scholarly journals A Translational Perspective of Maternal Immune Activation by SARS-CoV-2 on the Potential Prenatal Origin of Neurodevelopmental Disorders: The Role of the Cholinergic Anti-inflammatory Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
José Javier Reyes-Lagos ◽  
Eric Alonso Abarca-Castro ◽  
Juan Carlos Echeverría ◽  
Hugo Mendieta-Zerón ◽  
Alejandra Vargas-Caraveo ◽  
...  
Keyword(s):  
Immune Activation ◽  
Neurodevelopmental Disorders ◽  
Inflammatory Pathway ◽  
Maternal Immune Activation ◽  
Increased Risk ◽  
Anti Inflammatory ◽  
Psychophysiological Data

The emergent Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could produce a maternal immune activation (MIA) via the inflammatory response during gestation that may impair fetal neurodevelopment and lead to postnatal and adulthood mental illness and behavioral dysfunctions. However, so far, limited evidence exists regarding long-term physiological, immunological, and neurodevelopmental modifications produced by the SARS-CoV-2 in the human maternal-fetal binomial and, particularly, in the offspring. Relevant findings derived from epidemiological and preclinical models show that a MIA is indeed linked to an increased risk of neurodevelopmental disorders in the offspring. We hypothesize that a gestational infection triggered by SARS-CoV-2 increases the risks leading to neurodevelopmental disorders of the newborn, which can affect childhood and the long-term quality of life. In particular, disruption of either the maternal or the fetal cholinergic anti-inflammatory pathway (CAP) could cause or exacerbate the severity of COVID-19 in the maternal-fetal binomial. From a translational perspective, in this paper, we discuss the possible manifestation of a MIA by SARS-CoV-2 and the subsequent neurodevelopmental disorders considering the role of the fetal-maternal cytokine cross-talk and the CAP. Specifically, we highlight the urgent need of preclinical studies as well as multicenter and international databanks of maternal-fetal psychophysiological data obtained pre-, during, and post-infection by SARS-CoV-2 from pregnant women and their offspring.

Influence of Long-term Non-Aspirin NSAID use on Risk of Frailty in Men ≥60 years: The Physicians’ Health Study

2022 ◽  
Author(s):  
Ariela R Orkaby ◽  
Rachel Ward ◽  
Jiaying Chen ◽  
Akshay Shanbhag ◽  
Howard D Sesso ◽  
...  
Keyword(s):  
Propensity Score ◽  
Frailty Index ◽  
Health Study ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Propensity Score Adjustment

Abstract Background Inflammation is a central pathway leading to frailty but whether commonly used non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can prevent frailty is unknown. Methods Prospective cohort study of male physicians ≥60 who participated in the Physicians’ Health Study. Annual questionnaires collected data on NSAID use, lifestyle and morbidity. Average annual NSAID use was categorized as 0 days/year, 1-12 days/year, 13-60 days/year, and >60 days/year. Frailty was assessed using a validated 33-item frailty index. Propensity score inverse probability of treatment weighting was used to address confounding by indication and logistic regression models estimated odds ratios (ORs) of prevalent frailty according to non-aspirin NSAID use. Results 12,101 male physicians were included (mean age 70±7 years, mean follow-up 11 years). Reported NSAID use was 0 days/year for 2,234, 1-12 days/year for 5,812, 13-60 days/year for 2,833, and >60 days/year for 1,222 participants. 2,413 participants (20%) were frail. Higher self-reported NSAID use was associated with greater alcohol use, smoking, arthritis, hypertension, and heart disease, while less NSAID use was associated with coumadin use and prior bleeding. After propensity score adjustment, all characteristics were balanced. ORs (95% CIs) of prevalent frailty were 0.90 (0.80-1.02), 1.02 (0.89-1.17), and 1.26 (1.07-1.49) for average NSAID use of 1-12 days/year, 13-60 days/year, and >60 days/year, compared to 0 days/year (p-trend<0.001). Conclusions Long term use of NSAIDs at high frequency is associated with increased risk of frailty among older men. Additional study is needed to understand the role of anti-inflammatory medication in older adults and its implication for overall health.

scholarly journals Interferon-ɣ Exposure of Human iPSC-derived Neurons Alters Major Histocompatibility Complex I and Synapsin I Protein Expression

2021 ◽  
Author(s):  
Adam Pavelinek ◽  
Rugile Matuleviciute ◽  
Laura Sichlinger ◽  
Lucia Dutan Polit ◽  
Nikos Armeniakos ◽  
...  
Keyword(s):  
Immune Activation ◽  
Neurodevelopmental Disorders ◽  
Synapse Formation ◽  
Neurodevelopmental Disorder ◽  
Synaptic Proteins ◽  
Synapsin I ◽  
Mrna Levels ◽  
Maternal Immune Activation ◽  
Increased Risk

Human epidemiological data links maternal immune activation during gestation with increased risk for neurodevelopmental disorders including schizophrenia. Animal models of maternal immune activation (MIA) provide causal evidence for this association and strongly suggest that inflammatory cytokines act is a critical link between maternal infection and aberrant offspring brain and behavior development. This includes evidence for reduced synapse formation, consistent with post-mortem and in vivo evidence of reduced synaptic density in schizophrenia. However, to what extent specific cytokines are necessary and sufficient for these effects remains unclear. Using a human cellular model, we recently demonstrated that acute exposure to interferon-ɣ (IFNɣ) recapitulates molecular and cellular phenotypes associated with neurodevelopmental disorders. Here, we extend this work to test whether IFNɣ affects synapse formation in an induced neuron model that generates forebrain glutamatergic neurons. Using immunocytochemistry and quantitative PCR, we demonstrate that acute IFNɣ exposure results in significantly increased MHCI expression at the mRNA and protein level. Furthermore, acute IFNɣ exposure decreases synapsin I protein in neurons but does not affect synaptic gene mRNA levels. Interestingly, complement component 4A (C4A) mRNA is also significantly increased following acute IFNɣ exposure. This study builds on our previous work by showing that IFNɣ-mediated disruption of relevant synaptic proteins can occur at early stages of synapse formation, potentially contributing to neurodevelopmental disorder phenotypes such as schizophrenia.

Considerations of the technological quality assessment of sugarbeet

2011 ◽  
pp. 85-89 ◽  
Author(s):  
Giorgio Pezzi
Keyword(s):  
Quality Parameters ◽  
Northern Italy ◽  
Glucose Content ◽  
Long Term Storage ◽  
Interesting Correlation ◽  
Technological Quality ◽  
Thick Juice

No real improvement in the technological quality of beet has been recorded over the last 15 years in Northern Italy. Among the possible explanations for the quality stagnation is that the traditional formulae cannot correctly differentiate between sugarbeet varieties which produce thick juice of very high purity. This seems to be connected with the role of potassium. The use of a standard purification procedure gives reliable and accurate data which is immediately comparable with the factory data. Research projects on medium/long term storage are currently being performed by Co.Pro.B., Italy, in cooperation with Syngenta and Beta. Up to now the results have shown that storage of sugarbeet in autumn time in northern Italy is possible provided that suitable varieties and proper handling of the roots are employed. Results obtained in the storage trials are reported. Correlations have been found between quality parameters (purity, color and lime salts) of the purified juice with the glucose content of the raw juice. An interesting correlation is reported between purified juice purity and raw juice purity.

Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era

2020 ◽  
Vol 20 ◽  
Author(s):  
Giuseppe Lassandro ◽  
Valentina Palladino ◽  
Giovanni Carlo Del Vecchioa ◽  
Viviana Valeria Palmieri ◽  
Paola Carmela Corallo ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Treatment Options ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor ◽  
Related Quality ◽  
Health Related

Background and Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safety and effective for the treatment of pediatric ITP. The aim of our research is defining the role of thrombopoietin receptor agonists in the management of pediatric ITP. Method: This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in management of the disease. Results: Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Conclusion: Although TPO-RAs long term efficacy and safety still require further investigations, their use is gradually expanding in clinical practice of children with ITP.

Biopsychosocial Patterning of Multimorbidity and Its Consequences

2018 ◽  
pp. 220-236
Author(s):  
Elliot Friedman ◽  
Beth LeBreton ◽  
Lindsay Fuzzell ◽  
Elizabeth Wehrpsann
Keyword(s):  
Quality Of Life ◽  
Older Adults ◽  
Functional Outcomes ◽  
The United States ◽  
Chronic Medical Conditions ◽  
Quality Of Life Research ◽  
Increased Risk ◽  
Over Time

By many estimates the majority of adults over age 65 have two or more chronic medical conditions (multimorbidity) and are consequently at increased risk of adverse functional outcomes. Nonetheless, many older adults with multimorbidity are able to maintain high levels of function and retain good quality of life. Research presented here is designed to understand the influences that help ensure better functional outcomes in these older adults. This chapter presents findings that draw on data from the Midlife in the United States study. The independent and interactive contributions of diverse factors to multimorbidity and changes in multimorbidity over time are reviewed. The degree that multimorbidity increases risk of cognitive impairment and disability is examined. The role of inflammation as a mediator is considered. Multimorbidity is increasingly the norm for older adults, so better understanding of factors contributing to variability in multimorbidity-related outcomes can lead to improved quality of life.

The Role of α7nAChR-Mediated Cholinergic Anti-inflammatory Pathway in Immune Cells

Inflammation ◽  
2021 ◽  
Author(s):  
Yi-jin Wu ◽  
Li Wang ◽  
Chao-fan Ji ◽  
Shao-fei Gu ◽  
Qin Yin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

scholarly journals Role of diuretics on long-term mortality may differ in volume status in patients with acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Kawai ◽  
D Nakatani ◽  
T Yamada ◽  
T Watanabe ◽  
T Morita ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Propensity Score ◽  
Plasma Volume ◽  
Cox Regression ◽  
Volume Status ◽  
Increased Risk ◽  
Long Term Mortality

Abstract Background Diuretics has been reported to have a potential for an activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, leading to a possibility of poor clinical outcome in patients with cardiovascular disease. However, few data are available on clinical impact of diuretics on long-term outcome in patients with acute myocardial infarction (AMI) based on plasma volume status. Methods To address the issue, a total of 3,416 survived patients with AMI who were registered to a large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed with the estimated plasma volume status (ePVS) that was calculated at discharge as follows: actual PV = (1 − hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females), and ePVS = [(actual PV − ideal PV)/ideal PV] × 100 (%). Multivariable Cox regression analysis and propensity score matching were performed to account for imbalances in covariates. The endpoint was all-cause of death (ACD) within 5 years. Results During a median follow-up period of 855±656 days, 193 patients had ACD. In whole population, there was no significant difference in long-term mortality risk between patients with and without diuretics in both multivariate cox regression model and propensity score matching population. When patients were divided into 2 groups according to ePVS with a median value of 4.2%, 46 and 147 patients had ACD in groups with low ePVS and high ePVS, respectively. Multivariate Cox analysis showed that use of diuretics was independently associated with an increased risk of ACD in low ePVS group, (HR: 2.63, 95% confidence interval [CI]: 1.22–5.63, p=0.01), but not in high ePVS group (HR: 0.70, 95% CI: 0.44–1.10, p=0.12). These observations were consistent in the propensity-score matched cohorts; the 5-year mortality rate was significantly higher in patients with diuretics than those without among low ePVS group (4.7% vs 1.7%, p=0.041), but not among high ePVS group (8.0% vs 10.3%, p=0.247). Conclusion Prescription of diuretics at discharge was associated with increased risk of 5-year mortality in patients with AMI without PV expansion, but not with PV expansion. The role of diuretics on long-term mortality may differ in plasma volume status. Therefore, prescription of diuretics after AMI may be considered based on plasma volume status. Funding Acknowledgement Type of funding source: None

scholarly journals 106 - Environmental Influences on the Cognitive and Psychological Well Being of Older Adults with Dementia

2020 ◽  
Vol 32 (S1) ◽  
pp. 15-16
Author(s):  
William E. Reichman ◽  
L. Bradford Perkins ◽  
Hilde Verbeek
Keyword(s):  
Quality Of Life ◽  
Older Adults ◽  
Physical Environment ◽  
Culture Change ◽  
Long Term Care ◽  
Small Scale ◽  
Term Care

This symposium will review the latest data on the influence of environmental design and its attributes on the cognitive and psychological wellbeing of older adults living with dementia. The presenters will cover the myriad ways in which the physical environment of care can adapt to the changing demands of older adults with sensory, motor and cognitive deficits and foster optimal functioning and quality of life. The role of emerging technologies will also be reviewed as they complement the contribution of the design of the physical environment to the wellbeing of older adults with cognitive impairment. Information will be offered through a review of the existing research literature as well as case studies that illustrate the impact of environmental modification on fostering wellbeing and minimizing the emergence of the behavioral and psychological symptoms of dementia. The presenters will represent and integrate sensibilities that have emerged from the fields of architecture, cognitive neuroscience and psychology.How the Principles of the Culture Change Movement Inform Environmental Design and the Application of Technology in the Care of Older Adults Living with DementiaWilliam E. ReichmanThe culture change movement informs a number of principles that have been applied to more contemporary design concepts for the congregate care of older adults living with dementia. This talk will review the core tenets of the Culture Change Movement as exemplified by the Greenhouse, Dementia Village and other innovative models of congregate long-term care. Specific reference will be made to how these tenets have been operationalized around the world into the design of programming and the creation of residential care environments that foster a better quality of life for older adults and an enhanced work environment for care providers. This talk will also include the emerging role of technologies that complement innovative design of the environment and which foster optimized social and recreational functioning of older adults living with dementia.A Better Life Through a Better Nursing Home DesignL. Bradford PerkinsOver the last 20 years there has been extensive experimentation related to the role of the environment in the housing, care and treatment of persons with Alzheimer’s and other age related dementias. Prior to that time the typical housing and care environment was a locked unit in a skilled nursing or other restrictive senior living facility. In 1991 the Presbyterian Association on Aging in Western Pennsylvania opened Woodside Place on its Oakmont campus. This small 36 bed facility was designed to incorporate the latest research and care experience with persons suffering from these issues. This one small project, as well as the long post occupancy research led by Carnegie Mellon University, clearly demonstrated that individuals with Alzheimer’s and related forms of dementia could lead a healthier, happier, higher quality of life in a more residential, less restrictive environment. Not everything in this pioneering project worked, and five generations of living and care models have followed that have refined the ideas first demonstrated by Woodside Place. Bradford Perkins, whose firm designed Woodside Place and over 100 other related projects, will discuss what was learned from Woodside Place as well as the five generations of projects (and post occupancy research) that followed.Innovative dementia care environments as alternatives for traditional nursing homes: evidence and experiences from the NetherlandsHilde VerbeekKey goals of the dementia care environment focus on increasing autonomy, supporting independence and trying to enable one’s own lifestyle for as long as possible. To meet these goals, innovative, small-scale and homelike care environments have been developed that have radically changed the physical, social and organizational aspects of long-term care in the Netherlands. This presentation discusses various Dutch models that have implemented small-scale and homelike care environments, including green care farms, dementia village and citizen initiatives. The models reflect a common care concept, focusing on residents’ remaining strengths, providing opportunity for choice and aiming to sustain a sense of self and control. A small number of residents (usually 6 to 8) live together in a homelike environment and nursing staff are part of the household. Residents are encouraged to participate in daily household activities, emphasizing normalization of daily life with person-centred care. The physical environment resembles an archetypal home. This talk presents the scientific evidence on the impact and effects of these small-scale, homelike models on residents, their family caregivers and staff. Furthermore, the presentation will highlight working approaches and how these initiatives have positively influenced routine care across the long-term care spectrum.

scholarly journals Role of Glucose-Lowering Medications in Erectile Dysfunction

2021 ◽  
Vol 10 (11) ◽  
pp. 2501
Author(s):  
Angelo Cignarelli ◽  
Valentina Annamaria Genchi ◽  
Rossella D’Oria ◽  
Fiorella Giordano ◽  
Irene Caruso ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Current Knowledge ◽  
Smooth Muscle Contractility ◽  
Glucose Lowering ◽  
Glycation End Products ◽  
Altered Metabolism

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

Sign in / Sign up

Export Citation Format

Share Document