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Context: SMEs represent approximately 50% of world GDP and due to the Covid-19 pandemic, they have been severely affected. This document provides an overview of the factors that affected the economy of SMEs and presents some solutions to maintain their operation in times of difficulties. Methodology: The elaboration of the manuscript is supported in relevant literature published between 2019-2021. The search strategy was applied through the databases EMBASE, WEB OF SCIENCES, SCOPUS under key search terms COVID-19, pandemic, small enterprises, medium-sized enterprises, global economic, economic growth, developing countries, emerging economies, economic impact, financial fragility, government action*, credit risk, travel restriction*, e-commerce, digital technologie*, digital transformation, emerging market*, supply chain*, small business. Subsequently, the document classification and analysis were carried out through the Raceer method (compilation, storage, conceptual schematic elaboration, link of informative units, writing). Results: The analysis of the relevant information revealed that the economy of SMEs played an important role in the sharp drop in GDP and in the increase in poverty and unemployment levels worldwide, and that those that wanted to remain in operation, they had to reinvent themselves and dabble in new business strategies. Conclusions: The pandemic generated by Covid-19 produced significant changes in purchasing habits, manufacturing methods and ways of working that seriously impacted the performance of SMEs. To deal with this new economic scenario, technology and innovation are expected to lead to new rapidly adapting business models. ; Contexto: Las pymes representan aproximadamente el 50 % del PIB mundial, y debido a la pandemia por la covid-19, se han visto gravemente afectadas. Este documento proporciona un panorama general de factores que incidieron en la economía de las pymes y presenta algunas soluciones para mantener su operación en tiempos de dificultades. Metodología: La elaboración ...

Abstract
In the brain, environmental changes, such as neuroinflammation, can induce senescence, characterized by the decreased proliferation of neurons and dendrites and synaptic and vascular damage, resulting in cognitive decline. Senescence promotes neuroinflammatory disorders by senescence-associated secretory phenotypes and reactive oxygen species. In human brain microvascular endothelial cells (HBMVECs), we demonstrate that chronological aging and irradiation increase death-associated protein kinase 3 (DAPK3) expression. To confirm the role of DAPK3 in HBMVEC senescence, we disrupted DAPK3 activity using small interfering RNA (siRNA) or a dominant-negative mutant (DAPK3-P216S), which reduced cellular senescence phenotypes, as assessed by changes in tube formation, senescence-associated beta-galactosidase activity, and cell proliferation. In endothelial cells, DAPK3 promotes cellular senescence by regulating the phosphorylation and inactivation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) via the protein kinase B pathway, resulting in the decreased expression of mitochondrial metabolism-associated genes, such as ATP5G1, BDNF, and COX5A. Our studies show that DAPK3 is involved in cellular senescence and PGC1α regulation, suggesting that DAPK3 regulation may be important for treating aging-related brain diseases or the response to radiation therapy.

Abstract
The National Institute on Aging sponsored a symposium at the Gerontological Society of America (GSA) annual meeting in Indianapolis, Indiana, to discuss recent discoveries related to senescent and inflammatory mechanisms in aging and disease. Consistent with the 2022 Biological Sciences GSA program led by Dr. Rozalyn Anderson, the symposium featured early-stage investigators and a leader in the field of geroscience research. Cell senescence and immune interactions coordinate homeostatic and protective programming throughout the life span. Dysfunctional communication in this exchange eventuates in inflammation-related compositional changes in aged tissues, including propagation of the senescence-associated secretory phenotype and accumulation of senescent and exhausted immune cells. Presentations in this symposium explored senescent and immune-related dysfunction in aging from diverse viewpoints and featured emerging cellular and molecular methods. A central takeaway from the event was that the use of new models and approaches, including single-cell -omics, novel mouse models, and 3D culture systems, is revealing dynamic properties and interactions of senescent and immune cell fates. This knowledge is critical for devising new therapeutic approaches with important translational relevance.

Issue addressed: Exercising outdoors provide beneficial effect on mental and physical health for all ages. However, few older people exercise outdoors other than walking. While outdoor gyms have become increasingly common in Australia, limited outdoor exercise equipment specifically designed for older people is available in public spaces. We have set up and evaluated a unique purpose-built outdoor exercise park for older people in the community setting and demonstrated positive physical and well-being outcomes associated with the provision of this unique exercise mode and social programme. Methods: This study is a reflective narrative describing this innovative exercise approach and reports challenges associated with establishment of the exercise park, conducting the randomised trial, strategies adopted to address these challenges and recommendations for future implementation of this approach in the community. Results: Many challenges were encountered, including securing appropriate land to locate the exercise park, control of environmental factors for safety (non-slippery ground and equipment) as well as logistics in running the exercise programme itself. Several adjustments in the equipment were also required to ensure safe use by older people. Conclusion: The inclusion of outdoor equipment for older people in public spaces or urban parks is important and careful consideration needs to be taken by local/public authorities to provide access, amenities and safety for all as well as activities to suit all ages. So what?: Seniors' exercise parks can be installed in public places and may provide an enjoyable and effective approach to engage older individuals in a more active and healthier lifestyle.

BACKGROUND: The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities. METHOD: A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation. RESULTS: The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders. CONCLUSION: Partner characteristics such as local governments' structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on ...

Background: The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities. Method: A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation. Results: The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders. Conclusion: Partner characteristics such as local governments' structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on older people's physical activity levels.

Background: Creating inclusive and accessible outdoor environments that provide and encourage opportunities for older adults to engage in physical activity and social interaction is important for healthy ageing. The Senior Exercise Park is outdoor exercise equipment designed specifically for use by older people that provides physical and social benefits for older people in the community, and has the potential to be used widely as a sustainable mode of physical activity. The aim of this study is to implement and evaluate the effects of sustained engagement through the use of a community-based novel outdoor physical activity program (purpose-built exercise park) for older people on physical, mental and social health and physical activity outcomes (the ENJOY project). Methods: This is a prospective pre-post design study with 12 months follow up. Adults aged ≥60 years will be recruited from the general community from the suburbs close to the Senior Exercise Parks locations in Melbourne. Participants will undergo a 12 week structured supervised physical activity program using the outdoor Senior Exercise Park equipment followed by 6 months unstructured physical activity program. Participants will be assessed at baseline, 3, 9, and 12 months. The following outcomes will be assessed: physical activity, physical function, psychosocial and mental health outcomes, falls risk and falls occurrence, participants' feedback and satisfaction, and health care resource use. Discussion: The ENJOY trial is designed to operate in a community setting with local government engagement to maximise the usage of the exercise park and provide an outdoor space for older people to be physically active. This project will evaluate the effectiveness and sustainability of the outdoor exercise park on a range of health outcomes and its long-term usability in the community. Trial registration: This trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12618001727235 registered 18th of October 2018.

Background: Creating inclusive and accessible outdoor environments that provide and encourage opportunities for older adults to engage in physical activity and social interaction is important for healthy ageing. The Senior Exercise Park is outdoor exercise equipment designed specifically for use by older people that provides physical and social benefits for older people in the community, and has the potential to be used widely as a sustainable mode of physical activity. The aim of this study is to implement and evaluate the effects of sustained engagement through the use of a community-based novel outdoor physical activity program (purpose-built exercise park) for older people on physical, mental and social health and physical activity outcomes (the ENJOY project). Methods: This is a prospective pre-post design study with 12 months follow up. Adults aged ≥60 years will be recruited from the general community from the suburbs close to the Senior Exercise Parks locations in Melbourne. Participants will undergo a 12 week structured supervised physical activity program using the outdoor Senior Exercise Park equipment followed by 6 months unstructured physical activity program. Participants will be assessed at baseline, 3, 9, and 12 months. The following outcomes will be assessed: physical activity, physical function, psychosocial and mental health outcomes, falls risk and falls occurrence, participants' feedback and satisfaction, and health care resource use. Discussion: The ENJOY trial is designed to operate in a community setting with local government engagement to maximise the usage of the exercise park and provide an outdoor space for older people to be physically active. This project will evaluate the effectiveness and sustainability of the outdoor exercise park on a range of health outcomes and its long-term usability in the community. Trial registration: This trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12618001727235 registered ...

Abstract
Blood-based mitochondrial bioenergetic profiling is a feasible, economical, and minimally invasive approach that can be used to examine mitochondrial function and energy metabolism in human subjects. In this study, we use 2 complementary respirometric techniques to evaluate mitochondrial bioenergetics in both intact and permeabilized peripheral blood mononuclear cells (PBMCs) and platelets to examine sex dimorphism in mitochondrial function among older adults. Employing equal numbers of PBMCs and platelets to assess mitochondrial bioenergetics, we observe significantly higher respiration rates in female compared to male participants. Mitochondrial bioenergetic differences remain significant after controlling for independent parameters including demographic parameters (age, years of education), and cognitive parameters (mPACC5, COGDX). Our study illustrates that circulating blood cells, immune cells in particular, have distinctly different mitochondrial bioenergetic profiles between females and males. These differences should be taken into account as blood-based bioenergetic profiling is now commonly used to understand the role of mitochondrial bioenergetics in human health and aging.

Abstract
High engagement in lifestyle health behaviors appears to be protective against cognitive decline in aging. We investigated the association between patterns of modifiable lifestyle health behaviors and common brain neuropathologies of dementia as a possible mechanism. We examined 555 decedents from the Rush Memory and Aging Project, free of dementia at their initial concurrent report of lifestyle health behaviors of interest (physical, social, and cognitive activities, and healthy diet), and who underwent a postmortem neuropathology evaluation. First, we used latent profile analysis to group participants based on baseline behavior patterns. Second, we assessed the associations of profile membership with each neurodegenerative (global Alzheimer's disease [AD] pathology, amyloid-beta load, density of neurofibrillary tangles, and presence of cortical Lewy bodies and TAR DNA-binding protein 43 cytoplasmic inclusions) and neurovascular pathologies (presence of chronic gross or microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), using separate linear or logistic regression models, adjusted for age at death, sex (core model), vascular disease risk factors, and vascular conditions (fully adjusted model). Participants had either consistently lower (N = 224) or consistently higher (N = 331) engagement across 4 lifestyle health behaviors. We generally found no differences in neuropathologies between higher and lower engagement groups in core or fully adjusted models; for example, higher engagement in lifestyle health behaviors was not associated with global AD pathology after core or full adjustment (both p > .8). In conclusion, we found no evidence of associations between patterns of lifestyle health behaviors and neuropathology. Other mechanisms may underlie protective effects of health behaviors against dementia.

Abstract
There is converging evidence that young blood conveys cells, vesicles, and molecules able to revitalize function and restore organ integrity in old individuals. We assessed the effects of young plasma on the lifespan, epigenetic age, and healthspan of old female rats. Beginning at 25.6 months of age, a group of 9 rats (group T) was intraperitoneally injected with plasma from young rats until their natural death. A group of 8 control rats of the same age received no treatment (group C). Blood samples were collected every other week. Survival curves showed that from age 26 to 30 months, none of the group T animals died, whereas the survival curve of group C rats began to decline at age 26 months. Blood DNAm age versus chronological age showed that DNAm age in young animals increased faster than chronological age, then slowed down, entering a plateau after 27 months. The DNAm age of the treated rats fell below the DNAm age of controls and, in numerical terms, remained consistently lower until natural death. When rats were grouped according to the similarities in their differential blood DNA methylation profile, samples from the treated and control rats clustered in separate groups. Analysis of promoter differential methylation in genes involved in systemic regulatory activities revealed specific GO term enrichment related to the insulin-like factors pathways as well as to cytokines and chemokines associated with immune and homeostatic functions. We conclude that young plasma therapy may constitute a natural, noninvasive intervention for epigenetic rejuvenation and health enhancement.

Abstract
Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.

•Higher standardized hip fracture rates were seen for indigenous than non-indigenous persons from Canada and Australia.•Compared to non-indigenous persons, indigenous persons had higher standardized rates of craniofacial fractures.•There may be many varied reasons for differences in fracture rates and risk according to indigenous status.•Communities, governments and professionals need to act in order to prevent trauma-related fractures in indigenous persons.•Osteoporotic fractures are mostly preventable in all populations.

Abstract
Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, and low physical activity) often entails insufficient dental care. We assessed tooth loss, caries, and damaged teeth, in relation to cardiovascular and brain aging among the Tsimane, a subsistence population living a relatively traditional forager-horticulturalist lifestyle with poor dental health, but minimal cardiovascular disease and dementia. Dental health was assessed by a physician in 739 participants aged 40–92 years with cardiac and brain health measured by chest computed tomography (CT; n = 728) and brain CT (n = 605). A subset of 356 individuals aged 60+ were also assessed for dementia and mild cognitive impairment (n = 33 impaired). Tooth loss was highly prevalent, with 2.2 teeth lost per decade and a 2-fold greater loss in women. The number of teeth with exposed pulp was associated with higher inflammation, as measured by cytokine levels and white blood cell counts, and lower body mass index. Coronary artery calcium and thoracic aortic calcium were not associated with tooth loss or damaged teeth. However, aortic valve calcification and brain tissue loss were higher in those who had more teeth with exposed pulp. Overall, these results suggest that dental health is associated with indicators of chronic diseases in the absence of typical confounds, even in a population with low cardiovascular and dementia risk factors.