Search Results (30)

Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), cancer stemness, extracellular matrix (ECM) remodelling, and activation of key signalling pathways such as Wingless/Integrated (Wnt) Wnt/β-catenin and PI3K/Akt. Hypoxia also enhances the secretion of extracellular vesicles (EVs), enriched with pro-metastatic cargos, and upregulates bone-homing molecules including CXCR4, integrins, and PIM kinases, fostering pre-metastatic niche formation and skeletal colonisation. In this review, we analysed current evidence on how hypoxia orchestrates PCa dissemination to bone, focusing on the molecular crosstalk between HIF signalling, Wnt activation, EV-mediated communication, and cellular plasticity. We further explore therapeutic strategies targeting hypoxia-related pathways, such as HIF inhibitors, hypoxia-activated prodrugs, and Wnt antagonists, with an emphasis on overcoming therapy resistance in castration-resistant PCa (CRPC). By examining the mechanistic underpinnings of hypoxia-driven bone metastasis, we highlight promising translational avenues for improving patient outcomes in advanced PCa. Full article

Background: During the last two decades, a limited number of studies have provided echocardiographic details regarding the cardiac structure and function of individuals aged ≥100 years. These studies analyzed limited sample sizes of centenarians using different methodologies. The present systematic review was primarily designed to summarize the main findings of these studies and to examine the overall influence of extremely advanced age on cardiac structure and function. Methods: All echocardiographic studies that evaluated the cardiac structure and function in individuals aged ≥100 years, selected from the PubMed, Embase, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases, were included. There was no limitation on the time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: A total of eight studies with 1340 centenarians [median age 101.4 years (IQR 101–103 years)] met the eligibility criteria and were analyzed. The centenarians were predominantly females [76.3% (IQR 60–85%)] with a small body surface area, long history of hypertension and slightly impaired renal functional reserve. The centenarian population showed a reduced burden of cardiovascular disease but an increased comorbidity burden, as assessed using the Charlson [median value 3.7 (IQR 1.8–5.5)] and Katz [median value 2.1 (IQR 1.1–3.1)] indexes. The echocardiographic findings comprised left ventricular (LV) concentric remodeling, with first-degree diastolic dysfunction [median E/A ratio 0.8 (IQR 0.7–0.9)], a moderate increase in LV filling pressure [median E/e’ ratio 16.8 (IQR 16.2–17)], normal LV systolic function [median left ventricular ejection fraction (LVEF) 60.9% (IQR 55–84%)] and mild-to-moderate pulmonary hypertension [median systolic pulmonary artery pressure 42.1 mmHg (IQR 37–54 mmHg)]. The pooled prevalence of LV systolic dysfunction (LVEF < 50%) was 15.8%. Moderate-to-severe valvular heart diseases were detected in less than one-third of the centenarians. Compared with the outpatient and in-home cohorts, hospitalized centenarians were less commonly females and were more likely to be affected by significant LV hypertrophy with a supra-normal LVEF, higher degrees of valvulopathies and impaired pulmonary hemodynamics. Conclusions: The evidence currently suggests that centenarians have typical LV concentric remodeling with increased myocardial stiffness and diastolic dysfunction, which predispose them to heart failure with a preserved ejection fraction (HFpEF). Cardioprotective treatment should be considered for personalized implementation and uptitration in this special population. Full article

The design of age-friendly homes benefits vulnerable groups, such as frail people and older adults. Advances in smart home technologies, including robots, have important synergies with homes designed for health needs. Yet, focus on environmental and sustainable housing design and improvements misses important opportunities for collective impact. Stronger involvement of disciplines, such as those from the built environment for technological integration within homes and effects on space and the community, is needed. There is a need for a unified framework integrating the needs and factors of the resident, smart home technologies and robots, and the built environment, and that includes the concept of a “home”. With the remodeling of housing towards sustainable and environmental targets, as well as advances in smart home technologies such as robots, the timeliness of shared input for the benefit of residents now and in the future is of the essence. This would help target future research into effective and optimized cohabitation with technology within homes for the purpose of improving the wellbeing of residents. Full article

Tauroursodeoxycholic acid (TUDCA) increases the influx of primary bile acids into the gut. Results obtained on animal models suggested that Firmicutes and Proteobacteria phyla are more resistant to bile acids in rats. As part of a pilot study investigating the role of probiotics supplementation in elderly people with home enteral nutrition (HEN), a case of a 92-year-old woman with HEN is reported in the present study. She lives in a nursing home and suffers from Alzheimer’s disease (AD); the patient had been prescribed TUDCA for lithiasis cholangitis. The aim of this case report is therefore to investigate whether long-term TUDCA administration may play a role in altering the patient’s gut microbiota (GM) and the impact of an antibiotic therapy on the diversity of microbial species. Using next generation sequencing (NGS) analysis of the bacterial 16S ribosomal RNA (rRNA) gene a dominant shift toward Firmicutes and a remodeling in Proteobacteria abundance was observed in the woman’s gut microbiota. Considering the patient’s age, health status and type of diet, we would have expected to find a GM with a prevalence of Bacteroidetes phylum. This represents the first study investigating the possible TUDCA’s effect on human GM. Full article

The main problem this article addresses is that women are more vulnerable than men in economic terms. The aim of this research is to identify the differences in the destination of savings according to gender and its implications related to their economic rights. Chi-Square tests were performed to test for the existence of statistically significant differences in the destination of men’s and women’s savings, based on the National Survey on the Destination of Savings in Mexico (ENIF). The hypothesis to be tested is that there is a gender difference in the way in which the destination of savings is allocated. As a result, it is possible to see that women focus their savings on issues related to health and education at home, in contrast to men, who tend to protect their own economic future by focusing their savings on remodeling or buying real estate or starting or expanding a business. In this sense, the hypothesis is partially verified in 4 of the 8 savings destinations. This article is motivated by the desire to identify this possible economic gap between genders, considering that it is an issue that affects the economic and personal future of women. Full article

The deposition of stem cells at sites of injury is a clinically relevant approach to facilitate tissue repair and angiogenesis. However, insufficient cell engraftment and survival require the engineering of novel scaffolds. Here, a regular network of microscopic poly(lactic-co-glycolic acid) (PLGA) filaments was investigated as a promising biodegradable scaffold for human Adipose-Derived Stem Cell (hADSC) tissue integration. Via soft lithography, three different microstructured fabrics were realized where 5 × 5 and 5 × 3 μm PLGA ‘warp’ and ‘weft’ filaments crossed perpendicularly with pitch distances of 5, 10 and 20 μm. After hADSC seeding, cell viability, actin cytoskeleton, spatial organization and the secretome were characterized and compared to conventional substrates, including collagen layers. On the PLGA fabric, hADSC re-assembled to form spheroidal-like structures, preserving cell viability and favoring a nonlinear actin organization. Moreover, the secretion of specific factors involved in angiogenesis, the remodeling of the extracellular matrix and stem cell homing was favored on the PLGA fabric as compared to that which occurred on conventional substrates. The paracrine activity of hADSC was microstructure-dependent, with 5 μm PLGA fabric enhancing the expression of factors involved in all three processes. Although more studies are needed, the proposed PLGA fabric would represent a promising alternative to conventional collagen substrates for stem cell implantation and angiogenesis induction. Full article

Buildings are responsible for significant energy consumption and carbon emissions. Green buildings, which incorporate advanced building technologies, offer a solution to reducing energy use. However, high costs associated with green building development present a barrier to widespread adoption. Retrofit projects, involving remodeling, renovation, and redevelopment of existing buildings, offer a viable solution. While prior studies have examined the cost analysis of green and non-green buildings, there is a lack of evidence comparing new and retrofit projects. This study aims to address this gap by providing empirical evidence for the cost decomposition and benefits of new and retrofit projects. Data on energy use, building technology, and costs from 235 certified green homes in the United States were collected, and cost benefits were evaluated. Results show that retrofit projects cost, on average, $1270.5/m² ($118.0/ft²), which is 30% less than new projects. Land acquisition and development account for 35% of retrofit costs, six times greater than new projects. Excluding land costs, retrofit projects cost, on average, $733.88/m² ($68.2/ft²), 49% less than new projects. Retrofit projects use similar building technologies as new projects and produce larger energy savings. The cost-benefit values generated by retrofit projects are 86% greater than new projects when considering land costs and 142% greater without considering land costs. These findings contribute to cost management for complex building projects and energy policy for sustainable development. Retrofitting offers great potential to promote the green building movement and suggests effective subsidy programs as a public policy implication. Full article

Asthma is the most common chronic disease of the respiratory system in children and the number of new cases is constantly increasing. It is characterized by dyspnea, wheezing, tightness in the chest, or coughing. Due to diagnostic difficulties, disease monitoring, and the selection of safe and effective drugs, it has been shown that among the youngest patients, miRNAs fulfilling the above roles can be successfully used in common clinical practice. These biomolecules, by regulating the expression of the body’s genes, influence various biological processes underlying the pathogenesis of asthma, such as the inflammatory process, remodeling, and intensification of airway obstruction. They can be detected in blood serum and in exhaled breath condensate (EBC). Among children, common factors responsible for the onset or exacerbation of asthma, such as infections, allergens, air pollution, or tobacco smoke present in the home environment, cause a change the concentration of miRNAs in the body. This is related to their significant impact on the modulation of the disease process. In the following paper, we review the latest knowledge on miRNAs and their use, especially as diagnostic markers in assessing asthma exacerbation, with particular emphasis on the pediatric population. Full article

Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases. Full article

Ischemic heart disease (IHD) is one of the main focuses in today’s healthcare due to its implications and complications, and it is predicted to be increasing in prevalence due to the ageing population. Although the conventional pharmacological and interventional methods for the treatment of IHD presents with success in the clinical setting, the long-term complications of cardiac insufficiency are on a continual incline as a result of post-infarction remodeling of the cardiac tissue. The migration and involvement of stem cells to the cardiac muscle, followed by differentiation into cardiac myocytes, has been proven to be the natural process, though at a slow rate. SDF-1α is a novel candidate to mobilize stem cells homing to the ischemic heart. Endogenous SDF-1α levels are elevated after myocardial infarction, but their presence gradually decreases after approximately seven days. Additional administration of SDF-1α-releasing microspheres could be a tool for the extension of the time the stem cells are in the cardiac tissue after myocardial infarction. This, in turn, could constitute a novel therapy for more efficient regeneration of the heart muscle after injury. Through this practical study, it has been shown that the controlled release of SDF-1α from biodegradable microspheres into the pericardial sac fourteen days after myocardial infarction increases the concentration of exogenous SDF-1α, which persists in the tissue much longer than the level of endogenous SDF-1α. In addition, administration of SDF-1α-releasing microspheres increased the expression of the factors potentially involved in the involvement and retention of myocardial stem cells, which constitutes vascular endothelial growth factor A (VEGFA), stem cell factor (SCF), and vascular cell adhesion molecules (VCAMs) at the site of damaged tissue. This exhibits the possibility of combating the basic limitations of cell therapy, including ineffective stem cell implantation and the ability to induce the migration of endogenous stem cells to the ischemic cardiac tissue and promote heart repair. Full article

There have been changes in social attitudes in recent years. These changes have been a consequence of a new societal view of the common good, which manifests itself in social responsibility for a clean and healthy environment. The outbreak and spread of the COVID-19 epidemic has highlighted the socio-spatial variation across regions and countries. The epidemic necessitated restrictive measures by state authorities. In the initial period in many countries, the actions of the authorities were identical throughout the country. This was mainly due to a lack of information about the differentiation of areas in relation to the epidemic risk. The aim of the research was to present a model for classifying rural areas taking into account vulnerability to epidemic threats. The model takes into account demographic, social, economic and spatial-environmental development factors. A total of 33 indicators based on public statistics that can be used to determine the area’s vulnerability to epidemic threats were identified. The study showed that for Poland, 11 indicators are statistically significant to the developed classification model. The study found that social factors were vital in determining an area’s vulnerability to epidemic threats. We include factors such as average number of persons per one apartment, village centers (number), events (number), number of people per facility (cultural center, community center, club, community hall), residents of nursing homes per 1000 inhabitants, and the number of children in pre-school education establishments per 1000 children aged 3–5 years. The research area was rural areas in Poland. The results of the classification and the methods used should be made available as a resource for crisis management. This will enable a better response to threats from other epidemics in the future, and will influence the remodeling of the environment and social behavior to reduce risks at this risk, which has a significant impact on sustainable development in rural areas. Full article

A remodeled sperm swarm optimization (RMSSO) algorithm for a home energy management (HEM) system is proposed, and its real-time efficacy was evaluated using a hardware experimental model. This home environment comprised sixteen residential loads, a smart meter and a Raspberry Pi controller to optimize the energy consumption cost (ECC) in response to the Indian day-ahead pricing (DAP) scheme. A wired/wireless communication network was considered to communicate with the smart meter and controller. To address this optimization problem, the sperm swarm optimization (SSO) algorithm’s constriction coefficient was remodeled to improve its global searching capability and proposed as RMSSO. For the first time, salp swarm optimization (SSA), SSO, and RMSSO algorithms were employed to schedule home appliances in the Indian scenario. To validate the proposed technique’s outcome, the results were compared to those of the conventional SSO and SSA algorithms. This problem was solved using the Python/GUROBI optimizer tool. As a consequence, consumers can use this control strategy in real-time to reduce energy consumption costs. Full article

Peritoneal dialysis is a feasible, cost-effective, home-based treatment of renal replacement therapy, based on the dialytic properties of the peritoneal membrane. As compared with hemodialysis, peritoneal dialysis is cheaper, survival rate is similar, residual kidney function is better preserved, fluid and solutes are removed more gradually and continuously leading to minimal impact on hemodynamics, and risks related to a vascular access are avoided. Those features of peritoneal dialysis are useful to treat refractory congestive heart failure patients with fluid overload. It was shown that in such patients, peritoneal dialysis improves functional status and quality of life, reduces hospitalization rate, and may decrease mortality rate. High levels of serum proinflammatory cytokines and fibrosis markers, among other factors, play an important part in congestive heart failure pathogenesis and progression. We demonstrated that those levels decreased following peritoneal dialysis treatment in refractory congestive heart failure patients. The exact mechanism of beneficial effect of peritoneal dialysis in refractory congestive heart failure is currently unknown. Maintenance of fluid balance, leading to resetting of neurohumoral activation towards a more physiological condition, reduced remodeling due to the decrease in mechanical pressure on the heart, decreased inflammatory cytokine levels and oxidative stress, and a potential impact on uremic toxins could play a role in this regard. In this paper, we describe the unique characteristics of the peritoneal membrane, principals of peritoneal dialysis and its role in heart failure patients. Full article

The provision of housing for the elderly in Spain has been approached from a public policy perspective to understand social housing and the allocation of specialized social services. The lockdowns in cities and the need to remain at home with social isolation and social distance has especially affected the most vulnerable groups, creating situations that widen the gap in the provision of adequate housing. Research is being carried out by a team of researchers at the University of Málaga, funded by European FEDER funds awarded by the Andalusian Regional Government (VIDA project), to analyze the main characteristics connected with “ideal” adequate housing for a vulnerable senior person living alone or in social isolation due to the quarantine period. In this study, we draw a line between the need for adequate housing, the chance to remodel, and the opportunity to propose new Spanish legal approaches from an architectural perspective within the scope of alternative typologies of housing. This article deals with the preliminary findings of the research connected to the architectural review, exploring key elements for senior housing design, and highlighting the need to approach the issue by proposing a new regulation. Full article

Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form “type H” capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling. Full article