How can precision health care contribute to healthy aging?

The future of medicine will be closely linked to technological progress, to the great benefit of aging adults. Increasing knowledge in fields encompassing biology, physiology and functioning of the aging process, combined with the early detection of non-clinically apparent but significant changes will make it possible to promote healthy aging.

Dysregulation of intercellular communication in vitro and in vivo via extracellular vesicles secreted by pancreatic duct adenocarcinoma cells and generated under the influence of the AG9 elastin peptide-conditioned microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis due to its highly metastatic profile. Intercellular communication between cancer and stromal cells via extracellular vesicles (EVs) is crucial for the premetastatic microenvironment preparation leading to tumour metastasis. This study shows that under the influence of bioactive peptides derived from the extracellular matrix microenvironment, illustrated here by the AG-9 elastin-derived peptide (EDP), PDAC cells secrete more tumour-derived EVs. Compared to PDAC-derived EVs, tumour-derived EVs resulting from AG-9 treatment (PDAC AG-9-derived EVs) significantly stimulated cell proliferation. At constant amount, tumour-derived EVs were similarly taken up by PDAC and HMEC-1 cells. Tumour-derived EVs stimulated cell proliferation, migration, proteinase secretion, and angiogenesis. Bioluminescence imaging allowed tumour-derived EV/FLuc+ tracking in vivo in a PDAC mouse model. The biodistribution of PDAC AG-9-derived EVs was different to PDAC-derived EVs. Our results demonstrate that the microenvironment, through EDP release, may not only influence the genesis of EVs but may also affect tumour progression (tumour growth and angiogenesis), and metastatic homing by modifying the in vivo biodistribution of tumour-derived EVs. They are potential candidates for targeted drug delivery and modulation of tumour progression, and they constitute a new generation of therapeutic tools, merging oncology and genic therapy.

The assessment and detection rate of intrinsic capacity deficits among older adults: a systematic review and meta-analysis.

BACKGROUND: Assessing and monitoring intrinsic capacity (IC) is an effective strategy to promote healthy ageing by intervening early in high-risk populations. This review systematically analyzed the global detection rates of IC deficits and explored variations across diverse populations and data collection methods. METHODS: This study was preregistered with PROSPERO, CRD42023477315. In this systematic review and meta-analysis, we systematically searched ten databases from January 2015 to October 2023, for peer-reviewed, observational studies or baseline survey of trials that assessed IC deficits among older adults aged 50 and above globally following the condition, context and population approach. The main outcome was intrinsic capacity deficits which could be assessed by any tools. Meta-analyses were performed by a random-effect model to pool the detection rates across studies and subgroup analyses were conducted by populations and data collection methods. RESULTS: Fifty-six studies conducted in 13 countries were included in the review and 44 studies with detection rates of IC were included in the meta-analysis. The pooled detection rate of IC deficits was 72.0% (65.2%-78.8%) and deficits were most detected in sensory (49.3%), followed by locomotion (40.0%), cognition (33.1%), psychology (21.9%), and vitality (20.1%). Variations in detection rates of IC deficits were observed across studies, with higher rates observed in low- and middle-income countries (74.0%) and hyper-aged societies (85.0%). Study population and measurement tools also explained the high heterogeneity across studies. CONCLUSION: IC deficits are common among older adults, while heterogeneity exists across populations and by measurement. Early monitoring with standardized tools and early intervention on specific subdomains of IC deficits are greatly needed for effective strategies to promote healthy ageing.

Are telocytes related to maintenance of vascular homeostasis in normal and pathological aorta?

The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm or acute dissection (TAAD). In normal aortas the TCs were distributed throughout the connective tissue of the adventitial layer, in its innermost portion and at the zone of transition with the medial layer, with their long axes oriented parallel to the external elastic lamellae, forming a three-dimensional network, without prevalence in the media layer. In contrast, TAAD TCs were present in the medial layer and in regions of neovascularization. The most important feature of the adventitia of diseased aortas was the presence of numerous contacts between TCs and stem cells, including vascular progenitor cells. Although the biologically functional correlations need to be elucidated, the morphological observations presented here provide strong evidence of the involvement of TCs in maintaining vascular homeostasis in pathological situations of tissue injury.

LIPCAR levels in plasma-derived extracellular vesicles is associated with left ventricle remodeling post-myocardial infarction.

BACKGROUND: Long Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known. The aims of this study are (1) to characterize the transporter of LIPCAR from heart to circulation; (2) to determine whether LIPCAR levels in plasma isolated-extracellular vesicles (EVs) reflect the alteration of its expression in total plasma and could be used as biomarkers of LVR post-MI. METHODS: Since expression of LIPCAR is restricted to human species and the limitation of availability of cardiac biopsy samples, serum-free conditioned culture media from HeLa cells were first used to characterize the extracellular transporter of LIPCAR before validation in EVs isolated from human cardiac biopsies (non-failing and ischemic HF patients) and plasma samples (patients who develop or not LVR post-MI). Differential centrifugation at 20,000g and 100,000g were performed to isolate the large (lEVs) and small EVs (sEVs), respectively. Western blot and nanoparticle tracking (NTA) analysis were used to characterize the isolated EVs. qRT-PCR analysis was used to quantify LIPCAR in all samples. RESULTS: We showed that LIPCAR is present in both lEVs and sEVs isolated from all samples. The levels of LIPCAR are higher in lEVs compared to sEVs isolated from HeLa conditioned culture media and cardiac biopsies. No difference of LIPCAR expression was observed in tissue or EVs isolated from cardiac biopsies obtained from ischemic HF patients compared to non-failing patients. Interestingly, LIPCAR levels were increased in lEVs and sEVs isolated from MI patients who develop LVR compared to patients who did not develop LVR. CONCLUSION: Our data showed that large EVs are the main extracellular vesicle transporter of LIPCAR from heart into the circulation independently of the status, non-failing or HF, in patients. The levels of LIPCAR in EVs isolated from plasma could be used as biomarkers of LVR in post-MI patients.

Vaccines in Long-Term Care Settings: A Narrative Review.

BACKGROUND: Older people living in long-term care facilities represent a particularly vulnerable segment of the population, who disproportionately bear the burden of infectious diseases, as recently highlighted by the COVID-19 pandemic. SUMMARY: Older long-term care residents typically cumulate several risk factors for infection and experience serious life-threatening outcomes once infected. These common infections are often compounded by the collective living environment, where it is more difficult to contain the spread of infection. Moreover, the staff may represent an additional reservoir of potential infection and mode of transmission. In this paper, we review the burden of infectious respiratory diseases in residents in long-term care and discuss the potential gains from higher vaccine coverage in this older and most vulnerable population but also from higher vaccine coverage among the facility staff. We highlight the compelling need to integrate specific vaccine recommendations for residents of long-term care into national vaccination schedules, as well as the need to include vaccination campaigns in routine protocols for infection control. Surveillance, reporting, hygiene, and individual protective measures remain key aspects in basic infection control, both in ordinary times and during epidemics. KEY MESSAGE: Vaccination of residents in long-term care facilities against respiratory diseases including influenza, pneumococcal disease, pertussis, and COVID is a simple, inexpensive, and effective means to reduce the burden of infection in this segment of the population.

Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression.

AIMS: IgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression. METHODS AND RESULTS: Through histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression. CONCLUSIONS: Our data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.

Colonization routes uncovered in a widely introduced Mediterranean gecko, Tarentola mauritanica.

In this study, we aimed to understand the contemporary and ancient colonization routes of the Moorish gecko, Tarentola mauritanica, using simple sequence repeats. By analyzing the genetic diversity of populations in different regions, we found that Morocco is the genetic diversity hotspot for the species, followed by the Iberian Peninsula. However, historical gene flow estimates identified the Iberian Peninsula, not Morocco, as the primary contributor of colonizing individuals, along with continental Italy to a lesser extent. Currently, mainland Italy is the main source of introduced individuals, likely due to the plant nursery trade. The study suggests that human-facilitated introductions from various geographical origins, with numerous regions colonized through continental Italy during two distinct periods, are responsible for the recurrent entry of individuals belonging to the European lineage of T. mauritanica into the Mediterranean and Macaronesia. These findings can inform better monitoring surveys and conservation programs by identifying putative current colonization routes of alien species.

Thermodynamic and structural properties of lipid-photosensitizer conjugates mixed with phospholipids: Impact on the formation and stability of nano-assemblies.

The photosensitizer Phenalenone (PN) was grafted with one or two lipid (C18) chains to form pure nano-assemblies or mixed lipid vesicles suitable for photodynamic therapy. Mixtures of PN-C18 conjugates with stearoyl-oleoyl phosphatidylcholine (SOPC) form vesicles that disintegrate into bilayer sheets as the concentration of PN-C18 conjugates increases. We hypothesized that PN-C18 conjugates control the thermodynamic and structural properties of the mixtures and induce the disintegration of vesicles due to PN π-π-interactions. Monolayers were analyzed by surface pressure and grazing incidence X-ray diffraction (GIXD) measurements, and vesicles by differential scanning calorimetry and cryo-TEM. The results showed that PN-triazole-C18 (1A) and PN-NH-C18 (1B) segregate from the phospholipid domains. PN-(C18)2 (conjugate 2) develops favorable interactions with SOPC and distearoyl-phosphatidylcholine (DSPC). GIXD demonstrates the contribution of SOPC to the structuring of conjugate 2 and the role of the major component in controlling the structural properties of DSPC-conjugate 2 mixtures. Above 10 mol% conjugate 2 in SOPC vesicles, the coexistence of domains with different molecule packing leads to conjugate segregation, vesicle deformation, and the formation of small bilayer discs stabilized by the inter-bilayer π-π stacking of PN molecules.

Diminished Physical Activity in Older Hospitalised Patients with and without COVID-19.

Acute viral respiratory infections have proven to be a major health threat, even after the Corona Virus Disease 2019 (COVID-19) pandemic. We aimed to check whether the presence or absence of an acute respiratory infection such as COVID-19 can influence the physical activity of older hospitalised patients. We cross-sectionally studied patients aged ≥60 years, hospitalized during the pandemic in the non-COVID-19 and COVID-19 ward at the University Hospital, Kraków, Poland. Using activPAL3® technology, we assessed physical activity for 24 h upon admission and discharge. In addition, we applied the sarcopenia screening tool (SARC-F); measured the hand grip strength and calf circumference; and assessed the Modified Early Warning Score (MEWS), age-adjusted Charlson Index, SpO2%, and length of stay (LoS). Data were analysed using SAS 9.4. The mean (min, max) age of the 31 (58% women, eight with COVID-19) consecutive patients was 79.0 (62, 101, respectively) years. The daily time (activPAL3®, median [p5, p95], in hours) spent sitting or reclining was 23.7 [17.2, 24] upon admission and 23.5 [17.8, 24] at discharge. The time spent standing was 0.23 [0.0, 5.0] upon admission and 0.4 [0.0, 4.6] at discharge. The corresponding values for walking were 0.0 [0.0, 0.4] and 0.1 [0.0, 0.5]. SARC-F, admission hand grip strength, calf circumference, and LoS were correlated with physical activity upon admission and discharge (all p < 0.04). For every unit increase in SARC-F, there was a 0.07 h shorter walking time upon discharge. None of the above results differed between patients with and without COVID-19. The level of physical activity in older patients hospitalised during the pandemic was low, and was dependent on muscular function upon admission but not on COVID-19 status. This has ramifications for scenarios other than pandemic clinical scenarios.

Facile Synthesis of Ge@TiO2 Nanotube Hybrid Nanostructure Anode Materials for Li-Ion Batteries.

Utilizing nanostructures of Li-alloying anode materials (e.g., Si, Ge, Sn, etc.) has been proposed as a key strategy to improve the electrochemical performance. However, the main challenge lies in the costly and complex nanostructure synthesis processes. Notably, the nanostructure growth processes are mainly supported by Li-inactive templates, which later need to be removed, and the template removal process results in the destruction of the desired nanostructures. In this report, we demonstrated the use of a Li-active, self-organized TiO2 nanotube template to fabricate germanium (Ge)-based nanostructured anodes. This has been achieved as follows: first, TiO2 nanotubes are fabricated via electrochemical anodization of titanium foil. Then, the nanotubes are coated with a Ge film in the second step via electrodeposition. Besides the effective nanostructure growth using a Li-active template, the implemented electrochemical synthesis methods are cost-effective, accessible, and scalable. Furthermore, the electrochemical methods allow the fabrication of nanostructures with well-controlled structures, morphology, and compositions. Accordingly, a Ge-coated TiO2 nanotube (Ge@TiO2) nanocomposite anode has been successfully fabricated, and its electrochemical performance has been tested for Li-ion batteries. The study has shown the important roles of TiO2 nanotube arrays in improving the performance by providing strong mechanical support to buffer the volume expansion and offering a high surface area to enhance Ge-active mass loading. Moreover, the direct contact of the nanotubes with a Ti current collector facilitates one-dimensional (1D) electron transport and avoids the need of adding inactive binders or conductive additives.

Financial and relational impact of having a boy with posterior urethral valves.

Introduction: Childhood chronic diseases affect family functioning and well-being. The aim of this study was to measure the impact of caring for a child with PUV, and the factors that most impact the burden of care. Patients and method: We gave a questionnaire on the familial impact of having a child with posterior urethral valves to all parents of a child included in the CIRCUP trial from 2015 onwards. The questionnaire included questions about the parents' demographics, health, professional, financial and marital status and how these evolved since the child's birth as well as the "impact on family scale" (IOFS), which gives a total score ranging from 15 (no impact) to 60 (maximum impact). We then analyzed both the results of the specific demographic questions as well as the factors which influenced the IOFS score. Results: We retrieved answers for 38/51 families (74.5% response rate). The average IOFS score was 23.7 (15-51). We observed that the child's creatinine level had an effect on the IOFS score (p = 0.02), as did the parent's gender (p = 0.008), health status (p = 0.015), being limited in activity since the birth of the child (p = 0.020), being penalized in one's job (p = 0.009), being supported in one's job (p = 0.002), and decreased income (p = 0.004). Out of 38 mother/father binomials, 8/33 (24.2%) declared that they were no longer in the same relationship afterwards. Conclusion: In conclusion, having a boy with PUV significantly impacts families. The risk of parental separation and decrease in revenue is significant. Strategies aiming to decrease these factors should be put in place as soon as possible.

Fucoidan-coated coils improve healing in a rabbit elastase aneurysm model.

BACKGROUND: Recanalization of coiled aneurysms remains unresolved. To limit aneurysm recanalization after embolization with coils, we propose an innovative approach to optimize aneurysm healing using fucoidan-coated coils. OBJECTIVE: To evaluate the short-term efficacy and long-term safety of the new coil system with conventional angiography, histology, and multiphoton microscopy for follow-up of fibrosis and neointima formation. METHODS: We conducted a feasibility study on rabbit elastase-induced aneurysms. Embolization was carried out with bare platinum coils, fucoidan-coated coils, or dextran-coated coils. Aneurysms were controlled after 1 month by digital subtraction angiography (DSA). Aneurysm samples were collected and processed for histological analysis. Aneurysm healing and fibrosis were measured by quantifying collagen according to the histological healing score by combining standard light microscopy and multiphoton imaging. We divided 27 rabbits into three groups: bare platinum group, fucoidan group, and dextran group as controls. RESULTS: Angiographic grading showed a trend toward less recanalization in the fucoidan group, although there were no significant differences among the three groups (P=0.21). Histological healing was significantly different according to the presence of more collagen in the neck area of aneurysms in the fucoidan group versus the bare platinum group (P=0.011), but not in the dextran group. Histological index was significantly better at the aneurysm neck in the fucoidan group than in the bare platinum group (P=0.004). Collagen organization index was also significantly better in the fucoidan group than in the bare platinum group (P=0.007). CONCLUSION: This proof-of-concept study demonstrated the feasibility and efficacy of treatment with fucoidan-coated coils to improve aneurysm healing. The results in this rabbit in vivo model showed that fucoidan-coated coils have the potential to improve healing following endovascular treatment.

A novel online training programme for healthcare professionals caring for older adults.

The proportion of older people in the world population is growing rapidly. Training and retaining healthcare professionals in sufficient numbers in the field of ageing represents a major challenge for the future, to deal with the healthcare needs of this ageing population. The COVID pandemic has unfortunately compounded shortages of healthcare workers worldwide. There is therefore a pressing need to scale-up the education of healthcare professionals in geriatrics and gerontology. Over the last 30 years, a group of motivated geriatrics physicians from Europe have been striving to educate healthcare professionals in geriatrics and gerontology through various initiatives, and using innovative pedagogic approaches to train physicians, nurses and other healthcare professionals around the world. The COVID-19 pandemic unfortunately put a stop to presence-based training programmes, but prompted the development of the online International Association of Gerontology and Geriatrics (IAGG) eTRIGGER (e-Training In Geriatrics and GERontology) course, a new training course in geriatrics and gerontology for healthcare professionals from a wide range of backgrounds. We outline here the history of the educational initiatives that have culminated in the roll-out of this new programme, and the perspectives for the future.

Dementia, infections and vaccines: 30 years of controversy.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.

Life Course Education, Health, and Ageing Well: A Short Inter-Academic Report.

After the first wave of the COVID-19 pandemic, during which the severity of the disease in certain countries was attributed to a lack of basic education of the inhabitants, the authors of this paper initiated a literature review of educational trajectories, health, and ageing well. The findings strongly demonstrate that alongside genetics, the affective and educational family environment, as well as the general environment, greatly interact starting from the very first days of life. Thus, epigenetics plays a major role in the determination of health and disease [DOHAD] in the first 1,000 days of life as well as in the characterization of gender. Other factors such as socio-economic level, parental education, schooling in urban or rural areas, also play a major role in the differential acquisition of health literacy. This determines adherence (or lack thereof) to healthy lifestyles, risky behaviours, substance abuse, but also compliance with hygiene rules, and adherence to vaccines and treatments. The combination of all these elements and lifestyle choices facilitates the emergence of metabolic disorders (obesity, diabetes), which promote cardiovascular and kidney damage, and neurodegenerative diseases, explaining that the less well educated have shorter survival and spend more years of life in disability. After having demonstrated the impact of the educational level on health and longevity, the members of this inter-academic group propose specific educational actions at three levels: (1) teachers and health professionals, (2) parents, (3) the public, emphasizing that these crucial actions can only be carried out with the unfailing support of state and academic authorities.