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Handbook of Clinical Neurology 2018Multiple sclerosis is a potentially progressive, autoimmune neurologic disorder of the central nervous system, resulting from an autoimmune attack on central nervous... (Review)
Review
Multiple sclerosis is a potentially progressive, autoimmune neurologic disorder of the central nervous system, resulting from an autoimmune attack on central nervous system white matter. It is a leading cause of neurologic symptoms in young adults, with no known cure. Emerging disease-modifying therapies aim to control symptoms, with increasingly sophisticated immune function modulation. Though several environmental exposures increase the risk of developing the disease, a large fraction of overall risk is heritable and can be attributed to hundreds of common genetic variants influencing gene regulation in specific immune subsets. Here, we review the history of the disease, the realization that risk is heritable, and the recent revelation of hundreds of genetic variants driving this risk by international consortia studying tens of thousands of patients. Finally, we discuss how these results are revealing the specific pathobiology of multiple sclerosis and how this knowledge is transforming drug discovery.
Topics: Central Nervous System; Genetic Association Studies; Humans; Multiple Sclerosis; White Matter
PubMed: 29478610
DOI: 10.1016/B978-0-444-64076-5.00046-6 -
Przeglad Menopauzalny = Menopause Review Jun 2022Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not... (Review)
Review
Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.
PubMed: 36199735
DOI: 10.5114/pm.2022.116437 -
Human Brain Mapping Dec 2019Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease for which there is no cure. Mild cognitive impairment (MCI) is considered a prodromal... (Review)
Review
Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease for which there is no cure. Mild cognitive impairment (MCI) is considered a prodromal stage of the disease. Molecular imaging with positron emission tomography (PET) allows for the in vivo visualisation and tracking of pathophysiological changes in AD and MCI. PET is a very promising methodology for differential diagnosis and novel targets of PET imaging might also serve as biomarkers for disease-modifying therapeutic interventions. This review provides an overview of the current status and applications of in vivo molecular imaging of AD pathology, specifically amyloid, tau, and microglial activation. PET imaging studies were included and evaluated as potential biomarkers and for monitoring disease progression. Although the majority of radiotracers showed the ability to discriminate AD and MCI patients from healthy controls, they had various limitations that prevent the recommendation of a single technique or tracer as an optimal biomarker. Newer research examining amyloid, tau, and microglial PET imaging in combination suggest an alternative approach in studying the disease process.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Humans; Inflammation; Positron-Emission Tomography; tau Proteins
PubMed: 31520513
DOI: 10.1002/hbm.24782 -
Cornea Apr 2023The purpose of this study was to evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25%, compared with vehicle for the treatment of Demodex blepharitis. (Randomized Controlled Trial)
Randomized Controlled Trial
Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis: Results of a Prospective, Randomized, Vehicle-Controlled, Double-Masked, Pivotal Trial (Saturn-1).
PURPOSE
The purpose of this study was to evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25%, compared with vehicle for the treatment of Demodex blepharitis.
METHODS
In this prospective, randomized, controlled, double-masked, phase 2b/3 clinical trial, 421 patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution, 0.25% (study group), or vehicle without lotilaner (control group) bilaterally, twice daily for 43 days. Patients were evaluated at days 8, 15, 22, and 43. Outcome measures were complete collarette cure (collarette grade 0), clinically meaningful collarette cure (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes/erythema), and drop comfort. Adverse events were also evaluated.
RESULTS
At day 43, the study group achieved a statistically significantly higher proportion of patients with clinically meaningful collarette cure (81.3% vs. 23.0%; P < 0.0001), complete collarette cure (44.0% vs. 7.4%; P < 0.0001), mite eradication (67.9% vs. 17.6%; P < 0.0001), erythema cure (19.1% vs. 6.9%; P = 0.0001), and composite cure (13.9% vs. 1.0%; P < 0.0001) than the control group. Nearly 92.0% of patients rated the study drop as neutral to very comfortable. All ocular adverse events in the study group were mild, with the most common being instillation site pain.
CONCLUSIONS
Twice-daily treatment with a novel lotilaner ophthalmic solution, 0.25% for 43 days, is safe and effective for the treatment of Demodex blepharitis compared with the vehicle control.
Topics: Humans; Ophthalmic Solutions; Prospective Studies; Double-Blind Method; Blepharitis
PubMed: 35965392
DOI: 10.1097/ICO.0000000000003097 -
Animal Models and Experimental Medicine Dec 2022Zebrafish (Danio rerio) have attracted much attention over the past decade as a reliable model for gut microbiome research. Owing to their low cost, strong genetic and... (Review)
Review
Zebrafish (Danio rerio) have attracted much attention over the past decade as a reliable model for gut microbiome research. Owing to their low cost, strong genetic and development coherence, efficient preparation of germ-free (GF) larvae, availability in high-throughput chemical screening, and fitness for intravital imaging in vivo, zebrafish have been extensively used to investigate microbiome-host interactions and evaluate the toxicity of environmental pollutants. In this review, the advantages and disadvantages of zebrafish for studying the role of the gut microbiome compared with warm-blooded animal models are first summarized. Then, the roles of zebrafish gut microbiome on host development, metabolic pathways, gut-brain axis, and immune disorders and responses are addressed. Furthermore, their applications for the toxicological assessment of aquatic environmental pollutants and exploration of the molecular mechanism of pathogen infections are reviewed. We highlight the great potential of the zebrafish model for developing probiotics for xenobiotic detoxification, resistance against bacterial infection, and disease prevention and cure. Overall, the zebrafish model promises a brighter future for gut microbiome research.
Topics: Animals; Environmental Pollutants; Gastrointestinal Microbiome; Microbiota; Probiotics; Zebrafish
PubMed: 35415967
DOI: 10.1002/ame2.12227 -
Indian Journal of Sexually Transmitted... 2019HIV is a chronic well manageable disease. Highly active antiretroviral therapy improves the quality of life of people living with HIV, but the treatment has to be... (Review)
Review
HIV is a chronic well manageable disease. Highly active antiretroviral therapy improves the quality of life of people living with HIV, but the treatment has to be continued lifelong, as the total cure has not been established. Cost of treatment, drug toxicities, interaction with other drugs and persistence of inflammation and acceleration of the aging process, all put together, warrant an urgent need for a total cure. Even though one case had been proved to be cured, still a practical cure is far beyond the reach. Numerous approaches and strategies had been put forth to achieve a cure; still they are to be proved with human studies. This article reviews the major approaches, recent advances in the venture of HIV cure, and the safety concerns involved.
PubMed: 31143852
DOI: 10.4103/ijstd.IJSTD_112_15 -
BMC Medical Research Methodology Mar 2020The mortality risk among cancer patients measured from the time of diagnosis is often elevated in comparison to the general population. However, for some cancer types,... (Review)
Review
BACKGROUND
The mortality risk among cancer patients measured from the time of diagnosis is often elevated in comparison to the general population. However, for some cancer types, the patient mortality risk will over time reach the same level as the general population mortality risk. The time point at which the mortality risk reaches the same level as the general population is called the cure point and is of great interest to patients, clinicians, and health care planners. In previous studies, estimation of the cure point has been handled in an ad hoc fashion, often without considerations about margins of clinical relevance.
METHODS
We review existing methods for estimating the cure point and discuss new clinically relevant measures for quantifying the mortality difference between cancer patients and the general population, which can be used for cure point estimation. The performance of the methods is assessed in a simulation study and the methods are illustrated on survival data from Danish colon cancer patients.
RESULTS
The simulations revealed that the bias of the estimated cure point depends on the measure chosen for quantifying the excess mortality, the chosen margin of clinical relevance, and the applied estimation procedure. These choices are interdependent as the choice of mortality measure depends both on the ability to define a margin of clinical relevance and the ability to accurately compute the mortality measure. The analysis of cancer survival data demonstrates the importance of considering the confidence interval of the estimated cure point, as these may be wide in some scenarios limiting the applicability of the estimated cure point.
CONCLUSIONS
Although cure points are appealing in a clinical context and has widespread applicability, estimation remains a difficult task. The estimation relies on a number of choices, each associated with pitfalls that the practitioner should be aware of.
Topics: Colonic Neoplasms; Computer Simulation; Humans; Risk Factors
PubMed: 32216765
DOI: 10.1186/s12874-020-00946-8 -
Frontiers in Cell and Developmental... 2020Cancer is a complex disease and it is now clear that not only epithelial tumor cells play a role in carcinogenesis. The tumor microenvironment is composed of non-stromal... (Review)
Review
Cancer is a complex disease and it is now clear that not only epithelial tumor cells play a role in carcinogenesis. The tumor microenvironment is composed of non-stromal cells, including endothelial cells, adipocytes, immune and nerve cells, and a stromal compartment composed of extracellular matrix, cancer-associated fibroblasts and mesenchymal cells. Tumorigenesis is a dynamic process with constant interactions occurring between the tumor cells and their surroundings. Even though all connections have not yet been discovered, it is now known that crosstalk between actors of the microenvironment drives cancer progression. Taking into account this complexity, it is important to develop relevant models to study carcinogenesis. Conventional 2D culture models fail to represent the entire tumor microenvironment properly and the use of animal models should be decreased with respect to the 3Rs rule. To this aim, organotypic models have been significantly developed these past few years. These models have different levels of complexity and allow the study of tumor cells alone or in interaction with the microenvironment actors during the multiple stages of carcinogenesis. This review depicts recent insights into organotypic modeling of the tumor and its microenvironment all throughout cancer progression. It offers an overview of the crosstalk between epithelial cancer cells and their microenvironment during the different phases of carcinogenesis, from the early cell autonomous events to the late metastatic stages. The advantages of 3D over classical 2D or models are presented as well as the most promising organotypic models. A particular focus is made on organotypic models used for studying cancer progression, from the less complex spheroids to the more sophisticated body-on-a-chip. Last but not least, we address the potential benefits of these models in personalized medicine which is undoubtedly a domain paving the path to new hopes in terms of cancer care and cure.
PubMed: 33330508
DOI: 10.3389/fcell.2020.606039 -
The Lancet. HIV Jun 20189 years since the report of a cure for HIV after C-C chemokine receptor type 5 Δ32 stem cell transplantation, no other case of HIV cure has been reported, despite much... (Review)
Review
9 years since the report of a cure for HIV after C-C chemokine receptor type 5 Δ32 stem cell transplantation, no other case of HIV cure has been reported, despite much research. However, substantial progress has been made in understanding the biology of the latent HIV reservoir, and in measuring the amount of virus that persists after antiretroviral therapy (ART) with increasingly sophisticated approaches. This knowledge is being translated into a long pipeline of clinical trials seeking to reduce viral persistence in participants on suppressive treatment and ultimately to allow safe cessation of ART. In this Review, we discuss the main barriers preventing the development of an HIV cure, methods used to measure HIV persistence in individuals on ART, clinical strategies that aim to cure HIV, and future directions for studies in the field of HIV cure research.
Topics: AIDS Vaccines; Clinical Trials as Topic; Disease Eradication; HIV Infections; Humans; T-Lymphocytes; Viral Load; Virus Latency
PubMed: 29893245
DOI: 10.1016/S2352-3018(18)30039-0