Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Chest ; 157(4): 776-778, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32252931
2.
Clin Infect Dis ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32198501

RESUMO

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Current method of detection involves qPCR-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We here aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2 including IgA, IgM and IgG response were examined by using an ELISA based assay on the recombinant viral nucleocapsid protein. Total 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but had typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection were 5 days (IQR 3-6), while IgG was detected on 14 days (IQR 10-18) after symptom onset, with a positive rate of 85.4%, 92.7% and 77.9% respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR method after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combined IgM ELISA assay with PCR for each patient compare with a single qPCR test (51.9%). CONCLUSIONS: Humoral response to SARS-CoV-2 can aid to the diagnosis of COVID-19, including subclinical cases.

3.
Front Immunol ; 11: 91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117248

RESUMO

Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research have elucidated host mechanisms that contribute to the bacterial clearance where an indispensable role of immune cells has been established. However, the role of respiratory epithelial cells in bacterial clearance has garnered limited attention due to their weak inflammatory or phagocytic ability compared to immune cells such as macrophages and neutrophils. These studies often underappreciate the fact that epithelial cells are the most abundant cells in the lung, not only serving as building blocks but also providing immune protection throughout the lung. Epithelial cells function either independently to eradicate the pathogen or communicate with immune cells to orchestrate pathogen clearance. The epithelial cells have multiple mechanisms that include mucus production, antimicrobial peptide production, muco-ciliary clearance, and phagocytosis, all of which contribute to their direct antibacterial function. Secretion of cytokines to recruit immune cells and potentiate their antimicrobial activities is a pathway by which the epithelium contributes to bacterial clearance. Successful pathogens outsmart epithelial resistance and find a way to replicate in sufficient numbers to establish infections in the airway or lung epithelial surfaces. In this mini-review, we discuss evidences that establish important roles for epithelial host defense against invading respiratory bacterial pathogens and demonstrate how pathogens outsmart these epithelial immune mechanisms to successfully establish infection. Finally, we discuss briefly how to boost epithelial immunity to improve outcomes in bacterial lung infections.

5.
Environ Technol ; : 1-10, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32066333

RESUMO

There has been an increase in the discovery and usage of sensors for the detection of chemical compounds in the field of analytical chemistry since the last several years. This has led to progressive research in nanotechnology for developing efficient nanomaterials for bio-chemical sensing applications. Thereby, a deft synthesis of silver nanoparticles (Ag NPs) under microwave irradiation was achieved using sodium alginate as a reducing and capping agent in a fast and cost-effective approach. As per the X-ray diffraction analysis, the average particle size of Ag NPs was found to be 10 nm. X-ray photoelectron spectroscpopy analysis showed characteristic peaks at binding energies of 368.10 and 374.11 eV indicating the formation of Ag NPs. The synthesized Ag NPs-alginate composite was further used to develop a paper-based sensor for the detection of H2O2. Detection of H2O2 is based on the discolouration of the Ag NPs-alginate composite modified paper sensor as a function of H2O2 concentration. The analysis of the decoloured paper strips was done by a smartphone camera and an RGB Colour Reader application (app) to measure colour intensity. The sensing characteristics were found in the range of 0.1-10 mM. The colour analysis revealed piecewise linear relationship of intensity of RGB to H2O2 concentration in the range of 0.1-1.5 and 2-10 mM with R2 values of 0.97 and 0.9778, respectively. Owing to the high sensitivity, selectivity, and cost-effectiveness, the developed paper sensor can be a potential tool for real-time analysis of H2O2.

7.
Mol Med ; 26(1): 16, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013888

RESUMO

The Editors-in-Chief would like to alert readers that this article (Sitapara et al. 2014) is part of an investigation being conducted by the journal following the conclusions of an institutional enquiry at the University of Liverpool with respect to the quantitative mass spectrometry-generated results regarding acetylated and redox-modified HMGB1.

9.
Int J Dermatol ; 59(4): 428-433, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31898819

RESUMO

BACKGROUND: Adult acne has been classified into two major subtypes: "persistent acne" and "late onset acne". A surrogate marker of hyperandrogenism (HA) in adult female acne is the presence of clinical signs of HA and biochemical hyperandrogenemia. We compared the clinical and hormonal profiles of the two acne subtypes and evaluated the likely source of androgen excess - ovarian or adrenal. METHODS: Female acne patients 25 years of age and older were evaluated for clinical HA. Hormonal assessment included total testosterone (TT), sex hormone binding globulin (SHBG), free androgen index (FAI), anti-Mullerian hormone (AMH), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), and prolactin. DHEAS and 17-OHP represented adrenal androgens and AMH indicated ovarian reserve. RESULTS: Of 120 cases, clinical HA was seen in 71.67% while biochemical hyperandrogenemia was detected in only 18.33% of patients. Though late onset was more common in adult acne patients (56.6%), the persistent acne subgroup (43.33%) had a younger age at onset, a past history of adolescent acne (51.92%), truncal predilection (44.23%), polycystic ovary syndrome (PCOS) (44.23%), significant presence of irregular menses (40.38%) and hirsutism (57.69%), and increased TT (13.46%), 17-OHP (76.92%), AMH (44.23%), and increased LH/FSH (15.38%) ratio. PCOS was seen more in the persistent acne patients with clinical HA and increased 17-OHP levels. CONCLUSION: Persistent acne patients had marked clinical HA, PCOS, and hormonal abnormalities necessitating an endocrinological evaluation. As a corollary, this subgroup would benefit from antiandrogen therapy.

10.
J Dermatolog Treat ; : 1-4, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868042

RESUMO

Background: Adult female acne (AFA) occurs beyond 25 years of age and can present either as isolated acne or with hyperandrogenic signs.Methods: 120 females aged ≥ 25 years were evaluated for acne, hirsutism and androgenetic alopecia. Hormonal assessment included total testosterone (TT), sex hormone binding globulin (SHBG), free androgen index (FAI), Anti Mullerian Hormone (AMH), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH) and prolactin. Polycystic ovary syndrome (PCOS) was diagnosed using Rotterdam's criteria.Results: The mean GAGS score was 15.57 ± 4.04.71.66% females had acne with hyperandrogenic signs (hirsutism, 55.81%; hyperseborrhoea, 65.12%; irregular menses, 36.05%) and 18.33% had increased androgen levels. The group with hyperandrogenic signs had longer duration of disease, truncal acne, significant adolescent acne history, stress, inappropriate diet and PCOS compared to the isolated acne group. The mean androgen levels were higher in the former but the difference was statistically insignificant.Conclusions: Adult female acne can be associated with hyperandrogenic features though routine hormonal tests may not reveal an underlying abnormality except PCOS. End-organ hypersensitivity is the most plausible explanation and thus justifies the use of antiandrogens in its management.

13.
J Vis Exp ; (150)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31498326

RESUMO

Chitinases are the enzymes that cleave chitin. Even in the absence of chitin, mammalians have significant amounts of chitinases present in the body including at baseline. The precise role of chitinase is not known, however it was believed to play important role in digestion and host defense against chitin-containing food and pathogens, respectively. Recent work, including ours, has shown an important role of chitinase and chitinase-like proteins in host immunity and allergic diseases. Importantly, chitinase activities serve as important biomarkers of disease severity in a wide-range of diseases including type 2 inflammatory diseases such as asthma and pulmonary fibrosis. Similarly, patients with genetic disorders like Gaucher disease have significantly elevated chitinase levels, which not only correlate with disease severity but also serve as a reliable biomarker for therapeutic effectiveness. The protocol outlined here describes a simple, quick, and straightforward way to measure chitinase activity in BAL or serum samples of mice and can be widely adapted to human subjects and other model organisms due to the highly conserved nature of the enzymes.

15.
Nature ; 573(7772): 69-74, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31435009

RESUMO

Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.

16.
J Clin Med ; 8(9)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461884

RESUMO

Raman spectroscopy (RS) is widely used as a non-invasive technique in screening for the diagnosis of oral cancer. The potential of this optical technique for several biomedical applications has been proved. This work studies the efficacy of RS in detecting oral cancer using sub-site-wise differentiation. A total of 80 samples (44 tumor and 36 normal) were cryopreserved from three different sub-sites: The tongue, the buccal mucosa, and the gingiva of the oral mucosa during surgery. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were used with principal component analysis (PCA) to classify the samples and the classifications were validated by leave-one-out-cross-validation (LOOCV) and k-fold cross-validation methods. The normal and tumor tissues were differentiated under the PCA-LDA model with an accuracy of 81.25% (sensitivity: 77.27%, specificity: 86.11%). The PCA-QDA classifier model differentiated these tissues with an accuracy of 87.5% (sensitivity: 90.90%, specificity: 83.33%). The PCA-QDA classifier model outperformed the PCA-LDA-based classifier. The model studies revealed that protein, amino acid, and beta-carotene variations are the main biomolecular difference markers for detecting oral cancer.

17.
J Saudi Heart Assoc ; 31(4): 151-160, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31296977

RESUMO

Objectives: The primary aim was to investigate the efficacy and safety of dual antiplatelet therapy (DAPT) using ticagrelor (T-DAPT) versus clopidogrel (C-DAPT) in a real-world ST-elevation myocardial infarction (STEMI) population. Methods: We retrospectively analyzed 655 consecutive patients having primary percutaneous coronary intervention (PCI) for STEMI at Liverpool Hospital, Sydney, Australia (from January 2013 to April 2016). Medical and procedural therapies were at clinician discretion. Patient data were retrieved from hospital records and primary clinicians. Results: T-DAPT (65%) was used more frequently, and in patients with lower mean CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) score, than C-DAPT (24.6 vs. 32.2; p < 0.0001, respectively). All-cause mortality was 9.0% at 2.7 years follow-up, with fewer deaths for T-DAPT (4.5% vs. 17.2%; p < 0.0001). T-DAPT incurred less BARC (Bleeding Academic Research Consortium) 3-5 major bleeding (5.0% vs. 12.4%; p < 0.0001). Multivariate regression showed that C-DAPT, GRACE (Global Registry of Acute Cardiac Events) score, and renal insufficiency were independently associated with mortality. Intra-aortic balloon pump (IABP) and GRACE score independently predicted BARC 3-5 bleeding. Early DAPT discontinuation (1.7%) and ticagrelor intolerance (7.6%) was rare. Switching DAPT regimen was infrequent (21.7%) and mostly attributed to clinician preference (73.2%). Independent determinants of C-DAPT selection were older age, diabetes, prior PCI, IABP, and higher CRUSADE score. Conclusion: Ticagrelor was preferred in low bleeding risk patients, which may have contributed to less BARC 3-5 bleeding and lower mortality for T-DAPT. Thus, bleeding mitigation is a clinical priority when selecting DAPT for PCI-treated STEMI patients. Continuation of initial DAPT regimen was typical, but early switching from clopidogrel to ticagrelor shows willingness to optimize DAPT. Patients with very low CRUSADE scores (<21.5) may be appropriate for switching to a potent P2Y12 inhibitor.

18.
Infect Immun ; 87(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31262980

RESUMO

Pneumonia due to Gram-negative bacteria is associated with high mortality. Acinetobacter baumannii is a Gram-negative bacterium that is associated with hospital-acquired and ventilator-associated pneumonia. Bacteria have been described to release outer membrane vesicles (OMVs) that are capable of mediating systemic inflammation. The mechanism by which A. baumannii OMVs mediate inflammation is not fully defined. We sought to investigate the roles that Toll-like receptors (TLRs) play in A. baumannii OMV-mediated pulmonary inflammation. We isolated OMVs from A. baumannii cultures and intranasally introduced the OMVs into mice. Intranasal introduction of A. baumannii OMVs mediated pulmonary inflammation, which is associated with neutrophil recruitment and weight loss. In addition, A. baumannii OMVs increased the release of several chemokines and cytokines in the mouse lungs. The proinflammatory responses were partially inhibited in TLR2- and TLR4-deficient mice compared to those of wild-type mice. This study highlights the important roles of TLRs in A. baumannii OMV-induced pulmonary inflammation in vivo.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Pneumonia/microbiologia , Vesículas Secretórias/fisiologia , Receptor 2 Toll-Like/fisiologia , Receptor 4 Toll-Like/fisiologia , Infecções por Acinetobacter/metabolismo , Animais , Proteínas da Membrana Bacteriana Externa , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos
19.
Thorax ; 74(9): 865-874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331947

RESUMO

BACKGROUND: Uncontrolled lung inflammation is one of the prominent features in the pathogenesis of lung infection- associated acute lung injury (ALI). Microvesicles (MVs) are extracellular nanovesicles that are generated via direct membrane budding. METHODS: Bronchoalveolar lavage fluid (BALF) samples were collected from mice with or without intratracheal lipopolysaccharide (LPS) instillation. BALF MVs were characterised and MV-containing microRNA (miRNA) profiles were assessed and confirmed. Secretion and function of MV-containing miR-223/142 (MV-miR-223/142) were analysed in vivo. RESULTS: In BALF, MVs are mainly derived from macrophages in response to LPS. After intratracheal instillation (i.t.) of LPS or Klebsiella pneumoniae, MV-containing miR-223/142 are dramatically induced in both BALF and serum. Mechanistically, miRNA 3' end uridylation mediates the packing of miR-223/142 into MVs. To investigate the functional role of MV-miR-223/142, we loaded miR-223/142 mimics into unstimulated MVs and delivered them into the murine lungs via i.t. The miR-223/142 mimics-enriched MVs selectively targeted lung macrophages and suppressed the inflammatory lung responses that were triggered by LPS or K. pneumoniae. Mechanistically, miR-223 and miR-142 synergistically suppress Nlrp3 inflammasome activation in macrophages via inhibition of Nlrp3 and Asc, respectively. CONCLUSIONS: In the pathogenesis of lung macrophage-mediated inflammatory responses, MV-miR-223/142 secretion is robustly enhanced and detectable in BALF and serum. Furthermore, restoration of intracellular miR-223/142 via vesicle-mediated delivery suppresses macrophage activation and lung inflammation via inhibition of Nlrp3 inflammasome activation.

20.
BMC Infect Dis ; 19(1): 539, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217003

RESUMO

BACKGROUND: There is a pressing need for systematic approaches for monitoring how much TB treatment is ongoing in the private sector in India: both to cast light on the true scale of the problem, and to help monitor the progress of interventions currently being planned to address this problem. METHODS: We used commercially available data on the sales of rifampicin-containing drugs in the private sector, adjusted for data coverage and indication of use. We examined temporal, statewise trends in volumes (patient-months) of TB treatment from 2013 to 2016. We additionally analysed the proportion of drugs that were sold in combination packaging (designed to simplify TB treatment), or as loose pills. RESULTS: Drug sales suggest a steady trend of TB treatment dispensed by the private sector, from 18.4 million patient-months (95% CI 17.3-20.5) in 2013 to 16.8 patient-months (95% CI 15.5-19.0) in 2016. Overall, seven of 29 states in India accounted for more than 70% of national-level TB treatment volumes, including Uttar Pradesh, Maharashtra and Bihar. The overwhelming majority of TB treatment was dispensed not as loose pills, but in combination packaging with other TB drugs, accounting for over 96% of private sector TB treatment in 2017. CONCLUSIONS: Our findings suggest consistent levels of TB treatment in the private sector over the past 4 years, while highlighting specific states that should be prioritized for intervention. Drug sales data can be helpful for monitoring a system as large, disorganised and opaque as India's private sector.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Setor de Assistência à Saúde/tendências , Tuberculose/tratamento farmacológico , Setor de Assistência à Saúde/economia , Humanos , Índia , Rifampina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA