-
Repulsive guidance molecule A in the resolution of inflammation from ischemic stroke-associated pneumonia in mice.4 weeks agoStroke is an important global health concern. The most prevalent infectious complication after stroke is stroke-associated pneumonia (SAP), which severely impairs recovery of neurological function and has an adverse impact on the prognosis. However, the pathogenesis of SAP is largely unknown. We established a model of SAP by middle cerebral artery occlusion/reperfusion (MCAO/R) and identified spontaneous pneumonia in mice with MCAO/R by staining the lung tissue with hematoxylin-eosin and measuring the bacterial load in the lungs and expression levels of inflammatory factors in plasma. We also confirmed expression of repulsive guidance molecule A (RGMa) in splenic mononuclear cells (SpMNCs) following MCAO/R surgery. Recombinant mouse RGMa protein, propranolol, and the glucocorticoid receptor blocker RU486 were administered to investigate the effects of RGMa on SAP and elucidate the underlying mechanism. Marked spontaneous pneumonia was observed in the mice that had undergone MCAO/R. RGMa expression in SpMNCs from these mice was significantly reduced at 24 and 72 h following MCAO/R surgery. Exogenous administration of recombinant mouse RGMa markedly attenuated spontaneous pneumonia in MCAO/R mice. After administration of propranolol, there was a significant increase in the expression level of RGMa in SpMNCs and amelioration of spontaneous pneumonia in these mice. Administration of RU486 did not significantly change the RGMa expression level or ameliorate spontaneous pneumonia. RGMa attenuated spontaneous pneumonia in mice that had undergone MCAO/R. The underlying mechanism may involve regulation of sympathetic excitation. RGMa may play a key role in SAP.Chronic respiratory diseaseCardiovascular diseasesPolicy
-
miR-143-3p Inhibits the Differentiation of Th1 Cells in Rhinosinusitis by Regulating TET1/IFN-γ Signaling.4 weeks agoDysregulated microRNAs (miRNAs) are a hallmark of chronic rhinosinusitis, especially chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate the role of miR-143-3p in chronic rhinosinusitis. miR-143-3p and mRNA levels were calculated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expressed was determined by Western blot. The infiltration of CD4 cells and eosinophils was analyzed using immunohistochemistry and hematoxylin and eosin staining. The binding sites between miR-143-3p and TET1 were predicted with TargetScan and verified using luciferase assay. The DNA methylation of interferon-gamma (IFN-γ) was predicted using DNA methylation-specific RT-qPCR assay. The interaction between TET1 and IFN-γ was confirmed using the chromatin immunoprecipitation assay. CD4+ T cell polarization was analyzed using flow cytometry. miR-143-3p was downregulated in CRSwNP patients, mediating nasal polyp presence. Overexpressed miR-143-3p promoted the differentiation of T helper 1 (Th1) cells. miR-143-3p targeted and downregulated the expression of TET1, which was upregulated in CRSwNP patients. TET1-mediated DNA methylation of IFN-γ, inducing its downregulation. Overexpressed TET1 inhibited Th1 differentiation and promoted the Th1 cell to Th2 polarization. miR-143-3p promotes the differentiation of anti-inflammatory Th1 cells in CRSwNP via regulating TET1/IFN-γ axis.Chronic respiratory diseasePolicy
-
Epigenetic regulation of histone 3 acetylation and p53 by SIRT1 overexpression in an experimental model of alveolar epithelium damage.4 weeks agoPulmonary fibrosis is a chronic, life-threatening respiratory disease characterized by high incidence and lack of effective treatments. This disease is associated with damage to the alveolar epithelium and heightened proapoptotic activity of p53, attributed to increased acetylation of its Lys381 residue. On the other hand, SIRT1 has been proposed as a therapeutic target for its ability to deacetylate key proteins such as histone 3 (H3), NF-ĸB, and p53, thus modulating cellular processes such as inflammation, apoptosis, differentiation, and oxidative stress, which could improve epithelial damage and fibrogenesis. Because SIRT1 can modulate key molecules related to lung fibrosis, this study examined the effect and localization of SIRT1 overexpression in A549 alveolar epithelial cells after bleomycin-induced injury. Two plasmids were used, one with SIRT1 cDNA and the other with a mutant H363Y catalytic site. SIRT1 expression and localization were analyzed by double immunofluorescence. SIRT1 phosphorylation at serine 47 as well as acetylation of p53 and H3 at lysine 381 and lysine 9, respectively, were also analyzed. Our results indicate that SIRT1 overexpression promotes H3 deacetylation, impacting epithelial-mesenchymal transition (EMT) and preventing pulmonary fibrosis. Additionally, our findings reveal that SIRT1 overexpression boosts its nuclear translocation and phosphorylation, deacetylates p53 and H3 after bleomycin damage, and preserves cell survival. The effect of SIRT1 on p53 and H3 deacetylation supports epigenetic control which may prevent cell death and EMT in pulmonary fibrosis.Chronic respiratory diseasePolicy
-
China's COVID-19 aid in Africa: trends and implications for future pandemic preparedness.4 weeks agoChronic underfunding of pandemic preparedness remains a critical weakness in global health security. Without sustained, strategic investment, the world risks repeating the reactive approaches of past crises. This study examines the modes of COVID-19 aid delivered by the Chinese government across African countries and regions, offering a nuanced understanding of China's operational role in pandemic response. In doing so, it contributes to the global health assistance literature by providing a more comprehensive view of China's involvement in the prevention, treatment, and control of COVID-19.
Analysis of 727 Chinese health-related project commitments to African countries indicates that the majority targeted the provision of personal protective equipment (43.33%), followed by diagnostic and medical equipment (26%), and vaccination initiatives (17.88%). Regionally, Southern Africa received the highest average number of projects per country, while Northern Africa received the lowest. At the national level, South Africa (5.09%), Zimbabwe (4.00%), and Cameroon (3.85%) accounted for the largest shares of total projects, whereas Eritrea (0.001%), Cabo Verde (0.004%), and Somalia (0.004%) received the smallest proportions.
This research reveals the growing significance of Chinese aid in the global health agenda through its active role in combating COVID-19 across the African continent. It also highlights emerging trends and suggests potential adjustments needed in pandemic financing strategies for more effective future efforts.Chronic respiratory diseaseAdvocacy -
COVID-19 mortality among people living with HIV/AIDS in Brazil: a multilevel analysis.4 weeks agoThe simultaneous COVID-19 and HIV/AIDS pandemics have created unprecedented challenges, disrupting healthcare for people living with HIV/AIDS (PLWHA) and introducing an additional lethal threat. However, the impact of COVID-19 among PLWHA in Brazil remains unclear. We aimed to investigate the association between HIV infection and COVID-19 mortality in the Brazilian population.
A multilevel study was conducted using data from the Brazilian Mortality Information System. We examined COVID-19 mortality among individuals with and without mention of HIV on their death certificates from 2020 to 2022. Mixed generalized linear regression models were used, considering the COVID-19 dominant Variant of Concern (VOC) and the vaccine rollout period, adjusted for age group and sex, interaction between HIV and age group, and random effects for federative units.
A total of 4,773,337 deaths were analyzed, including 39,011 among PLWHA. Younger (18-39) and older (80+) PLWHA had higher odds of COVID-19 death, particularly during Delta and Omicron periods. Mortality odds among PLWHA were lower during the vaccination expansion phase but increased during the consolidated phase. Regional disparities were observed, with higher mortality odds in Northern and Northeastern Brazil.
HIV infection was associated with higher COVID-19 mortality in Brazil, particularly in specific age groups and regions. Older adults with HIV had an elevated risk of COVID-19 death across all periods. The vaccine rollout reduced COVID-19 mortality among PLWHA, but the results did not hold over time, as evidenced by the increased odds of death in all age groups following vaccination coverage consolidation in the population.Chronic respiratory diseaseAdvocacy -
Impact of COVID-19 pandemic on Legionella testing and infection rates in Ontario.4 weeks agoThe disruption of healthcare systems during the COVID-19 pandemic had widespread effects on patient care, including interruption of scheduled visits and diagnostic testing. Many diseases were under-investigated due to the focus on the SARS-CoV-2 virus and the redeployment of resources to the pandemic response. This study aimed to assess Legionella trends in Ontario during the COVID-19 pandemic years, by comparing the demographics of individuals tested for Legionella prior to pandemic (2018 and 2019) to those during the pandemic (2020, 2021 and 2022). Additionally, for individuals who underwent Legionella testing, testing for additional respiratory pathogens was examined in the context of Legionella co-detection.
Two Poisson regression models were constructed to compare testing rate and positivity rate during the pre-pandemic years with the pandemic years, adjusted for age, sex, year, and Ontario population.
Relative to the pre-pandemic years, the testing rates significantly decreased by 8% in 2020, decreased by 8% in 2021 and increased by 14% in 2022. The positivity rate for Legionella decreased by 13% only in 2020 but did not reach significance for the other two years. Individuals older than 50 years of age and males remained the population with highest positivity rate of Legionella infection across all years. Co-detection of Legionella with SARS-CoV-2 or seasonal respiratory viruses was rare but present during the pandemic.
Legionella testing rates decreased by 8% in 2020 and 8% in 2021 and increased by 14% in 2022, which was associated with a decrease in positivity rate only in 2020, at 13%, but not in the other two years. Maintaining vigilance for Legionella testing in future pandemics may support timely diagnosis and treatment, leading to improved patient outcomes. Co-detection of Legionella with SARS-CoV-2 or seasonal respiratory viruses was rare but present during the pandemic. Accordingly, Legionella testing remains essential among high-risk groups, such as the elderly with co-morbidities, critically ill patients, or those with severe or unresponsive pneumonia. Such an approach can aid in differential diagnosis, prompt appropriate treatment, and improve patient outcomes.Chronic respiratory diseaseAdvocacy -
Lightweight multiscale early warning system for influenza A spillovers.4 weeks agoSpillovers of zoonotic Influenza A viruses (IAVs) into farmed animals and humans have the potential to trigger epidemics or even global pandemics. We introduce FluWarning, a highly efficient and elegant computational method based on anomaly detection of codon bias and dinucleotide composition for early identification of divergent viral HA segments. We applied FluWarning to the 2009 influenza pandemic as a test case. FluWarning successfully identified the emergence of pdm09, the virus that caused the pandemic, with warnings preceding the observed global spread. Applied to H5N1 specimens collected between 2019 and 2025, FluWarning flagged genotypes D1.1 and B3.13, both associated with recent spillovers in dairy cows in the United States. In summary, FluWarning is an effective, lightweight, multiscale warning system for IAVs, detecting spillovers with few available sequences.Chronic respiratory diseaseAdvocacy
-
Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis.4 weeks agoIndividuals with weakened immune systems, such as those living with Human Immunodeficiency Virus (HIV), are more vulnerable to opportunistic bacterial infections, which include tuberculosis and pneumonia. This systematic review and meta-analysis looked at the pooled prevalence of opportunistic bacterial infections among people living with HIV in different regions of Ethiopia.
By looking through open online databases, articles written in English were considered. Joanna Briggs Institute's critical appraisal tool for prevalence study was used to check the quality of each article. Inverse variance (I2), sensitivity analysis, funnel plot, and Egger's regression tests were used to check heterogeneity and publication bias. Because of a high heterogeneity, a random-effects model was used to estimate the pooled prevalence of opportunistic bacterial infections among people living with HIV.
About 18.06% (1824/9651) with (95% CI: 14.09-22.02) of the pooled population had opportunistic tuberculosis from 20 studies included, while from 16 included studies, the pneumonia infection was 11.64% (1040/8095/) with (95% CI: 8.45-14.83).
The prevalence of tuberculosis and pneumonia among people living with HIV in Ethiopia is high. Therefore, policymakers and health planners should put a great deal of emphasis on the implementation of relevant prevention and control measures.
The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number "CRD42024587645", on September 17, 2024.Chronic respiratory diseaseAdvocacy -
Adults with adverse childhood experiences report greater coronavirus anxiety.4 weeks agoAdults with early life adversity exhibit heightened response to threat signals in the environment, which makes them vulnerable to developing stress-related mental health problems, including anxiety disorders. Yet, the impact of the COVID-19 pandemic on adults who have experienced early life adversity is understudied. Recently, researchers have characterized dysfunctional cognitions about the pandemic, which are associated with negative mental health outcomes, as coronavirus anxiety. We conducted a study to examine the relation between exposure to early life adversity, perceived threat from COVID-19, and coronavirus anxiety.
Adults (N = 975; 18-78 years of age; 585 = Women) living in the United States were recruited online in October 2020. Two forms of early life adversity, maltreatment and household dysfunction, were assessed using the Adverse Childhood Experiences scale. Participants' state anxiety was measured using the State-Trait Anxiety Inventory, and coronavirus anxiety was measured via the Coronavirus Anxiety Scale. Three items were used to measure perceived threat from COVID-19. Additionally, as reduced flexibility is implicated in the development and maintenance of anxiety disorders, participants' cognitive flexibility was assessed using the Cognitive Flexibility Inventory.
The data were analyzed using parallel mediation regression analyses. Exposure to early life adversity, in the form of maltreatment and household dysfunction, were the key predictor variables. Coronavirus anxiety and state anxiety were the outcome variables. Perceived threat from COVID-19 and cognitive flexibility were added as parallel mediators into all the regression models. The regression analyses revealed that both perceived threat from COVID-19 and cognitive flexibility mediated the relation between early life adversity and anxiety. The data demonstrate that exposure to early life adversity, in the form of maltreatment or household dysfunction, was associated with higher levels of perceived threat from COVID-19, which, in turn, predicted increased coronavirus anxiety and state anxiety. In contrast, appraisal of everyday challenges as controllable, one of the two types of cognitive flexibility assessed, predicted lower levels of coronavirus anxiety and state anxiety. However, exposure to maltreatment and household dysfunction was associated with reduced cognitive flexibility.
This study replicates and extends prior research showing that adults with early life adversity experienced increased anxiety during the pandemic. The findings bolster existing theories that highlight the importance of threat appraisal as a mechanism for the development of anxiety disorders in this population. Additionally, this report adds to the limited body of work on the impact of COVID-19 in adults who have experienced early life adversity.Chronic respiratory diseaseMental HealthAdvocacy -
Exploring the Role of Relationship Dynamics and Chronic Illness in Psychological Outcomes Among Cohabiting Couples During the COVID-19 Pandemic.4 weeks agoThe Coronavirus Disease 2019 (COVID-19) pandemic has exacerbated mental health difficulties among couples. Factors such as chronic physical illness, perceived threat of COVID-19, dyadic coping, and relationship quality may influence levels of psychological distress, including symptoms of anxiety, depression, and stress. This study aimed to examine how these individual and relational variables are associated with psychological outcomes in cohabiting couples during the first national lockdown in Portugal.
A mixed-methods study was conducted with a sample of 956 individuals (83.9% women), aged 18 to 81 years (M = 40.76, SD = 10.42), living with a romantic partner for at least one year. Participants completed validated self-report instruments: Depression, Anxiety, and Stress Scales - 21 Items (DASS-21) to assess anxiety, depression, and stress; the Brief Illness Perception Questionnaire (B-IPQ) to evaluate COVID-19 threat perception; the Perceived Relationship Quality Component - Short Version (PRQC-SV) to assess relationship quality; and the Dyadic Coping Inventory (DCI) to measure dyadic coping. Hierarchical linear regression and fuzzy-set Qualitative Comparative Analysis (fsQCA) were used to examine associations between variables. The study received prior approval from the Ethics Committee of the Faculty of Psychology and Educational Sciences of the University of Coimbra.
The regression models accounted from between 17% to 21% of the variances of the dependent variables. In the case of the Qualitative Comparative Analysis (QCA) models, the models explained between 11% and 85% of the cases. Hierarchical regression models (HRMs) showed that COVID-19 threat perception and relationship quality were significantly associated with mental health outcomes. In QCA models, low threat perception and high relationship quality and coping skills correlated with lower psychological distress.
Chronic illness was not significantly associated with psychological distress when compared to COVID-19 threat perception, relationship quality, and dyadic coping. These insights are vital for managing mental health of couples during crises. By underscoring the importance of threat perception, relationship quality, and coping for psychological well-being management during health crises, this study offers valuable insights for supporting couples through periods of adversity.Chronic respiratory diseaseMental HealthAdvocacy