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Functional dependence for the performance of basic activities of daily living (ADLs) is one of the main causes of institutionalization. This study analyzed the interrelationships between basic and instrumental activities of daily living, use of assistive mobility devices, socioeconomic factors, changes during COVID-19 pandemic confinement, and 3-year survival in the ADL-dependent people of the Orcasitas neighborhood of Madrid (Spain). A longitudinal descriptive study, carried out on the entire population of functional dependent patients (Barthel ≤ 60) in the Orcasitas neighborhood. We included 127 patients, 78.7% women and 21.3% men, with a mean age of 86 years. Pre-pandemic, post-confinement (June 2020) and June 2023 data were contrasted. Results: The use of crutches-cane was associated with a higher probability of being independent in performing ADLs, leaving home (OR 4.848; CI 1.428-16.458), improving functional capacity during confinement (OR 3.621; CI 1.409-9.308), and even ceasing to be functionally dependent (OR 0.394; CI 0.165-0.941). Using a wheelchair was associated with a higher level of dependency (OR 2.583; CI 1.167-5.714) and higher mortality (HR 1.913; CI 1.106-3.309). After COVID-19 pandemic confinement, having a financial income of less than 11,200 euros/year (OR 2.413; CI 1.159-5.023), or using a wheelchair (OR 2.464; CI 1.009-6.017), increased the risk of living homebound. Living homebound decreased the probability of survival, while maintaining the ability to leave home increased it (OR 3.880; CI 1.834-8.211). Economic capacity modulated the results. Lower economic capacity was associated with higher mortality (HR 2.47 (Exp(B) 0.405; CI 0.232-0.708). Living in confinement and having a low economic income were associated with higher mortality (OR 0.127; CI 0.029-0.562), mortality that was also higher with respect to those who could leave their home (OR 6.697; CI 2.084-21.525). Functional ADL-dependence affects multiple facets of the person. Confinement triggered changes in the baseline conditions of this cohort, which were influenced by the level of dependency, mobility capacity and economic income level. Economic capacity modulated the results, showing that social inequalities influence survival. The ability to leave home and the use of a wheelchair should be included in the assessment of the risk level of this population group.

Functional dependence for the performance of basic activities of daily living (ADLs) is one of the main causes of institutionalization. This study analyzed the interrelationships between basic and instrumental activities of daily living, use of assistive mobility devices, socioeconomic factors, changes during COVID-19 pandemic confinement, and 3-year survival in the ADL-dependent people of the Orcasitas neighborhood of Madrid (Spain). A longitudinal descriptive study, carried out on the entire population of functional dependent patients (Barthel [less than or equal to] 60) in the Orcasitas neighborhood. We included 127 patients, 78.7% women and 21.3% men, with a mean age of 86 years. Pre-pandemic, post-confinement (June 2020) and June 2023 data were contrasted. Functional ADL-dependence affects multiple facets of the person. Confinement triggered changes in the baseline conditions of this cohort, which were influenced by the level of dependency, mobility capacity and economic income level. Economic capacity modulated the results, showing that social inequalities influence survival. The ability to leave home and the use of a wheelchair should be included in the assessment of the risk level of this population group.

The overexpression of α 2 δ-1 is related to the development and degree of malignancy of diverse types of cancer. This protein is an auxiliary subunit of voltage-gated Ca 2+ (Ca V ) channels, whose expression favors the trafficking of the main pore-forming subunit of the channel complex (α 1 ) to the plasma membrane, thereby generating an increase in Ca 2+ entry. Interestingly, TLR-4, a protein belonging to the family of toll-like receptors that participate in the inflammatory response and the transcription factor Sp1, have been linked to the progression of glioblastoma multiforme (GBM). Therefore, this report aimed to evaluate the role of the α 2 δ-1 subunit in the progression of GBM and investigate whether Sp1 regulates its expression after the activation of TLR-4. To this end, the expression of α 2 δ-1, TLR-4, and Sp1 was assessed in the U87 human glioblastoma cell line, and proliferation and migration assays were conducted using different agonists and antagonists. The actions of α 2 δ-1 were also investigated using overexpression and knockdown strategies. Initial luciferase assays and Western blot analyses showed that the activation of TLR-4 favors the transcription and expression of α 2 δ-1, which promoted the proliferation and migration of the U87 cells. Consistent with this, overexpression of α 2 δ-1, Sp1, and TLR-4 increased cell proliferation and migration, while their knockdown with specific siRNAs abrogated these actions. Our data also suggest that TLR-4-mediated regulation of α 2 δ-1 expression occurs through the NF-kB signaling pathway. Together, these findings strongly suggest that the activation of TLR-4 increases the expression of α 2 δ-1 in U87 cells, favoring their proliferative and migratory potential, which might eventually provide a theoretical basis to examine novel biomarkers and molecular targets for the diagnosis and treatment of GBM.

Cardiovascular disease (CVD) is the leading cause of death worldwide. With atherosclerosis as the underlying cause for many CVD events, prevention or reduction of subclinical atherosclerotic plaque burden (SAPB) through a healthier lifestyle may have substantial public health benefits. The objective was to describe the protocol of a randomized controlled trial investigating the effectiveness of a 30-month worksite-based lifestyle program aimed to promote cardiovascular health in participants having a high or a low degree of SAPB compared with standard care. We will conduct a randomized controlled trial including middle-aged bank employees from the Progression of Early Subclinical Atherosclerosis cohort, stratified by SAPB (high SAPB n=260, low SAPB n=590). Within each stratum, participants will be randomized 1:1 to receive a lifestyle program or standard care. The program consists of 3 elements: (a) 12 personalized lifestyle counseling sessions using Motivational Interviewing over a 30-month period, (b) a wrist-worn physical activity tracker, and (c) a sit-stand workstation. Primary outcome measure is a composite score of blood pressure, physical activity, sedentary time, body weight, diet, and smoking (ie, adapted Fuster-BEWAT score) measured at baseline and at 1-, 2-, and 3-year follow-up. The study will provide insights into the effectiveness of a 30-month worksite-based lifestyle program to promote cardiovascular health compared with standard care in participants with a high or low degree of SAPB.

Emerging evidence suggests that the adenosine (Ado) receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer. Together, these data suggest important roles of the A2B receptors and NaV1.5 channels in the Ado-induced increase in proliferation and migration of the MDA-MB 231 cells.

Neuropathic pain is one of the primary forms of chronic pain and is the consequence of the somatosensory system’s direct injury or disease. It is a relevant public health problem that affects about 10% of the world’s general population. In neuropathic pain, alteration in neurotransmission occurs at various levels, including the dorsal root ganglia, the spinal cord, and the brain, resulting from the malfunction of diverse molecules such as receptors, ion channels, and elements of specific intracellular signaling pathways. In this context, there have been exciting advances in elucidating neuropathic pain’s cellular and molecular mechanisms in the last decade, including the possible role that long non-coding RNAs (lncRNAs) may play, which open up new alternatives for the development of diagnostic and therapeutic strategies for this condition. This review focuses on recent studies associated with the possible relevance of lncRNAs in the development and maintenance of neuropathic pain through their actions on the functional expression of ion channels. Recognizing the changes in the function and spatio-temporal patterns of expression of these membrane proteins is crucial to understanding the control of neuronal excitability in chronic pain syndromes.

The overexpression of [alpha].sub.2 [delta]-1 is related to the development and degree of malignancy of diverse types of cancer. This protein is an auxiliary subunit of voltage-gated Ca.sup.2+ (Ca.sub.V) channels, whose expression favors the trafficking of the main pore-forming subunit of the channel complex ([alpha].sub.1) to the plasma membrane, thereby generating an increase in Ca.sup.2+ entry. Interestingly, TLR-4, a protein belonging to the family of toll-like receptors that participate in the inflammatory response and the transcription factor Sp1, have been linked to the progression of glioblastoma multiforme (GBM). Therefore, this report aimed to evaluate the role of the [alpha].sub.2 [delta]-1 subunit in the progression of GBM and investigate whether Sp1 regulates its expression after the activation of TLR-4. To this end, the expression of [alpha].sub.2 [delta]-1, TLR-4, and Sp1 was assessed in the U87 human glioblastoma cell line, and proliferation and migration assays were conducted using different agonists and antagonists. The actions of [alpha].sub.2 [delta]-1 were also investigated using overexpression and knockdown strategies. Initial luciferase assays and Western blot analyses showed that the activation of TLR-4 favors the transcription and expression of [alpha].sub.2 [delta]-1, which promoted the proliferation and migration of the U87 cells. Consistent with this, overexpression of [alpha].sub.2 [delta]-1, Sp1, and TLR-4 increased cell proliferation and migration, while their knockdown with specific siRNAs abrogated these actions. Our data also suggest that TLR-4-mediated regulation of [alpha].sub.2 [delta]-1 expression occurs through the NF-kB signaling pathway. Together, these findings strongly suggest that the activation of TLR-4 increases the expression of [alpha].sub.2 [delta]-1 in U87 cells, favoring their proliferative and migratory potential, which might eventually provide a theoretical basis to examine novel biomarkers and molecular targets for the diagnosis and treatment of GBM.

Functional dependence for the performance of basic activities of daily living (ADLs) is one of the main causes of institutionalization. This study analyzed the interrelationships between basic and instrumental activities of daily living, use of assistive mobility devices, socioeconomic factors, changes during COVID-19 pandemic confinement, and 3-year survival in the ADL-dependent people of the Orcasitas neighborhood of Madrid (Spain). A longitudinal descriptive study, carried out on the entire population of functional dependent patients (Barthel [less than or equal to] 60) in the Orcasitas neighborhood. We included 127 patients, 78.7% women and 21.3% men, with a mean age of 86 years. Pre-pandemic, post-confinement (June 2020) and June 2023 data were contrasted. Functional ADL-dependence affects multiple facets of the person. Confinement triggered changes in the baseline conditions of this cohort, which were influenced by the level of dependency, mobility capacity and economic income level. Economic capacity modulated the results, showing that social inequalities influence survival. The ability to leave home and the use of a wheelchair should be included in the assessment of the risk level of this population group.