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1.
BMJ Open ; 14(7): e082275, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39053955

ABSTRACT

INTRODUCTION: Global surveillance of physical activity (PA) of children and adolescents with questionnaires is limited by the use of instruments developed in high-income countries (HICs) lacking sociocultural adaptation, especially in low- and middle-income countries (LMICs); under-representation of some PA domains; and omission of active play, an important source of PA. Addressing these limitations would help improve international comparisons, and facilitate the cross-fertilisation of ideas to promote PA. We aim to develop and assess the reliability and validity of the app-based Global Adolescent and Child Physical Activity Questionnaire (GAC-PAQ) among 8-17 years old in 14 LMICs and HICs representing all continents; and generate the 'first available data' on active play in most participating countries. METHODS AND ANALYSIS: Our study involves eight stages: (1) systematic review of psychometric properties of existing PA questionnaires for children and adolescents; (2) development of the GAC-PAQ (first version); (3) content validity assessment with global experts; (4) cognitive interviews with children/adolescents and parents in all 14 countries; (5) development of a revised GAC-PAQ; (6) development and adaptation of the questionnaire app (application); (7) pilot-test of the app-based GAC-PAQ; and, (8) main study with a stratified, sex-balanced and urban/rural-balanced sample of 500 children/adolescents and one of their parents/guardians per country. Participants will complete the GAC-PAQ twice to assess 1-week test-retest reliability and wear an ActiGraph wGT3X-BT accelerometer for 9 days to test concurrent validity. To assess convergent validity, subsamples (50 adolescents/country) will simultaneously complete the PA module from existing international surveys. ETHICS AND DISSEMINATION: Approvals from research ethics boards and relevant organisations will be obtained in all participating countries. We anticipate that the GAC-PAQ will facilitate global surveillance of PA in children/adolescents. Our project includes a robust knowledge translation strategy sensitive to social determinants of health to inform inclusive surveillance and PA interventions globally.


Subject(s)
Exercise , Psychometrics , Humans , Adolescent , Child , Surveys and Questionnaires/standards , Reproducibility of Results , Male , Female , Developing Countries , Research Design
2.
J Int AIDS Soc ; 27 Suppl 2: e26269, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38988042

ABSTRACT

INTRODUCTION: Effective HIV prevention programme coverage is necessary to achieve Nigeria's goal of ending the epidemic by 2030. Recent evidence highlights gaps in service coverage and utilization across the country. The Effective Programme Coverage framework is a Programme Science tool to optimize a programme's population-level impact by examining gaps in programme coverage using data generated through programme-embedded research and learning. We apply the framework using Integrated Biological and Behavioural Surveillance Survey (IBBSS) data from Nigeria to examine coverage of four prevention interventions-condoms, HIV testing, and needle and syringe programmes (NSP)-among four key population groups-female sex workers (FSW), men who have sex with men (MSM), people who inject drugs (PWID) and transgender people. METHODS: Data from Nigeria's 2020 IBBSS, implemented in 12 states, were analysed to examine HIV prevention programme coverage among key populations. For each key population group and prevention intervention of interest, weighted IBBSS data were used to retrospectively generate coverage cascades that identify and quantify coverage gaps. Required coverage targets were informed by targets articulated in Nigeria's National HIV/AIDS Strategic Framework or, in their absence, by guidelines from policy normative bodies. Availability-, outreach- and utilization coverage proxy indicators were defined using variables from IBBSS data collection tools. Sankey diagrams are presented to visualize pathways followed by participants between coverage cascade steps. RESULTS: Required coverage targets were missed for HIV testing and NSP among all key population groups. Condom availability coverage surpassed required coverage targets among FSW and MSM, while utilization coverage only among FSW exceeded the 90% required coverage target. Outreach coverage was low for all key population groups, falling below all required coverage targets. CONCLUSIONS: Our findings identify critical gaps in HIV prevention programme coverage for key populations in Nigeria and demonstrate non-linear movement across coverage cascades, signalling the need for innovative solutions to optimize coverage of prevention services. Programme-embedded research is required to better understand how key population groups in Nigeria access and use different HIV prevention services so that programmes, policies and resource allocation decisions can be optimized to achieve effective programme coverage and population-level impact.


Subject(s)
HIV Infections , Sex Workers , Humans , Nigeria/epidemiology , HIV Infections/prevention & control , HIV Infections/epidemiology , Male , Female , Sex Workers/statistics & numerical data , Adult , Young Adult , Transgender Persons/statistics & numerical data , Adolescent , HIV Testing/statistics & numerical data , HIV Testing/methods , Condoms/statistics & numerical data , Middle Aged , Surveys and Questionnaires , Homosexuality, Male/statistics & numerical data , Needle-Exchange Programs/statistics & numerical data
3.
Int J Behav Nutr Phys Act ; 21(1): 79, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039543

ABSTRACT

BACKGROUND: Early childhood educators play a critical role in promoting physical activity and reducing sedentary time in childcare centres. However, early childhood educators receive limited specialised pre- and in-service learning opportunities relating to these behaviours and may lack the capacity to effectively engage children in healthy movement behaviours. This study aimed to examine the efficacy of an e-Learning course on increasing early childhood educators' physical activity and sedentary behaviour-related capacities. METHODS: A two-group parallel randomized controlled trial was conducted with early childhood educators in Canada (Mage = 41.78, 97% female). Participants randomized to the intervention group were asked to complete a physical activity and sedentary behaviour e-Learning course within a 4-week period. Participants randomized to the waitlist control condition were assigned to a waitlist to receive the intervention after the testing period. Participants reported on their self-efficacy, knowledge, intentions, and perceived behavioural control relating to physical activity and sedentary behaviours at baseline, post-intervention, and 3 months follow-up. Linear mixed effects models were estimated to determine difference in changes in outcomes from baseline to post-intervention, and follow-up. RESULTS: A total of 209 early childhood educators participated in the study (intervention n = 98; control n = 111). The TEACH e-Learning course was found to be efficacious at improving all of the examined outcomes, with standardized effect sizes ranging from d = 0.58 to d = 0.65 for self-efficacy outcomes, d = 0.66 to d = 1.20 for knowledge outcomes, d = 0.50 to d = 0.65 for intention outcomes, and d = 0.33 to d = 0.69 for perceived behavioural control outcomes post-intervention. The intervention effects were sustained at follow-up for all outcomes apart from perceived behavioural control to limit screen time. Additionally, the magnitude of the effect for knowledge outcomes decreased at follow-up, with standardized effect sizes ranging from d = 0.49 to d = 0.67. CONCLUSIONS: The e-Learning course was highly successful at improving early childhood educators' capacity pertaining to physical activity and sedentary behaviours. Providing training content through e-Learning may be an efficacious approach to providing continual professional learning opportunities relating to physical activity and sedentary time to early childhood educators on a large scale.


Subject(s)
Exercise , Health Knowledge, Attitudes, Practice , Intention , Sedentary Behavior , Self Efficacy , Humans , Female , Male , Adult , Canada , Child, Preschool , Health Promotion/methods , Health Behavior
4.
Intern Med J ; 54(7): 1208-1213, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39013777

ABSTRACT

The assessment of gas exchange under varying ambient and metabolic conditions is an important and fundamental investigation of respiratory function. The gold standard is an arterial blood gas (ABG) sample; however, the procedure is not universally performed by medical scientists, is not standardised, and is typically taught by a subjective Halsted 'see one, do one' approach. The Australian and New Zealand Society of Respiratory Science recognised the need to create an ABG position statement that includes the required pre-requisite education, an evidence-based procedure and the minimum reporting and competency assessment requirements. This position statement aims to minimise patient discomfort, to improve puncture success rate and reduce the potential for sample handling and analysis error. Importantly, this position statement translates to all relevant health professionals, including medical officers, scientists, nursing staff and allied health.


Subject(s)
Blood Gas Analysis , Societies, Medical , Humans , New Zealand , Australia , Blood Gas Analysis/methods , Blood Gas Analysis/standards , Societies, Medical/standards , Pulmonary Medicine/standards
5.
NPJ Vaccines ; 9(1): 126, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997302

ABSTRACT

Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

6.
J Int AIDS Soc ; 27 Suppl 3: e26309, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39030857

ABSTRACT

INTRODUCTION: Since the onset of the Russian invasion on 24 February 2022, the health system in Ukraine has been placed under tremendous pressure, with damage to critical infrastructure, large losses of human resources, restricted mobility and significant supply chain interruptions. Based on a longstanding partnership between the Ukrainian Institute for Social Research after Oleksandr Yaremenko (UISR after O. Yaremenko) and the Institute for Global Public Health at the University of Manitoba, we explore the impact of the full-scale war on non-governmental organizations (NGOs, including charitable organizations) providing services for key population groups in Ukraine. METHODS: We conducted in-depth qualitative interviews with key representatives from NGOs working with key population groups (i.e., people living with HIV, sex workers, men who have sex with men, people who inject drugs and transgender people) throughout Ukraine. Members of the UISR after O. Yaremenko research team recruited participants from organizations working at national, regional and local levels. The research team members conducted 26 interviews (22 with women and four with men) between 15 May and 7 June 2023. Interviews were conducted virtually in Ukrainian and interpretively analysed to draw out key themes. RESULTS: Applying Roels et al.'s notion of "first responders", our findings explore how the full-scale war personally and organizationally impacted workers at Ukrainian NGOs. Despite the impacts to participants' physical and mental health, frontline workers continued to support HIV prevention and treatment while also responding to the need for humanitarian aid among their clients and the wider community. Furthermore, despite inadequate pay and compensation for their work, frontline workers assumed additional responsibilities, thereby exceeding their normal workload during the extraordinary conditions of war. CONCLUSIONS: NGOs play a vital role as responders, adapting their services to meet the emergent needs of communities during structural shocks, such as war. There is an urgent need to support NGOs with adequate resources for key population service delivery and to increase support for their important role in humanitarian aid.


Subject(s)
HIV Infections , Organizations , Qualitative Research , Humans , Ukraine/epidemiology , HIV Infections/prevention & control , HIV Infections/psychology , HIV Infections/drug therapy , Male , Female , Interviews as Topic , Adult , Armed Conflicts
7.
Res Sq ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38947034

ABSTRACT

Objective and design: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. Treatment: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 mg/kg/day, i.p.) at day 3 post-infection. Methods: Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7. Results: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in FPR2/3 -/- animals. In mice treated with LXA4 (50mg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of anti-inflammatory T cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. Conclusions: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.

8.
JMIR Public Health Surveill ; 10: e54313, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896842

ABSTRACT

BACKGROUND: Assessing HIV outcomes in key population prevention programs is a crucial component of the program cycle, as it facilitates improved planning and monitoring of anticipated results. The Joint United Nations Programme on HIV and AIDS recommends using simple, rapid methods to routinely measure granular and differentiated program outcomes for key populations. Following a program science approach, Partners for Health and Development in Africa, in partnership with the Nairobi County Government and the University of Manitoba, aims to conduct an outcome assessment using a novel, expanded polling booth survey (ePBS) method with female sex workers and men who have sex with men in Nairobi County, Kenya. OBJECTIVE: This study aims to (1) estimate the incidence and prevalence of HIV; (2) assess biomedical, behavioral, and structural outcomes; and (3) understand barriers contributing to gaps in access and use of available prevention and treatment services among female sex workers and men who have sex with men in Nairobi. METHODS: The novel ePBS approach employs complementary data collection methods, expanding upon the traditional polling booth survey (PBS) method by incorporating additional quantitative, qualitative, and biological data collection components and an improved sampling methodology. Quantitative methods will include (1) PBS, a group interview method in which individuals provide responses through a ballot box in an unlinked and anonymous way, and (2) a behavioral and biological survey (BBS), including a face-to-face individual interview and collection of linked biological samples. Qualitative methods will include focus group discussions. The ePBS study uses a 2-stage, population- and location-based random sampling approach involving the random selection of locations from which random participants are selected at a predetermined time on a randomly selected day. PBS data will be analyzed at the group level, and BBS data will be analyzed at an individual level. Qualitative data will be analyzed thematically. RESULTS: Data were collected from April to May 2023. The study has enrolled 759 female sex workers (response rate: 759/769, 98.6%) and 398 men who have sex with men (response rate: 398/420, 94.7%). Data cleaning and analyses are ongoing, with a focus on assessing gaps in program coverage and inequities in program outcomes. CONCLUSIONS: The study will generate valuable HIV outcome data to inform program improvement and policy development for Nairobi County's key population HIV prevention program. This study served as a pilot for the novel ePBS method, which combines PBS, BBS, and focus group discussions to enhance its programmatic utility. The ePBS method holds the potential to fill an acknowledged gap for a rapid, low-cost, and simple method to routinely measure HIV outcomes within programs and inform incremental program improvements through embedded learning processes.


Subject(s)
HIV Infections , Homosexuality, Male , Sex Workers , Humans , HIV Infections/prevention & control , HIV Infections/epidemiology , Male , Female , Sex Workers/statistics & numerical data , Sex Workers/psychology , Kenya/epidemiology , Homosexuality, Male/statistics & numerical data , Homosexuality, Male/psychology , Surveys and Questionnaires , Outcome Assessment, Health Care , Adult , Program Evaluation
9.
Article in English | MEDLINE | ID: mdl-38843440

ABSTRACT

Pulmonary fibrosis can be a fatal disease characterized by progressive lung scarring. It is still poorly understood how the pulmonary endothelium is involved in the disease pathogenesis. Differences of the pulmonary vasculature between patients and donors were analysed using transmission electron microscopy, immunohistochemistry and single-cell-RNA-sequencing. Vascular barrier resistance, endothelial-immune cell adhesion, and sensitivity to an inflammatory milieu were studied in-vitro. Integrity and activation markers were measured by ELISA in human plasma. Transmission electron microscopy demonstrated abnormally swollen endothelial cells in fibrotic lungs as compared to donors. A more intense CD31 and vWF and patchy VE-Cadherin staining in fibrotic lungs supported the presence of a dysregulated endothelium. Integrity markers CD31, VE-Cadherin, Thrombomodulin and VEGFR-2 and activation marker von-Willebrand-Factor gene expression was increased in different endothelial subpopulations (e.g. arterial, venous, gCap, aCap) in pulmonary fibrosis. This was associated with a heightened sensitivity of fibrotic endothelial cells to TNF-α or IFN-γ and elevated immune cell adhesion. The barrier strength was overall reduced in endothelial cells from fibrotic lungs. vWF and IL-8 were increased in the plasma of patients, while VE-Cadherin, Thrombomodulin and VEGFR-2 were decreased. VE-Cadherin staining was also patchy in biopsy tissue and was decreased in plasma samples of PF patients six months after the initial diagnosis. Our data demonstrate highly abnormal endothelial cells in PF. The vascular compartment is characterized by hyper-activation and increased immune cell adhesion, as well as dysfunctional endothelial barrier function. Re-establishing endothelial cell homeostasis and function might represent a new therapeutic option for fibrotic lung diseases.

11.
Meat Sci ; 214: 109522, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38692014

ABSTRACT

Verification of beef production systems and authentication of origin is becoming increasingly important as consumers base purchase decisions on a greater number of perceived values including the healthiness and environmental impact of products. Previously Raman spectroscopy has been explored as a tool to classify carcases from grass and grain fed cattle. Thus, the aim of the current study was to validate Partial Least Squares Discriminant Analysis (PLS-DA) models created using independent samples from carcases sampled from northern and southern Australian production systems in 2019, 2020 and 2021. Validation of the robustness of discrimination models was undertaken using spectral measures of fat from 585 carcases which were measured in 2022 using a Raman handheld device with a sample excised for fatty acid analysis. PLS-DA models were constructed and then employed to classify samples as either grass or grain fed in a two-class model. Overall, predictions were high with accuracies of up to 95.7% however, variation in the predictive ability was noted with models created for southern cattle yielding an accuracy of 73.2%. While some variation in fatty acids and therefore models can be attributed to differences in genetics, management and diet, the impact of duration of feeding is currently unknown and thus further work is warranted.


Subject(s)
Animal Feed , Diet , Fatty Acids , Red Meat , Spectrum Analysis, Raman , Animals , Cattle , Spectrum Analysis, Raman/methods , Red Meat/analysis , Australia , Fatty Acids/analysis , Animal Feed/analysis , Diet/veterinary , Discriminant Analysis , Edible Grain , Poaceae , Least-Squares Analysis
12.
Food Chem ; 452: 139504, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38744135

ABSTRACT

Cu(II)-organic acid (fraction I) and Cu(I)-thiol (fraction II) complexes can suppress sulfhydryl off-aromas in wine. This study investigated the impact of light exposure on the protective fractions of Cu of bottled white wine. Fluorescent light-exposed Chardonnay with two initial concentrations of dissolved oxygen (0.5 and 10 mg/L) was stored in different coloured bottles and concentrations of Cu fractions and riboflavin, a photo-initiator at 370-440 nm, were measured during 110 days storage. Light-exposed wines with lower oxygen concentrations resulted in a 100-fold decrease in the Cu fraction I half-life, and a 60-fold decrease for Cu fractions I and II combined. The half-life for Cu fraction I decay during light exposure was extended 30-fold with the use of brown compared to flint glass. Light exposure can rapidly exhaust the protective Cu fractions in wine, and bottles with less light transmission below 440 nm can slow this loss.


Subject(s)
Color , Copper , Light , Oxygen , Wine , Wine/analysis , Oxygen/chemistry , Oxygen/analysis , Copper/chemistry , Copper/analysis , Food Packaging/instrumentation , Food Storage
13.
medRxiv ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38766048

ABSTRACT

Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, B-cell and CD4+ T-cell responses emerged post-vaccination. Five vaccinees developed serum autologous tier-2 nAbs (ID50 titer, 1:28-1:8647) after 2-3 doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B-cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes. KEY TAKEAWAY/TAKE-HOME MESSAGES: HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that map to diverse Env epitopes with relatively high titers. The novel adjuvant may be an important mediator of vaccine response.

14.
Am J Physiol Lung Cell Mol Physiol ; 327(2): L173-L188, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38771138

ABSTRACT

Changes in the extracellular matrix of pulmonary arteries (PAs) are a key aspect of vascular remodeling in pulmonary hypertension (PH). Yet, our understanding of the alterations affecting the proteoglycan (PG) family remains limited. We sought to investigate the expression and spatial distribution of major vascular PGs in PAs from healthy individuals and various PH groups (chronic obstructive pulmonary disease: PH-COPD, pulmonary fibrosis: PH-PF, idiopathic: IPAH). PG regulation, deposition, and synthesis were notably heightened in IPAH, followed by PH-PF, with minor alterations in PH-COPD. Single-cell analysis unveiled cell-type and disease-specific PG regulation. Agrin expression, a basement membrane PG, was increased in IPAH, with PA endothelial cells (PAECs) identified as a major source. PA smooth muscle cells (PASMCs) mainly produced large-PGs, aggrecan and versican, and small-leucine-like proteoglycan (SLRP) biglycan, whereas the major PGs produced by adventitial fibroblasts were SLRP decorin and lumican. In IPAH and PF-PH, the neointima-forming PASMC population increased the expression of all investigated large-PGs and SLRPs, except fibroblast-predominant decorin (DCN). Expression of lumican, versican, and biglycan also positively correlated with collagen 1α1/1α2 expression in PASMCs in patients with IPAH and PH-PF. We demonstrated that transforming growth factor-beta (TGF-ß) regulates versican and biglycan expression, indicating their contribution to vessel fibrosis in IPAH and PF-PH. We furthermore show that certain circulating PG levels display a disease-dependent pattern, with increased decorin and lumican across all patient groups, while versican was elevated in PH-COPD and IPAH and biglycan reduced in IPAH. These findings suggest unique compartment-specific PG regulation in different forms of PH, indicating distinct pathological processes.NEW & NOTEWORTHY Idiopathic pulmonary arterial hypertension (IPAH) pulmonary arteries (PAs) displayed the greatest proteoglycan (PG) changes, with PH associated with pulmonary fibrosis (PH-PF) and PH associated with chronic obstructive pulmonary disease (PH-COPD) following. Agrin, an endothelial cell-specific PG, was solely upregulated in IPAH. Among all cells, neo-intima-forming smooth muscle cells (SMCs) displayed the most significant PG increase. Increased levels of circulating decorin, lumican, and versican, mainly derived from SMCs, and adventitial fibroblasts, may serve as systemic indicators of pulmonary remodeling, reflecting perivascular fibrosis and neointima formation.


Subject(s)
Hypertension, Pulmonary , Myocytes, Smooth Muscle , Proteoglycans , Pulmonary Artery , Humans , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Proteoglycans/metabolism , Male , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/pathology , Female , Middle Aged , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Vascular Remodeling , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Aged , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Biglycan/metabolism , Decorin/metabolism , Adult , Fibroblasts/metabolism , Fibroblasts/pathology , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Lumican/metabolism , Extracellular Matrix/metabolism , Extracellular Matrix/pathology
15.
Am J Physiol Lung Cell Mol Physiol ; 327(2): L189-L202, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38810239

ABSTRACT

Children are susceptible to influenza infections and can experience severe disease presentation due to a lack of or limited pre-existing immunity. Despite the disproportionate impact influenza has on this population, there is a lack of focus on pediatric influenza research, particularly when it comes to identifying the pathogenesis of long-term outcomes that persist beyond the point of viral clearance. In this study, juvenile outbred male and female mice were infected with influenza and analyzed following viral clearance to determine how sex impacts the persistent inflammatory responses to influenza. It was found that females maintained a broader cytokine response in the lung following clearance of influenza, with innate, type I and type II cytokine signatures in almost all mice. Males, on the other hand, had higher levels of IL-6 and other macrophage-related cytokines, but no evidence of a type I or type II response. The immune landscape was similar in the lungs between males and females postinfection, but males had a higher regulatory T cell to TH1 ratio compared with female mice. Cytokine production positively correlated with the frequency of TH1 cells and exudate macrophages, as well as the number of cells in the bronchoalveolar lavage fluid. Furthermore, female lungs were enriched for metabolites involved in the glycolytic pathway, suggesting glycolysis is higher in female lungs compared with males after viral clearance. These data suggest juvenile female mice have persistent and excessive lung inflammation beyond the point of viral clearance, whereas juvenile males had a more immunosuppressive phenotype.NEW & NOTEWORTHY This study identifies sex-based differences in persistent lung inflammation following influenza infection in an outbred, juvenile animal model of pediatric infection. These findings indicate the importance of considering sex and age as variable in infectious disease research.


Subject(s)
Cytokines , Orthomyxoviridae Infections , Pneumonia , Sex Characteristics , Animals , Female , Male , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/metabolism , Mice , Cytokines/metabolism , Pneumonia/virology , Pneumonia/pathology , Pneumonia/immunology , Pneumonia/metabolism , Lung/virology , Lung/pathology , Lung/immunology , Lung/metabolism , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Macrophages/virology , Sex Factors
16.
Respirol Case Rep ; 12(5): e01360, 2024 May.
Article in English | MEDLINE | ID: mdl-38680667

ABSTRACT

A 64-year-old obese gentleman attended for further evaluation of ongoing dyspnoea in the context of a previous diagnosis of moderate COPD treated with dual long-acting bronchodilators. A cardiopulmonary exercise test (CPET) was performed, which demonstrated reduced peak work and oxygen consumption with evidence of dynamic hyperinflation, abnormal gas exchange and ventilatory limitation despite cardiac reserve. The CPET clarified the physiological process underpinning the patient's dyspnoea and limiting the patient's activities. This, in turn, helped the clinician tailor the patient's management plan.

17.
bioRxiv ; 2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38559180

ABSTRACT

Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Early antibody responses to easily accessible epitopes on these antigens are directed to non-neutralizing epitopes instead of bnAb epitopes. Autologous neutralizing antibody responses appear upon boosting once immunodominant epitopes are saturated. Here we report another type of antibody response that arises after repeated immunizations with HIV Env immunogens and present the structures of six anti-immune complexes discovered using polyclonal epitope mapping. The anti-immune complex antibodies target idiotopes composed of framework regions of antibodies bound to Env. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens, in which repeated exposure to antigen is required.

18.
PeerJ ; 12: e17193, 2024.
Article in English | MEDLINE | ID: mdl-38563002

ABSTRACT

The COVID-19 pandemic has negatively impacted the mental health of individuals globally. However, less is known about the characteristics that contributed to some people having mental health problems during the pandemic, while others did not. Mental health problems can be understood on a continuum, ranging from acute (e.g., depression following a stressful event) to severe (e.g., chronic conditions that disrupt everyday functioning). Therefore, the purpose of this article was to generate profiles of adults who were more or less at risk for the development of mental health problems, in general, during the first 16-months of the COVID-19 pandemic in Ontario, Canada. Data were collected via online surveys at two time points: April-July 2020 and July-August 2021; 2,188 adults (Mage = 43.15 years; SD = 8.82) participated. Surveys included a demographic questionnaire and four previously validated tools to measure participants' mental health, subjective wellbeing, physical activity and sedentary behaviour, and sleep. A decision tree was generated at each time point for those with mental health problems, and those with no mental health problems. Results showed that subjective wellbeing was the biggest contributor to mental health status. Characteristics associated with no mental health problems among adults included having good wellbeing, being a good sleeper (quantity, quality, and patterns of sleep), and being over the age of 42. Characteristics associated with mental health problems included having poor wellbeing and being a poor sleeper. Findings revealed that specific characteristics interacted to contribute to adults' mental health status during the first 16 months of the COVID-19 pandemic. Given that wellbeing was the biggest contributor to mental health, researchers should focus on targeting adults' wellbeing to improve their mental health during future health crises.


Subject(s)
COVID-19 , Adult , Humans , Ontario/epidemiology , COVID-19/epidemiology , Pandemics , Mental Health , Decision Trees
19.
Curr Opin Infect Dis ; 37(3): 170-175, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38437245

ABSTRACT

PURPOSE OF REVIEW: Prevention of acute respiratory illnesses (ARI) in children is a global health priority, as these remain a leading cause of pediatric morbidity and mortality throughout the world. As new products and strategies to prevent respiratory infections caused by important pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, respiratory syncytial virus and pneumococcus are advancing, increasing evidence suggests that these and other respiratory viruses and pneumococci may exhibit interactions that are associated with altered colonization and disease dynamics. We aim to review recent data evaluating interactions between respiratory viruses and pneumococci in the upper respiratory tract and their potential impact on pneumococcal colonization patterns and disease outcomes. RECENT FINDINGS: While interactions between influenza infection and subsequent increased susceptibility and transmissibility of colonizing pneumococci have been widely reported in the literature, emerging evidence suggests that human rhinovirus, SARS-CoV-2, and other viruses may also exhibit interactions with pneumococci and alter pneumococcal colonization patterns. Additionally, colonizing pneumococci may play a role in modifying outcomes associated with respiratory viral infections. Recent evidence suggests that vaccination with pneumococcal conjugate vaccines, and prevention of colonization with pneumococcal serotypes included in these vaccines, may be associated with reducing the risk of subsequent viral infection and the severity of the associated illnesses. SUMMARY: Understanding the direction and dynamics of viral-pneumococcal interactions may elucidate the potential effects of existing and emerging viral and bacterial vaccines and other preventive strategies on the health impact of these important respiratory pathogens.


Subject(s)
Nasopharynx , Pneumococcal Infections , Respiratory Tract Infections , Streptococcus pneumoniae , Humans , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Child , Pneumococcal Infections/prevention & control , Pneumococcal Infections/microbiology , Nasopharynx/microbiology , Nasopharynx/virology , COVID-19/microbiology , SARS-CoV-2 , Pneumococcal Vaccines , Child, Preschool , Coinfection/microbiology , Virus Diseases
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