Objective We compared peripheral blood (PBL) chemokine ligand/receptor profiles in children and adolescents with type 1 diabetes mellitus (T1D) or obesity (OB) (both involving inflammation and ...vascular complications) to identify their associations with cardiometabolic risk factors. Materials and methods PBL samples from children and adolescents (12–18 years) included: healthy controls (n=29), patients with T1D (n=31) and OB subjects (n=34). Frequency of mononuclear cell populations and chemokine receptor expression (CCR2, CCR4, CXCR3, CXCR4) were determined by flow cytometry. Chemokine levels of CCL2, CCL5, CXCL10 and CXCL11 were measured by bead-based assay and CXCL12 by ELISA. Data were correlated with cardiovascular, metabolic and inflammatory parameters. Results The proportion of CD14 + monocytes was higher in T1D, whereas the proportion of CD19 + B lymphocytes was higher and CD3 + T lymphocytes was lower in OB. The level of CCL2 was higher in T1D (241.0 (IQR 189.6–295.3) pg/mL in T1D vs 191.5 (IQR 158.0–254.7) pg/mL in control, p=0.033), CXCL11 was lower in OB (6.6 (IQR 4.9–7.7) pg/mL in OB vs 8.2 (IQR 6.9–11.3) pg/mL in control, p=0.018) and CXCL12 was lower in both diseases (2.0 (IQR 1.8–2.5) ng/mL in T1D, 2.1 (IQR 1.9–2.4) ng/mL in OB vs 2.4 (IQR 2.2–2.5) ng/mL in control, p=0.016). Numerous significant associations were found for chemokine ligand/receptor profiles and clinical data. Among these, we are suggesting the most important indicators of cardiometabolic risk in T1D: positive associations of CCR2 + monocytes with blood pressure and CCL12 levels with urine albumin-to-creatinine ratio (ACR), inverse association of CXCR3 + B lymphocytes with AST but positive with triglycerides; and OB: positive associations of CXCL12 levels with triglycerides and AST/ALT, inverse association of CCR4 + and CXCR3 + monocytes with ACR. Both diseases share positive associations for CCR4 + T lymphocytes and blood pressure, inverse associations of CXCR4 + subsets with ACR and CXCR3 + T lymphocytes with lipid profile. Conclusion Significantly changed chemokine ligand/receptor profiles were found in both T1D and OB even at a young age. Although different associations with cardiometabolic risk factors indicate disease-specific changes, overlapping pattern was found for the associations between CCR4 + T lymphocytes and vascular inflammation, CXCR4 + subsets and albuminuria as well as CXCR3 + T lymphocytes and dyslipidemia. Thus, chemokine axes might present potential therapeutic targets for disease-related morbidity.
Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone ...resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA). OCPs were expanded in periarticular as well as circulatory compartment of arthritic mice, particularly the CCR2
hi
subset. This subset demonstrated enhanced osteoclastogenic activity in arthritis, whereas its migratory potential was susceptible to CCR2 blockade
in vitro
. Intravascular compartment of the periarticular area contained increased frequency of OCPs with the ability to home to the arthritic bone, as demonstrated
in vivo
by intravascular staining and adoptive transfer of splenic LysMcre/Ai9 tdTomato-expressing cells. Simultaneously, CCL2 levels were increased locally and systemically in arthritic mice. Mouse cohorts were treated with the small-molecule inhibitor (SMI) of CCR2 alone or in combination with methotrexate (MTX). Preventive CCR2/CCL2 axis blockade
in vivo
reduced bone resorption and OCP frequency, whereas combining with MTX treatment also decreased disease clinical score, number of active osteoclasts, and OCP differentiation potential. In conclusion, our study characterized the functional properties of two distinct OCP subsets in CIA, based on their CCR2 expression levels, implying that the CCR2
hi
circulatory-like subset is specifically induced by arthritis. Signaling through the CCL2/CCR2 axis contributes to OCP homing in the inflamed joints and to their increased osteoclastogenic potential. Therefore, addition of CCL2/CCR2 blockade early in the course of arthritis is a promising approach to reduce bone pathology.
The available treatments for cholestatic liver fibrosis are limited, and the disease often progresses to liver cirrhosis. Tamoxifen is a selective modulator of estrogen receptors, commonly used in ...breast cancer therapy. A recent in vitro study showed that tamoxifen deactivates hepatic stellate cells, suggesting its potential as an antifibrotic therapeutic, but its effects in vivo remain poorly investigated. In the present study, we show that tamoxifen protects against the cholestatic fibrosis induced by a diet supplemented with 0.025% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Mice fed with a DDC-supplemented diet for four weeks and treated with tamoxifen developed a significantly milder degree of liver fibrosis than vehicle-treated mice, as evidenced by a lower percentage of Sirius red-stained area (60.4% decrease in stained area in male and 42% decrease in female mice, p < 0.001 and p < 0.01, respectively) and by lower hydroxyproline content. The finding was further confirmed by qPCR analysis, which showed a lower expression of genes for Col1a1, Acta2, Sox9, Pdgf, and Krt19, indicating the inhibitory effect on hepatic stellate cells, collagen production, and biliary duct proliferation. The degree of protection was similar in male and female mice. Tamoxifen per se, injected into standard-diet-fed mice, increased the expression of genes for Il6 (p < 0.01 and p < 0.001 in male and female mice, respectively) and Tgfβ (p < 0.01 for both sexes), and had no adverse effects. We showed that tamoxifen sex-independently protects against cholestatic DDC-induced liver fibrosis. The increased expression of Il6 and Tgfβ seems to be a plausible protective mechanism that should be the primary focus of further research.
A significant amount of research has been done in the United States and Western European countries regarding influences on the sense of neighborhood. However, it is less clear whether the influences ...discovered in the Western context also apply to Eastern European countries. Slovenia is a post-communist country which means that potentially different processes have been significant. In this article, the influence of individual and contextual factors on the sense of neighborhood in Slovenia is tested and compared. The analysis is made on the basis of a survey carried out in 2005 on a representative sample of Slovenian households. The findings are in some ways similar to those of the Western research. However, certain findings ran contrary to some of the cited research, like the absence of gender differences and the opposite influence of education and income. This might indicate different processes of establishing a sense of neighborhood in Central and Eastern Europe.
•Relationship between social support networks and proxy Internet use is examined.•Ego-centered social network data from a nation-wide representative sample are used.•The size of the social support ...networks is not associated with proxy Internet use.•(Grand-)children in socializing networks increase the odds of proxy Internet use.•Socio-demographic characteristics have an important role in proxy Internet use.
Digital inequalities research has documented a set of practices related to people’s Internet use that questions the binary division between Internet users and non-users. In particular, among older adults, a considerably large group of individuals has been identified as not using the Internet by themselves; rather, they ask members of their personal networks to do things online for them—they “use” the Internet by proxy. Since previous research shows that children and grandchildren are important sources of help when it comes to Internet use, the current paper indicates that the notion of intergenerational solidarity is a sound conceptual basis for understanding the relationship between social support networks and proxy Internet use among Internet non-users. Notably, the concept of functional solidarity as a dimension of intergenerational solidarity is advanced, as this relates to the frequency of the intergenerational exchange of resources and services encompassing various types of assistance and support offered between two generations. Empirically, this paper investigates how the two types of social support networks and their characteristics are associated with proxy Internet use. The results from multivariate analyses of survey data from a nation-wide representative sample show that when comparing emotional support and socializing networks, only the latter is associated with proxy Internet use: Internet non-users who have (grand-)children in their socializing support network are more likely to engage in proxy Internet use. The results also indicate that non-users who are younger, more educated, have children, and live in urban areas are more inclined to engage in proxy Internet use, regardless of the type of social support. The findings indicate the importance of empirical investigation related to different aspects of functional solidarity, as the effects on proxy Internet use depend on the type of social support.
In countries with prevalent family care and less developed care services, it is important to understand the ways families cope with the care needs of their frail family members as part of policy ...learning to make care systems more sustainable. Filial care is a vital element of family care, yet is significantly restrained by the involvement of carers in the labour market; unequal gender distribution of the care burden; and insufficient recognition of, and policy support, for family care. This article considered the issue of the sustainability of elderly care in a familialist country, Slovenia, by identifying the coping strategies families adopt for the provision of care. To this end, in-depth qualitative data based on a purposeful sample of 55 community-resident users of social home care services and their 55 family carers were used. We identified five external coping strategies: use of formal care services, use of extended family network, use of wider community network, cohabitation, and home adjustments. Among internal strategies, we detected work-related adjustments; abandoning leisure activities; abandoning vacations; establishing new routines; accepting and finding satisfaction in care; increased psychological distress, such as worries and overburdening; and some unmet care recipient needs. Very few strategies may be described as supported by policy actions, despite such support being essential for increasing the sustainability of the family-based care model.
The transformations in the welfare state regimes that have occurred globally, over the last three decades or so, have seriously affected the capacity of states to sustain the previous levels of ...social care and protection. These changes, already being manifested, inter alia, in trends in declining earnings of pensioners have inspired some researchers in this field to explore alternative ways of mitigating their impact on the well-being of the elderly during the retirement period. One of the theories that has been advanced to this effect is the so-called asset-based welfare concept which suggests that the wealth accumulated by people in the form of housing assets presents a financial reservoir that may serve as a source of income for pensioners in time of need. To address these issues, a variety of mechanisms have been developed and presented as ‘equity release products’ that may be used by senior homeowners to improve their living situation. This article contributes to the debate from the perspective of a country in Central and Eastern Europe (CEE), a region that has been rarely included in the scholarly discourse on the topic. While there might have been some level of success in the implementation of these instruments in some countries, the survey findings presented and discussed in this article show that Slovenian elderly homeowners strongly reject all the equity release products that were presented to them as potential options for alleviating financial hardship in old age. These findings lead us to the conclusion that it is highly unlikely that Slovenian elderly homeowners would ever accept and exploit, at any meaningful level of uptake, the investigated equity release mechanisms.
A poor person-environment fit may bring various negative effects to older people's independence and physical and psychological well-being. The presented study is especially valuable as it explores ...the challenges of living in cities in a country located in central and eastern Europe; namely, a less researched area when it comes to the quality of life of older people dwelling in an urban environment. The research questions that were explored are (1) what environmental pressures have people identified in the urban environment in Slovenia; and (2) what strategies have they used to deal with them? The study is based on 22 interviews with older people and three focus groups, that were then analysed using a thematic analysis approach. The study results identify a number of environmental pressures, which were divided into structural housing pressures, structural neighbourhood pressures, and formal and informal pressures. The analysis shows important behavioural responses, such as strategies of using formal and informal help, moving away from environmental pressures, mobility, actively involved in changing the environment, as well as attitudinal adaptation strategies, such as acceptance, resilience, using distraction, modesty and planning for the future. We further emphasize how these coping strategies are linked to individual and community capabilities, which function as a conversion factor.
Despite the development of various housing options across Europe, older people often face the choice of staying at home with the support of family and/or formal services or moving to a care home, but ...how people vary regarding these preferences and how newer cohorts will be different is under-researched. This study explores the housing choices of older people under the condition of liminality, which is defined as the hypothetical condition of high care needs. The most common choices available are compared; that is, staying at home (with social home-care support or visits to a daycare centre) or moving to supported housing or a care home. Cluster analysis revealed five distinct groups of older people that were differentiated in their choices between various options of moving versus staying at home, either by using home care or daycare. Differences between the clusters along three dimensions that influence decisions to move or stay, namely levels of attachment, satisfaction with housing and availability of support, which often function as limits on the options that are preferred, were explored. The results present the complexity of the decision-making process under imagined conditions of liminality and show a great diversity among people’s preferences. They also indicate that a significant share of older people have a strong preference for only one option (two of the cluster groups).
•Research on unmet care needs lacks contributions based on qualitative data.•Only practical or physical care needs are recognized whereas psychosocial needs are ignored.•With content analysis of ...interview data, the psychosocial nature of care needs is revealed.•Informal carers may act as buffers and meet unmet needs on behalf of care users.
Unmet care needs are usually defined in terms of receiving sufficient help in instrumental activities and activities of daily living. Research on unmet needs is mostly based on quantitative data. Older persons’ and informal carers’ views and experiences have received less attention.
In this paper, we rely on a definition of unmet needs which includes both unmet needs due to insufficient care and those situations where informal carers experience undue strain. Using theory-driven content analysis, we examine community-dwelling older adults’ and their informal carers’ experiences of unmet needs: what kind of unmet needs they have, why and in which ways these needs are left unmet and what would they want to do to improve the situation. The data consists of interviews gathered in Austria, Finland and Slovenia.
Results of the analysis reveal that unmet needs are largely psychosocial in nature. The predominating task-oriented care systems often do not consider these as care needs. Using methods of qualitative content analysis, we conclude that care users’ unmet psychosocial needs are related to lacking a personal relationship with care workers; means to maintain or develop social contacts and pursue activities and interests; and adequate home care services or respite care. Excessive responsibilities are put on informal carers as they top up and fill in the insufficient care.
This study contributes to a broader understanding of unmet care needs: the relational aspects of care and the universal nature of psychosocial care needs should be addressed in care services.
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