scholarly journals The microbiome in bronchiectasis

2019 ◽  
Vol 28 (153) ◽  
pp. 190048 ◽  
Author(s):  
Hollian Richardson ◽  
Alison J. Dicker ◽  
Heather Barclay ◽  
James D. Chalmers
Keyword(s):  
Disease Progression ◽  
Bacterial Communities ◽  
Interindividual Variability ◽  
Severe Disease ◽  
Novel Treatments ◽  
Lung Microbiome ◽  
Rrna Sequencing ◽  
Recent Developments ◽  
Disease Subtypes ◽  
Generation Sequencing

Bronchiectasis is increasing in prevalence worldwide, yet current treatments available are limited to those alleviating symptoms and reducing exacerbations. The pathogenesis of the disease and the inflammatory, infective and molecular drivers of disease progression are not fully understood, making the development of novel treatments challenging. Understanding the role bacteria play in disease progression has been enhanced by the use of next-generation sequencing techniques such as 16S rRNA sequencing. The microbiome has not been extensively studied in bronchiectasis, but existing data show lung bacterial communities dominated by Pseudomonas, Haemophilus and Streptococcus, while exhibiting intraindividual stability and large interindividual variability. Pseudomonas- and Haemophilus-dominated microbiomes have been shown to be linked to severe disease and frequent exacerbations. Studies completed to date are limited in size and do not fully represent all clinically observed disease subtypes. Further research is required to understand the microbiomes role in bronchiectasis disease progression. This review discusses recent developments and future perspectives on the lung microbiome in bronchiectasis.

scholarly journals The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study

2020 ◽  
Vol 58 (7) ◽  
pp. 1106-1115 ◽  
Author(s):  
Yufen Zheng ◽  
Ying Zhang ◽  
Hongbo Chi ◽  
Shiyong Chen ◽  
Minfei Peng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Platelet Count ◽  
Disease Progression ◽  
Neutrophil Count ◽  
Calibration Curve ◽  
Lymphocyte Count ◽  
Severe Disease ◽  
Clinical Impact ◽  
Predictive Tool ◽  
Potential Biomarker

AbstractObjectivesIn December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19.MethodsIn this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy.ResultsThe data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954–10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097–0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111–0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746–0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients.ConclusionsWe designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

scholarly journals THU0070 DEFINING SYNOVIAL SIGNATURES IN THE RAT CIA MODEL: WHAT CAN WE LEARN ABOUT RA PROGRESSION?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 247.2-248
Author(s):  
D. Ruelas ◽  
R. LI ◽  
C. Franci ◽  
V. Lira ◽  
D. Lopez ◽  
...  
Keyword(s):  
Disease Progression ◽  
Synovial Tissue ◽  
Current Knowledge ◽  
Severe Disease ◽  
Unmet Need ◽  
Poor Response ◽  
Multiple Time ◽  
Combination Therapies ◽  
Course Of Disease ◽  
Time Point

Background:Patients showing inadequate or no response to current therapies represent a key unmet need in rheumatoid arthritis (RA). To address this, novel or combination therapies are of high clinical interest. Identification of novel therapeutic targets requires a greater understanding of the pathogenic molecular drivers in the RA synovium. However, our current knowledge of human molecular patterns that emerge as a result of disease progression is complicated by patient-to-patient heterogeneity and access to synovial tissue.Objectives:Here we use the current knowledge of human synovial heterogeneity to conduct a longitudinal study of global molecular responses in the rat collagen-induced arthritis (CIA) model to better understand synovial biology, improve the preclinical modeling of human disease, and discover novel targets for RA.Methods:A rat CIA model was performed as previously described.1RNA-Seq was performed on 56 knee synovial tissues collected at multiple time points throughout the course of disease. Differential gene expression was determined at each individual time point and longitudinally with disease progression. Published human synovial datasets were used to categorize these genes into myeloid, lymphoid, fibroid, and low inflammatory signatures.2Differentially expressed genes (DEGs) at each time point were compared to human synovial datasets of RA patients before and after treatment. In addition, we compared disease-driven genes in CIA to genes in RA patients that are unchanged following therapy to identify possible combination therapies.Results:Disease pathology in the rat CIA natural history study progressed as expected: significant decreases were seen in body weight, as well as increases in ankle diameter, paw weight, and histopathology scores of joints in collagen-injected vs noninjected rats. There were 1900 DEGs identified between diseased and naïve rats over the course of disease, representing disease-induced gene signatures (Fig. 1). Comparing these DEGs to reported human RA synovial signatures, both the lymphoid and myeloid signatures were found to be highly upregulated. Interestingly, there were no significant DEGs representing the human fibroid and low inflammatory synovial signatures identified in the CIA rat model. This suggests that the rat CIA model most closely models RA patients with an immune synovial phenotype. In addition, we examined the overlap between disease-driven genes in CIA and genes in RA patients that are unchanged following therapy to identify signaling pathways that may be of utility in combination therapy. Of genes that were upregulated in CIA, 94% of genes that mapped to extracellular matrix-receptor pathways remained unchanged in the synovial tissue of RA patients following tocilizumab treatment.Conclusion:Previous studies have shown that nearly 30% of treatment-naïve early RA patients exhibit a strong fibroid phenotype that correlates with less severe disease and a relatively poor response to disease-modifying anti-rheumatic drugs.3These data indicate that the synovial biology associated with such patients (fibroid or pauci-immune) is not well captured in CIA, the most common preclinical RA model. To assess potential new therapies targeting these patients, it will be necessary to develop alternative animal models with more intact fibroid signatures. In addition to these findings, we also characterized the global molecular changes that occur with disease progression in the CIA rat and made a comparison to RA patients on treatment, providing an overall understanding of disease-relevant pathways in the synovium that may point to possible combination therapies.References:[1]Trentham DE, et al.J Exp Med. 1977;146(3):857-868.[2]Dennis G Jr, et al.Arthritis Res Ther. 2014;16(2):R90.[3]Humby F, et al.Ann Rheum Dis. 2019;78(6):761-772.Disclosure of Interests:Debbie Ruelas Employee of: Gilead, Ruidong Li Employee of: Gilead, Christian Franci Employee of: Gilead, Victor Lira Employee of: Gilead, David Lopez Employee of: Gilead, Li Li Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, Julie A. Di Paolo Employee of: Gilead

MICROBIOMA: AMIGO O ENEMIGO EN PACIENTES CON COVID - 19

SCIENTIARVM ◽  
2015 ◽  
Vol 1 (1) ◽  
pp. 15-21
Author(s):  
Katherine Milagros Quispe Medina ◽  
◽  
Angel Sixto Mamani Ruelas ◽  
Brenda Jasmin Alvarez Vera ◽  
Yasmin Yessenia Silvestre Gutierrez ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gastrointestinal Tract ◽  
Molecular Biology ◽  
Gut Microbiome ◽  
Next Generation ◽  
Multiple Factors ◽  
Lung Microbiome ◽  
The Relationship ◽  
Generation Sequencing ◽  
Clinical Cases

The research of the microbiome concerning various diseases has grown in the last ten years due to the advances in molecular biology and next-generation sequencing, finding interactions with various pathologies. The new coronavirus 19 (SARS-COV 2) pandemic has aroused interest in the study of multiple factors that could influence in the development of symptoms mainly due to the interaction of the microbiome whether of the respiratory or gastrointestinal tract finally in the prognosis. Therefore, in this study, we focus on reviewing and analyzing the current bibliography of research and clinical cases about the relationship between the lung and gut microbiome and COVID-19, highlighting its effect on infected patients, aiming to contribute to this new line of research. Keywords: Microbiome, COVID-19, SARS-COV 2, gut microbiome, lung microbiome.

scholarly journals Research benefits of storing genitourinary samples: 16S rRNA sequencing to evaluate vaginal bacterial communities

2017 ◽  
Vol 28 (3) ◽  
pp. 315-317 ◽  
Author(s):  
Josef Wagner ◽  
Sarah Kerry-Barnard ◽  
ST Sadiq ◽  
Pippa Oakeshott
Keyword(s):  
16S Rrna ◽  
Bacterial Communities ◽  
16S Rrna Sequencing ◽  
Rrna Sequencing

scholarly journals Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1713 ◽  
Author(s):  
Timothy A. McKinsey ◽  
Thomas M. Vondriska ◽  
Yibin Wang
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Loss Of Function ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Non Coding Rnas ◽  
Epigenomic Regulation ◽  
Generation Sequencing ◽  
Epigenetic Processes

Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis of cardiac disease in adults. Investigations using genetic and pharmacologic gain- and loss-of-function approaches have interrogated the function of distinct epigenetic regulators, while the increased deployment of the suite of next-generation sequencing technologies have fundamentally altered our understanding of the genomic targets of these chromatin modifiers. Here, we review recent developments in basic and translational research that have provided tantalizing clues that may be used to unlock the therapeutic potential of the epigenome in heart failure. Additionally, we provide a hypothesis to explain how signal-induced crosstalk between histone tail modifications and long non-coding RNAs triggers chromatin architectural remodeling and culminates in cardiac hypertrophy and fibrosis.

scholarly journals Disease Progression in Frontotemporal Dementia and Alzheimer Disease: The Contribution of Staging Scales

2020 ◽  
pp. 089198872094423
Author(s):  
Thaís Bento Lima-Silva ◽  
Eneida Mioshi ◽  
Valéria Santoro Bahia ◽  
Mário Amore Cecchini ◽  
Luciana Cassimiro ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Disease Progression ◽  
Frontotemporal Dementia ◽  
Rating Scale ◽  
Severe Disease ◽  
Primary Progressive Aphasia ◽  
Behavioral Changes ◽  
Clinical Dementia Rating ◽  
Dementia Rating Scale ◽  
Disease Stages

Introduction: There is a shortage of validated instruments to estimate disease progression in frontotemporal dementia (FTD). Objectives: To evaluate the ability of the FTD Rating Scale (FTD-FRS) to detect functional and behavioral changes in patients diagnosed with the behavioral variant of FTD (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD) after 12 months of the initial evaluation, compared to the Clinical Dementia Rating scale−frontotemporal lobar degeneration (CDR-FTLD) and the original Clinical Dementia Rating scale (CDR). Methods: The sample consisted of 70 individuals, aged 40+ years, with at least 2 years of schooling, 31 with the diagnosis of bvFTD, 12 with PPA (8 with semantic variant and 4 with non-fluent variant), and 27 with AD. The FTD-FRS, the CDR, and the 2 additional CDR-FTLD items were completed by a clinician, based on the information provided by the caregiver with frequent contact with the patient. The Addenbrooke Cognitive Examination-Revised was completed by patients. After 12 months, the same protocol was applied. Results: The FTD-FRS, CDR-FTLD, and CDR detected significant decline after 12 months in the 3 clinical groups (exception: FTD-FRS for PPA). The CDR was less sensitive to severe disease stages. Conclusions: The FTD-FRS and the CDR-FTLD are especially useful tools for dementia staging in AD and in the FTD spectrum.

scholarly journals Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Li ◽  
Nianzhi Ning ◽  
Bo Li ◽  
Deyan Luo ◽  
Enqiang Qin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Disease Progression ◽  
Metabolic Disorders ◽  
Acid Metabolism ◽  
Severe Disease ◽  
Essential Amino Acids ◽  
Dynamic Changes ◽  
Metabolic Recovery ◽  
Global Pandemic ◽  
Highly Correlated

COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.

scholarly journals Epidemiological impact of SARS-CoV-2 vaccination: mathematical modeling analyses

2020 ◽  
Author(s):  
Monia Makhoul ◽  
Houssein H. Ayoub ◽  
Hiam Chemaitelly ◽  
Shaheen Seedat ◽  
Ghina R Mumtaz ◽  
...  
Keyword(s):  
Decision Making ◽  
Disease Progression ◽  
Vaccine Development ◽  
Severe Disease ◽  
Herd Immunity ◽  
Social Contact ◽  
Population Level ◽  
Contact Rate ◽  
Disease Case ◽  
Vaccine Impact

AbstractBackgroundSeveral SARS-CoV-2 vaccine candidates are currently in the pipeline. This study aims to inform SARS-CoV-2 vaccine development, licensure, decision-making, and implementation by determining key preferred vaccine product characteristics and associated population-level impact.MethodsVaccination impact was assessed at various efficacies using an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression, with application for China.ResultsA prophylactic vaccine with efficacy against acquisition (VES) of ≥70% is needed to eliminate this infection. A vaccine with VES <70% will still have a major impact, and may control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, or alternatively if supplemented with a moderate social-distancing intervention (<20% reduction in contact rate), or complemented with herd immunity. Vaccination is cost-effective. For a vaccine with VES of 50%, number of vaccinations needed to avert one infection is only 2.4, one severe disease case is 25.5, one critical disease case is 33.2, and one death is 65.1. Gains in effectiveness are achieved by initially prioritizing those ≥60 years. Probability of a major outbreak is virtually zero with a vaccine with VES ≥70%, regardless of number of virus introductions. Yet, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact.ConclusionsEven a partially-efficacious vaccine can offer a fundamental solution to control SARS-CoV-2 infection and at high cost-effectiveness. In addition to the primary endpoint on infection acquisition, developers should assess natural history and disease progression outcomes and/or proxy biomarkers, since such secondary endpoints may prove critical in licensure, decision-making, and vaccine impact.

scholarly journals Monitoring disease activity noninvasively in the mdx model of Duchenne muscular dystrophy

2018 ◽  
Vol 115 (30) ◽  
pp. 7741-7746 ◽  
Author(s):  
Antonio Filareto ◽  
Katie Maguire-Nguyen ◽  
Qiang Gan ◽  
Garazi Aldanondo ◽  
Léo Machado ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Premature Death ◽  
Response To Therapy ◽  
Luciferase Reporter ◽  
Luciferase Expression ◽  
Muscle Degeneration ◽  
Reporter Strain ◽  
Novel Treatments

Duchenne muscular dystrophy (DMD) is a rare, muscle degenerative disease resulting from the absence of the dystrophin protein. DMD is characterized by progressive loss of muscle fibers, muscle weakness, and eventually loss of ambulation and premature death. Currently, there is no cure for DMD and improved methods of disease monitoring are crucial for the development of novel treatments. In this study, we describe a new method of assessing disease progression noninvasively in the mdx model of DMD. The reporter mice, which we term the dystrophic Degeneration Reporter strains, contain an inducible CRE-responsive luciferase reporter active in mature myofibers. In these mice, muscle degeneration is reflected in changes in the level of luciferase expression, which can be monitored using noninvasive, bioluminescence imaging. We monitored the natural history and disease progression in these dystrophic report mice and found that decreases in luciferase signals directly correlated with muscle degeneration. We further demonstrated that this reporter strain, as well as a previously reported Regeneration Reporter strain, successfully reveals the effectiveness of a gene therapy treatment following systemic administration of a recombinant adeno-associated virus-6 (rAAV-6) encoding a microdystrophin construct. Our data demonstrate the value of these noninvasive imaging modalities for monitoring disease progression and response to therapy in mouse models of muscular dystrophy.

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