Back to normal? The health care situation of home care receivers across Europe during the COVID-19 pandemic and its implications on health.

The COVID-19 pandemic began impacting Europe in early 2020, posing significant challenges for individuals requiring care. This group is particularly susceptible to severe COVID-19 infections and depends on regular health care services. In this article, we examine the situation of European care recipients aged 50 years and older 18 months after the pandemic outbreak and compare it to the initial phase of the pandemic. In the descriptive section, we illustrate the development of (unmet) care needs and access to health care throughout the pandemic. Additionally, we explore regional variations in health care receipt across Europe. In the analytical section, we shed light on the mid- and long-term health consequences of COVID-19-related restrictions on accessing health care services by making comparisons between care recipients and individuals without care needs. We conducted an analysis using data from the representative Corona Surveys of the Survey of Health, Ageing and Retirement in Europe (SHARE). Our study examines changes in approximately 3,400 care-dependent older Europeans (aged 50+) interviewed in 2020 and 2021, comparing them with more than 45,000 respondents not receiving care. The dataset provides a cross-national perspective on care recipients across 27 European countries and Israel. Our findings reveal that in 2021, compared to the previous year, difficulties in obtaining personal care from someone outside the household were significantly reduced in Western and Southern European countries. Access to health care services improved over the course of the pandemic, particularly with respect to medical treatments and appointments that had been canceled by health care institutions. However, even 18 months after the COVID-19 outbreak, a considerable number of treatments had been postponed either by respondents themselves or by health care institutions. These delayed medical treatments had adverse effects on the physical and mental health of both care receivers and individuals who did not rely on care.

Oral supplementation with fish cartilage hydrolysate in an adult population suffering from knee pain and function discomfort: results from an innovative approach combining an exploratory clinical study and an ex vivo clinical investigation.

BACKGROUND: Aging is frequently associated with impairments of the musculoskeletal system and many elderly people experience joint discomfort or pain which might reduce their ability to move and consequently alter their quality of life. A beneficial effect of fish cartilage hydrolysate (FCH) on pain and joint function has recently been shown in an ACLT/pMMx osteoarthritis rat model. METHODS: We therefore performed an exploratory, non-comparative, multi-centric clinical trial including 33 subjects with moderate knee joint discomfort and loss of functionality to investigate the efficacy of FCH on their algo-functional status. We further determined the potential health benefit of FCH in an original clinical ex vivo study investigating the role of FCH human metabolites on primary human chondrocytes. RESULTS: FCH significantly improved knee pain and function, as assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS). Moreover, FCH significantly reduced pain at rest and while walking, and patient global assessment (PGA), as assessed by the Visual Analogue Scale (VAS), and improved patients' quality of life (SF-36). FCH metabolites decreased the synthesis of catabolic factors (MMP-13) and pro-inflammatory mediators (NO, PGE2) and limited the inhibitory effect of IL-1ß on the synthesis of cartilage matrix components (GAG and collagen). CONCLUSIONS: Thus, these data provide insights on the mode of action of FCH in humans and contribute to explain how FCH may relieve pain and improve joint function in subjects with knee discomfort. Although these preliminary data need to be confirmed in a randomized controlled trial, they strongly support the potential health benefit of such an active ingredient. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov with the identifier NCT04420091 (09/06/2020).

Who uses technical aids in old age? Exploring the implementation of technology-based home modifications in Europe.

Introduction: Home modifications and features, e.g., handrails or ramps for people using wheelchairs, should allow residents with functional limitations to maintain social participation, health, and wellbeing for aging in place. However, there is little evidence in relation to the individual characteristics shaping this implementation of technology-based home modifications. Current studies often focus on describing the distribution of certain implementations in households but do not provide information on factors predicting the implementation or detailed and multifaceted data on associations with characteristics of the older user. This article, therefore, examines the use of well-established technological aids and home modifications (e.g., ramps, handrails, automatic doors, bathroom or kitchen modifications, chair lifts, and alerting devices) in the households of older adults in Europe. We refer to Lawton's and Nahemow's concept of personal-environment fit and describe the use of technical aids across 18 countries, analyze associations with individual characteristics and social resources, and compare those associations and variance explanation between older adults in their third age ("young-old", 65-79 years) and older adults in their fourth age ("old-old", 80+). Methods: Drawing on representative data from the Survey of Health, Ageing, and Retirement in Europe (SHARE), wave 6, a total of N = 38,553 older adults aged 65-105 years (M = 74.4 years, SD = 7.1; 55% women) were analyzed by performing hierarchical logistic regression analyses. Results: Indicators of functioning explained the highest proportion of variance, followed by social resources, and variance explanation was higher for the fourth age than for the third age. In particular, older adults with physical limitations, a larger social network, and those who received care from a child outside the household were more likely to have home modifications installed. Discussion: The study provides an overview of associations of diverse variables with assistive devices and modifications in the home and can serve as a starting point for public health activities concerning the heterogeneity of people aged 65 years and older.

Socioeconomic differences in informal caregiving in Europe.

Disclosing socioeconomic differences in informal care provision is increasingly important in aging societies as it helps to identify the segments of the population that may need targeted support and the types of national investments to support family caregivers. This study examines the association between individual-level socioeconomic status and informal care provision within the household. We also examine the role of contextual factors, income inequality, and the generosity of social spending, to identify how macro-level socioeconomic resource structures shape individuals' provision of care to household members. We use pooled data from the Survey of Health, Ageing and Retirement in Europe (SHARE, waves 1, 2, 4, 5, 6) and the English Longitudinal Study of Ageing (ELSA, waves 2, 3, 4, 6, 7). Poisson regression multilevel models estimate the associations between household socioeconomic status (education, income, and wealth), and country socioeconomic resources (income inequality and social spending as a percentage of GDP), and the likelihood of older adults' informal care provision within the household. Results indicate that lower individual socioeconomic resources-education, income, and wealth-were associated with a higher incidence of older adults' informal care provision within the household. At the macro-level, income inequality was positively associated while social spending was negatively associated with older adults' care provision within the household. Our findings suggest that socioeconomically disadvantaged groups are more likely to provide informal care, which may reinforce socioeconomic inequalities. At the national level, more equitable resource distribution and social spending may reduce intensive family caregiving.

Screening for mineral oil hydrocarbons in vegetable oils by silver ion-planar solid phase extraction.

The analysis of mineral oil hydrocarbons in vegetable oils is challenging especially regarding the analysis of mineral oil aromatic hydrocarbons (MOAH) since native terpenes like squalene or ß-carotene are usually extracted along with the MOAH fraction and interfere their detection. When applying a recently developed screening method for the analysis of mineral oil saturated hydrocarbons (MOSH) and MOAH in paper and cardboard by planar solid phase extraction (pSPE) to vegetable oils, native terpenes expectably interfered with MOAH analysis. Thus, an adaption of pSPE employing silver ions, named silver ion-planar solid phase extraction (Ag-pSPE), was developed in this study. Impregnation of thin-layers with silver nitrate (AgNO3) was found to be very successful in retaining squalene and ß-carotene. MOAH analysis of vegetable oils after saponification showed good repeatability (relative standard deviation (%RSD) <10%) and recoveries of 73.4-112.4% at a spiking level of 4.5 mg/kg (n = 4). For MOSH analysis, a simple solid phase extraction (SPE) clean-up with aluminum oxide removed native n-alkanes prior to Ag-pSPE. Recoveries for MOSH were 55.3-84.5% with %RSD <11% at a spiking level of 45.5 mg/kg (n = 4). Limits of decision and quantitation were at 7.2 and 22.2 ng/zone for MOSH and 1.1 and 3.4 ng/zone for MOAH, respectively, which corresponded to the recently introduced pSPE method, thus showing that analytes were not affected by the impregnation of HPTLC plates with AgNO3. The method comparison with LC-GC showed similar results for MOSH, while the amounts for MOAH determined by Ag-pSPE were higher.

The Impact of COVID-19 on Informal Caregiving and Care Receiving Across Europe During the First Phase of the Pandemic.

Purpose: We analyzed the effects of COVID-19 as well as its accompanying epidemiological control measures on health-related outcomes (physical and mental health) and unmet care needs of both caregivers and care recipients across Europe and Israel by taking into account country differences. Methods: We applied comparisons of adjusted predictions, controlling for a large set of relevant respondent characteristics, to investigate changes in the physical and mental health of caregivers and care recipients due to COVID-19. Furthermore, multilevel regression models were used to analyze the effect of individual and contextual indicators on the probability of reporting difficulties in receiving care. For the analyses, we used data from 26 countries with 51,983 respondents over 50 years based on the eighth wave of the Survey of Health, Aging and Retirement in Europe (SHARE), which had to be suspended in March 2020, and the SHARE Corona Survey fielded from June to August 2020. Results: During the first phase of the pandemic in spring/summer 2020, the frequency of providing personal care to parents increased in almost all European countries, while care to children, in turn, decreased. Parental caregivers who increased the frequency of providing personal care reported significantly more mental health strains, that is, feeling sad/depressed and anxious/nervous more often since the outbreak of the pandemic. With respect to receiving care, about one out of five care recipients had difficulty in obtaining adequate care from outside the household during the pandemic. The perception of unmet care needs was significantly associated with country differences regarding the duration of the stay-at-home orders. In contrast, the number of confirmed deaths did not have a significant effect on perceiving difficulties related to receiving care. Conclusions: Our findings show the extent of the burden to which caregivers and care recipients were exposed with respect to the unintended consequences of COVID-19-related epidemiological control measures. There is a great need within this population for interventions, which effectively reduce the burden as well as the symptoms of anxiety or depression for caregivers as well as care recipients. This should be recognized by (health) policymakers and social organizations.

[Distance caregiving : Empirical findings from the Survey of Health, Ageing and Retirement in Europe]. / Pflege über räumliche Distanz hinweg : Ergebnisse einer Datenanalyse des Survey of Health, Ageing and Retirement in Europe.

BACKGROUND: The support of relatives living far away in terms of distance caregiving between children and their parents has gained in importance in Europe. At the same time, little is known about these care arrangements based on representative European survey data. OBJECTIVE: This article is concerned with the following questions: which statements are possible in Europe about the prevalence of persons caring for at least one parent from a geographical distance? Which forms of support are provided and which other specific socioeconomic and health-related aspects characterize these care situations? In this respect special attention is paid to differences to relatives who provide help close to their parents who are in need of care. MATERIAL AND METHODS: Data from the Survey of Health, Ageing and Retirement in Europe (SHARE) from the sixth wave of the survey in 2015 were used to perform a descriptive analysis and multivariate logistic regression. RESULTS AND CONCLUSION: The analysis showed that distance caregiving is more than a marginal phenomenon in Europe with a prevalence of 11% for a relatively close terminology (over 100 km distance between locations) and 23% for a broader terminology (over 25 km); however, the various countries are very different in terms of prevalence. The findings also point to some significant differences in terms of resources, care tasks and quality of life compared to caregivers in the same household. In light of these dynamically developing distance caregiving arrangements, this article can provide further discussion, critical reflection, and advancement to the operationalization of informal care.

Screening for mineral oil saturated and aromatic hydrocarbons in paper and cardboard directly by planar solid phase extraction and by its coupling to gas chromatography.

Mineral oil saturated and aromatic hydrocarbons (MOSH/MOAH) are food contaminants, mainly due migration from packaging materials made from recycled fibers, but other routes of entry into food have also been identified. Legal limits for MOSH and MOAH in food and food contact materials currently are not set, but are to be expected in the near future. For the analysis of MOSH and MOAH, the very well developed and highly automated on-line liquid chromatography-gas chromatography with flame ionization detection (LC-GC-FID) is commonly used. However, this approach is time-consuming, and data interpretation is a very challenging task. Therefore, a planar solid phase extraction (pSPE) method was developed for a rapid and efficient MOSH and MOAH screening in paper and cardboard. Based on high-performance thin-layer chromatography (HPTLC), pSPE offers the simultaneous clean-up and analysis of up to 20 samples in parallel, while MOSH and MOAH analytes were focused in two distinct target zones on silica gel HPTLC plates after a twofold development. Plate impregnation with primuline allowed the detection of MOSH by fluorescence, while MOAH were detected by UV light absorption. The pSPE screening approach provided limits of detection of 7.2 and 2.3 ng/zone for MOSH and MOAH, respectively, corresponding to 1.8 and 0.6 mg/kg paper. Coupling of pSPE with GC revealed the common MOSH and MOAH peak humps, while marker substances offered the identification of the mineral oil origin or information about recycled fiber materials. As compared to SPE-GC-FID analyses, the determined quantities of MOSH and MOAH in cardboard samples indicated pSPE as a rapid and suitable screening tool. The co-migration of polyolefin oligomeric saturated hydrocarbons, native n-alkanes, terpenes and possibly essential oils or sterol esters, however, can result in an overestimation of MOSH and MOAH. Hence, samples with pSPE results above a given limit are subsequently analyzed by GC (pSPE-GC) for confirmation and detailed evaluation.

Long-term Care Provision and the Well-Being of Spousal Caregivers: An Analysis of 138 European Regions.

Objectives: The individual burden of caring for one's relatives not only depends on care characteristics but is also related to contextual factors. The objective of this study is to determine whether regional formal long-term care provision is linked to the well-being of spousal caregivers introducing the concept of "control" as central pathway to explain this link. Method: We applied multilevel analysis using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) from over 29,000 Europeans and 1,800 spousal caregivers located in 138 regions in 11 countries to analyze the effects of regional contexts on caregiver well-being. The provision of formal care in a region was measured by the number of long-term care beds in nursing and residential homes among the older population. Results: We found that spousal caregivers' well-being, measured in terms of life satisfaction, loneliness, and depression, was positively linked to the regional availability of formal care, which is partly due to higher perceived control in regions with more formal care provision. Discussion: Our results suggest that formal care supply is essential not only for care recipients but also for caregivers: perceived alternatives to the private care arrangement go along with greater well-being of informal caregivers.

Use of a Yeast tRNase Killer Toxin to Diagnose Kti12 Motifs Required for tRNA Modification by Elongator.

Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin's action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence, loss of anticodon modification in mutants lacking Elongator or related KTI (K. lactis Toxin Insensitive) genes protects against tRNA cleavage and confers resistance to the toxin. Here, we show that zymocin can be used as a tool to genetically analyse KTI12, a gene previously shown to code for an Elongator partner protein. From a kti12 mutant pool of zymocin survivors, we identify motifs in Kti12 that are functionally directly coupled to Elongator activity. In addition, shared requirement of U34 modifications for nonsense and missense tRNA suppression (SUP4; SOE1) strongly suggests that Kti12 and Elongator cooperate to assure proper tRNA functioning. We show that the Kti12 motifs are conserved in plant ortholog DRL1/ELO4 from Arabidopsis thaliana and seem to be involved in binding of cofactors (e.g., nucleotides, calmodulin). Elongator interaction defects triggered by mutations in these motifs correlate with phenotypes typical for loss of U34 modification. Thus, tRNA modification by Elongator appears to require physical contact with Kti12, and our preliminary data suggest that metabolic signals may affect proper communication between them.

A novel, lactase-based selection and strain improvement strategy for recombinant protein expression in Kluyveromyces lactis.

BACKGROUND: The Crabtree-negative yeast species Kluyveromyces lactis has been established as an attractive microbial expression system for recombinant proteins at industrial scale. Its LAC genes allow for utilization of the inexpensive sugar lactose as a sole source of carbon and energy. Lactose efficiently induces the LAC4 promoter, which can be used to drive regulated expression of heterologous genes. So far, strain manipulation of K. lactis by homologous recombination was hampered by the high rate of non-homologous end-joining. RESULTS: Selection for growth on lactose was applied to target the insertion of heterologous genes downstream of the LAC4 promoter into the K. lactis genome and found to yield high numbers of positive transformants. Concurrent reconstitution of the ß-galactosidase gene indicated the desired integration event of the expression cassette, and ß-galactosidase activity measurements were used to monitor gene expression for strain improvement and fermentation optimization. The system was particularly improved by usage of a cell lysis resistant strain, VAK367-D4, which allowed for protein accumulation in long-term fermentation. Further optimization was achieved by increased gene dosage of KlGAL4 encoding the activator of lactose and galactose metabolic genes that led to elevated transcription rates. Pilot experiments were performed with strains expressing a single-chain antibody fragment (scFvox) and a viral envelope protein (BVDV-E2), respectively. scFvox was shown to be secreted into the culture medium in an active, epitope-binding form indicating correct processing and protein folding; the E2 protein could be expressed intracellularly. Further data on the influence of protein toxicity on batch fermentation and potential post-transcriptional bottlenecks in protein accumulation were obtained. CONCLUSIONS: A novel Kluyveromyces lactis host-vector system was developed that places heterologous genes under the control of the chromosomal LAC4 promoter and that allows monitoring of its transcription rates by ß-galactosidase measurement. The procedure is rapid and efficient, and the resulting recombinant strains contain no foreign genes other than the gene of interest. The recombinant strains can be grown non-selectively in rich medium and stably maintained even when the gene product exerts protein toxicity.

Neurotrophin expression is not affected in uteri of women with adenomyosis.

To investigate the involvement of neurotrophins and nerve fibres in the pathogenesis of adenomyosis, we performed a retrospective, clinical study. Hysterectomy specimens from 40 patients with histologically proven adenomyosis and from 20 patients without adenomyosis or endometriosis were used for immunohistochemical analysis. In order to investigate neurotrophic properties in adenomyosis, the antibodies against nerve growth factor (NGF), neurotrophin 3 (NT-3), the high-affinity NGF receptor (TrkA), the low-affinity neurotrophin receptor (p75(NTR)), the neuronal marker S100 (for myelinated nerve fibres) and protein gene product 9.5 (PGP9.5; for intact nerve fibres) were used. There was no significant difference in the NGF, NT-3 and p75(NTR) expression in the myometrium or endometrium between the adenomyosis and the control group. The nerve fibre density (S100, PGP9.5 and p75(NTR)) did not significantly differ between the adenomyosis and control group, the nerve fibre density of the adenomyosis group was tendentially decreased when compared with the nonporous control group. The present study suggests that endometrial and uterine neurotrophin expression and endometrial innervation are not altered in adenomyosis; however, women with adenomyosis or with adenomyosis/endometriosis tendentially had less myometrial nerve fibres than the control group.

Synthesis and application of fluorescent ras proteins for live-cell imaging.

Semisynthetic Ras proteins are efficient probes for cell-biology experiments. With a Bodipy FL fluorophore introduced at an appropriate site on the Ras peptide by solid-phase synthesis, the resulting Ras chimera is processed by the cellular machinery and the intracellular localization of the protein can then be visualized by means of confocal laser fluorescence microscopy at relatively low concentrations. The absence of a large N-terminal protein tag overcomes possible interferences in the interaction with cellular partner proteins. The fluorescence emission from Bodipy FL is continuous and disappears only after irreversible bleaching. These characteristics make Ras proteins with nonprotein fluorophores suitable for biophysical analysis. The easy accessibility of the lipopeptide moiety by chemical synthesis opens up numerous options for further biological investigations.

Generation and characterization of ras lipoproteins based on chemical coupling.

Chemically synthesized truncated Ras proteins are coupled to C-terminal Ras peptides via a maleimidocaproyl linker. The resulting product is isolated by extraction with Triton X-114. The biological activity of these oncogenic Ras lipoproteins can be determined in a cell-based differentiation assay by microinjection into PC12 cells.

The cholesterol membrane anchor of the Hedgehog protein confers stable membrane association to lipid-modified proteins.

The Hedgehog proteins are potent organizers of animal development. They carry a cholesterol ester at the C terminus of their signaling domain. The membrane anchoring mediated by this lipophilic modification was studied by means of an approach integrating cell biology, biochemistry, biophysics, and organic chemistry techniques. Sterol-modified and fluorescent-labeled Hedgehog-derived peptides and proteins were synthesized and investigated in biophysical and cell-biological assays. These experiments revealed that cholesterol alone anchors proteins to membranes with significant strength and half-times for spontaneous desorption of several hours. Its membrane anchoring ability is comparable to dual lipidation motifs such as double geranylgeranylation or S-palmitoylation plus S-farnesylation found in other lipidated proteins. The experiments also demonstrate that membrane binding changes dramatically if short lipidated peptides are equipped with a large protein. These data suggest that for Hedgehog release and subsequent signaling an interaction partner such as the Dispatched protein is necessary. In addition to these findings the described approach allows one to correlate biophysical data obtained with model peptides with data determined with fully functional proteins and to combine results from in vitro and in vivo experiments. It should be generally applicable to other membrane anchors and proteins.

Synthesis and biological activity of photoactivatable N-ras peptides and proteins.

A modular strategy for the assembly of farnesylated N-Ras heptapeptides carrying a photoactivatable benzophenone (BP) group within the lipid residue is described. This strategy is based on the fragment condensation of a N-terminal hexapeptide synthesized on the solid support with a cysteine methyl ester which is modified with different farnesyl analogues, incorporating the photophor. At the N-terminus of the peptides different functional groups can be attached, e.g., biotin for product enrichment and detection after photoactivation or a maleimido (MIC) linker, allowing for the coupling to proteins carrying a C-terminal free cysteine. Using this strategy, 24 peptides were synthesized, incorporating farnesyl analogues with four different chain lengths. Two of these photoactivatable conjugates were ligated to oncogenic human N-RasG12V Delta 181. A cellular transformation assay revealed that the semisynthetic proteins retain their biological activity despite the photolabel. The first photolabeling experiments with a geranyl-BP-labeled N-Ras construct and the farnesyl-sensitive guanine nucleotide exchange factor hSos1 indicate that this photoaffinity labeling system can be particularly useful for studying protein-protein interactions, e.g., the participation of the farnesyl group in Ras signaling, which is still discussed with controversy.