The effect of a non-congregate, integrated care shelter on health: A qualitative study.

OBJECTIVE: To describe the experiences of unstably housed, medically vulnerable residents living at the Haven, a novel, non-congregate integrated care shelter operating in a historic hotel during the COVID-19 pandemic. DESIGN: A qualitative descriptive design. SAMPLE/MEASUREMENT: Semi-structured qualitative interviews were conducted in February and March 2022 with a purposive sample of 20 residents living in the integrated care shelter. Data were analyzed in May and June 2022 using the thematic analysis methods described by Braun and Clarke. RESULTS: Six women and 14 men, ages 23-71 (M = 50, SD = 14), were interviewed. Lengths of stay at the time of the interview ranged from 74 to 536 days (M = 311 days). Medical co-morbidities and substance use details were collected at baseline. Three themes were identified: (1) Autonomy, (2) supportive environments, and (3) stability and the need for permanent housing. Participants characterized the integrated care, non-congregate model as having multiple advantages over traditional shelter systems. Participants emphasized the role of nurses and case managers in providing a respectful, caring environment in the integrated shelter model. CONCLUSION: Participants described acute physical and mental health needs which were largely met by the innovative integrated shelter care model. The effect of homelessness and housing insecurity on health is well documented, but few solutions exist that promote autonomy. Participants in this qualitative study emphasized the benefits of living in a non-congregate integrated care shelter and the services which promoted their self-management of chronic diseases. PATIENT OR PUBLIC CONTRIBUTION: Patients were the participants in the study, but were not involved in the design, analysis of interpretation of the data, or preparation of the manuscript. Due to this project's small scope, we could not involve patients or the public after the study concluded data collection.

Management of Acute Coronary Syndrome in the Older Adult Population: A Scientific Statement From the American Heart Association.

Diagnostic and therapeutic advances during the past decades have substantially improved health outcomes for patients with acute coronary syndrome. Both age-related physiological changes and accumulated cardiovascular risk factors increase the susceptibility to acute coronary syndrome over a lifetime. Compared with younger patients, outcomes for acute coronary syndrome in the large and growing demographic of older adults are relatively worse. Increased atherosclerotic plaque burden and complexity of anatomic disease, compounded by age-related cardiovascular and noncardiovascular comorbid conditions, contribute to the worse prognosis observed in older individuals. Geriatric syndromes, including frailty, multimorbidity, impaired cognitive and physical function, polypharmacy, and other complexities of care, can undermine the therapeutic efficacy of guidelines-based treatments and the resiliency of older adults to survive and recover, as well. In this American Heart Association scientific statement, we (1) review age-related physiological changes that predispose to acute coronary syndrome and management complexity; (2) describe the influence of commonly encountered geriatric syndromes on cardiovascular disease outcomes; and (3) recommend age-appropriate and guideline-concordant revascularization and acute coronary syndrome management strategies, including transitions of care, the use of cardiac rehabilitation, palliative care services, and holistic approaches. The primacy of individualized risk assessment and patient-centered care decision-making is highlighted throughout.

Perspectives on Implementing a Multidomain Approach to Caring for Older Adults With Heart Failure.

BACKGROUND/OBJECTIVES: The American College of Cardiology (ACC) Geriatric Cardiology Section Leadership Council recently outlined 4 key domains (which are composed of 14 subdomains) that are important to assess in older adults with heart failure (HF). We sought to determine which geriatric domains/subdomains are routinely assessed, how they are assessed, and how they impact clinical management in the care of ambulatory older adults with HF. DESIGN: Survey. SETTING: Ambulatory. PARTICIPANTS: Fifteen active ACC member physicians from the geriatric cardiology community. MEASUREMENTS: Electronic survey assessing which domains/subdomains are currently assessed in these selected real-world practices, how they are assessed, and how they are incorporated into clinical management. RESULTS: Of 15 clinicians, 14 responded to the survey. The majority routinely assess 3 to 4 domains (median, 3; interquartile range, 3-4) and a range of 4 to 12 subdomains (median, 8; interquartile range, 6-11). All respondents routinely assess the medical and physical function domains, 71% routinely assess the mind/emotion domain, and 50% routinely assess the social domain. The most common subdomains included comorbidity burden (100%), polypharmacy (100%), basic function (93%), mobility (86%), falls risk (71%), frailty (64%), and cognition (57%). Sensory impairment (50%), social isolation (50%), nutritional status (43%), loneliness (7%), and financial means (7%) were least frequently assessed. There was significant heterogeneity with regard to the tools used to assess subdomains. Common themes for how the subdomains influenced clinical care included informing prognosis, informing risk-benefit of pharmacologic therapy and invasive procedures, and consideration for palliative care. CONCLUSIONS: While respondents routinely assess multiple domains and subdomains and view these as important to clinical care, there is substantial heterogeneity regarding which subdomains are assessed and the tools used to assess them. These observations provide a foundation that inform a research agenda with regard to providing holistic and patient-centered care to older adults with HF. J Am Geriatr Soc 67:2593-2599, 2019.

Implementation of a Mindfulness Intervention for Women in Treatment for Opioid Use Disorder and Its Effects on Depression Symptoms.

Background: Many women in treatment for opioid use disorder (OUD) also experience mental health co-morbidities. Mindfulness intervention has demonstrated effectiveness for improving mental health in the general population, but has not been tested with female populations in OUD treatment. The purpose of this study was to describe characteristics associated with participation in a mindfulness intervention provided to women in treatment for OUD, and also to evaluate the effectiveness of a mindfulness intervention on depression symptoms. Aims: To evaluate participation characteristics associated with a mindfulness intervention and to assess the impact of a mindfulness intervention on depression symptoms for women with OUD. Methods: A secondary data analysis of a mindfulness intervention with women in treatment for OUD was accomplished. Bivariate analysis was conducted to determine any sociodemographic variables associated with intervention participation. Depression scores were assessed pre and post intervention using paired samples t tests for the intervention group (n = 65) and the control group (n = 8). Results: A 45% of women in the study reported moderate to severe depression symptoms at baseline, and 63% reported high levels of childhood trauma. There was a significant decrease in depression scores (M = 3.6 [1.2,6.1]) following the mindfulness intervention for the intervention group (t(64) = 3.1, p = .003). Participants entering the intervention group with moderate to severe depression scores experienced the most significant decrease in depression symptoms (M = 6.6, SD = 13.5), (t(64) = -2.1, p < .05). Conclusions: Women in treatment for OUD experience high levels of depression symptoms and past trauma, and mindfulness is a feasible intervention for OUD populations which may improve depression symptoms.

c-Abl phosphorylation of Yin Yang 1's conserved tyrosine 254 in the spacer region modulates its transcriptional activity.

Yin Yang 1 (YY1) is a multifunctional transcription factor that can activate or repress transcription depending on the promotor and/or the co-factors recruited. YY1 is phosphorylated in various signaling pathways and is critical for different biological functions including embryogenesis, apoptosis, proliferation, cell-cycle regulation and tumorigenesis. Here we report that YY1 is a substrate for c-Abl kinase phosphorylation at conserved residue Y254 in the spacer region. Pharmacological inhibition of c-Abl kinase by imatinib, nilotinib and GZD824, knock-down of c-Abl using siRNA, and the use of c-Abl kinase-dead drastically reduces tyrosine phosphorylation of YY1. Both radioactive and non-radioactive in vitro kinase assays, as well as co-immunoprecipitation in different cell lines, show that the target of c-Abl phosphorylation is tyrosine residue 254. c-Abl phosphorylation has little effect on YY1 DNA binding ability or cellular localization in asynchronous cells. However, functional studies reveal that c-Abl mediated phosphorylation of YY1 regulates YY1's transcriptional ability in vivo. In conclusion, we demonstrate the novel role of c-Abl kinase in regulation of YY1's transcriptional activity, linking YY1 regulation with c-Abl tyrosine kinase signaling pathways.

Domain Management Approach to Heart Failure in the Geriatric Patient: Present and Future.

Heart failure (HF) is a quintessential geriatric cardiovascular condition, with more than 50% of hospitalizations occurring in adults age 75 years or older. In older patients, HF is closely linked to processes inherent to aging, which include cellular and structural changes to the myocardium, vasculature, and skeletal muscle. In addition, HF cannot be considered in isolation of physical functioning, or without the social, psychological, and behavioral dimensions of illness. The role of frailty, depression, cognitive impairment, nutrition, and goals of care are each uniquely relevant to the implementation and success of medical therapy. In this paper, we discuss a model of caring for older adults with HF through a 4-domain framework that can address the unique multidimensional needs and vulnerabilities of this population. We believe that clinicians who embrace this approach can improve health outcomes for older adults with HF.

Integrative Review of the Relationship Between Mindfulness-Based Parenting Interventions and Depression Symptoms in Parents.

OBJECTIVE: To synthesize the research findings about the relationship between mindfulness-based parenting interventions and symptoms of depression in parents. DATA SOURCES: The terms mindfulness, parent or mother, and depression were used to search PubMed, the Cumulative Index for Nursing and Allied Health Literature (CINAHL), Scopus, and PsychInfo/OVID databases. A limitation was not set for date of publication. STUDY SELECTION: The database searches resulted in 198 articles for abstract review, 7 of which remained after the application of inclusion and exclusion criteria. Three randomized controlled trials and four descriptive studies were included in the review. Three studies included mothers as the only participants; the other studies included a small to moderate percentage of fathers. DATA EXTRACTION: Studies were reviewed for findings relevant to the relationship between mindfulness-based parenting interventions and symptoms of depression in parents according to their respective research designs. DATA SYNTHESIS: Analysis of the randomized controlled trials showed that mindfulness-based parenting interventions had significant positive treatment effects on symptoms of depression. Analysis of the descriptive studies showed significant inverse associations between mindfulness and depression scores. Although findings were consistent across the studies, the studies varied significantly in participant characteristics, intervention frequency and duration, and measurement tools. CONCLUSION: Further research is recommended with regard to the use of mindfulness-based parenting interventions to influence symptoms of depression in diverse populations. Samples of parents with culturally, economically, or racially diverse backgrounds have not been well-studied in relation to mindfulness-based parenting. Consistent use of frameworks, intervention types, and measurement tools across studies will strengthen the body of evidence.

Aurora A Phosphorylation of YY1 during Mitosis Inactivates its DNA Binding Activity.

Successful execution of mitotic cell division requires the tight synchronisation of numerous biochemical pathways. The underlying mechanisms that govern chromosome segregation have been thoroughly investigated. However, the mechanisms that regulate transcription factors in coordination with mitotic progression remain poorly understood. In this report, we identify the transcription factor YY1 as a novel mitotic substrate for the Aurora A kinase, a key regulator of critical mitotic events, like centrosome maturation and spindle formation. Using in vitro kinase assays, we show that Aurora A directly phosphorylates YY1 at serine 365 in the DNA-binding domain. Using a new phospho-specific antibody, we show that YY1 phosphorylation at serine 365 occurs during mitosis, and that this phosphorylation is significantly reduced upon inhibition of Aurora A. Furthermore, we show, using electrophoretic mobility shift and chromatin immunoprecipitation assays, that phosphorylation of YY1 at this site abolishes its DNA binding activity in vitro and in vivo. In conformity with this loss of binding activity, phosphorylated YY1 also loses its transctivation ability as demonstrated by a luciferase reporter assay. These results uncover a novel mechanism that implicates Aurora A in the mitotic inactivation of transcription factors.

The transcription factor YY1 is a novel substrate for Aurora B kinase at G2/M transition of the cell cycle.

Yin Yang 1 (YY1) is a ubiquitously expressed and highly conserved multifunctional transcription factor that is involved in a variety of cellular processes. Many YY1-regulated genes have crucial roles in cell proliferation, differentiation, apoptosis, and cell cycle regulation. Numerous mechanisms have been shown to regulate the function of YY1, such as DNA binding affinity, subcellular localization, and posttranslational modification including phosphorylation. Polo-like kinase 1(Plk1) and Casein kinase 2α (CK2 α) were the first two kinases identified to phosphorylate YY1. In this study, we identify a third kinase. We report that YY1 is a novel substrate of the Aurora B kinase both in vitro and in vivo. Serine 184 phosphorylation of YY1 by Aurora B is cell cycle regulated and peaks at G2/M and is rapidly dephosphorylated, likely by protein phosphatase 1 (PP1) as the cells enter G1. Aurora A and Aurora C can also phosphorylate YY1 in vitro, but at serine/threonine residues other than serine 184. We present evidence that phosphorylation of YY1 in the central glycine/alanine (G/A)-rich region is important for DNA binding activity, with a potential phosphorylation/acetylation interplay regulating YY1 function. Given their importance in mitosis and overexpression in human cancers, Aurora kinases have been identified as promising therapeutic targets. Increasing our understanding of Aurora substrates will add to the understanding of their signaling pathways.

Phosphorylation of the transcription factor YY1 by CK2α prevents cleavage by caspase 7 during apoptosis.

In this report, we describe the phosphorylation of Yin Yang 1 (YY1) in vitro and in vivo by CK2α (casein kinase II), a multifunctional serine/threonine protein kinase. YY1 is a ubiquitously expressed multifunctional zinc finger transcription factor implicated in regulation of many cellular and viral genes. The products of these genes are associated with cell growth, the cell cycle, development, and differentiation. Numerous studies have linked YY1 to tumorigenesis and apoptosis. YY1 is a target for cleavage by caspases in vitro and in vivo as well, but very little is known about the mechanisms that regulate its cleavage during apoptosis. Here, we identify serine 118 in the transactivation domain of YY1 as the site of CK2α phosphorylation, proximal to a caspase 7 cleavage site. CK2α inhibitors, as well as knockdown of CK2α by small interfering RNA, reduce S118 phosphorylation in vivo and enhance YY1 cleavage under apoptotic conditions, whereas increased CK2α activity by overexpression in vivo elevates S118 phosphorylation. A serine-to-alanine substitution at serine 118 also increases the cleavage of YY1 during apoptosis compared to wild-type YY1. Taken together, we have discovered a regulatory link between YY1 phosphorylation at serine 118 and regulation of its cleavage during programmed cell death.

Global mitotic phosphorylation of C2H2 zinc finger protein linker peptides.

Cessation of transcriptional activity is a hallmark of cell division. Many biochemical pathways have been shown and proposed over the past few decades to explain the silence of this phase. In particular, many individual transcription factors have been shown to be inactivated by phosphorylation. In this report, we show the simultaneous phosphorylation and mitotic redistribution of a whole class of modified transcription factors. C(2)H(2) zinc finger proteins (ZFPs) represent the largest group of gene expression regulators in the human genome. Despite their diversity, C(2)H(2) ZFPs display striking conservation of small linker peptides joining their adjacent zinc finger modules. These linkers are critical for DNA binding activity. It has been proposed that conserved phosphorylation of these linker peptides could be a common mechanism for the inactivation of the DNA binding activity of C(2)H(2) ZFPs, during mitosis. Using a novel antibody, raised against the phosphorylated form of the most conserved linker peptide sequence, we are able to visualize the massive and simultaneous mitotic phosphorylation of hundreds of these proteins. We show that this wave of phosphorylation is tightly synchronized, starting in mid-prophase right after DNA condensation and before the breakdown of the nuclear envelope. This global phosphorylation is completely reversed in telophase. In addition, the exclusion of the phospho-linker signal from condensed DNA clearly demonstrates a common mechanism for the mitotic inactivation of C(2)H(2) ZFPs.

The transcription factor YY1 is a substrate for Polo-like kinase 1 at the G2/M transition of the cell cycle.

Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate.

Synthesis and biological evaluation of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as adenosine kinase inhibitors.

The synthesis and structure-activity relationship of a series of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as novel non-nucleoside adenosine kinase inhibitors is described. A variety of substituents, primarily aryl, at the C6 and C7 positions of the pyridopyrimidine core were found to yield analogues that are potent inhibitors of adenosine kinase. In contrast to the 5,7-disubstituted and 5,6,7-trisubstituted pyridopyrimidine series, these analogues exhibited only modest potency to inhibit AK in intact cells.