bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2021–11–07
nineteen papers selected by
Ayesh Seneviratne, University of Toronto
  1. Mediterranean Diet In Healthy Aging.
  2. Avoid shocking your hematopoietic stem cells to keep them young and growing.
  3. Integrated Single-Cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging.
  4. NAD+, Senolytics, or Pyruvate for Healthy Aging?
  5. Is Myelodysplasia a Consequence of Normal Aging?
  6. Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities.
  7. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.
  8. Editorial: Healthy Aging and the Community Environment.
  9. Making an impact through diet.
  10. Emerging Role of Dermal White Adipose Tissue in Modulating Hair Follicle Development During Aging.
  11. Editorial: Nutrition and the Hallmarks of Aging.
  12. Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy.
  13. The contribution of musculoskeletal factors to physical frailty: a cross-sectional study.
  14. Development of a health data derived frailty index as a predictor of adverse outcomes in older patients with pancreatic cancer.
  15. Lipid synthesis at the trophic base as the source for energy management to build complex structures.
  16. Transtheoretical model for lifestyle changes in older persons: a systematic review protocol.
  17. Epigenetic Signaling of Cancer Stem Cells During Inflammation.
  18. Why Is COVID-19 More Concentrated in Countries with High Economic Status?
  19. Aging in Place.
  1. J Nutr Health Aging. 2021 ;25(9): 1076-1083
    Mediterranean Diet In Healthy Aging.
    E Mazza, Y Ferro, R Pujia, R Mare, S Maurotti, T Montalcini, A Pujia.
      The World elderly population is expected to double before 2050. Unhealthy habits and unhealthy lifestyles are commonly associated with age-related diseases or their worsening. Modification in daily lifestyle and diet may help preventing age-related diseases onset and efficiently affecting their evolution, thus promoting the Healthy Aging process, concept recently coined to describe the disease-free aging process. This review highlights the role of nutrition science in promoting healthy aging. Since the Mediterranean Model demonstrated to be a useful style in supporting healthy aging, promotion of this correct lifestyle by health policies seems to be the best approach to achieve this target.
    Keywords:  Healthy Aging; Mediterranean diet; food intake; lifestyle; nutrition; prevention
    DOI:  https://doi.org/10.1007/s12603-021-1675-6
  2. Cell Stem Cell. 2021 Nov 04. pii: S1934-5909(21)00419-7. [Epub ahead of print]28(11): 1887-1889
    Avoid shocking your hematopoietic stem cells to keep them young and growing.
    Maria-Eleni Lalioti, Jasmin Rettkowski, Nina Cabezas-Wallscheid.
      Expanding hematopoietic stem cells (HSCs) ex vivo has historically been a very challenging process. In this issue of Cell Stem Cell, Kruta et al. (2021) identify heat shock factor 1 (Hsf1) as a new target to maintain HSC fitness and protein homeostasis, not only in culture conditions but also upon aging.
    DOI:  https://doi.org/10.1016/j.stem.2021.10.007
  3. Front Genet. 2021 ;12 745786
    Integrated Single-Cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging.
    Xiangjun Zeng, Xia Li, Mi Shao, Yulin Xu, Wei Shan, Cong Wei, Xiaoqing Li, Limengmeng Wang, Yongxian Hu, Yanmin Zhao, Pengxu Qian, He Huang.
      Hematopoietic stem cell (HSC) aging, which is accompanied by loss of self-renewal capacity, myeloid-biased differentiation and increased risks of hematopoietic malignancies, is an important focus in stem cell research. However, the mechanisms underlying HSC aging have not been fully elucidated. In the present study, we integrated 3 independent single-cell transcriptome datasets of HSCs together and identified Stat3 and Ifngr1 as two markers of apoptosis-biased and inflammatory aged HSCs. Besides, common differentially expressed genes (DEGs) between young and aged HSCs were identified and further validated by quantitative RT-PCR. Functional enrichment analysis revealed that these DEGs were predominantly involved in the cell cycle and the tumor necrosis factor (TNF) signaling pathway. We further found that the Skp2-induced signaling pathway (Skp2→Cip1→CycA/CDK2→DP-1) contributed to a rapid transition through G1 phase in aged HSCs. In addition, analysis of the extrinsic alterations on HSC aging revealed the increased expression levels of inflammatory genes in bone marrow microenvironment. Colony formation unit assays showed that inflammatory cytokines promoted cellular senescence and that blockade of inflammatory pathway markedly rejuvenated aged HSC functions and increased B cell output. Collectively, our study elucidated the biological characteristics of HSC aging, and the genes and pathways we identified could be potential biomarkers and targets for the identification and rejuvenation of aged HSCs.
    Keywords:  aging; cell cycle; hematopoietic stem cells; inflammation; single cell integrated analysis
    DOI:  https://doi.org/10.3389/fgene.2021.745786
  4. Nutr Metab Insights. 2021 ;14 11786388211053407
    NAD+, Senolytics, or Pyruvate for Healthy Aging?
    Fang-Qiang Zhou.
      In last decades, healthy aging has become one of research hotspots in life science. It is well known that the nicotinamide adenine dinucleotide oxidized form (NAD+) level in cells decreases with aging and aging-related diseases. Several years ago, one of NAD+ precursors was first demonstrated with its new role in DNA damage repairing in mice, restoring old mice to their physical state at young ones. The finding encourages extensive studies in animal models and patients. NAD+ and its precursors have been popular products in nutrition markets. Alternatively, it was also evidenced that clearance of cellular senescence by senolytics preserved multiorgan (kidney and heart) function and extended healthy lifespan in mice. Subsequent studies confirmed findings in elderly patients subjected with idiopathic pulmonary fibrosis. The senolytic therapy is now focused on various diseases in animal and clinical studies. However, pyruvate, as both a NAD+ substitute and a new senolytic, may be advantageous, on the equimolar basis, over current products above in preventing and treating diseases and aging. Pyruvate-enriched fluids, particularly pyruvate oral rehydration salt, may be a novel intervention for diseases and aging besides critical care. Albeit the direct evidence that benefits healthy aging is still limited to date, pyruvate, as both NAD+ provider and senolytic agent, warrants intensive research to compare NAD+ or senolytics for healthy aging, specifically on the equimolar basis, in effective blood levels. This review briefly discussed the recognition of healthy aging by comparing NAD+ and Senolytics with sodium pyruvate from the clinical point of view.
    Keywords:  Healthy aging; NAD+; pyruvate; senescence; senolytics
    DOI:  https://doi.org/10.1177/11786388211053407
  5. Curr Oncol Rep. 2021 Nov 04. 23(12): 142
    Is Myelodysplasia a Consequence of Normal Aging?
    Sonja Heibl, Reinhard Stauder, Michael Pfeilstöcker.
       PURPOSE OF REVIEW: To review available data on the relationship of MDS and aging and to address the question if biological changes of (premature) aging are a prerequisite for the development of MDS.
    RECENT FINDINGS: Whereas the association of MDS with advanced age and some common biologic features of aging and MDS are well established, additional evidence for both, especially on the role of stem cells, the stem cell niche, and inflammation, has been recently described. Biologically, many but not all drivers of aging also play a role in the development and propagation of MDS and vice versa. As a consequence, aging contributes to the development of MDS which can be seen as an interplay of clonal disease and normal and premature aging. The impact of aging may be different in specific MDS subtypes and risk groups.
    Keywords:  Aging; CHIP; Clonality; Elderly; Myelodysplastic syndromes; Myeloid neoplasia
    DOI:  https://doi.org/10.1007/s11912-021-01136-5
  6. Front Immunol. 2021 ;12 775128
    Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities.
    Tony Marchand, Sandra Pinho.
      Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. While complete remission can be obtained with intensive chemotherapy in young and fit patients, relapse is frequent and prognosis remains poor. Leukemic cells are thought to arise from a pool of leukemic stem cells (LSCs) which sit at the top of the hierarchy. Since their discovery, more than 30 years ago, LSCs have been a topic of intense research and their identification paved the way for cancer stem cell research. LSCs are defined by their ability to self-renew, to engraft into recipient mice and to give rise to leukemia. Compared to healthy hematopoietic stem cells (HSCs), LSCs display specific mutations, epigenetic modifications, and a specific metabolic profile. LSCs are usually considered resistant to chemotherapy and are therefore the drivers of relapse. Similar to their HSC counterpart, LSCs reside in a highly specialized microenvironment referred to as the "niche". Bidirectional interactions between leukemic cells and the microenvironment favor leukemic progression at the expense of healthy hematopoiesis. Within the niche, LSCs are thought to be protected from genotoxic insults. Improvement in our understanding of LSC gene expression profile and phenotype has led to the development of prognosis signatures and the identification of potential therapeutic targets. In this review, we will discuss LSC biology in the context of their specific microenvironment and how a better understanding of LSC niche biology could pave the way for new therapies that target AML.
    Keywords:  acute myeloid leukemia; genetic heterogeneity; leukemic stem cell (LSC); stem cell niche; therapeutic targets
    DOI:  https://doi.org/10.3389/fimmu.2021.775128
  7. Science. 2021 11 05. 374(6568): 768-772
    Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.
    S Avagyan, J E Henninger, W P Mannherz, M Mistry, J Yoon, S Yang, M C Weber, J L Moore, L I Zon.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.aba9304
  8. Front Public Health. 2021 ;9 737955
    Editorial: Healthy Aging and the Community Environment.
    Chanam Lee, Xuemei Zhu, Anna Patricia Lane, Erja Portegijs.
      
    Keywords:  active aging; age-friendly community; aging in place; aging-friendly community; community environment; healthy aging
    DOI:  https://doi.org/10.3389/fpubh.2021.737955
  9. Vet Rec. 2021 Nov;189 Suppl 2 6-7
    Making an impact through diet.
      Evidence suggests that feeding companion animals makes a considerable contribution to carbon emissions. However, making pets' diets more sustainable presents some challenges.
    DOI:  https://doi.org/10.1002/vetr.1123
  10. Front Cell Dev Biol. 2021 ;9 728188
    Emerging Role of Dermal White Adipose Tissue in Modulating Hair Follicle Development During Aging.
    Jian Chen, Zhe-Xiang Fan, De-Cong Zhu, Yi-Long Guo, Ke Ye, Damao Dai, Zhi Guo, Zhi-Qi Hu, Yong Miao, Qian Qu.
      Hair follicle stem cells are extensively reprogrammed by the aging process, manifesting as diminished self-renewal and delayed responsiveness to activating cues, orchestrated by both intrinsic microenvironmental and extrinsic macroenvironmental regulators. Dermal white adipose tissue (dWAT) is one of the peripheral tissues directly adjacent to hair follicles (HFs) and acts as a critical macroenvironmental niche of HF. dWAT directly contributes to HF aging by paracrine signal secretion. However, the altered interrelationship between dWAT and HF with aging has not been thoroughly understood. Here, through microdissection, we separated dWAT from the skin of aged mice (18 months) and young mice (2 months) in telogen and depilation-induced anagen for transcriptome comparing. Notably, compared with young dWAT, aberrant inflammatory regulators were recapitulated in aging dWAT in telogen, including substantial overexpressed inflammatory cytokines, matrix metalloproteinases, and prostaglandin members. Nonetheless, with anagen initiation, inflammation programs were mostly abolished in aging dWAT, and instead of which, impaired collagen biosynthesis, angiogenesis, and melanin synthesis were identified. Furthermore, we confirmed the inhibitory effect on hair growth of CXCL1, one of the most significantly upregulated inflammation cytokines in aging dWAT. Besides this, we also identified the under-expressed genes related to Wnt signaling fibroblast growth factor family members and increased BMP signaling in aging dWAT, further unraveling the emerging role of dWAT in aging HFs malfunction. Finally, we proved that relieving inflammation of aging dWAT by injecting high-level veratric acid stimulated HF regenerative behavior in aged mice. Concomitantly, significantly decreased TNF-a, CCL2, IL-5, CSF2, and increased IL10 in dWAT was identified. Overall, the results elaborated on the complex physiological cycling changes of dWAT during aging, providing a basis for the potential regulatory effect of dWAT on aging HFs.
    Keywords:  aging; dermal white adipose tissue; hair follicle; inflamm-aging; microenvironment
    DOI:  https://doi.org/10.3389/fcell.2021.728188
  11. J Nutr Health Aging. 2021 ;25(9): 1039-1041
    Editorial: Nutrition and the Hallmarks of Aging.
    K Virecoulon Giudici.
      
    DOI:  https://doi.org/10.1007/s12603-021-1686-3
  12. Jpn J Clin Oncol. 2021 Nov 05. pii: hyab170. [Epub ahead of print]
    Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy.
    Kazuhito Yamamoto, Atsushi Shinagawa, Courtney D DiNardo, Keith W Pratz, Kenichi Ishizawa, Toshihiro Miyamoto, Norio Komatsu, Yasuhiro Nakashima, Chikashi Yoshida, Noriko Fukuhara, Kensuke Usuki, Takahiro Yamauchi, Noboru Asada, Norio Asou, Ilseung Choi, Yasushi Miyazaki, Hideyuki Honda, Sumiko Okubo, Misaki Kurokawa, Ying Zhou, Jiuhong Zha, Jalaja Potluri, Itaru Matsumura.
       BACKGROUND: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.
    METHODS: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1-7 of each 28-day cycle.
    RESULTS: Median follow-up was 16.3 months (range, 1.0-20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation.
    CONCLUSIONS: This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.
    Keywords:  Japan; VIALE-A; acute myeloid leukemia; azacitidine; venetoclax
    DOI:  https://doi.org/10.1093/jjco/hyab170
  13. BMC Musculoskelet Disord. 2021 Nov 01. 22(1): 921
    The contribution of musculoskeletal factors to physical frailty: a cross-sectional study.
    Monica C Tembo, Mohammadreza Mohebbi, Kara L Holloway-Kew, James Gaston, Sophia X Sui, Sharon L Brennan-Olsen, Lana J Williams, Mark A Kotowicz, Julie A Pasco.
       BACKGROUND: Musculoskeletal conditions and physical frailty have overlapping constructs. We aimed to quantify individual contributions of musculoskeletal factors to frailty.
    METHODS: Participants included 347 men and 360 women aged ≥60 yr (median ages; 70.8 (66.1-78.6) and 71.0 (65.2-77.5), respectively) from the Geelong Osteoporosis Study. Frailty was defined as ≥3, pre-frail 1-2, and robust 0, of the following; unintentional weight loss, weakness, low physical activity, exhaustion, and slowness. Measures were made of femoral neck BMD, appendicular lean mass index (ALMI, kg/m2) and whole-body fat mass index (FMI, kg/m2) by DXA (Lunar), SOS, BUA and SI at the calcaneus (Lunar Achilles Insight) and handgrip strength by dynamometers. Binary and ordinal logistic regression models and AUROC curves were used to quantify the contribution of musculoskeletal parameters to frailty. Potential confounders included anthropometry, smoking, alcohol, prior fracture, FMI, SES and comorbidities.
    RESULTS: Overall, 54(15.6%) men and 62(17.2%) women were frail. In adjusted-binary logistic models, SI, ALMI and HGS were associated with frailty in men (OR = 0.73, 95%CI 0.53-1.01; OR=0.48, 0.34-0.68; and OR = 0.11, 0.06-0.22; respectively). Muscle measures (ALMI and HGS) contributed more to this association than did bone (SI) (AUROCs 0.77, 0.85 vs 0.71, respectively). In women, only HGS was associated with frailty in adjusted models (OR = 0.30 95%CI 0.20-0.45, AUROC = 0.83). In adjusted ordinal models, similar results were observed in men; for women, HGS and ALMI were associated with frailty (ordered OR = 0.30 95%CI 0.20-0.45; OR = 0.56, 0.40-0.80, respectively).
    CONCLUSION: Muscle deficits appeared to contribute more than bone deficits to frailty. This may have implications for identifying potential musculoskeletal targets for preventing or managing the progression of frailty.
    Keywords:  Ageing; Frailty; Lean mass; Osteoporosis; Osteosarcopenia; Physical performance; Sarcopenia
    DOI:  https://doi.org/10.1186/s12891-021-04795-4
  14. J Geriatr Oncol. 2021 Nov 02. pii: S1879-4068(21)00241-1. [Epub ahead of print]
    Development of a health data derived frailty index as a predictor of adverse outcomes in older patients with pancreatic cancer.
    Juan-Pablo Negrete-Najar, Marina Sehovic, Maria Grazia Rodriquenz, Juan Garcia-Martinez, Martine Extermann.
      Pancreatic cancer is a prevalent disease among older adults. Well-selected patients, based on a geriatric assessment for risk stratification, could be good candidates for chemotherapy and/or curative resection. Deficits accumulation frailty indices (FI) utilize readily available clinical data and easily obtained patient-reported information to predict hospitalization and mortality of older individuals. Retrospective data from 440 older adults (median age 76 years) with pancreatic cancer, obtained from electronic health records, was used to develop a FI and its ability to predict mortality and other geriatric and cancer related outcomes was tested. Fatigue (n = 45), infection (n = 40) and neutropenia (n = 36) were the most common registered adverse events of treatment; 153 subjects had no adverse events. The mean FI score was 0.26, 112 subjects were fit (0.0 < 0.2), 255 pre-frail (0.2 < 0.35), and 73 frail (≥ 0.35). Median survival was twelve months for the whole sample; at one year 62.5% of fit patients, 46.3% of pre-frail, and 26% of frail patients were alive. The FI categories correlated with institutionalization (p < 0.001) and non-planned hospitalization (p < 0.001). The FI categories did not correlate with the presence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 adverse events (p = 0.377). We conclude that patients with pancreatic cancer classified as frail with our FI had worse survival than those fit and pre-frail. Non-fit patients were also more prone to be institutionalized and have non-planned hospitalizations. The items used for this FI can be usually acquired from electronic health records and could be automated in the future, which could simplify its use as a helping tool for decisions in older patients with pancreatic cancer.
    Keywords:  Frailty; Older adults; Pancreatic cancer
    DOI:  https://doi.org/10.1016/j.jgo.2021.10.009
  15. Curr Opin Biotechnol. 2021 Nov 01. pii: S0958-1669(21)00191-9. [Epub ahead of print]73 364-373
    Lipid synthesis at the trophic base as the source for energy management to build complex structures.
    Stephanie L Schnorr, David Berry.
      The review explores the ecological basis for bacterial lipid metabolism in marine and terrestrial ecosystems. We discuss ecosystem stressors that provoked early organisms to modify their lipid membrane structures, and where these stressors are found across a variety of environments. A major role of lipid membranes is to manage cellular energy utility, including how energy is used for signal propagation. As different environments are imbued with properties that necessitate variation in energy regulation, bacterial lipid synthesis has undergone incalculable permutations of functional trial and error. This may hold clues for how biotechnology can improvise a short-hand version of the evolutionary gauntlet to stimulate latent functional competences for the synthesis of rare lipids. Reducing human reliance on marine resources and deriving solutions for production of essential nutrients is a pressing problem in sustainable agriculture and aquaculture, as well as timely considering the increasing fragility of human health in an aging population.
    DOI:  https://doi.org/10.1016/j.copbio.2021.09.014
  16. Ann N Y Acad Sci. 2021 Nov 06.
    Transtheoretical model for lifestyle changes in older persons: a systematic review protocol.
    Melissa Côrtes da Rosa, Carolina Böettge Rosa, Raquel de Melo Boff, Margareth Silva Oliveira, Carla Helena Augustin Schwanke.
      Adherence to lifestyle changes is a major challenge for healthcare professionals. The transtheoretical model (TTM) was proposed to promote behavioral changes, used in different health conditions (smoking, alcoholism, drug addiction, and obesity) and age groups. However, the effectiveness of the model in older persons is not yet known. This systematic review protocol follows the PRISMA-P guidance. The question the review will address is, Are interventions based on the TTM, compared with conventional interventions, associated with lifestyle changes in older adults? Databases MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, WoS, and PsycINFO will be searched. Randomized clinical controlled trials and quasi-experimental studies describing the effectiveness of TTM-based interventions in changing the lifestyle of individuals aged 65 and over, compared with conventional interventions for lifestyle changes, will be included. Studies that do not address the stages of change characteristic of TTM or that use pharmacological interventions as a comparator will be excluded. Reviewers independently will screen papers for eligibility criteria, and, extracting data, assess the risk of bias for included studies and will evaluate the overall quality of evidence (GRADE system). If possible, a meta-analysis will be conducted. Otherwise, a narrative synthesis will be prepared according to the SWiM guideline.
    Keywords:  aged; biobehavioral science; health behavior; healthy lifestyle; transtheoretical model
    DOI:  https://doi.org/10.1111/nyas.14714
  17. Front Cell Dev Biol. 2021 ;9 772211
    Epigenetic Signaling of Cancer Stem Cells During Inflammation.
    Zaoqu Liu, Yuqing Ren, Lingfang Meng, Lifeng Li, Richard Beatson, Jinhai Deng, Tengfei Zhang, Junqi Liu, Xinwei Han.
      Malignant tumors pose a great challenge to human health, which has led to many studies increasingly elucidating the tumorigenic process. Cancer Stem Cells (CSCs) have profound impacts on tumorigenesis and development of drug resistance. Recently, there has been increased interest in the relationship between inflammation and CSCs but the mechanism underlying this relationship has not been fully elucidated. Inflammatory cytokines produced during chronic inflammation activate signaling pathways that regulate the generation of CSCs through epigenetic mechanisms. In this review, we focus on the effects of inflammation on cancer stem cells, particularly the role of signaling pathways such as NF-κB pathway, STAT3 pathway and Smad pathway involved in regulating epigenetic changes. We hope to provide a novel perspective for improving strategies for tumor treatment.
    Keywords:  cancer stem cells; epigenetics; inflammation; inflammatory factors; signaling pathway
    DOI:  https://doi.org/10.3389/fcell.2021.772211
  18. Iran J Public Health. 2021 Sep;50(9): 1926-1929
    Why Is COVID-19 More Concentrated in Countries with High Economic Status?
    Mohsen Bayati.
      
    DOI:  https://doi.org/10.18502/ijph.v50i9.7081
  19. Home Healthc Now. 2021 Nov-Dec 01;39(6):39(6): 301
    Aging in Place.
    Maureen Anthony.
      
    DOI:  https://doi.org/10.1097/NHH.0000000000001026
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