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Stroke Oct 2023Cerebral microbleeds (CMBs) are associated with cognitive decline, but their importance outside of cerebral amyloid angiopathy and the mechanisms of their impact on...
BACKGROUND
Cerebral microbleeds (CMBs) are associated with cognitive decline, but their importance outside of cerebral amyloid angiopathy and the mechanisms of their impact on cognition are poorly understood. We evaluated the cross-sectional association between CMB patterns and cerebral Aβ (amyloid-β) deposition, by florbetapir positron emission tomography.
METHODS
The longitudinal ARIC study (Atherosclerosis Risk in Communities) recruited individuals from 4 US communities from 1987 to 1989. From 2012 to 2014, the ARIC-PET (Atherosclerosis Risk in Communities - Positron Emission Tomography) ancillary recruited 322 nondemented ARIC participants who completed 3T brain magnetic resonance imaging with T2*GRE as part of ARIC visit 5 to undergo florbetapir positron emission tomography imaging. Magnetic resonance imaging images were read for CMBs and superficial siderosis; on positron emission tomography, global cortical standardized uptake value ratio >1.2 was considered a positive Aβ scan. Multivariable logistic regression models evaluated CMB characteristics in association with Aβ positivity. Effect modification by sex, race, status, and cognition was evaluated.
RESULTS
CMBs were present in 24% of ARIC-PET participants. No significant associations were found between CMBs and Aβ positivity, but a pattern of isolated lobar CMBs or superficial siderosis was associated with over 4-fold higher odds of elevated Aβ when compared with those with no CMBs (odds ratio, 4.72 [95% CI, 1.16-19.16]). A similar elevated risk was not observed in those with isolated subcortical or mixed subcortical and either lobar CMBs or superficial siderosis. Although no significant interactions were found, effect estimates for elevated Aβ were nonsignificantly lower (>0.10, odds ratio, 0.4-0.6) for a mixed CMB pattern, and odds ratios were nonsignificantly higher for lobar-only CMBs for 4 subgroups: women (versus men); Black participants (versus White participants), ε4 noncarriers (versus carriers), and cognitively normal (versus mild cognitive impairment).
CONCLUSIONS
In this community-based cohort of nondemented adults, lobar-only pattern of CMBs or superficial siderosis is most strongly associated with brain Aβ, with no elevated risk for a mixed CMB pattern. Further studies are needed to understand differences in CMB patterns and their meaning across subgroups.
Topics: Male; Humans; Female; Cerebral Hemorrhage; Siderosis; Cross-Sectional Studies; Cerebral Amyloid Angiopathy; Amyloid beta-Peptides; Positron-Emission Tomography; Magnetic Resonance Imaging; Atherosclerosis
PubMed: 37638398
DOI: 10.1161/STROKEAHA.123.042835 -
Cureus Jan 2024This systematic review examines the transformative impact of artificial intelligence (AI) in managing lung disorders through a comprehensive analysis of articles... (Review)
Review
This systematic review examines the transformative impact of artificial intelligence (AI) in managing lung disorders through a comprehensive analysis of articles spanning 2014 to 2023. Evaluating AI's multifaceted roles in radiological imaging, disease burden prediction, detection, diagnosis, and molecular mechanisms, this review presents a critical synthesis of key insights from select articles. The findings underscore AI's significant strides in bolstering diagnostic accuracy, interpreting radiological imaging, predicting disease burdens, and deepening the understanding of tuberculosis (TB), chronic obstructive pulmonary disease (COPD), silicosis, pneumoconiosis, and lung fibrosis. The synthesis positions AI as a revolutionary tool within the healthcare system, offering vital implications for healthcare workers, policymakers, and researchers in comprehending and leveraging AI's pivotal role in lung disease management.
PubMed: 38313926
DOI: 10.7759/cureus.51581 -
Journal of Hazardous Materials Sep 2023Silica is utilized extensively in industrial and commercial applications as a chemical raw material, increasing its exposure and hazardous potential to populations, with...
Silica is utilized extensively in industrial and commercial applications as a chemical raw material, increasing its exposure and hazardous potential to populations, with silicosis serving as an important representative. Silicosis is characterized by persistent lung inflammation and fibrosis, for which the underlying pathogenesis of silicosis is unclear. Studies have shown that the stimulating interferon gene (STING) participates in various inflammatory and fibrotic lesions. Therefore, we speculated that STING might also play a key role in silicosis. Here we found that silica particles drove the double-stranded DNA (dsDNA) release to activate the STING signal pathway, contributing to alveolar macrophages (AMs) polarization by secreting diverse cytokines. Then, multiple cytokines could generate a micro-environment to exacerbate inflammation and promote the activation of lung fibroblasts, hastening fibrosis. Intriguingly, STING was also crucial for the fibrotic effects induced by lung fibroblasts. Loss of STING could effectively inhibit silica particles-induced pro-inflammatory and pro-fibrotic effects by regulating macrophages polarization and lung fibroblasts activation to alleviate silicosis. Collectively, our results have revealed a novel pathogenesis of silica particles-caused silicosis mediated by the STING signal pathway, indicating that STING may be regarded as a promising therapeutic target in the treatment of silicosis.
Topics: Humans; Silicon Dioxide; Macrophages, Alveolar; Silicosis; Fibrosis; Cytokines; Fibroblasts
PubMed: 37379600
DOI: 10.1016/j.jhazmat.2023.131907 -
Iranian Journal of Public Health Nov 2023Pneumoconiosis is a collection of lung diseases caused by inhaling mineral dust that poses an important risk to public health worldwide. Effective clinical treatments... (Review)
Review
Pneumoconiosis is a collection of lung diseases caused by inhaling mineral dust that poses an important risk to public health worldwide. Effective clinical treatments are currently limited, but pulmonary rehabilitation (PR) has shown promise in treating respiratory diseases. This review aims to assess the effectiveness of PR strategies for treating pneumoconiosis. We searched research studies that investigated the effectiveness of PR interventions for pneumoconiosis patients in international scientific databases and comprehensively reviewed PR strategies for the treatment of pneumoconiosis. Pneumoconiosis patients are increasingly being treated with a multimodal PR program. PR interventions could save healthcare costs, reduce dyspnea, improve exercise performance, and enhance overall health-related quality of life in patients with pneumoconiosis. PR interventions are effective in improving respiratory function and quality of life in patients with pneumoconiosis. However, further research is needed to determine the optimal PR strategies for pneumoconiosis patients and to investigate the long-term effects of these interventions.
PubMed: 38106829
DOI: 10.18502/ijph.v52i11.14024 -
Neurology India Jan 2024
Topics: Humans; Siderosis
PubMed: 38443043
DOI: 10.4103/neurol-india.Neurol-India-D-24-00018 -
Journal of Neuroinflammation Aug 2023Cortical superficial siderosis (cSS) has recently emerged as one of the most important predictors of symptomatic intracerebral hemorrhage and is a risk factor for...
BACKGROUND
Cortical superficial siderosis (cSS) has recently emerged as one of the most important predictors of symptomatic intracerebral hemorrhage and is a risk factor for post-stroke dementia in cerebral amyloid angiopathy (CAA). However, it remains unknown whether cSS is just a marker of severe CAA pathology or may itself contribute to intracerebral hemorrhage risk and cognitive decline. cSS is a chronic manifestation of convexal subarachnoid hemorrhage and is neuropathologically characterized by iron deposits in the superficial cortical layers. We hypothesized that these iron deposits lead to local neuroinflammation, a potentially contributory pathway towards secondary tissue injury.
METHODS
Accordingly, we assessed the distribution of inflammatory markers in relation to cortical iron deposits in post-mortem tissue from CAA cases. Serial sections from the frontal, parietal, temporal, and occipital lobes of nineteen autopsy cases with CAA were stained with Perls' Prussian blue (iron) and underwent immunohistochemistry against glial fibrillary acidic protein (GFAP, reactive astrocytes) and cluster of differentiation 68 (CD68, activated microglia/macrophages). Digitized sections were uploaded to the cloud-based Aiforia platform, where deep-learning algorithms were utilized to detect tissue, iron deposits, and GFAP-positive and CD68-positive cells.
RESULTS
We observed a strong local relationship between cortical iron deposits and reactive astrocytes. Like cSS-related iron, reactive astrocytes were mainly found in the most superficial layers of the cortex. Although we observed iron within both astrocytes and activated microglia/macrophages on co-stains, there was no clear local relationship between the density of microglia/macrophages and the density of iron deposits.
CONCLUSION
Iron deposition resulting from cSS is associated with local reactive astrogliosis.
Topics: Humans; Siderosis; Gliosis; Inflammation; Cerebral Amyloid Angiopathy; Iron; Cerebral Hemorrhage
PubMed: 37635208
DOI: 10.1186/s12974-023-02872-0 -
International Journal of Stroke :... Jul 2023Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions...
OBJECTIVE
Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum.
PATIENTS AND METHODS
Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group.
RESULTS
cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for -tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without.
CONCLUSION
Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.
Topics: Humans; Aged; Retrospective Studies; Magnetic Resonance Imaging; Stroke; Cerebral Hemorrhage; Subarachnoid Hemorrhage; Cerebral Amyloid Angiopathy; Siderosis; Alzheimer Disease
PubMed: 36622021
DOI: 10.1177/17474930231152124 -
Pathologie (Heidelberg, Germany) Apr 2024When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of... (Review)
Review
BACKGROUND
When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease.
OBJECTIVES
The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods.
MATERIALS AND METHODS
Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented.
RESULTS
Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM).
CONCLUSION
The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a concern.
PubMed: 38662022
DOI: 10.1007/s00292-024-01332-7 -
Particle and Fibre Toxicology Jul 2023Chronic exposure to silica can lead to silicosis, one of the most serious occupational lung diseases worldwide, for which there is a lack of effective therapeutic drugs...
Chronic exposure to silica can lead to silicosis, one of the most serious occupational lung diseases worldwide, for which there is a lack of effective therapeutic drugs and tools. Epithelial mesenchymal transition plays an important role in several diseases; however, data on the specific mechanisms in silicosis models are scarce. We elucidated the pathogenesis of pulmonary fibrosis via single-cell transcriptome sequencing and constructed an experimental silicosis mouse model to explore the specific molecular mechanisms affecting epithelial mesenchymal transition at the single-cell level. Notably, as silicosis progressed, glycoprotein non-metastatic melanoma protein B (GPNMB) exerted a sustained amplification effect on alveolar type II epithelial cells, inducing epithelial-to-mesenchymal transition by accelerating cell proliferation and migration and increasing mesenchymal markers, ultimately leading to persistent pulmonary pathological changes. GPNMB participates in the epithelial-mesenchymal transition in distant lung epithelial cells by releasing extracellular vesicles to accelerate silicosis. These vesicles are involved in abnormal changes in the composition of the extracellular matrix and collagen structure. Our results suggest that GPNMB is a potential target for fibrosis prevention.
Topics: Mice; Animals; Transcriptome; Silicosis; Lung; Pulmonary Fibrosis; Silicon Dioxide; Epithelial Cells; Transcription Factors; Epithelial-Mesenchymal Transition
PubMed: 37468937
DOI: 10.1186/s12989-023-00543-9 -
Frontiers in Public Health 2024To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout.
OBJECTIVES
To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout.
METHODS
The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs).
RESULTS
There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, = 0.74; OR = 1.00, 95% CI: 0.999-1.000, = 0.50; OR = 1.00, 95% CI: 1.000-1.001, = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, = 0.66; OR = 1.00, 95% CI: 1.00-1.00, = 0.68; OR = 1.00, 95% CI: 1.00-1.00, = 0.20].
CONCLUSION
Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.
Topics: Humans; Mendelian Randomization Analysis; Pneumoconiosis; Gout; Immune System Diseases; Lupus Erythematosus, Systemic
PubMed: 38601492
DOI: 10.3389/fpubh.2024.1373044