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102 result(s) for "Debacq"
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Protocols to detect senescence-associated beta-galactosidase (SA-βgal) activity, a biomarker of senescent cells in culture and in vivo
Normal cells can permanently lose the ability to proliferate when challenged by potentially oncogenic stress, a process termed cellular senescence. Senescence-associated beta-galactosidase (SA-βgal) activity, detectable at pH 6.0, permits the identification of senescent cells in culture and mammalian tissues. Here we describe first a cytochemical protocol suitable for the histochemical detection of individual senescent cells both in culture and tissue biopsies. The second method is based on the alkalinization of lysosomes, followed by the use of 5-dodecanoylaminofluorescein di-β- D -galactopyranoside (C 12 FDG), a fluorogenic substrate for βgal activity. The cytochemical method takes about 30 min to execute, and several hours to a day to develop and score. The fluorescence methods take between 4 and 8 h to execute and can be scored in a single day. The cytochemical method is applicable to tissue sections and requires simple reagents and equipment. The fluorescence-based methods have the advantages of being more quantitative and sensitive.
Neuroinflammation: A Possible Link Between Chronic Vascular Disorders and Neurodegenerative Diseases
Various age-related diseases involve systemic inflammation, i.e. a stereotyped series of acute immune system responses, and aging itself is commonly associated with low-grade inflammation or inflamm’aging. Neuroinflammation is defined as inflammation-like processes inside the central nervous system, which this review discusses as a possible link between cardiovascular disease-related chronic inflammation and neurodegenerative diseases. To this aim, neuroinflammation mechanisms are first summarized, encompassing the cellular effectors and the molecular mediators. A comparative survey of the best-known physiological contexts of neuroinflammation (neurodegenerative diseases and transient ischemia) reveals some common features such as microglia activation. The recently published transcriptomic characterizations of microglia have pointed a marker core signature among neurodegenerative diseases, but also unraveled the discrepancies with neuroinflammations related with acute diseases of vascular origin. We next review the links between systemic inflammation and neuroinflammation, beginning with molecular features of respective pro-inflammatory cells, i.e. macrophages and microglia. Finally, we point out a gap of knowledge concerning the atherosclerosis-related neuroinflammation, which is for the most surprising given that atherosclerosis is established as a major risk factor for neurodegenerative diseases.
Exploring the Communication of the SASP: Dynamic, Interactive, and Adaptive Effects on the Microenvironment
Cellular senescence is a complex cell state that can occur during physiological ageing or after exposure to stress signals, regardless of age. It is a dynamic process that continuously evolves in a context-dependent manner. Senescent cells interact with their microenvironment by producing a heterogenous and plastic secretome referred to as the senescence-associated secretory phenotype (SASP). Hence, understanding the cross-talk between SASP and the microenvironment can be challenging due to the complexity of signal exchanges. In this review, we first aim to update the definition of senescence and its associated biomarkers from its discovery to the present day. We detail the regulatory mechanisms involved in the expression of SASP at multiple levels and develop how SASP can orchestrate microenvironment modifications, by focusing on extracellular matrix modifications, neighboring cells’ fate, and intercellular communications. We present hypotheses on how these microenvironmental events may affect dynamic changes in SASP composition in return. Finally, we discuss the various existing approaches to targeting SASP and clarify what is currently known about the biological effects of these modified SASPs on the cellular environment.
Targeting ATF6α Attenuates UVB‐Induced Senescence and Improves Skin Homeostasis by Regulating IL8 Expression
Skin aging is influenced by both intrinsic and extrinsic factors, particularly UV radiation, and is characterized by an accumulation of senescent cells. Remarkably, exposure to UV can trigger senescence in different skin cell types, including dermal fibroblasts. However, the molecular mechanisms underlying UV‐induced senescence and the impact of the related senescence‐associated secretory phenotype (SASP) on the homeostasis of the overlying epidermis remain poorly understood. Here, we identified that both chronological aging and photoaging induce the unfolded protein response (UPR) in human dermal samples. We demonstrated that silencing ATF6α disrupts the establishment of the UVB‐induced senescent phenotype by preventing the onset of several senescent biomarkers and alters the composition of the SASP, consequently affecting its impact on the increased proliferation of keratinocytes embedded in reconstructed human epidermis. Moreover, we found that ATF6α partially mediates IL8 expression involved in the hyperproliferation of cultured keratinocytes. Together, our findings highlight the importance of the ATF6α/IL8 axis in regulating the homeostasis of neighboring cells during skin photoaging, thus suggesting ATF6α as a potentially promising target for senotherapeutic interventions. UVB exposure can trigger senescence in dermal fibroblasts. We show that silencing ATF6α disrupts the establishment of the UVB‐induced senescent phenotype by preventing the onset of several senescent biomarkers and altering the composition of the SASP, consequently affecting its impact on the skin microenvironment.
Systematic review and meta-analysis estimating association of cysticercosis and neurocysticercosis with epilepsy
We reviewed studies that analyzed cysticercosis (CC), neurocysticercosis (NCC) and epilepsy across Latin America, Asia and Sub-Saharan Africa, to estimate the odds ratio and etiologic fraction of epilepsy due to CC in tropical regions. We conducted a systematic review of the literature on cysticercosis and epilepsy in the tropics, collecting data from case-control and cross-sectional studies. Exposure criteria for CC included one or more of the following: serum ELISA or EITB positivity, presence of subcutaneous cysts (both not verified and unverified by histology), histology consistent with calcified cysts, and brain CT scan consistent with NCC. A common odds-ratio was then estimated using meta-analysis. 37 studies from 23 countries were included (n = 24,646 subjects, 14,934 with epilepsy and 9,712 without epilepsy). Of these, 29 were case-control (14 matched). The association between CC and epilepsy was significant in 19 scientific articles. Odds ratios ranged from 0.2 to 25.4 (a posteriori power 4.5-100%) and the common odds ratio was 2.7 (95% CI 2.1-3.6, p <0.001). Three subgroup analyses performed gave odds ratios as: 2.2 (EITB-based studies), 3.2 (CT-based studies), 1.9 (neurologist-confirmed epilepsy; door-to-door survey and at least one matched control per case). Etiologic fraction was estimated to be 63% in the exposed group among the population. Despite differences in findings, this meta-analysis suggests that cysticercosis is a significant contributor to late-onset epilepsy in tropical regions around the world, and its impact may vary depending on transmission intensity.
Influenza vaccination as a novel means of preventing coronary heart disease: Effectiveness in older adults
•Evidence shows that infection is an independent risk factor for CVD.•Preliminary data also indicates that vaccination can prevent cardiovascular disease.•We studied the association mentioned above in a review focused on older persons.•Influenza vaccination gives promising results that are still not completely understood.•Given the innovative perspectives, our review points to a need to intensify research on vaccine. Atherosclerosis can have various etiologies, including several newly recognized immunoinflammatory mechanisms. A growing body of evidence suggests that influenza infection is chronologically linked to acute myocardial infarction (AMI), and thus that the virus is a novel cardiovascular disease (CVD) risk factor. Morbidity and mortality rates for both influenza infection and AMI rise markedly with age. Epidemiological studies have demonstrated that influenza vaccination (IV) has a cardioprotective effect, especially in people aged 65 and over; hence, IV may be of value in the management of CVD. These observations justify efforts to better understand the underlying mechanisms and to identify therapeutic targets in older adults. In view of the above, the objective of the present study was to review the literature data on the cellular mechanisms that link IV to the prevention of atherosclerotic complications. Given the greater burden of CVD in older subjects, we also questioned the impact of aging on this association. The most widely recognized benefit of IV is the prevention of influenza infection and the latter’s cardiovascular complications. In a new hypothesis, however, an influenza-independent effect is driven by vaccine immunity and modulation of the ongoing immunoinflammatory response in individuals with CVD. Although influenza infection and IV both induce a proinflammatory response, they have opposite effects on the progression of atherosclerosis – suggesting a hormetic phenomenon. Aging is characterized by chronic inflammation (sometimes referred to as “inflammaging”) that progresses insidiously during the course of aging-related diseases, including CVD. It remains to be determined whether vaccination has an effect on aging-related diseases other than CVD. Although the studies of this topic had various limitations, the results highlight the potential benefits of vaccination in protecting the health of older adults, and should drive research on the molecular immunology of the response to IV and its correlation with atheroprotective processes.
Health and frailty among older spousal caregivers: an observational cohort study in Belgium
Background Among older couples, spouses are first in line to provide care, and they are key elements in the home support of dependent older persons. In this context, ensuring the health of these older spousal caregivers should be an important issue for all of the providers who care for older adults. The aim of this study was to longitudinally assess the health of older spousal caregivers considering frailty, nutrition, cognition, physical performance and mood disorders. Methods In this longitudinal, observational cohort study, participants were assessed at home in Wallonia, Belgium. At baseline, 82 community-dwelling spouses of older patients with cognitive deficits or functional impairment were assessed; 78 caregivers were assessed at follow-up (16 months). The clinical instruments used included Frailty Phenotype (Fried), the Mini Nutritional Assessment-short form (MNA-SF), Short Physical Performance Battery (SPPB), Geriatric Depression Scale (GDS-15), clock drawing test, medications, Zarit Burden Index (ZBI), and Caregiver Reaction Assessment (CRA). Biological assessments included plasma interleukin-6 (IL-6), ultrasensitive C-reactive protein (CRP), cortisol, albumin and insulin growth factor-1 (IGF-1). Results Among caregivers, 54% were women, and the mean age was 80 years. Among care-receivers, 83% had cognitive impairment. Caregivers were more likely to be in a pre-frail stage. In one-third of the caregivers, the frailty status worsened. Transitions were observed between each of the states, except from frail to robust. In contrast to frailty, items including nutrition, cognitive status, SPPB and mood assessments were stable over time, with approximately 70% of the caregivers not experiencing significant change at follow-up. Caregiver experiences assessed with the Zarit Burden Interview and CRA were relatively stable over 16 months. Conclusion Many caregivers of geriatric patients are spouses who are old themselves. A failure in the health of the caregiver may anticipate an undesired care breakdown. Caregiver health and its determinants should be explored in future longitudinal studies that cover a longer time period.
Long-range quantum entanglement in dielectric mu-near-zero metamaterials
Entanglement is paramount in quantum information processing. Many quantum systems suffer from spatial decoherence in distances over a wavelength and cannot be sustained over short time periods due to dissipation. However, long range solutions are required for the development of quantum information processing on chip. Photonic reservoirs mediating the interactions between qubits and their environment are suggested. Recent research takes advantage of extended wavelength inside near-zero refractive index media to solve the long-range problem along with less sensitivity on the position of quantum emitters. However, those recent proposals use plasmonic epsilon near-zero waveguides that are intrinsically lossy. Here, we propose a fully dielectric platform, compatible with the Nitrogen Vacancy (NV) diamond centers on-chip technology, to drastically improve the range of entanglement over 17 free-space wavelengths, or approximatively 12.5 µm, using mu near-zero metamaterials. We evaluate transient and steady state concurrence demonstrating an order of magnitude enhancement compared to previous works. This is, to the best of our knowledge, the first time that such a long distance is reported using this strategy. Moreover, value of the zero time delay second order correlation function g 12 ( 2 ) ( 0 ) are provided, showing antibunching signature correlated with a high degree of concurrence. We propose a mu-near-zero index platform, a kind of near-zero refractive index materials, that enable long-range entanglement between on-chip quantum emitters. Transient and steady state concurrence demonstrating an order of magnitude enhancement compared to previous works.
Analysis of the Impact of Selected Vitamins Deficiencies on the Risk of Disability in Older People
Vitamin deficiencies have a serious impact on healthy aging in older people. Many age-related disorders have a direct or indirect impact on nutrition, both in terms of nutrient assimilation and food access, which may result in vitamin deficiencies and may lead to or worsen disabilities. Frailty is characterized by reduced functional abilities, with a key role of malnutrition in its pathogenesis. Aging is associated with various changes in body composition that lead to sarcopenia. Frailty, aging, and sarcopenia all favor malnutrition, and poor nutritional status is a major cause of geriatric morbidity and mortality. In the present narrative review, we focused on vitamins with a significant risk of deficiency in high-income countries: D, C, and B (B6/B9/B12). We also focused on vitamin E as the main lipophilic antioxidant, synergistic to vitamin C. We first discuss the role and needs of these vitamins, the prevalence of deficiencies, and their causes and consequences. We then look at how these vitamins are involved in the biological pathways associated with sarcopenia and frailty. Lastly, we discuss the critical early diagnosis and management of these deficiencies and summarize potential ways of screening malnutrition. A focused nutritional approach might improve the diagnosis of nutritional deficiencies and the initiation of appropriate clinical interventions for reducing the risk of frailty. Further comprehensive research programs on nutritional interventions are needed, with a view to lowering deficiencies in older people and thus decreasing the risk of frailty and sarcopenia.
Providing information about medication changes upon discharge from a geriatric unit: the community healthcare professionals’ point of view
Introduction It is well known that polypharmacy is associated with adverse drug events. Accordingly, specialist geriatric units have to pay particular attention to the appropriateness of prescription and the withdrawal of potentially inappropriate medications. Even though community healthcare professionals are keen to received medication reconciliation results, the literature data show that the quality of communication between the hospital and the community needs to be improved. Objective To assess community healthcare professionals’ opinions about the receipt of medication reconciliation results when a patient is discharged from a specialist geriatric unit. Method We performed a qualitative study of general practitioners, community pharmacists and retirement home physicians recruited by phone in the Indre-et-Loire region of France. A grounded theory method was used to analyze interviews in multidisciplinary focus groups. Results The 17 community healthcare professionals first explained why the receipt of medication reconciliation results was important to them: clarifying the course and outcomes of hospital stays and reducing the lack of dialogue with the hospital, so that the interviewees could provide the care expected of them. The interviewees also described mistrust of the hospital and uncertainty when the modifications were received; these two concepts accentuated each other over time. Lastly, they shared their opinions about the information provided by the hospital, which could improve patient safety and provide leverage for treatment changes but also constituted a burden. Perspectives Our participants provided novel feedback and insight, constituting the groundwork for an improved medication reconciliation form that could be evaluated in future research. Exploring hospital-based professionals’ points of view might help to determine whether the requested changes in the medication reconciliation form are feasible and might provide a better understanding of community-to-hospital communication.