A new paradigm of matrix metalloproteinase-2 (MMP-2) action in the heart undergoing oxidative stress has emerged. Although best known for its role in the proteolysis of extracellular protein targets, ...MMP-2 is also localized to the sarcomere within the cardiomyocyte. Oxidative stress activates full-length MMP-2 without need for proteolytic processing and inactivates an endogenous inhibitor, tissue inhibitor of metalloproteinase-4. MMP-2 proteolyzes specific targets within the cell to cause acute, reversible contractile dysfunction. Inhibitors of MMPs are discussed and their possible use for the therapy of acute heart injury caused by oxidative stress is examined.
This review addresses conceptual and empirical research about how individual agency and motivation influences development during adulthood and old age. The major life-span approaches to individual ...agency and developmental regulation are discussed, with a focus on the motivational theory of life-span development. Developmental agency unfolds through action cycles of pursuing long-term goals for optimal development. Individuals differ in their capacity to regulate their goal engagements effectively within the age-graded structure of opportunities and constraints in their life courses. We discuss a set of research examples about specific developmental challenges, such as transition to adulthood, biological aging, illness, and societal transformation, and show how individuals, as agents in their own development, navigate change for better or worse. We conclude with suggestions for future research.
Matrix metalloproteinases (MMPs) are zinc‐dependent endopeptidases that were first discovered as proteases, which target and cleave extracellular proteins. During the past 20 years, however, ...intracellular roles of MMPs were uncovered and research on this new aspect of their biology expanded. MMP‐2 is the first of this protease family to be reported to play a crucial intracellular role where it cleaves several sarcomeric proteins inside cardiac myocytes during oxidative stress‐induced injury. Beyond MMP‐2, currently at least eleven other MMPs are known to function intracellularly including MMP‐1, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐10, MMP‐11, MMP‐12, MMP‐14, MMP‐23 and MMP‐26. These intracellular MMPs are localized to different compartments inside the cell including the cytosol, sarcomere, mitochondria, and the nucleus. Intracellular MMPs contribute to the pathogenesis of various diseases. Cardiovascular renal disorders, inflammation, and malignancy are some examples. They also exert antiviral and bactericidal effects. Interestingly, MMPs can act intracellularly through both protease‐dependent and protease‐independent mechanisms. In this review, we will highlight the intracellular mechanisms of MMPs activation, their numerous subcellular locales, substrates, and roles in different pathological conditions. We will also discuss the future direction of MMP research and the necessity to exploit the knowledge of their intracellular targets and actions for the design of targeted inhibitors.
Matrix metalloproteinases (MMPs) were first discovered as secreted proteases that cleave extracellular matrix proteins. However, by different mechanisms, they can also remain inside the cell and localize to different subcellular compartments and organelles including, for example, the cytosol, mitochondria, nuclei, and sarcomere. When intracellularly activated, MMPs can also proteolyze specific intracellular proteins to affect both pathological and physiological responses.
This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive ...account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the action-phase model of developmental regulation with their original life-span theory of control to present a comprehensive theory of development. Third, they reviewed the relevant empirical literature testing key propositions of the Motivational Theory of Life-Span Development. Finally, because the conceptual reach of their theory goes far beyond the current empirical base, they pointed out areas that deserve further and more focused empirical inquiry.
Abstract
Background and Objectives
The coronavirus disease 2019 (COVID-19) pandemic has negatively affected persons with existing chronic health conditions. The pandemic also has the potential to ...exacerbate the stresses of family caregiving. We compare family caregivers with noncaregivers on physical, psychosocial, and financial well-being outcomes during the pandemic and determine family caregivers most at risk for adverse outcomes.
Research Design and Methods
We conducted a cross-sectional online survey of 576 family caregivers and 2,933 noncaregivers from April to May 2020 in Pittsburgh, PA region with a national supplement. Outcome measures included concurrent anxiety, depression, fatigue, sleep disturbance, social participation, and financial well-being and perceived changes due to COVID-19 (loneliness, financial well-being, food security). We also measured sociodemographic, caregiving contextual variables, and COVID-19-related caregiver stressors (COVID Caregiver Risk Index).
Results
Controlling for sociodemographics, family caregivers reported higher anxiety, depression, fatigue, sleep disturbance, lower social participation, lower financial well-being, increased food insecurity (all p < .01), and increased financial worries (p = .01). Caregivers who reported more COVID-19-related caregiver stressors and disruptions reported more adverse outcomes (all p < .01). In addition, caregivers who were female, younger, lower income, providing both personal/medical care, and providing care for cognitive/behavioral/emotional problems reported more adverse outcomes.
Discussion and Implications
Challenges of caregiving are exacerbated by the COVID-19 pandemic. Family caregivers reported increased duties, burdens, and resulting adverse health, psychosocial, and financial outcomes. Results were generally consistent with caregiver stress–health process models. Family caregivers should receive increased support during this serious public health crisis.
Objective: Older adults who live alone are more likely to report feelings of depression than those who live with a spouse or other family members. This study examines the effects of residential ...status and perceived neighborhood characteristics on depression in middle-aged and older adults.
Methods: This study is based on a probability sample of 1049 adults aged 55-98 years (M = 69 years) residing in Allegheny County, Pittsburgh, PA, USA in 2014. Thirty percent of participants reported living alone. We tested a multivariate model using living alone (vs. living with a family member or others) and perceived neighborhood physical and social quality as predictors of depressive symptomatology while controlling for age, sex, race, education, and disability.
Results: Living alone (compared to living with a family member) was associated with elevated levels of depressive symptomatology. However, perceptions of neighborhood social quality moderated this association. Living alone was more highly associated with depression when the perceived social quality of the neighborhood was low. Neighborhood social quality was not associated with depression among older adults who lived with a family member. Perceptions of neighborhood physical quality were not significantly associated with depression.
Conclusions: Perceptions of good neighborhood social quality is important for adults who live alone, in terms of fewer symptoms of depression.
Interest in technology for older adults is driven by multiple converging trends: the rapid pace of technological development; the unprecedented growth of the aging population in the United States and ...worldwide; the increase in the number and survival of persons with disability; the growing and unsustainable costs of caring for the elderly people; and the increasing interest on the part of business, industry, and government agencies in addressing health care needs with technology. These trends have contributed to the strong conviction that technology can play an important role in enhancing quality of life and independence of older individuals with high levels of efficiency, potentially reducing individual and societal costs of caring for the elderly people. The purpose of this "Forum" position article is to integrate what we know about older adults and technology systems in order to provide direction to this vital enterprise. We define what we mean by technology for an aging population, provide a brief history of its development, introduce a taxonomy for characterizing current technology applications to older adults, summarize research in this area, describe existing development and evaluation processes, identify factors important for the acceptance of technology among older individuals, and recommend future directions for research in this area.
Obstructive sleep apnea (OSA) is a frequent disease mainly affecting obese people and caused by repetitive collapse of the upper airways during sleep. The increased morbidity and mortality of OSA are ...mainly thought to be the consequence of its adverse effects on cardiovascular (CV) health. In this context, oxidative stress induced by nocturnal intermittent hypoxia has been identified to play a major role. This is suggested by biomarker studies in OSA patients showing excessively generated reactive oxygen species from leukocytes, reduced plasma levels of nitrite and nitrate, increased lipid peroxidation, and reduced antioxidant capacity. Biopsy studies complement these findings by demonstrating reduced endothelial nitric oxide synthase expression and increased nitrotyrosine immunofluorescence in the vasculature of these patients. Furthermore, oxidative stress in OSA correlates with surrogate markers of CV disease such as endothelial function, intima-media thickness, and high blood pressure. Continuous positive airway pressure therapy reverses oxidative stress in OSA. The same may be true for antioxidants; however, more studies are needed to clarify this issue.
Objectives
To determine the effect of integrating informal caregivers into discharge planning on postdischarge cost and resource use in older adults.
Design
A systematic review and metaanalysis of ...randomized controlled trials that examine the effect of discharge planning with caregiver integration begun before discharge on healthcare cost and resource use outcomes. MEDLINE, EMBASE, and the Cochrane Library databases were searched for all English‐language articles published between 1990 and April 2016.
Setting
Hospital or skilled nursing facility.
Participants
Older adults with informal caregivers discharged to a community setting.
Measurements
Readmission rates, length of and time to post‐discharge rehospitalizations, costs of postdischarge care.
Results
Of 10,715 s identified, 15 studies met the inclusion criteria. Eleven studies provided sufficient detail to calculate readmission rates for treatment and control participants. Discharge planning interventions with caregiver integration were associated with a 25% fewer readmissions at 90 days (relative risk (RR) = 0.75, 95% confidence interval (CI) = 0.62–0.91) and 24% fewer readmissions at 180 days (RR = 0.76, 95% CI = 0.64–0.90). The majority of studies reported statistically significant shorter time to readmission, shorter rehospitalization, and lower costs of postdischarge care among discharge planning interventions with caregiver integration.
Conclusion
For older adults discharged to a community setting, the integration of caregivers into the discharge planning process reduces the risk of hospital readmission.
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