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2.
Annu Rev Microbiol ; 76: 435-460, 2022 09 08.
Article in English | MEDLINE | ID: covidwho-2246760

ABSTRACT

Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.


Subject(s)
Disease , Gastrointestinal Microbiome , Therapeutics , Fecal Microbiota Transplantation , Humans , Probiotics/therapeutic use , Therapeutics/trends
3.
Copenhagen; World Health Organization. Regional Office for Europe; 2022. (WHO/EURO:2022-6108-45873-66068).
in English | WHOIRIS | ID: gwh-362637
4.
Cytokine ; 148: 155684, 2021 12.
Article in English | MEDLINE | ID: covidwho-1355591

ABSTRACT

The classification of interleukin-6 (IL-6) as a pro-inflammatory cytokine undervalues the biological impact of this cytokine in health and disease. With broad activities affecting the immune system, tissue homeostasis and metabolic processes, IL-6 displays complex biology. The significance of these involvements has become increasingly important in clinical settings where IL-6 is identified as a prominent target for therapy. Here, clinical experience with IL-6 antagonists emphasises the need to understand the context-dependent properties of IL-6 within an inflammatory environment and the anticipated or unexpected consequences of IL-6 blockade. In this review, we will describe the immunobiology of IL-6 and explore the gamut of IL-6 bioactivity affecting the clinical response to biological drugs targeting this cytokine pathway.


Subject(s)
Disease , Health , Interleukin-6/metabolism , Animals , Humans , Pain Perception , Signal Transduction
5.
Rev. bras. saúde ocup ; 47: ecov3, 2022.
Article in Portuguese | WHO COVID, LILACS (Americas) | ID: covidwho-1865371

ABSTRACT

O rápido desenrolar da pandemia de COVID-19 no ano de 2020 estimulou pesquisadores a rapidamente tentar entender o comportamento do vírus e da doença e a propor soluções de modo a tentar contê-la o quanto antes. Uma das questões fundamentais a serem respondidas é se o vírus também pode ser transmitido por aerossóis, posto que a forma de transmissão determina a velocidade e as condições em que a doença consegue se espalhar pela população. A busca por essa resposta reacendeu uma discussão de décadas sobre a relevância dessa via de transmissão, bem como sobre os diferentes conceitos e medidas de controle e prevenção atualmente usados para bloquear a transmissão de doenças infecciosas no âmbito da atenção à saúde humana. Este ensaio tem o objetivo de contribuir para esse debate e, mais especificamente, subsidiar programas para a proteção de trabalhadores e pacientes em serviços de saúde referentes à COVID-19 e a outras doenças infecciosas


The rapid advance of the COVID-19 pandemic in the year 2020 has spurred researchers to try to understand quickly the behavior of the virus and the disease, and to propose solutions in order to attempt containing it as soon as possible. One of the core questions to be answered is whether the virus can also be transmitted by aerosols, since the mode of transmission determines the speed and conditions under which the disease can spread through the population. The search for this answer has rekindled a decades-long discussion about the relevance of this transmission route, as well as the different concepts and control and prevention measures currently used to block the transmission of infectious diseases in human healthcare. This essay aims to contribute to this debate and, more specifically, to support programs for the protection of workers and patients in healthcare services regarding COVID-19 and other infectious diseases


Subject(s)
Research Personnel , Viruses , Disease , Aerosols , Delivery of Health Care , Disease Prevention , Protective Factors , COVID-19 , Health Services
6.
Int J Mol Sci ; 23(1)2021 Dec 23.
Article in English | MEDLINE | ID: covidwho-1855640

ABSTRACT

Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.


Subject(s)
Cell Polarity/physiology , Macrophages/pathology , Animals , Cytokines/metabolism , Disease , Humans , Macrophages/metabolism
7.
Int J Mol Sci ; 23(3)2022 Feb 03.
Article in English | MEDLINE | ID: covidwho-1674668

ABSTRACT

CRISPR/Cas is a prokaryotic self-defense system, widely known for its use as a gene-editing tool. Because of their high specificity to detect DNA and RNA sequences, different CRISPR systems have been adapted for nucleic acid detection. CRISPR detection technologies differ highly among them, since they are based on four of the six major subtypes of CRISPR systems. In just 5 years, the CRISPR diagnostic field has rapidly expanded, growing from a set of specific molecular biology discoveries to multiple FDA-authorized COVID-19 tests and the establishment of several companies. CRISPR-based detection methods are coupled with pre-existing preamplification and readout technologies, achieving sensitivity and reproducibility comparable to the current gold standard nucleic acid detection methods. Moreover, they are very versatile, can be easily implemented to detect emerging pathogens and new clinically relevant mutations, and offer multiplexing capability. The advantages of the CRISPR-based diagnostic approaches are a short sample-to-answer time and no requirement of laboratory settings; they are also much more affordable than current nucleic acid detection procedures. In this review, we summarize the applications and development trends of the CRISPR/Cas13 system in the identification of particular pathogens and mutations and discuss the challenges and future prospects of CRISPR-based diagnostic platforms in biomedicine.


Subject(s)
Diagnostic Techniques and Procedures/trends , Disease/genetics , Gene Editing/methods , COVID-19/genetics , CRISPR-Cas Systems/genetics , DNA/genetics , Diagnosis , Humans , Reproducibility of Results , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
9.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1569333

ABSTRACT

Regional quarantine policies, in which a portion of a population surrounding infections is locked down, are an important tool to contain disease. However, jurisdictional governments-such as cities, counties, states, and countries-act with minimal coordination across borders. We show that a regional quarantine policy's effectiveness depends on whether 1) the network of interactions satisfies a growth balance condition, 2) infections have a short delay in detection, and 3) the government has control over and knowledge of the necessary parts of the network (no leakage of behaviors). As these conditions generally fail to be satisfied, especially when interactions cross borders, we show that substantial improvements are possible if governments are outward looking and proactive: triggering quarantines in reaction to neighbors' infection rates, in some cases even before infections are detected internally. We also show that even a few lax governments-those that wait for nontrivial internal infection rates before quarantining-impose substantial costs on the whole system. Our results illustrate the importance of understanding contagion across policy borders and offer a starting point in designing proactive policies for decentralized jurisdictions.


Subject(s)
Disease , Policy , Quarantine , COVID-19/prevention & control , Humans , Models, Theoretical , Pandemics/prevention & control , Quarantine/methods , SARS-CoV-2
10.
Science ; 374(6569): eabj1541, 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1526448

ABSTRACT

Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.


Subject(s)
Blood Proteins/genetics , Disease/genetics , Genome, Human , Genomics , Proteins/genetics , Proteome , Aging , Alternative Splicing , Blood Proteins/metabolism , COVID-19/genetics , Connective Tissue Diseases/genetics , Disease/etiology , Drug Development , Female , Gallstones/genetics , Genetic Association Studies , Genetic Variation , Genome-Wide Association Study , Humans , Internet , Male , Phenotype , Proteins/metabolism , Quantitative Trait Loci , Sex Characteristics
11.
Genome ; 64(4): v-vii, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1523064
12.
PLoS One ; 16(10): e0258182, 2021.
Article in English | MEDLINE | ID: covidwho-1496505

ABSTRACT

BACKGROUND: Healthcare spending in the emergency department (ED) setting has received intense focus from policymakers in the United States (U.S.). Relatively few studies have systematically evaluated ED spending over time or disaggregated ED spending by policy-relevant groups, including health condition, age, sex, and payer to inform these discussions. This study's objective is to estimate ED spending trends in the U.S. from 2006 to 2016, by age, sex, payer, and across 154 health conditions and assess ED spending per visit over time. METHODS AND FINDINGS: This observational study utilized the National Emergency Department Sample, a nationally representative sample of hospital-based ED visits in the U.S. to measure healthcare spending for ED care. All spending estimates were adjusted for inflation and presented in 2016 U.S. Dollars. Overall ED spending was $79.2 billion (CI, $79.2 billion-$79.2 billion) in 2006 and grew to $136.6 billion (CI, $136.6 billion-$136.6 billion) in 2016, representing a population-adjusted annualized rate of change of 4.4% (CI, 4.4%-4.5%) as compared to total healthcare spending (1.4% [CI, 1.4%-1.4%]) during that same ten-year period. The percentage of U.S. health spending attributable to the ED has increased from 3.9% (CI, 3.9%-3.9%) in 2006 to 5.0% (CI, 5.0%-5.0%) in 2016. Nearly equal parts of ED spending in 2016 was paid by private payers (49.3% [CI, 49.3%-49.3%]) and public payers (46.9% [CI, 46.9%-46.9%]), with the remainder attributable to out-of-pocket spending (3.9% [CI, 3.9%-3.9%]). In terms of key groups, the majority of ED spending was allocated among females (versus males) and treat-and-release patients (versus those hospitalized); those between age 20-44 accounted for a plurality of ED spending. Road injuries, falls, and urinary diseases witnessed the highest levels of ED spending, accounting for 14.1% (CI, 13.1%-15.1%) of total ED spending in 2016. ED spending per visit also increased over time from $660.0 (CI, $655.1-$665.2) in 2006 to $943.2 (CI, $934.3-$951.6) in 2016, or at an annualized rate of 3.4% (CI, 3.3%-3.4%). CONCLUSIONS: Though ED spending accounts for a relatively small portion of total health system spending in the U.S., ED spending is sizable and growing. Understanding which diseases are driving this spending is helpful for informing value-based reforms that can impact overall health care costs.


Subject(s)
Disease/economics , Emergency Service, Hospital/economics , Health Care Costs , Health Care Costs/trends , Humans , Time Factors , United States
13.
Cells ; 10(9)2021 09 13.
Article in English | MEDLINE | ID: covidwho-1468387

ABSTRACT

Neutrophils are key cells of the innate immune system. It is now understood that this leukocyte population is diverse in both the basal composition and functional plasticity. Underlying this plasticity is a post-translational framework for rapidly achieving early activation states, but also a transcriptional capacity that is becoming increasingly recognized by immunologists. Growing interest in the contribution of neutrophils to health and disease has resulted in more efforts to describe their transcriptional activity. Whilst initial efforts focused predominantly on understanding the existing biology, investigations with advanced methods such as single cell RNA sequencing to understand interactions of the entire immune system are revealing higher flexibility in neutrophil transcription than previously thought possible and multiple transition states. It is now apparent that neutrophils utilise many forms of RNA in the regulation of their function. This review collates current knowledge on the nuclei structure and gene expression activity of human neutrophils across homeostasis and disease, before highlighting knowledge gaps that are research priority areas.


Subject(s)
Disease/etiology , Gene Expression Regulation , Immunity, Innate/immunology , Neutrophils/immunology , Neutrophils/pathology , Transcriptome , Animals , Homeostasis , Humans , Neutrophils/metabolism , Signal Transduction
14.
Life Sci ; 284: 119908, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1370630

ABSTRACT

Genetic disorders and congenital abnormalities are present in 2-5% of births all over the world and can cause up to 50% of all early childhood deaths. The establishment of sophisticated and controlled techniques for customizing DNA manipulation is significant for the therapeutic role in such disorders and further research on them. One such technique is CRISPR that is significant towards optimizing genome editing and therapies, metabolic fluxes as well as artificial genetic systems. CRISPR-Cas9 is a molecular appliance that is applied in the areas of genetic and protein engineering. The CRISPR-CAS system is an integral element of prokaryotic adaptive immunity that allows prokaryotic cells to identify and kill any foreign DNA. The Gene editing property of CRISPR finds various applications like diagnostics and therapeutics in cancer, neurodegenerative disorders, genetic diseases, blindness, etc. This review discusses applications of CRISPR as a therapeutic in various disorders including several genetic diseases (including sickle cell anemia, blindness, thalassemia, cystic fibrosis, hereditary tyrosinemia type I, duchenne muscular dystrophy, mitochondrial disorders), Cancer, Huntington's disease and viral infections (like HIV, COVID, etc.) along with the prospects concerning them. CRISPR-based therapy is also being researched and defined for COVID-19. The related mechanism of CRISPR has been discussed alongside highlighting challenges involved in therapeutic applications of CRISPR.


Subject(s)
CRISPR-Cas Systems/genetics , Animals , COVID-19/therapy , COVID-19/virology , Clinical Trials as Topic , Disease/genetics , Gene Editing , Humans , SARS-CoV-2/physiology
15.
Cells ; 10(7)2021 07 13.
Article in English | MEDLINE | ID: covidwho-1323128

ABSTRACT

Programmed cell death is a conserved evolutionary process of cell suicide that is central to the development and integrity of eukaryotic organisms [...].


Subject(s)
Apoptosis , Disease , Health , Animals , Apoptosis/drug effects , Biological Products/pharmacology , Caenorhabditis elegans/drug effects , Caspase 2/metabolism , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Neoplasms/pathology , Nerve Degeneration/pathology
16.
Arthritis Rheumatol ; 73(7): 1347-1348, 2021 07.
Article in English | MEDLINE | ID: covidwho-1298462
17.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Article in English | MEDLINE | ID: covidwho-1287854

ABSTRACT

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.


Subject(s)
Gastrointestinal Microbiome , Health Status Disparities , Disease , Health , Humans , Mental Health , Publications
18.
Int Immunopharmacol ; 101(Pt B): 107598, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1240398

ABSTRACT

MCP-1 (Monocyte chemoattractant protein-1), also known as Chemokine (CC-motif) ligand 2 (CCL2), is from family of CC chemokines. It has a vital role in the process of inflammation, where it attracts or enhances the expression of other inflammatory factors/cells. It leads to the advancement of many disorders by this main mechanism of migration and infiltration of inflammatory cells like monocytes/macrophages and other cytokines at the site of inflammation. MCP-1 has been inculpated in the pathogenesis of numerous disease conditions either directly or indirectly like novel corona virus, cancers, neuroinflammatory diseases, rheumatoid arthritis, cardiovascular diseases. The elevated MCP-1 level has been observed in COVID-19 patients and proven to be a biomarker associated with the extremity of disease along with IP-10. This review will focus on involvement and role of MCP-1 in various pathological conditions.


Subject(s)
Chemokine CCL2/immunology , Animals , Biomarkers , Chemokine CCL2/genetics , Chemokine CCL2/physiology , Chemotaxis , Disease , Humans , Monocytes/physiology , Oxidative Stress
20.
Int J Mol Sci ; 22(5)2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1134169

ABSTRACT

Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.


Subject(s)
Blood Chemical Analysis/methods , Disease , Fibrinolysin/analysis , Fibrinolysin/metabolism , Animals , Antifibrinolytic Agents/blood , Fibrin/analysis , Fibrin/chemistry , Fibrinolytic Agents/blood , Humans , Plasminogen/analysis , Plasminogen/chemistry , Plasminogen/metabolism
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