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1.
Genes Immun ; 24(5): 263-269, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37573430

ABSTRACT

Nebulized hypertonic saline (3-7%) is commonly used to increase mucociliary clearance in patients with chronic airway disease and/or virus infections. However, altered salt concentrations may contribute to inflammatory responses. The aim of this study was to investigate whether 500 mM NaCl (3%) triggers inflammation in human macrophages and identify the molecular mechanisms involved. NaCl-induced pyroptosis, IL-1ß, IL-18 and ASC speck release were measured in primary human monocyte-derived macrophages. Treatment with the recombinant IL-1 receptor antagonist anakinra or the NLRP3 inhibitor MCC950 did not affect NaCl-mediated inflammasome assembly. Knock-down of NLRP1 expression, but not of NLRP3 and NLRC4, reduced NaCl-induced pyroptosis, pro-inflammatory cytokine and ASC speck release from human THP-1-derived macrophages. Data from this study suggest that 3% NaCl-induced inflammatory responses in human macrophages depend on NLRP1 and inflammasome assembly. Targeting inflammation in addition to inhalation with hypertonic saline may benefit patients with inflammatory airway disease.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Sodium Chloride/metabolism , Inflammation/metabolism , Macrophages/metabolism , Interleukin-1beta , NLR Proteins/metabolism
2.
Radiology ; 303(3): 675-681, 2022 06.
Article in English | MEDLINE | ID: mdl-35289662

ABSTRACT

Background Although spirometry is an important marker in the management of pulmonary exacerbations in cystic fibrosis (CF), it is a forced maneuver and can generate aerosol. Therefore, it may be difficult to perform in some individuals. Dynamic chest radiography (DCR) provides real-time information regarding pulmonary dynamics alongside fluoroscopic-style thoracic imaging. Purpose To assess the effect of pulmonary exacerbation treatment by using both spirometry and DCR and assess the clinical utility of DCR in participants with CF experiencing pulmonary exacerbations. Materials and Methods In this prospective, observational, single-center pilot study, spirometry and DCR were performed before and after treatment of pulmonary exacerbations in participants with CF between December 2019 and August 2020. Spirometry measured forced expiratory volume in 1 second (FEV1) and forced vital capacity. DCR helped to measure projected lung area (PLA), hemidiaphragm midpoint position, and speed during tidal and deep breathing. Data were analyzed by using the paired t test or Wilcoxon signed-rank test. Correlation was assessed by using the Spearman rank correlation coefficient. Results Twenty participants with CF (mean age, 25 years ± 7 [standard deviation]; 14 women) were evaluated. Spirometry showed that percentage predicted FEV1 improved from a median of 44% (interquartile range [IQR], 17%) before treatment to 55% (IQR, 16%) after treatment (P = .004). DCR showed improvement in median deep breathing excursion for left and right hemidiaphragms (from 18 [IQR, 11] to 25 [IQR, 16] mm [P = .03] and from 13 [IQR, 6] to 19 [IQR, 14] mm [P = .03], respectively) and in median expiratory speed following deep breathing for left and right hemidiaphragms (from 7 [IQR, 2] to 11 [IQR, 5] mm/sec [P = .004] and 6 [IQR, 3] to 9 [IQR, 6] mm/sec [P = .004], respectively). PLA rate of change during full expiration and change in PLA during tidal breathing improved (from a mean of 42 cm2/sec ± 16 to 56 cm2/sec ± 24 [P = .03] and from a mean of 29 cm2 ± 14 to 35 cm2 ± 10 [P = .03], respectively). Conclusion Dynamic chest radiography demonstrated improvement in diaphragm speed and range of chest wall movement during respiration aftere treatment for pulmonary exacerbations in cystic fibrosis and showed potential as a tool to investigate the effect of pulmonary exacerbations on lung mechanics. Clinical trials registration no. NCT01234567 Published under a CC BY 4.0 license. Online supplemental material is available for this article.


Subject(s)
Cystic Fibrosis , Adult , Cystic Fibrosis/diagnostic imaging , Female , Forced Expiratory Volume , Humans , Lung , Pilot Projects , Polyesters , Prospective Studies , Radiography
3.
BMC Vet Res ; 18(1): 121, 2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35354473

ABSTRACT

BACKGROUND: Canine idiopathic pulmonary fibrosis (CIPF) is a chronic, progressive, interstitial fibrosing lung disease, manifesting as cough, exercise intolerance and ultimately, dyspnea and respiratory failure. It mainly affects West Highland white terriers (WHWTs), lacks curable treatment and has a poor prognosis. Aspiration of gastroesophageal refluxate may play a role in the development of CIPF. In the first part of this study, we completed label-free quantitative proteomic analysis of bronchoalveolar lavage fluid (BALF) from CIPF and healthy WHWTs. In the second part, we evaluated potential protein markers of reflux aspiration from canine gastric juice and vomitus and whether these were present in BALF from the two groups. RESULTS: Across all BALF samples, 417 proteins were identified, and of these, 265 proteins were identified by two or more unique tryptic peptides. Using the 265 high confidence assignments, the quantitative proteome profiles were very similar in the two cohorts, but they could be readily resolved by principal component analysis on the basis of differential protein expression. Of the proteins that were differentially abundant in the two groups, several (including inflammatory and fibrotic markers) were elevated in CIPF, and a smaller, more diverse group of proteins were diminished in CIPF. No protein markers indicative of reflux aspiration were identified. CONCLUSIONS: Label-free proteomics allowed discrimination between CIPF and healthy WHWTs, consistent with fibrotic process but did not provide clear evidence for gastrointestinal aspiration. The measurement of proteins may provide a proteomics signature of CIPF that could be used to evaluate treatment options.


Subject(s)
Dog Diseases , Gastroesophageal Reflux , Idiopathic Pulmonary Fibrosis , Animals , Bronchoalveolar Lavage Fluid , Dog Diseases/diagnosis , Dog Diseases/metabolism , Dogs , Gastroesophageal Reflux/veterinary , Idiopathic Pulmonary Fibrosis/veterinary , Proteomics
4.
J Infect Dis ; 224(8): 1305-1315, 2021 10 28.
Article in English | MEDLINE | ID: mdl-34161567

ABSTRACT

BACKGROUND: A notable feature of coronavirus disease 2019 (COVID-19) is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. METHODS: We investigated the presence of cross-reactive anti-SARS-CoV-2 IgG antibodies to spike 1 (S1), S1-receptor-binding domain (S1-RBD), and nucleocapsid protein (NP) by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralization assay, in prepandemic sera collected from children (n = 50) and adults (n = 45), and compared with serum samples from convalescent COVID-19 patients (n = 16). RESULTS: A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD, and NP antigens, and the anti-S1 and anti-S1-RBD antibody levels correlated with anti-HCoV-HKU1 and anti-HCoV-OC43 S1 antibody titers in prepandemic samples (P < .001). There were marked increases of anti-HCoV-HKU1 and - OC43 S1 (but not anti-NL63 and -229E S1-RBD) antibody titers in serum samples from convalescent COVID-19 patients (P < .001), indicating an activation of cross-reactive immunological memory to ß-coronavirus spike. CONCLUSIONS: We demonstrated cross-reactive anti-SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/virology , Child , Child, Preschool , Convalescence , Coronavirus 229E, Human/immunology , Coronavirus Envelope Proteins/immunology , Coronavirus OC43, Human/immunology , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Female , HEK293 Cells , Humans , Immunoglobulin G/immunology , Immunologic Memory , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Young Adult
5.
J Infect Dis ; 222(5): 807-819, 2020 08 04.
Article in English | MEDLINE | ID: mdl-31740938

ABSTRACT

BACKGROUND: Increasing evidence supports a critical role of CD8+ T-cell immunity against influenza. Activation of mucosal CD8+ T cells, particularly tissue-resident memory T (TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1 (M1) is a well-conserved internal protein. METHODS: We studied the capacity of modified vaccinia Ankara (MVA)-vectored vaccine expressing nucleoprotein (NP) and M1 (MVA-NP+M1) to activate M1-specific CD8+ T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue from children and adults. RESULTS: After MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated a marked interferon γ-secreting T-cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158-66 peptide-specific CD8+ T cells in tonsillar mononuclear cells of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T-cell phenotype. On recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and proinflammatory cytokines, leading to target cell killing. CONCLUSIONS: MVA-NP+M1 elicits a substantial M1-specific T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue, demonstrating its strong capacity to expand memory T-cell pool exhibiting effector memory T-cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Influenza A Virus, H3N2 Subtype/immunology , Nucleocapsid Proteins/immunology , Viral Matrix Proteins/immunology , Viral Vaccines/immunology , Adenoids/cytology , Adenoids/immunology , Adolescent , Adult , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/physiology , Cell Degranulation , Cell Proliferation , Cells, Cultured , Child , Child, Preschool , Granzymes/metabolism , Humans , Immunity, Cellular , Immunologic Memory , Interferon-gamma/metabolism , Lymphocyte Activation , Lysosomal-Associated Membrane Protein 1/metabolism , Nasopharynx , Palatine Tonsil/cytology , Palatine Tonsil/immunology , Respiratory Mucosa/immunology , Vaccines, DNA , Young Adult
6.
Clin Immunol ; 215: 108448, 2020 06.
Article in English | MEDLINE | ID: mdl-32353634

ABSTRACT

The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2 , Azithromycin/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/genetics , Cytokines/immunology , Disease Management , Gene Expression Regulation , Humans , Hydroxychloroquine/therapeutic use , Immune Evasion/genetics , Immune Evasion/immunology , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics , Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/immunology
7.
Clin Infect Dis ; 68(5): 731-737, 2019 02 15.
Article in English | MEDLINE | ID: mdl-29982302

ABSTRACT

BACKGROUND: Infection with nontuberculous mycobacteria (NTM) is of growing clinical concern in people with cystic fibrosis (CF). The epidemiology of infection in children and young people remains poorly understood. Our goal was to investigate the epidemiology of NTM infection in the pediatric age group using data from the UK CF Registry. METHODS: Data from 2010-2015 for individuals aged <16 years (23200 observations from 5333 unique individuals) were obtained. Univariate analysis of unique individuals comparing all key clinical factors and health outcomes to NTM status was performed. The significant factors that were identified were used to generate a multivariate logistic regression model that, following step-wise removal, generated a final parsimonious model. RESULTS: The prevalence of individuals with a NTM-positive respiratory culture increased every year from 2010 (45 [1.3%]) to 2015 (156 [3.8%]). Allergic bronchopulmonary aspergillosis (odds ratio [OR], 2.66; P = 5.0 × 10-8), age (OR, 1.08; P = 3.4 × 10-10), and intermittent Pseudomonas aeruginosa infection (OR, 1.51; P = .004) were significantly associated with NTM infection. CONCLUSIONS: NTM infection is of increasing prevalence in the UK pediatric CF population. This study highlights the urgent need for work to establish effective treatment and prevention strategies for NTM infection in young people with CF.


Subject(s)
Cystic Fibrosis/complications , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium Infections, Nontuberculous/epidemiology , Adolescent , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Humans , Infant , Mycobacterium Infections, Nontuberculous/drug therapy , Odds Ratio , Registries , Risk Factors , United Kingdom
8.
Hum Mol Genet ; 26(22): 4315-4326, 2017 11 15.
Article in English | MEDLINE | ID: mdl-28973288

ABSTRACT

Congenital hypopituitarism (CH) is characterized by the deficiency of one or more pituitary hormones and can present alone or in association with complex disorders. Congenital hyperinsulinism (CHI) is a disorder of unregulated insulin secretion despite hypoglycaemia that can occur in isolation or as part of a wider syndrome. Molecular diagnosis is unknown in many cases of CH and CHI. The underlying genetic etiology causing the complex phenotype of CH and CHI is unknown. In this study, we identified a de novo heterozygous mutation in the developmental transcription factor, forkhead box A2, FOXA2 (c.505T>C, p.S169P) in a child with CHI and CH with craniofacial dysmorphic features, choroidal coloboma and endoderm-derived organ malformations in liver, lung and gastrointestinal tract by whole exome sequencing. The mutation is at a highly conserved residue within the DNA binding domain. We demonstrated strong expression of Foxa2 mRNA in the developing hypothalamus, pituitary, pancreas, lungs and oesophagus of mouse embryos using in situ hybridization. Expression profiling on human embryos by immunohistochemistry showed strong expression of hFOXA2 in the neural tube, third ventricle, diencephalon and pancreas. Transient transfection of HEK293T cells with Wt (Wild type) hFOXA2 or mutant hFOXA2 showed an impairment in transcriptional reporter activity by the mutant hFOXA2. Further analyses using western blot assays showed that the FOXA2 p.(S169P) variant is pathogenic resulting in lower expression levels when compared with Wt hFOXA2. Our results show, for the first time, the causative role of FOXA2 in a complex congenital syndrome with hypopituitarism, hyperinsulinism and endoderm-derived organ abnormalities.


Subject(s)
Craniofacial Abnormalities/genetics , Hepatocyte Nuclear Factor 3-beta/genetics , Hepatocyte Nuclear Factor 3-beta/metabolism , Hyperinsulinism/genetics , Hypopituitarism/genetics , Adult , Animals , Child, Preschool , Craniofacial Abnormalities/metabolism , Female , HEK293 Cells , Humans , Hyperinsulinism/metabolism , Hypopituitarism/metabolism , Male , Mice , Mutation , Pregnancy , Transcription Factors/genetics , Transfection
9.
J Virol ; 92(11)2018 06 01.
Article in English | MEDLINE | ID: mdl-29563292

ABSTRACT

There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. The antibody response is critical for vaccine-induced protection, and T follicular helper cells (TFH) are considered important for mediating the antibody response. Most data supporting the role for TFH in the antibody response are from animal studies, and direct evidence from humans is limited, apart from the presence of TFH-like cells in blood. We studied the activation and induction of TFH and their role in the anti-influenza antibody response induced by a live-attenuated influenza vaccine (LAIV) in human nasopharynx-associated lymphoid tissue (NALT). TFH activation in adenotonsillar tissues was analyzed by flow cytometry, and anti-hemagglutinin (anti-HA) antibodies were examined following LAIV stimulation of tonsillar mononuclear cells (MNC). Induction of antigen-specific TFH by LAIV was studied by flow cytometry analysis of induced TFH and CD154 expression. LAIV induced TFH proliferation, which correlated with anti-HA antibody production, and TFH were shown to be critical for the antibody response. Induction of TFH from naive T cells by LAIV was shown in newly induced TFH expressing BCL6 and CD21, followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced TFH was demonstrated by expression of the antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced TFH differentiation was inhibited by BCL6, interleukin-21 (IL-21), ICOS, and CD40 signaling blocking, and that diminished anti-HA antibody production. In conclusion, we demonstrated the induction by LAIV of antigen-specific TFH in human NALT that provide critical support for the anti-influenza antibody response. Promoting antigen-specific TFH in NALT by use of intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans.IMPORTANCE Airway infections, such as influenza, are common in humans. Intranasal vaccination has been considered a biologically relevant and effective way of immunization against airway infection. The vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest that one type of T cells, TFH, are important for the antibody response. However, data on whether TFH-mediated help for antibody production operates in humans are limited due to the lack of access to human immune tissue containing TFH In this study, we demonstrate the induction of TFH in human immune tissue, providing critical support for the anti-influenza antibody response, by use of an intranasal influenza vaccine. Our findings provide direct evidence that TFH play a critical role in vaccine-induced immunity in humans and suggest a novel strategy for promoting such cells by use of intranasal vaccines against respiratory infections.


Subject(s)
Antibodies, Viral/immunology , Hemagglutinins, Viral/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , Lymphocyte Activation/immunology , T-Lymphocytes, Helper-Inducer/immunology , Vaccines, Attenuated/immunology , Administration, Intranasal , Adolescent , Adult , Antibody Formation/immunology , B-Lymphocytes/immunology , CD40 Antigens/antagonists & inhibitors , CD40 Ligand/biosynthesis , Cells, Cultured , Child , Child, Preschool , Humans , Immunity, Mucosal/immunology , Inducible T-Cell Co-Stimulator Protein/antagonists & inhibitors , Influenza, Human/prevention & control , Influenza, Human/virology , Interleukins/antagonists & inhibitors , Mucous Membrane/immunology , Nasopharynx/immunology , Proto-Oncogene Proteins c-bcl-6/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-6/biosynthesis , Receptors, Complement 3d/biosynthesis , Young Adult
10.
Qual Health Res ; 29(6): 846-856, 2019 05.
Article in English | MEDLINE | ID: mdl-30371143

ABSTRACT

The benefits of improved treatments for cystic fibrosis (CF) depend on optimal adherence, which remains problematic, particularly to aerosol therapy. In this study, we explored the process of adhering to aerosol therapy from the perspective of both adolescents with CF and their parents. Interviews were conducted individually with six adolescents and six parents, informed by accurate adherence data from an electronically chipped, aerosol device. Interview transcripts from audio-recordings were analyzed using grounded theory method (GTM). Major themes revealed differences in perspective between parent and adolescent, with this relationship mediating the cognitive and emotional processes that play a significant role in adherence behavior. These processes are further influenced by interactions with the aerosol therapy treatment regimen, device characteristics, and the context in which adherence is taking place. Parents and adolescents have different views of treatment and how to manage it. Both need to be addressed if optimal adherence is to be achieved.


Subject(s)
Cystic Fibrosis/drug therapy , Cystic Fibrosis/psychology , Medication Adherence/psychology , Parent-Child Relations , Parents/psychology , Patients/psychology , Administration, Inhalation , Adolescent , Child , Female , Health Behavior , Humans , Interviews as Topic , Male , Nebulizers and Vaporizers , United Kingdom
11.
Cytokine ; 110: 267-271, 2018 10.
Article in English | MEDLINE | ID: mdl-29396045

ABSTRACT

Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection. Following infection with A2 strain RSV, the highest RSV N gene expression was observed at day 4 after challenge with virus. In contrast, two peaks of elevated BAFF expression at days 2 and 7 were observed. CXCL13 was significantly elevated at days 1, 2 and 7. CXCL12, CCL19 and CCL21 were expressed within lung tissue from control and RSV challenged animals but no significant difference in expression was found. Immunofluorescence showed BAFF to be present throughout the tissue however CXCL13 expression was localized to cell rich areas probably constituting lymphoid aggregates. Our results define the kinetics of B cell chemoattractant and growth factor expression during RSV infection and indicate an important role for these cytokines in the airway response to RSV infection.


Subject(s)
B-Cell Activating Factor/metabolism , Chemokine CXCL13/metabolism , Chemokines/metabolism , Respiratory Syncytial Virus Infections/metabolism , Animals , B-Lymphocytes/metabolism , B-Lymphocytes/virology , Disease Models, Animal , Epithelial Cells/metabolism , Lung/metabolism , Lung/virology , Mice , Mice, Inbred BALB C , Respiratory Syncytial Virus Infections/virology
12.
Respir Res ; 19(1): 15, 2018 01 22.
Article in English | MEDLINE | ID: mdl-29357863

ABSTRACT

BACKGROUND: Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure. This study aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airways disease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor 4 (TLR-4). METHODS: The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatory infiltrate and cytokine responses were compared between wildtype mice and mice not expressing TLR-4. RESULTS: The presence of LPS administered with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independent of TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS administered alone. Treatment with AMP induced macrophage recruitment independent of TLR-4 expression. CONCLUSIONS: These findings suggest AMP-LPS as a stronger stimulus for allergic inflammation in the airways then LPS alone.


Subject(s)
Inflammation Mediators/metabolism , Lipopolysaccharides/toxicity , Lung/metabolism , Particulate Matter/toxicity , Toll-Like Receptor 4/biosynthesis , Airway Resistance/physiology , Animals , Inflammation/chemically induced , Inflammation/metabolism , Lung/drug effects , Mice , Mice, Inbred C3H , Mice, Knockout
13.
Appl Opt ; 57(25): 7377, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30182958

ABSTRACT

This erratum is submitted to correct information regarding Fig. 8 of Appl. Opt.57, E142 (2018)APOPAI0003-693510.1364/AO.57.00E142.

14.
Appl Opt ; 57(22): E142-E146, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-30117912

ABSTRACT

The characterization of an amplified piezoelectric actuator (APA) as a new axial scanning method for multiple-reference optical coherence tomography (MR-OCT) is described. MR-OCT is a compact optical imaging device based on a recirculating reference-arm-scanning optical delay using a partial mirror that can enhance the imaging depth range by more than 10 times the reference mirror's scanning amplitude. The scanning amplitude of the used APA was varied between 30 µm and 250 µm, depending on the scanning frequency of between 0.8 kHz and 1.2 kHz. A silver-coated miniature mirror was attached to the APA via ultraviolet-cured optical adhesive, and the light source was a super-luminescent diode with 1310 nm center wavelength and 56 nm bandwidth. The sensitivity was measured with and without the partial mirror in the reference delay line as a function of scan speed, frequency, and range, therefore providing results for MR-OCT and TD-OCT modes. It was found that the APA provides more than twice the mechanical scanning range compared to other opto-mechanic actuators, but results indicate degradation of signal-to-noise ratio and sensitivity at larger imaging depths. In conjunction with MR-OCT, the scan range of maximum 200 µm can be enhanced up to 1-1.5 mm by using a reduced amount of orders of reflections, which could be of interest to increase sensitivity in the future.

15.
Int J Food Sci Nutr ; 69(1): 108-116, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28610456

ABSTRACT

Consumers make dietary choices based on information they have. This study examines consumer choice of food products considering the healthfulness of multiple nutrients. We focus on high levels of sugars because higher levels of intake are associated with adverse health and nutritional outcomes. We find an important association of sugar consumption with the healthfulness of a diet based on saturated fat intake and cholesterol intake. Consumers making healthier choices in one nutrient are not making healthier choices on other nutrients. Our results suggest that individuals who were making better dietary choices based on saturated fats were consuming more sugars. This could indicate challenges with the existing standard nutrition label as an information tool towards making healthful choices on multiple nutrients.


Subject(s)
Cholesterol, Dietary/administration & dosage , Consumer Behavior , Dietary Fats/administration & dosage , Dietary Sugars/administration & dosage , Adult , Aged , Choice Behavior , Diet , Ethnicity , Female , Food Labeling , Food Preferences , Health Behavior , Humans , Male , Middle Aged , Models, Theoretical , Nutrition Policy , Nutrition Surveys , Socioeconomic Factors
16.
J Med Virol ; 88(1): 58-63, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26100591

ABSTRACT

Human rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterize the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. Nasopharyngeal aspirates were collected from 630 children <5 years with ARI. Clinical diagnosis and disease severity were also recorded. Samples were analyzed by multiplex PCR for 18 viral and atypical bacterial pathogens; RV positive samples underwent partial sequencing to determine species and type. RV was the fourth commonest pathogen accounting for 18.7% of pathogens detected. RV was commonly detected in children with bronchiolitis, pneumonia, and asthma/episodic viral wheeze (EVW). Species and type were assigned in 112 cases (73% RV-A; 27% RV-C; 0% RV-B). Generally, there were no differences in clinical or demographic characteristics between those infected with RV-A and RV-C. However, in children with asthma/EVW, RV-C was detected relatively more frequently than RV-A (23% vs. 5%; P = 0.04). Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV-A and C species were detected. However, RV-C was more frequently found in children with asthma/EVW than RV-A.


Subject(s)
Picornaviridae Infections/epidemiology , Picornaviridae Infections/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Rhinovirus/classification , Rhinovirus/isolation & purification , Bacteria/classification , Bacteria/isolation & purification , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Bacterial Infections/pathology , Brazil/epidemiology , Child, Preschool , Cross-Sectional Studies , Female , Hospitals , Humans , Infant , Infant, Newborn , Male , Multiplex Polymerase Chain Reaction , Nasopharynx/virology , Picornaviridae Infections/pathology , Prevalence , Prospective Studies , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/pathology , Severity of Illness Index
17.
AIDS Care ; 28(4): 416-22, 2016.
Article in English | MEDLINE | ID: mdl-26513366

ABSTRACT

Poor mental health functioning among persons living with HIV (PLHIV) has gained considerable attention particularly in low-income countries that disproportionately carry the global HIV/AIDS burden. Fewer studies, however, have examined the relationship between poverty indicators and mental health among PHLIV in India. Based on this cross-sectional study of 196 HIV-seropositive adults who received medical services at Shalom AIDS Project in Delhi, India, structural equation modeling and mediation analysis were employed to estimate the associations between poverty indices (household asset index, food security, unemployment, water treatment, sanitation), HIV-health factors (illness in the past 3 months, co-morbid medical conditions), and psychological distress. In the final model, ownership of fewer household assets was associated with higher levels of food insecurity, which in turn was associated with higher psychological distress. Also, the household asset index, food insecurity, and unemployment had a larger effect on psychological distress than new opportunistic infections. These findings build on increasing evidence that support concerted efforts to design, evaluate, and refine HIV mental health interventions that are mainstreamed with livelihood programming in high poverty regions in India.


Subject(s)
Food Supply , HIV Infections/psychology , Mental Health/statistics & numerical data , Poverty/psychology , Stress, Psychological/psychology , AIDS-Related Opportunistic Infections/epidemiology , Adult , Comorbidity , Cross-Sectional Studies , Family Characteristics , Female , HIV Infections/economics , HIV Infections/epidemiology , Humans , India/epidemiology , Male , Poverty/statistics & numerical data , Regression Analysis , Socioeconomic Factors , Stress, Psychological/epidemiology , Unemployment
18.
Lasers Surg Med ; 48(1): 77-82, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26612183

ABSTRACT

BACKGROUND AND OBJECTIVES: Monitoring the curing kinetics of light-activated resin is a key area of research. These resins are used in restorative applications and particularly in dental applications. They can undergo volumetric shrinkage due to poor control of the depth dependent curing process, modulated by the intensity and duration of the curing light source. This often results in the formation of marginal gaps, causing pain and damage to the restoration site. In this study, we demonstrate the capabilities of a correlation method applied using a multiple references optical coherence tomography (MR-OCT) architecture to monitor the curing of the resin. STUDY DESIGN/MATERIALS AND METHODS: A MR-OCT system is used in this study to monitor the curing of the resin. The system operates at the center wavelength of 1310 nm with an A-scan rate of 1200 A-scans per second. The axial and lateral resolution of the system is ∼13 µm and ∼27 µm. The method to determine the intensity correlation between adjacent B-frames is based on the Pearson correlation coefficient for a region of interest. Calculating the correlation coefficient for multiple B-frames related to the first B-frame at regular spaced time points, shows for a noncured resin a reduction of the correlation coefficient over time due to Brownian motion. The time constant of the reduction of the correlation value is a measure for the progress of the polymerization during LED light irradiation of the resin. The proposed approach is potentially a low-cost, powerful and unique optical imaging modality for measuring the curing behavior of dental resin and other resins, coatings, and adhesives in medical and industrial applications. RESULTS: To demonstrate the proposed method to monitor the curing process, a light-activated resin composite from GRADIA DIRECT ANTERIOR (GC Corporation, Japan) is studied. The curing time of resin was measured and monitored as a function of depth. The correlation coefficient method is highly sensitive to Brownian motion. The process of curing results in a change in intensity as measured by the MR-OCT signal and hence can be monitored using this method. CONCLUSIONS: These results show that MR-OCT has the potential to measure the curing time and monitor the curing process as a function of depth. Moreover, MR-OCT as a product has potential to be compact, low-cost and to fit into a smartphone. Using such a device for monitoring the curing of the resin will be suitable for dentists in stationary and mobile clinical settings.


Subject(s)
Composite Resins/pharmacokinetics , Curing Lights, Dental , Tomography, Optical Coherence
19.
Collegian ; 22(4): 433-8, 2015.
Article in English | MEDLINE | ID: mdl-26775530

ABSTRACT

Mental Health First Aid training is designed to equip people with the skills to help others who may be developing mental health problems or experiencing mental health crises. This training has consistently been shown to increase: (1) the recognition of mental health problems; (2) the extent to which course trainees' beliefs about treatment align with those of mental health professionals; (3) their intentions to help others; and (4) their confidence in their abilities to assist others. This paper presents a discussion of the potential role of Mental Health First Aid training in undergraduate mental health nursing education. Three databases (CINAHL, Medline, and PsycINFO) were searched to identify literature on Mental Health First Aid. Although Mental Health First Aid training has strong benefits, this first responder level of education is insufficient for nurses, from whom people expect to receive professional care. It is recommended that: (1) Mental Health First Aid training be made a prerequisite of preregistration nurse education, (2) registered nurses make a larger contribution to addressing the mental health needs of Australians requiring care, and (3) current registered nurses take responsibility for ensuring that they can provided basic mental health care, including undertaking training to rectify gaps in their knowledge.


Subject(s)
Education, Nursing/organization & administration , Psychiatric Nursing/education , Australia , Humans
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