scholarly journals The Role of Molecular Imaging as a Marker of Remyelination and Repair in Multiple Sclerosis

2021 ◽  
Vol 23 (1) ◽  
pp. 474
Author(s):  
Ido Ben-Shalom ◽  
Arnon Karni ◽  
Hadar Kolb
Keyword(s):  
Multiple Sclerosis ◽  
Molecular Imaging ◽  
Disease Progression ◽  
Acute Inflammation ◽  
Imaging Biomarkers ◽  
Underlying Mechanisms

The appearance of new disease-modifying therapies in multiple sclerosis (MS) has revolutionized our ability to fight inflammatory relapses and has immensely improved patients’ quality of life. Although remarkable, this achievement has not carried over into reducing long-term disability. In MS, clinical disability progression can continue relentlessly irrespective of acute inflammation. This “silent” disease progression is the main contributor to long-term clinical disability in MS and results from chronic inflammation, neurodegeneration, and repair failure. Investigating silent disease progression and its underlying mechanisms is a challenge. Standard MRI excels in depicting acute inflammation but lacks the pathophysiological lens required for a more targeted exploration of molecular-based processes. Novel modalities that utilize nuclear magnetic resonance’s ability to display in vivo information on imaging look to bridge this gap. Displaying the CNS through a molecular prism is becoming an undeniable reality. This review will focus on “molecular imaging biomarkers” of disease progression, modalities that can harmoniously depict anatomy and pathophysiology, making them attractive candidates to become the first valid biomarkers of neuroprotection and remyelination.

scholarly journals SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

2021 ◽  
Vol 10 (15) ◽  
pp. 3441
Author(s):  
Hashir Ali Awan ◽  
Mufaddal Najmuddin Diwan ◽  
Alifiya Aamir ◽  
Muneeza Ali ◽  
Massimo Di Giannantonio ◽  
...  
Keyword(s):  
Olfactory Pathway ◽  
Cognitive Sequelae ◽  
Significant Burden ◽  
Inflammatory State ◽  
Underlying Mechanisms ◽  
Acute Changes ◽  
A Minor

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.

Epilepsy as a predictor of disease progression in multiple sclerosis

2021 ◽  
pp. 135245852110467
Author(s):  
Matthias Grothe ◽  
David Ellenberger ◽  
Felix von Podewils ◽  
Alexander Stahmann ◽  
Paulus S Rommer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Disease Onset ◽  
Walking Distance ◽  
Disability Status ◽  
Cortical Pathology ◽  
Underlying Mechanisms ◽  
Patients With Epilepsy

Background: Epilepsy development during the course of multiple sclerosis (MS) is considered to be the result of cortical pathology. However, no long-term data exist on whether epilepsy in MS also leads to increasing disability over time. Objective: To examine if epilepsy leads to more rapid disease progression. Methods: We analyzed the data of 31,052 patients on the German Multiple Sclerosis Register in a case–control study. Results: Secondary progressive disease course (odds ratio (OR) = 2.23), age (OR = 1.12 per 10 years), and disability (OR = 1.29 per Expanded Disability Status Scale (EDSS) point) were associated with the 5-year prevalence of epilepsy. Patients who developed epilepsy during the course of the disease had a higher EDSS score at disease onset compared to matched control patients (EDSS 2.0 vs 1.5), progressed faster in each dimension, and consequently showed higher disability (EDSS 4.4 vs 3.4) and lower employment status (40% vs 65%) at final follow-up. After 15 years of MS, 64% of patients without compared to 54% of patients with epilepsy were not severely limited in walking distance. Conclusion: This work highlights the association of epilepsy on disability progression in MS, and the need for additional data to further clarify the underlying mechanisms.

THE ROLE OF POLYETHYLENIMINE IN ENHANCING PERFORMANCE OF GLUTAMATE BIOSENSORS

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
Diep Do Thi Hong ◽  
Duong Le Phuoc ◽  
Hoai Nguyen Thi ◽  
Serra Pier Andrea ◽  
Rocchitta Gaia
Keyword(s):  
First Generation ◽  
Good Reproducibility ◽  
Complex Matrices ◽  
Long Term Stability ◽  
In Vitro Characterization ◽  
Glutamate Oxidase

Background: The first biosensor was constructed more than fifty years ago. It was composed of the biorecognition element and transducer. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples Glutamate is important biochemicals involved in energetic metabolism and neurotransmission. Therefore, biosensors requires the development a new approach exhibiting high sensibility, good reproducibility and longterm stability. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples. The aims of this work: To find out which concentration of polyethylenimine (PEI) exhibiting the most high sensibility, good reproducibility and long-term stability. Methods: We designed and developed glutamate biosensor using different concentration of PEI ranging from 0% to 5% at Day 1 and Day 8. Results: After Glutamate biosensors in-vitro characterization, several PEI concentrations, ranging from 0.5% to 1% seem to be the best in terms of VMAX, the KM; while PEI content ranging from 0.5% to 1% resulted stable, PEI 1% displayed an excellent stability. Conclusions: In the result, PEI 1% perfomed high sensibility, good stability and blocking interference. Furthermore, we expect to develop and characterize an implantable biosensor capable of detecting glutamate, glucose in vivo. Key words: Glutamate biosensors, PEi (Polyethylenimine) enhances glutamate oxidase, glutamate oxidase biosensors

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.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

scholarly journals Remediation of mercury-contaminated soils and sediments using biochar: a critical review

Biochar ◽  
2021 ◽  
Author(s):  
Qian Yang ◽  
Yongjie Wang ◽  
Huan Zhong
Keyword(s):  
Health Risks ◽  
Contaminated Soils ◽  
Functional Materials ◽  
Redox Conditions ◽  
Existing Problems ◽  
Soils And Sediments ◽  
Underlying Mechanisms ◽  
Biochar Amendment

AbstractThe transformation of mercury (Hg) into the more toxic and bioaccumulative form methylmercury (MeHg) in soils and sediments can lead to the biomagnification of MeHg through the food chain, which poses ecological and health risks. In the last decade, biochar application, an in situ remediation technique, has been shown to be effective in mitigating the risks from Hg in soils and sediments. However, uncertainties associated with biochar use and its underlying mechanisms remain. Here, we summarize recent studies on the effects and advantages of biochar amendment related to Hg biogeochemistry and its bioavailability in soils and sediments and systematically analyze the progress made in understanding the underlying mechanisms responsible for reductions in Hg bioaccumulation. The existing literature indicates (1) that biochar application decreases the mobility of inorganic Hg in soils and sediments and (2) that biochar can reduce the bioavailability of MeHg and its accumulation in crops but has a complex effect on net MeHg production. In this review, two main mechanisms, a direct mechanism (e.g., Hg-biochar binding) and an indirect mechanism (e.g., biochar-impacted sulfur cycling and thus Hg-soil binding), that explain the reduction in Hg bioavailability by biochar amendment based on the interactions among biochar, soil and Hg under redox conditions are highlighted. Furthermore, the existing problems with the use of biochar to treat Hg-contaminated soils and sediments, such as the appropriate dose and the long-term effectiveness of biochar, are discussed. Further research involving laboratory tests and field applications is necessary to obtain a mechanistic understanding of the role of biochar in reducing Hg bioavailability in diverse soil types under varying redox conditions and to develop completely green and sustainable biochar-based functional materials for mitigating Hg-related health risks.

Long-Term Effectiveness of Fingolimod for Multiple Sclerosis in a Real-World Clinical Setting

2021 ◽  
pp. 1-6
Author(s):  
Cihat Uzunköprü ◽  
Yesim Beckmann ◽  
Sabiha Türe
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Real Life ◽  
Life Assessment ◽  
Health Related Quality ◽  
Serious Adverse Events ◽  
Related Quality ◽  
Health Related

<b><i>Introduction:</i></b> The primary aim of the present study was to evaluate the long-term efficacy of fingolimod in patients with multiple sclerosis (MS); secondary aims were to describe the safety of fingolimod with the evaluation of treatment satisfaction and impact on the quality of life in real life. <b><i>Methods:</i></b> We collected clinical, demographical, neuroradiological, and treatment data, including pre- and posttreatment status health-related quality of life from 286 MS patients consecutively treated with fingolimod. Clinical assessment was based on the Expanded Disability Status Scale (EDSS), and quality of life assessment was performed with MS-related quality of life inventory (MSQOLI). The data were recorded at baseline and every 6 months for 2 years. <b><i>Results:</i></b> One hundred and fourteen males and 172 females were enrolled. The annualized relapse rate and EDSS showed a statistically significant reduction during the observation period (<i>p</i> &#x3c; 0.001). The patients also demonstrated substantial improvements in magnetic resonance imaging (MRI) outcomes (<i>p</i> &#x3c; 0.001). Health-related quality of life scores improved significantly between baseline and 24-month visit (<i>p</i> &#x3c; 0.001). No serious adverse events occurred. <b><i>Conclusion:</i></b> In our cohort, fingolimod treatment was associated with reduced relapse, MRI activity, and improved EDSS and MSQOLI scores. Additionally, fingolimod has been able to maintain its effectiveness over a considerable long period of treatment.

scholarly journals Genetic Suppressor Element 1 (GSE1) Promotes the Oncogenic and Recurrent Phenotypes of Castration-Resistant Prostate Cancer by Targeting Tumor-Associated Calcium Signal Transducer 2 (TACSTD2)

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3959
Author(s):  
Oluwaseun Adebayo Bamodu ◽  
Yuan-Hung Wang ◽  
Chen-Hsun Ho ◽  
Su-Wei Hu ◽  
Chia-Da Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Therapy Resistance ◽  
Calcium Signal ◽  
Signal Transducer ◽  
Castration Resistance ◽  
Castration Resistant

Background: prostate cancer (PCa) is a principal cause of cancer-related morbidity and mortality. Castration resistance and metastasis are clinical challenges and continue to impede therapeutic success, despite diagnostic and therapeutic advances. There are reports of the oncogenic activity of genetic suppressor element (GSE)1 in breast and gastric cancers; however, its role in therapy resistance, metastasis, and susceptibility to disease recurrence in PCa patients remains unclear. Objective: this study investigated the role of aberrantly expressed GSE1 in the metastasis, therapy resistance, relapse, and poor prognosis of advanced PCa. Methods: we used a large cohort of multi-omics data and in vitro, ex vivo, and in vivo assays to investigate the potential effect of altered GSE1 expression on advanced/castration-resistant PCa (CRPC) treatment responses, disease progression, and prognosis. Results: using a multi-cohort approach, we showed that GSE1 is upregulated in PCa, while tumor-associated calcium signal transducer 2 (TACSTD2) is downregulated. Moreover, the direct, but inverse, correlation interaction between GSE1 and TACSTD2 drives metastatic disease, castration resistance, and disease progression and modulates the clinical and immune statuses of patients with PCa. Patients with GSE1highTACSTD2low expression are more prone to recurrence and disease-specific death than their GSE1lowTACSTD2high counterparts. Interestingly, we found that the GSE1–TACSTD2 expression profile is associated with the therapy responses and clinical outcomes in patients with PCa, especially those with metastatic/recurrent disease. Furthermore, we demonstrate that the shRNA-mediated targeting of GSE1 (shGSE1) significantly inhibits cell proliferation and attenuates cell migration and tumorsphere formation in metastatic PC3 and DU145 cell lines, with an associated suppression of VIM, SNAI2, and BCL2 and the concomitant upregulation of TACSTD2 and BAX. Moreover, shGSE1 enhances sensitivity to the antiandrogens abiraterone and enzalutamide in vitro and in vivo. Conclusion: these data provide preclinical evidence of the oncogenic role of dysregulated GSE1–TACSTD2 signaling and show that the molecular or pharmacological targeting of GSE1 is a workable therapeutic strategy for inhibiting androgen-driven oncogenic signals, re-sensitizing CRPC to treatment, and repressing the metastatic/recurrent phenotypes of patients with PCa.

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.

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