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The American Journal of Cardiology Jun 2024Mitral annular calcification (MAC) may be a potential marker of biological aging. However, the association of MAC with non-cardiovascular measures, including bone...
Mitral annular calcification (MAC) may be a potential marker of biological aging. However, the association of MAC with non-cardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and non-cardiovascular mortality, is not well studied in a multiracial cohort. We used data from 6,814 participants (mean age:62.2±10.2 years; 52.9%-females) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with non-contrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed cross-sectional association of MAC with BMD and walking pace. Also, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. Additionally, we assessed the association of MAC with cardiovascular and non-cardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient: -0.04; 95%CI: -0.06 - -0.02) with significant interaction by sex (p-interaction:0.035). MAC was, however, not associated with impaired walking pace (odds ratio:1.09; 95%CI:0.89-1.33). Compared to individuals without MAC, those with MAC had an increased risk of incident renal failure albeit nonsignificant (hazard ratio [HR]:1.18; 95%CI:0.95-1.45) but a significantly higher hazards of dementia (HR:1.36; 95%CI:1.10-1.70). Additionally, persons with MAC had a substantially higher risk of all-cause (HR:1.47; 95%CI:1.29-1.69), cardiovascular (sub-distribution HR:1.39; 95%CI:1.04-1.87), and non-cardiovascular mortality (sub-distribution HR:1.35; 95%CI:1.14-1.60), compared to those without MAC. MAC≥100 vs <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and non-cardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia, as well as all-cause, cardiovascular, and non-cardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of non-cardiovascular outcomes and death from other causes.
PubMed: 38914415
DOI: 10.1016/j.amjcard.2024.06.017 -
Journal of Stroke and Cerebrovascular... Jun 2024Stroke is a leading cause of death and disability in Nigeria. Effective stroke management is essential to reduce morbidity and mortality. Few trained neurologists in...
BACKGROUND
Stroke is a leading cause of death and disability in Nigeria. Effective stroke management is essential to reduce morbidity and mortality. Few trained neurologists in Nigeria are mostly concentrated in the cities, making non-specialists the backbone of acute stroke management in Nigeria. Physicians-related factors have been identified as one of the factors leading to sub-optimal stroke care. This study aimed to describe the knowledge of medical doctors in acute stroke care and the factors responsible for the disparity in their skills.
METHODS
A descriptive cross-sectional survey was conducted among 404 medical doctors across all the six geo-political zones in Nigeria using the Acute Stroke Management Questionnaire (ASMaQ). Data were analysed using descriptive statistics and simple logistics regression to predict the relationship between independent variables and the outcome variable (good knowledge vs poor knowledge).
RESULTS
67% (95% CI =63% - 72%) of respondents had good overall knowledge of stroke management. Most respondents [88.6%, 95% CI =85% - 92%] had good knowledge of General Stroke Knowledge (GSK) followed by Hyperacute Stroke Management (HSM) [52.5%, 95% CI=47.3% - 57.7%] and Advanced Stroke Management (ASM) [49.5%, 95%CI= 49.5% -54.4%]. Working in a primary healthcare center (PHCs) and government hospital were significant predictor of overall poor knowledge of stroke. Physicians at PHCs had 2.29 times the odds of poor knowledge compared to those in tertiary hospital CONCLUSIONS: It is essential to retrain doctors on stroke management regularly, as part of their professional development.
PubMed: 38914357
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107832 -
The Science of the Total Environment Jun 2024Sewage sludge is a significant reservoir of nano/microplastics (NPs/MPs) and antibiotic resistance genes (ARGs). Research has revealed that NPs/MPs may exert an...
Sewage sludge is a significant reservoir of nano/microplastics (NPs/MPs) and antibiotic resistance genes (ARGs). Research has revealed that NPs/MPs may exert an inhibitory effect on anaerobic digestion (AD) of sludge. Moreover, NPs/MPs can influence microbial community diversity and composition, potentially increasing ARGs dissemination. The morphological changes to NPs/MPs surface due to aging contribute to modifying hydrophobic properties. To date, there is limited comprehension regarding how various surface properties of NPs influence ARGs dissemination during AD. This study investigated the impact of primary aged/non-aged and secondary aged/non-aged polystyrene nanoplastics (PSNPs) on ARGs and mobile genetic elements (MGEs) propagation during AD. The findings indicated that the UV-aging process resulted in surface oxidation and distinct morphological characteristics in both primary and secondary PSNPs, while the surface oxidation effect was more pronounced in the secondary aged PSNPs. High concentrations (150 μg/L) of primary and secondary PSNPs inhibited methane production, with secondary PSNPs causing greater inhibition by 16 to 20 % compared to control. In contrast, low concentration (25 μg/L) had negligible or slightly positive effects on methane production. PSNPs at 150 μg/L reduced total VFA concentration, indicating an inhibitory effect on the fermentation step in the AD process. Primary and secondary PSNPs exhibited changes in EPS characteristics. ARGs abundance was enriched in reactors amended with PSNPs, with the highest abundance of 8.54 × 10 copies/g sludge observed in the secondary aged PSNPs (150 μg/L) reactor. Reactors exposed to aged PSNPs exhibited a relatively higher abundance of ARGs compared to reactors exposed to non-aged PSNPs. Exposure to PSNPs increased the microbial community diversity within the digesters and triggered the enrichment of Comamonadaceae and Syntrophaceae, belonging to Proteobacteria phylum. On the other hand, archaeal communities tended to shift towards hydrogenotrophic methanogens in PSNPs reactors. The correlation analysis showed that Comamonadaceae were positively correlated with the majority of ARGs and intl1. A positive correlation was observed between MGEs and most ARGs, suggesting that the increased proliferation of ARGs under PSNPs exposure may be linked to the abundance of MGEs, which in turn promotes the growth of hosts carrying ARGs. These findings suggest that aged and non-aged NPs could substantially impact the spread of ARGs and MGEs, which also led to notable alterations in the composition of the microbial community. Overall, this study provides valuable insights into the multifaceted impacts of PSNPs with various characteristics on AD processes, microbial communities, and ARGs proliferation, highlighting the urgent need for comprehensive assessments of NPs pollutants in the environment.
PubMed: 38914331
DOI: 10.1016/j.scitotenv.2024.174213 -
The Science of the Total Environment Jun 2024Growing awareness acknowledges ambient fine particulate matter (PM) as an environmental risk factor for mental disorders, especially among older people. However, there...
Growing awareness acknowledges ambient fine particulate matter (PM) as an environmental risk factor for mental disorders, especially among older people. However, there remains limited evidence regarding which specific chemical components of PM may be more detrimental. This nationwide prospective cohort study included 22,126 middle-aged and older adult participants of the China Health and Retirement Longitudinal Study (CHARLS, 2011-2016), to explore the individual and joint association between long-term exposure to various PM components (sulfate, nitrate, ammonium, organic matter, and black carbon) and depressive symptoms. The depressive symptoms were assessed using the 10-item Center for Epidemiological Studies-Depression Scale (CES-D-10). Using the novel quantile-based g-computation for multi-pollutant mixture analysis, we found that exposure to the mixture of major PM components was significantly associated with aggravating depressive symptoms, with the exposure-response curve exhibiting consistent linear or supra-linear shape without a lower threshold. The estimated weight index indicated that, among major PM components, only nitrate, sulfate, and black carbon significantly contributed to the exacerbation of depressive symptoms. Given the expanding aging population, stricter regulation on the emissions of particularly toxic PM components may mitigate the escalating disease burden of depression.
PubMed: 38914329
DOI: 10.1016/j.scitotenv.2024.174228 -
The Science of the Total Environment Jun 2024Microplastics and metal-based nanoparticles (NPs) are environmental pollutants that have attracted significant attention. However, there have been relatively few studies...
Microplastics and metal-based nanoparticles (NPs) are environmental pollutants that have attracted significant attention. However, there have been relatively few studies on the combined pollution of these substances in the soil-plant system. To investigate the environmental impact and interaction mechanisms of these two pollutants, a pot experiment was conducted to examine the effects of soil exposure on peanut growth. The experiment results revealed that polyethylene (PE) had a minimal effect on peanut growth, while CuO NPs significantly inhibited peanut growth. Peanut biomass decreased by over 50 % in all Cu treatments. The presence of PE significantly impacted the dissolution and absorption of CuO NPs. When 0.5 % PE was present, the dissolution and transformation of CuO NPs were limited, resulting in a total Cu concentration of 458 mg/kg. Conversely, when 5 % PE was present, the dissolution and transformation of CuO NPs were promoted, leading to a DTPA-Cu concentration of 141 mg/kg, the highest level observed. The distribution of trace elements in peanut stems also responded to the differences in Cu concentration. Both pollutants significantly disrupted soil bacteria, with CuO NPs having a more pronounced effect than PE. Throughout the entire growth cycle of peanuts, no chemical adsorption occurred between PE and CuO NPs, and CuO NPs had no significant impact on the aging rate of PE. In summary, this study provides insights into the environmental impact and transport mechanisms of composite pollution involving microplastics and metal-based nanoparticles in the soil-peanut system.
PubMed: 38914321
DOI: 10.1016/j.scitotenv.2024.174206 -
Contemporary Clinical Trials Jun 2024Providing healthcare for older adults with multiple chronic conditions (MCC) is challenging. Polypharmacy and complex treatment plans can lead to high treatment burden...
An innovative approach to aligning healthcare with what matters most to patients: A hybrid type 1 trial protocol of patient priorities care for older adults with multiple chronic conditions.
BACKGROUND
Providing healthcare for older adults with multiple chronic conditions (MCC) is challenging. Polypharmacy and complex treatment plans can lead to high treatment burden and risk for adverse events. For clinicians, managing the complexities of patients with MCC leaves little room to identify what matters and align care options with patients' health priorities. New care approaches are needed to navigate these challenges. In this clinical trial, we evaluate implementation and effectiveness outcomes of an innovative, structured, patient-centered care approach (Patient Priorities Care; PPC) for reducing treatment burden and aligning health care decisions with the health priorities of older adults with MCC.
METHODS
This is a multisite, assessor-blind, two-arm, parallel hybrid type 1 randomized controlled trial. We are enrolling 396 older (65+) Veterans with MCC who receive primary care at the Veterans Affairs Medical Center. Veterans are randomly assigned to either PPC or usual care. In the PPC arm, Veterans have a brief telephone call with a study facilitator to identify their personal health priorities. Then, primary care providers use this information to align healthcare with Veteran priorities during their established clinic appointments. Data are collected at baseline and 4-month follow up to assess for changes in treatment burden and use of home and community services. Formative and summative evaluations are also collected to assess for implementation outcomes according to Proctor's implementation framework.
CONCLUSIONS
This work has the potential to significantly improve the standard of care by personalizing healthcare and helping patients achieve what is most important to them.
PubMed: 38914308
DOI: 10.1016/j.cct.2024.107613 -
Experimental Neurology Jun 2024An ischemic stroke (IS) is caused due to the lack of blood flow to cerebral tissue. Most of the studies have focused on how stroke affects the localized tissue, but it...
An ischemic stroke (IS) is caused due to the lack of blood flow to cerebral tissue. Most of the studies have focused on how stroke affects the localized tissue, but it has been observed that a stroke can cause secondary complications in distant organs, such as Bone Marrow (BM). Our study focused on the effect of ischemic strokes on the bone marrow microenvironment. Bone marrow (BM) is a vital organ that maintains inflammatory homeostasis and aids in the repair of damaged tissue after injury/IS. We used the middle cerebral artery occlusion (MCAO) model of ischemic stroke on adult mice (6 months) and investigated the changes in the BM environment. BM cells were used for western blot and RT-PCR, and the BM supernatant was used for cytokine analysis and extracellular vesicle (EVs) isolation. We observed a significant increase in the total cell number within the BM and an increase in TNF-alpha and MCP-1, which are known for inducing a pro-inflammatory environment. Western blots analysis on the whole BM cell lysate demonstrated elevated levels of inflammatory factors (IL-6, TNF-alpha, and TLR-4) and senescence markers (p21 p16). EVs isolated from the BM supernatant showed no change in size or concentration; however, we found that the EVs carried increased miRNA-141-3p and miRNA-34a. Proteomic analysis on BM-derived EVs showed an alteration in the protein cargo of IS. We observed an increase in FgB, C3, Fn1, and Tra2b levels. The signaling pathway analysis showed mitochondrial function is most affected within the bone marrow. Our study demonstrated that IS induces changes in the BM environment and EVs secreted in the BM.
PubMed: 38914274
DOI: 10.1016/j.expneurol.2024.114867 -
Ageing Research Reviews Jun 2024Cellular senescence (CS) is recognized as one of the hallmarks of aging, and an important player in a variety of age-related pathologies. Accumulation of senescent cells... (Review)
Review
Cellular senescence (CS) is recognized as one of the hallmarks of aging, and an important player in a variety of age-related pathologies. Accumulation of senescent cells can promote a pro-inflammatory and pro-cancerogenic microenvironment. Among potential senotherapeutics are extracellular vesicles (EVs) (40-1000nm), including exosomes (40-150nm), that play an important role in cell-cell communications. Here, we review the most recent studies on the impact of EVs derived from stem cells (MSCs, ESCs, iPSCs) as well as non-stem cells of various types on CS and discuss potential mechanisms responsible for the senotherapeutic effects of EVs. The analysis revealed that (i) EVs derived from stem cells, pluripotent (ESCs, iPSCs) or multipotent (MSCs of various origin), can mitigate the cellular senescence phenotype both in vitro and in vivo; (ii) this effect is presumably senomorphic; (iii) EVs display cross-species activity, without apparent immunogenic responses. In summary, stem cell-derived EVs appear to be promising senotherapeutics, with a feasible application in humans.
PubMed: 38914266
DOI: 10.1016/j.arr.2024.102391 -
Ageing Research Reviews Jun 2024Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE)... (Review)
Review
Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-β plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.
PubMed: 38914265
DOI: 10.1016/j.arr.2024.102388 -
Ageing Research Reviews Jun 2024Caffeine is one of the most consumed psychoactive substances globally. Caffeine-gene interactions in Parkinson's disease (PD) has not been systematically examined. (Review)
Review
BACKGROUND
Caffeine is one of the most consumed psychoactive substances globally. Caffeine-gene interactions in Parkinson's disease (PD) has not been systematically examined.
OBJECTIVES
To conduct a systematic review on the interaction between caffeine consumption and genetic susceptibility to PD.
METHODOLOGY
We conducted PubMed and Embase search using terms "Genetic association studies", "Caffeine", "polymorphism" and "Parkinson's disease", from inception till 2023. Of the initial 2391 studies, 21 case control studies were included. The demographics, genetic and clinical data were extracted and analyzed.
RESULTS
We identified 21 studies which involved a total of 607,074 study subjects and 17 gene loci (SNCA, MAPT, HLA-DRA, NOS1, NOS3, GBA, ApoE, BST1, ESR2, NAT2, SLC2A13, LRRK2, NOS2A, GRIN2A, CYP1A2, ESR1, ADORA2A) have been investigated for the effect of gene-caffeine interaction and PD risk. The genes were identified through PD GWAS or involved in caffeine or related metabolism pathways. Based on the genetic association and interaction studies, only MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A have been shown by at least one study to have a positive caffeine-gene interaction influencing the risk of PD.
CONCLUSION
Studies have shown an interaction between caffeine with genetic variants of MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A in modulating the risk of PD. Due to the potential limitations of these discovery/pilot studies, further independent replication studies are needed. Better designed genetic association studies in multi-ancestry and admixed cohorts to identify potential shared or unique multivariate gene-environmental interactions, as well as functional studies of gene-caffeine interactions will be useful.
PubMed: 38914264
DOI: 10.1016/j.arr.2024.102381