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Objectives: The guiding principle of current aging policies has been to promote older adults to live in their private homes, but little attention has been paid to social exclusion of older adults receiving home-based care. The aim of this study is to increase understanding on different patterns of multidimensional social exclusion among older adults receiving formal home care services, and through this to shed light on the possible challenges of current aging-in-place policies., Methods: The survey data were collected in 2022 among older adults aged 65 to 102 years receiving home care services in Finland and merged with administrative data (n = 733). A latent class analysis was used to identify different types of social exclusion. Multinomial logistic regression modeling examined factors associated with different social exclusion types., Results: Four social exclusion types were identified: (1) not excluded (16.9%), (2) homebound economically excluded (40.1%), (3) excluded from social relations (28.6%), and (4) multidimensionally excluded (14.3%). Poor self-rated health and poor functional ability significantly increase the risk of being multidimensionally excluded or homebound economically excluded. The group using home care and medical services the most are the most multidimensionally excluded. The group living in urban areas are more likely to be excluded from social relations., Discussion: Different types of social exclusion should be acknowledged when addressing social exclusion among home care clients. Enhanced measures should be developed to support older adults using home and healthcare services the most, as they are at high risk of severe exclusion., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

The study examines former home care workers' reasons for leaving their jobs from the perspective of reforms in public services and eldercare policies impacted by New Public Management (NPM) in Finland. Written narratives from former home care workers ( n = 39) were collected online and analyzed using thematic content analysis. Former home care workers' reasons for leaving their jobs were connected to four interconnecting themes: mismatch between needs and resources , measurement-driven practices , unbalancing work - life , and ethical burden . These reasons reflected critical changes in the organization of care work and the work environment in older adults' home care. Contradictions between needs, resources, and values lead to ethical dilemmas and push away from the workforce in eldercare. To improve care workers' willingness to remain in the eldercare sector, changes are needed in the resourcing and organization of home care, including managerial support in everyday care work., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In Finland, the 'day activity service' is targeted at older home care clients who are unable to participate in other available activities due to poor health or functional disabilities. The aim of the day activity service is to support home care client's ability to live at home and to enhance their wellbeing and social inclusion. This mixed method study examines the effectiveness, cost-effectiveness and process of the day activity service., Methods: The target sample size is 200 participants. The intervention group (n = 100) is composed of home care clients who begin to participate in the day activity service. The comparison group (n = 100) are home care clients who do not participate in the day activity service, and whose functioning and care needs are similar to the participants of the intervention group. The primary outcome is social inclusion (ESIS-scale). Secondary outcomes are loneliness (single item and De Jong Gierveld Loneliness Scale) and social care related quality of life (ASCOT). Baseline, three-month and six-month follow-up surveys are gathered from intervention and comparison group participants in order to compare outcomes between groups pre- and post-intervention. Costs of health and social services, based on administrative data, and the costs of the intervention are utilized in examining the cost-effectiveness of the intervention with the above-described measurements. Qualitative data are collected by interviewing the intervention participants (n = 10) and professionals working at the day activity centres and older people's services (4 focus groups) to explore the perceived outcomes and process of the intervention to find out how and why the intervention is effective or ineffective., Discussion: The study seeks to produce a comprehensive understanding of the effectiveness, cost-effectiveness and implementation process of the day activity service., Trial Registration: ISRCTN13146087, Registration date 03/04/2022., (© 2022. The Author(s).)

Background and Objectives: More knowledge is needed of the effectiveness of complex interventions that aim to promote the wellbeing of older people. This study examines the effects of 'participatory group-based care management' conducted among community-dwelling older adults living alone in Central and Eastern Finland. The intervention aimed to promote wellbeing and quality of life (QoL) using a needs-based and participatory approach., Methods: The study was carried out as a randomized control trial (intervention group n = 185, control group n = 207). In this article, baseline and 6-month follow-up surveys were used. QoL (WHOQOL-Bref instrument), loneliness (Revised UCLA Loneliness Scale; single-item question), and trust (two items of generalized trust and six items of institutional trust) were used as outcome measurements, and generalized estimating equations (GEE) modeling as the analysis method. Both per-protocol and intention-to-treat analyses were applied., Results: According to the per-protocol analysis, the intervention had no effects on QoL. Loneliness decreased among older people with poor QoL at the baseline. Additionally, the intervention enhanced trust in other people and some dimensions of institutional trust. The intention-to-treat analysis did not result in any significant effects on QoL or loneliness, but some small positive changes in institutional trust were found., Conclusions: Based on some evidence of small positive effects, the intervention may be beneficial in alleviating loneliness and enhancing trust among older people living alone. Because of the contradictory results, more research is needed to examine the complexity of 'participatory group-based care management´ from the perspective of process evaluation., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.

Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs. The MutSigCV ranking identified several well-established MSI CRC driver genes and provided additional evidence for previously proposed CRC candidate genes as well as shortlisted genes that have to our knowledge not been linked to CRC before. Two genes, SMARCB1 and STK38L , were also functionally scrutinized, providing evidence of a tumorigenic role, for SMARCB1 mutations in particular., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Approximately 15% of colorectal cancers exhibit microsatellite instability (MSI), which leads to accumulation of large numbers of small insertions and deletions (indels). Genes that provide growth advantage to cells via loss-of-function mutations in microsatellites are called MSI target genes. Several criteria to define these genes have been suggested, one of them being simple mutation frequency. Microsatellite mutation rate, however, depends on the length and nucleotide context of the microsatellite. Therefore, assessing the general impact of mismatch repair deficiency on the likelihood of mutation events is paramount when following this approach. To identify MSI target genes, we developed a statistical model for the somatic background indel mutation rate of microsatellites to assess mutation significance. Exome sequencing data of 24 MSI colorectal cancers revealed indels at 54 million mononucleotide microsatellites of three or more nucleotides in length. The top 105 microsatellites from 71 genes were further analyzed in 93 additional MSI colorectal cancers. Mutation significance and estimated clonality of mutations determined the most likely MSI target genes to be the aminoadipate-semialdehyde dehydrogenase AASDH and the solute transporter SLC9A8 Our findings offer a systematic profiling of the somatic background mutation rate in protein-coding mononucleotide microsatellites, allowing a full cataloging of the true targets of MSI in colorectal cancer. Cancer Res; 77(15); 4078-88. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.

ARID1A has been identified as a novel tumor suppressor gene in ovarian cancer and subsequently in various other tumor types. ARID1A belongs to the ARID domain containing gene family, which comprises of 15 genes involved, for example, in transcriptional regulation, proliferation and chromatin remodeling. In this study, we used exome sequencing data to analyze the mutation frequency of all the ARID domain containing genes in 25 microsatellite unstable (MSI) colorectal cancers (CRCs) as a first systematic effort to characterize the mutation pattern of the whole ARID gene family. Genes which fulfilled the selection criteria in this discovery set (mutations in at least 4/25 [16%] samples, including at least one nonsense or splice site mutation) were chosen for further analysis in an independent validation set of 21 MSI CRCs. We found that in addition to ARID1A, which was mutated in 39% of the tumors (18/46), also ARID1B (13%, 6/46), ARID2 (13%, 6/46) and ARID4A (20%, 9/46) were frequently mutated. In all these genes, the mutations were distributed along the entire length of the gene, thus distinguishing them from typical MSI target genes previously described. Our results indicate that in addition to ARID1A, other members of the ARID gene family may play a role in MSI CRC., (© 2013 UICC.)

Microsatellite instability can be found in approximately 15% of all colorectal cancers. To detect new oncogenes we sequenced the exomes of 25 colorectal tumors and respective healthy colon tissue. Potential mutation hot spots were confirmed in 15 genes; ADAR, DCAF12L2, GLT1D1, ITGA7, MAP1B, MRGPRX4, PSRC1, RANBP2, RPS6KL1, SNCAIP, TCEAL6, TUBB6, WBP5, VEGFB, and ZBTB2; these were validated in 86 tumors with microsatellite instability. ZBTB2, RANBP2, and PSRC1 also were found to contain hot spot mutations in the validation set. The form of ZBTB2 associated with colorectal cancer increased cell proliferation. The mutation hot spots might be used to develop personalized tumor profiling and therapy., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)