectiveness In Diabetes Mellitus

2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Paul C Langley ◽  
Taeho Greg Rhee
Keyword(s):  
Diabetes Mellitus ◽  
Cost Effectiveness ◽  
Simulation Modeling ◽  
Decision Makers ◽  
The Past ◽  
The Status ◽  
The Impact

Over the past 20 years a number of simulations or models have been developed as a basis for tracking and evaluating the impact of pharmacological and other interventions in type 1 and type 2 diabetes mellitus. These models have typically tracked the natural course of these diseases generating long-term composite claims for cost-effectiveness. These claims can extend over the lifetime of the modeled patient cohort. Set against the standards of normal science, however, these claims lack credibility. The claims presented are all too often either immune to failure or are presented in a form that is non-testable. As such they fail to meet the key experimental requirements of falsification and replication. Unfortunately, there is a continuing belief that long-term or lifetime models are essential to decision-making. This is misplaced. The purpose of this review is to argue that there is a pressing need to reconsider the needs of health system decision makers and focus on modeled or simulated claims that are meaningful, testable, reportable and replicable in evaluating interventions in diabetes mellitus.   Type: Commentary

scholarly journals Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection

2014 ◽  
Vol 92 (5) ◽  
pp. 436-448 ◽  
Author(s):  
Kara J Filbey ◽  
John R Grainger ◽  
Katherine A Smith ◽  
Louis Boon ◽  
Nico Rooijen ◽  
...  
Keyword(s):  
Helminth Infection ◽  
Immune Cell ◽  
Intestinal Helminth ◽  
Cell Responses

scholarly journals Multiplatform Integrative Analyses of Immunosuppressive Signatures in Cortisol-secreting Adrenocortical Carcinoma

2021 ◽  
Author(s):  
Jordan J. Baechle ◽  
David N. Hanna ◽  
Sekhar R. Konjeti ◽  
Jeffrey C. Rathmell ◽  
W. Kimryn Rathmell ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Expression Profiles ◽  
Prognostic Indicators ◽  
Cell Responses ◽  
Patient Prognosis ◽  
Computational Analyses ◽  
The Impact

AbstractAdrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy and nearly half of ACC tumors have been shown to overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials demonstrated significant immunoresistance among cortisol-secreting ACC (CS-ACC) patients when compared to their non-Cortisol-secreting (nonCS-ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and secretion is well established, however, the impact of the cortisol hypersecretion on ACC tumor microenvironment (TME), immune expression profiles, and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS-ACC and CS-ACC tumors to assess the impact of differentially expressed genes (DEGs) related to immune processes on patient prognosis. Comprehensive multiplatform immunogenomic computational analyses of ACC tumors deciphered an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary immunogenomic prognostic indicators and potential targets within the tumor immune landscape of CS-ACC that define a distinct TME and provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS-ACC.

scholarly journals Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI

2020 ◽  
Vol 8 (1) ◽  
pp. e001135 ◽  
Author(s):  
Sazan Rasul ◽  
Barbara Katharina Geist ◽  
Helmut Brath ◽  
Pascal Baltzer ◽  
Lalith Kumar Shiyam Sundar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Function ◽  
Fdg Pet ◽  
Renal Tubules ◽  
Initiation Of Therapy ◽  
The Impact

IntroductionInhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.MethodsPET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls.ResultsMTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; p<0.001). The higher the GRP value in kidneys of T2DMSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation.ConclusionMTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy.Trial registration numberNCT03557138.

scholarly journals Hypertension and Its Impact on Stroke Recovery: From a Vascular to a Parenchymal Overview

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Benjamin Maïer ◽  
Nathalie Kubis
Keyword(s):  
Risk Factor ◽  
Vascular Risk Factor ◽  
Vascular Cognitive Impairment ◽  
Stroke Recovery ◽  
Stroke Outcome ◽  
Vascular Risk ◽  
Cell Responses ◽  
The Impact ◽  
Worse Prognosis

Hypertension is the first modifiable vascular risk factor accounting for 10.4 million deaths worldwide; it is strongly and independently associated with the risk of stroke and is related to worse prognosis. In addition, hypertension seems to be a key player in the implementation of vascular cognitive impairment. Long-term hypertension, complicated or not by the occurrence of ischemic stroke, is often reviewed on its vascular side, and parenchymal consequences are put aside. Here, we sought to review the impact of isolated hypertension or hypertension associated to stroke on brain atrophy, neuron connectivity and neurogenesis, and phenotype modification of microglia and astrocytes. Finally, we discuss the impact of antihypertensive therapies on cell responses to hypertension and functional recovery. This attractive topic remains a focus of continued investigation and stresses the relevance of including this vascular risk factor in preclinical investigations of stroke outcome.

scholarly journals Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

Diabetologia ◽  
2012 ◽  
Vol 55 (8) ◽  
pp. 2109-2117 ◽  
Author(s):  
N. Saleh ◽  
P. Petursson ◽  
B. Lagerqvist ◽  
H. Skúladóttir ◽  
A. Svensson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Angiography ◽  
Glucose Lowering ◽  
The Impact ◽  
Long Term Mortality

scholarly journals The role of synovial T-cell infiltration following knee joint injury in symptoms and progression to osteoarthritis

2019 ◽  
Author(s):  
Babak Moradi ◽  
Miriam T Jackson ◽  
Cindy C. Shu ◽  
Susan M Smith ◽  
Margaret M Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Post Injury ◽  
Joint Injury ◽  
Cell Responses ◽  
Cellular Events ◽  
Bona Fide

AbstractObjectivesIdentification of osteoarthritis(OA)-specific synovial inflammatory pathways, and when in the clinical course they are active, is critical for their utility as therapeutic targets. We directly compared the mononuclear inflammatory/immune-cell responses following joint injury that does and does-not lead to OA, to define bona-fide OA-associated cellular events.MethodsWe undertook detailed temporal flow-cytometric and mRNA expression analysis in mice after sham or medial-meniscal-destiblization (DMM) surgery. We compared this with patients with meniscal injury and OA, and evaluated the role of synovial monocytes/macrophages versus lymphocytes in catabolic metalloproteinase secrection in vitro. We determined the effect of transient acute or delayed systemic T-cell depletion on DMM-induced OA pathology.ResultsOA-inducing/DMM and non-OA-inducing/Sham surgery had identical synovial monocyte/macrophage number, activation and polarization. The number and activation of synovial (not splenic or peripheral-blood) CD4 and CD8 lymphocytes was increased from 1-day after DMM versus Sham, and showed a persistent cyclical elevation throughout OA onset and progression. There was a temporal imbalance in synovial Th17/Treg and Th1/Th2 lymphocytes during DMM-induced OA initiation and progression. We confirmed early post-injury and late-OA CD3/CD8 T-cell responses in synovial tissues from patients, identified an association between CD8 and early post-injury symptoms, and defined a significant role for CD3+T-cells in synovial metalloproteinase secretion. Anti-CD3 cell-depletion studies in mice confirmed a key role for the earliest post-injury T-cell response in long-term OA pathology.ConclusionsWe identify a hitherto unappreciated pathophysiological role of acute T-cell activation after joint injury in long-term post-traumatic OA risk, providing a novel diagnostic and therapeutic target.Key MessagesWhat is already known about this subject?The presence of synovitis/joint-inflammation increases the risk not only of osteoarthritis (OA) progression but incident disease. While numerous inflammatory effectors including macrophages and lymphocytes have been identified in OA, their disease-specificity, temporal regulation, and association with risk of pathology onset and progression is lacking.How does this study add?By directly comparing the mononuclear inflammatory/immune-cell responses following significant joint injury that does (medial-meniscal-destabilization; DMM) and does-not (Sham-surgery) lead to OA in mice, we have defined bona-fide OA-associated cellular events. There was no difference in synovial or systemic monocyte/macrophage cell number, activation or polarization between DMM and Sham, both showing a successful wound-healing response. In contrast, increases in number and activation of synovial Th1- and Th17-CD4, and CD8 T-cells in DMM compared with Sham occurred within the first 3 days, and while recurring cyclically through subsequent disease onset, depletion studies indicated this initial influx was key to long-term ptOA risk.How might this impact on clinical practice of future developments?Acute increases in synovial T-cells following jont injury may be both a novel marker of OA risk, and a target to reduce long term structural damage.

scholarly journals Religion and Corporate Innovation

2018 ◽  
Vol 4 (1) ◽  
pp. 81
Author(s):  
Meng Wang ◽  
Lining Gan
Keyword(s):  
Inhibitory Effect ◽  
Promotion Effect ◽  
Positive Correlation ◽  
Informal System ◽  
Financial Position ◽  
Input And Output ◽  
Corporate Innovation ◽  
Innovation Ability ◽  
The Impact

Innovation ability is an important factor to measure firms’ strength and is vital to the long-term development of the enterprises, previous studies have shown that financial position and corporate governance can have effects on corporate innovation, but put little attention on the informal system which may influence on innovation. This article selects religion as one of the informal system and tries to explore the impact of religion on the innovation input and output of enterprises. Using the data of A-sh are listed companies from 2008 to 2015, the empirical results show that there is a significantly positive correlation between religion and innovation inputs and outputs, and this positive correlation between religion and innovation is negatively regulated by the politics and marketization index. The results prove that politics and marketization index are substitution of religion on corporate innovation. In further analysis, the religion is divided into eastern and western parts, the results show that both eastern and western religions can promote corporate innovation, but the promotion effect of western religions is stronger. Negative moderating effect of political and marketization index on the positive correlation between religion and innovation still exists, and basically showing a more forceful inhibitory effect made by western religions on corporate innovation.

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