Abstract Background Living will (LW) documents have been suggested to act in patients’ best interests in end-of-life care. It is unclear, however, whether the LWs influence medical decisions when ...death is impending. Aim To explore, whether a LW among the community-dwelling older people has an influence on intensity of end-of-life treatment, place of death, or length of the dying process. Design A 10-year follow-up; data concerning place and cause of death, event history, intensity of care, decision-making process, and length of the dying process were collected from the death certificates. Setting/Participants In a community-based longitudinal cardiovascular prevention trial (DEBATE) in Helsinki, home-dwelling older people with an atherosclerotic disease ( n = 378, mean age 80.2 years) were questioned about the pre-existence of a written LW at baseline ( n = 44) in 2000. In 2010, all death certificates ( n = 207) were analysed, comparing people with a LW ( n = 30) at baseline with those without ( n = 177). Results Of the deceased, 77% died in hospital. Intensity of end-of-life treatment or cause of death did not differ between the groups. However, dying at home was more common among persons with a LW at baseline (16.7% vs. 5.6%, P = 0.031), and length of the dying process was shorter in this group (< 1 week in 50.0% vs. 27.1%, P = 0.013). Conclusions Length of the dying process was often shorter and home death more common among those with a LW at the beginning of the follow-up. More insight into the dying process is required to ensure that the decision-making process better accommodates the preferences of older people.
Abstract Background There are scarce studies exploring effectiveness and feasibility of intensive and long-lasting exercise among patients with dementia. Purpose To present baseline findings of a ...randomized controlled trial exploring effectiveness of intensive physical exercise among home-dwelling patients with Alzheimer disease (AD), and to evaluate feasibility of the intervention by exploring feedback from spousal caregivers. Subjects and methods We used central AD registers in Finland to recruit AD patients ( n = 210) living with their spousal caregiver in the community. They were randomized into three arms: 1): tailored home-based exercise twice weekly ( n = 70); 2): group-based exercise in rehabilitation centers twice weekly in ( n = 70), and; 3): a control group with usual care and information of exercise and nutrition ( n = 70). Anonymous feedback from spousal caregivers was collected at 6 months of the intervention. Results The mean age of AD patients was 78.1 years (SD 5.3), 81 (39%) were women, and 104 (50%) were at moderate stage of dementia according to the Clinical Dementia Rating Scale (CDR). Of the caregivers, 94% had made the decision to participate in the trial because of their spouse's need for rehabilitation, and 93% felt that the study nurses’ assessments had been beneficial for them. Only 16 participants (8%) had dropped out before the first (3-month) follow-up assessment. Conclusion We have successfully randomized 210 patients with Alzheimer's disease and their spousal caregivers into an intensive exercise rehabilitation trial. The feedback from spousal caregivers was favourable and drop-out rate low at 6 months.
Abstract Background Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD) and are associated with admission to institutional care. Current guidelines recommend non-pharmacological ...interventions as the first-line treatment for NPS. However, high-quality randomized studies focused on NPS are scarce. The objective here was to examine whether a regular and long-term exercise programme either at home or as a group-based exercise at an adult day care centre has beneficial effects on AD patients’ NPS or permanent institutionalizations. Design, setting, and participants A randomized, controlled trial with 210 community-dwelling AD patients. Intervention Two types of intervention comprising (1) group-based exercise in day care centres (GE) and (2) tailored home-based exercise (HE), both twice a week for 12 months, were compared with (3) a control group (CG) receiving usual community care. Measurements NPS were measured with the Neuropsychiatric Inventory (NPI) at baseline and 6 months, and depression with the Cornell Scale for Depression in Dementia (CSDD) at baseline and 12 months. Data on institutionalizations were retrieved from central registers. Results No significant differences between the groups were detected in NPI at 6 months or in CSDD at 12 months when analyses were adjusted for age, sex, baseline Clinical Dementia Rating, and Functional Independence Measure. There was no difference in admissions to permanent institutional care between the groups. Conclusions Regular, long-term exercise intervention did not decrease NPS in patients with AD.
The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor ...receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via Delta like Canonical Notch Ligand 4 (DLL4). BMP6 modulated VEGF signaling by regulating VEGFR2 expression and acted via Hippo signaling effector TAZ, known to regulate cell survival/proliferation, and to be dysregulated in cancer. In a matrigel plug assay in nude mice BMP6 was further demonstrated to induce angiogenesis. BMP6 is the first member of BMP family found to directly regulate both Hippo signaling and neovessel formation. It may thus serve as a target in pro/anti-angiogenic therapies.
We conducted a cross-sectional survey of a random sample of 1943 spouses of home-dwellers with Alzheimer’s disease (AD) to examine the prevalence of court-appointed guardians or financial powers of ...attorney for persons with AD, related factors and the need for information about these issues among caregiving families. The questionnaire consisted questions on variables of demographic characteristics, disability, symptoms and care needs of the person with dementia, the strain of caregiving, the use of court-appointed legal guardians or powers of attorney, as well as discussions about these issues—and the need for them—with a doctor. The response rate was 77% and the mean ages of those with AD and caregivers were 80.2 and 78.2 years, respectively. The use of legal guardians was rare (4.3%), while the use of financial powers of attorney was more common (37.8%). Only 9.9% of the couples had discussed these issues with their doctor, whereas 47.9% expressed a need for it. The factors associated with the use of these legal arrangements were related to the severity of dementia, including experiencing dementia symptoms for more than 3 years, poor functioning, incontinence and behavioural symptoms. There is a clear need for information on medico-legal issues related to dementia among caregivers of AD patients. If held soon after the diagnosis, such discussions could support the autonomy of these persons in spite of AD and enable them to plan for the future as they wish.
Glutamine synthetase (GS) and glucose-6-phosphate isomerase (GPI) were identified as novel adhesive moonlighting proteins of Lactobacillus crispatus ST1. Both proteins were bound onto the bacterial ...surface at acidic pHs, whereas a suspension of the cells to pH 8 caused their release into the buffer, a pattern previously observed with surface-bound enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of L. crispatus. The pH shift was associated with a rapid and transient increase in cell wall permeability, as measured by cell staining with propidium iodide. A gradual increase in the release of the four moonlighting proteins was also observed after the treatment of L. crispatus ST1 cells with increasing concentrations of the antimicrobial cationic peptide LL-37, which kills bacteria by disturbing membrane integrity and was here observed to increase the cell wall permeability of L. crispatus ST1. At pH 4, the fusion proteins His6-GS, His6-GPI, His6-enolase, and His6-GAPDH showed localized binding to cell division septa and poles of L. crispatus ST1 cells, whereas no binding to Lactobacillus rhamnosus GG was detected. Strain ST1 showed a pH-dependent adherence to the basement membrane preparation Matrigel. Purified His6-GS and His6-GPI proteins bound to type I collagen, and His6-GS also bound to laminin, and their level of binding was higher at pH 5.5 than at pH 6.5. His6-GS also expressed a plasminogen receptor function. The results show the strain-dependent surface association of moonlighting proteins in lactobacilli and that these proteins are released from the L. crispatus surface after cell trauma, under conditions of alkaline stress, or in the presence of the antimicrobial peptide LL-37 produced by human cells.
We present evidence of mitochondrial and nuclear introgression from the Atlantic herring
Clupea harengus
into the Pacific herring
C. pallasii
in northern European seas, where the two species have ...come into secondary contact following the post-glacial trans-Arctic invasion of Pacific herring to the Atlantic realm. Although the breeding areas of the two species are thought to be separate, 7 % of the resident Pacific herring in samples from the White Sea were found to possess Atlantic herring mitochondria. The percentage was even higher (21 %) in the local Balsfjord stock of the Norwegian Sea, whereas it was nil in Pechora Sea samples. Similar or somewhat lower levels of genomic admixture were estimated from four diagnostic or nearly diagnostic nuclear allozyme loci. The absences of inter-locus and cytonuclear disequilibria, together with the patterns of mtDNA haplotype diversity, suggest recurrent backcrossing and hybridization over a long period in the post-glacial time frame. From a reassessment of published allozyme data, a hypothesis is presented that the patterns of intra-species geographical variation previously recorded in North European herrings may largely reflect varying levels of introgression. The study presents new information on the processes that affect the genetic structure of one of the most abundant fishes of the northern seas. It also adds to the knowledge on the occurrence of inter-species gene flow in marine fishes and on the consequences of trans-Arctic biotic invasions in general.
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