Isolate Specific Cold Response of Yersinia enterocolitica in Transcriptional, Proteomic, and Membrane Physiological Changes

Yersinia enterocolitica, a zoonotic foodborne pathogen, is able to withstand low temperatures. This psychrotrophic ability allows it to multiply in food stored in refrigerators. However, little is known about the Y. enterocolitica cold response. In this study, isolate-specific behavior at 4°C was demonstrated and the cold response was investigated by examining changes in phenotype, gene expression, and the proteome. Altered expression of cold-responsive genes showed that the ability to survive at low temperature depends on the capacity to acclimate and adapt to cold stress. This cold acclimation at the transcriptional level involves the transient induction and effective repression of cold-shock protein (Csp) genes. Moreover, the resumption of expression of genes encoding other non-Csp is essential during prolonged adaptation. Based on proteomic analyses, the predominant functional categories of cold-responsive proteins are associated with protein synthesis, cell membrane structure, and cell motility. In addition, changes in membrane fluidity and motility were shown to be important in the cold response of Y. enterocolitica. Isolate-specific differences in the transcription of membrane fluidity- and motility-related genes provided evidence to classify strains within a spectrum of cold response. The combination of different approaches has permitted the systematic description of the Y. enterocolitica cold response and gives a better understanding of the physiological processes underlying this phenomenon

The psychometric properties of the German version of the WHOQOL-OLD in the German population aged 60 and older

Background: The WHOQOL-OLD is an instrument for the assessment of subjective quality of life in elderly people. It is based on the WHO definition of quality of life and is available in more than 20 languages. However, in most countries, the psychometric properties of the WHOQOL-OLD have been assessed only on the basis of small local samples and not in representative studies. In this study, the psychometric properties of the WHOQOL-OLD are evaluated based on a representative sample of Germany\''s elderly population. Methods: Face-to-face interviews with 1133 respondents from the German population aged 60 years and older were conducted. Quality of life was assessed by means of the WHOQOL-BREF, the WHOQOL-OLD and the SF12. Moreover, the GDS, the DemTect and the IADL were applied for the assessment of depressive symptoms, cognitive capacities and capacity for carrying out daily activities. Psychometric properties of the WHOQOL-OLD were evaluated by means of classical and probabilistic test theory, confirmatory factor analysis and multivariate regression model.Results: Cronbach\''s alpha was found to be above 0.85 for four and above .75 for two of the six facets of the WHOQOL-OLD. IRT analyses indicated that all items of the WHOQOL-OLD contribute considerably to the measurement of the associated facets. While the six-facet structure of the WHOQOL-OLD was well supported by the results of the confirmatory factor analysis, a common latent factor for the WHOQOL-OLD total scale could not be identified. Correlations with other quality of life measures and multivariate regression models with GDS, IADL and the DemTect indicate a good criterion validity of all six WHOQOL-OLD facets.Conclusions: Study results confirm that the good psychometric properties of the WHOQOL-OLD that have been found in international studies could be replicated in a representative study of the German population. These results suggest that the WHOQOL-OLD is an instrument that is well suited to identify the needs and the wishes of an aging population

Differences in the Transcriptomic Response of Campylobacter coli and Campylobacter lari to Heat Stress

Campylobacter spp. are one of the most important food-borne pathogens, which are quite susceptible to environmental or technological stressors compared to other zoonotic bacteria. This might be due to the lack of many stress response mechanisms described in other bacteria. Nevertheless, Campylobacter is able to survive in the environment and food products. Although some aspects of the heat stress response in Campylobacter jejuni are already known, information about the stress response in other Campylobacter species are still scarce. In this study, the stress response of Campylobacter coli and Campylobacter lari to elevated temperatures (46°C) was investigated by survival assays and whole transcriptome analysis. None of the strains survived at 46°C for more than 8 h and approximately 20% of the genes of C. coli RM2228 and C. lari RM2100 were differentially expressed. The transcriptomic profiles showed enhanced gene expression of several chaperones like dnaK, groES, groEL, and clpB in both strains, indicating a general involvement in the heat stress response within the Campylobacter species. However, the pronounced differences in the expression pattern between C. coli and C. lari suggest that stress response mechanisms described for one Campylobacter species might be not necessarily transferable to other Campylobacter species

Do self-reported hearing and visual impairments predict longitudinal dementia in older adults?

Background Sensory impairments have been associated with dementia in older adults. However, the contribution of different impairments and how they interact in the development of dementia is not clear. We examined the independent and interaction effects of hearing impairment (HI) and visual impairment (VI) on incident dementia. Design Multi-centric population-based prospective cohort study. Setting Data were taken from the AgeDifferent.de platform, pooling participants aged 75 and older from the German LEILA75+ and AgeCoDe/AgeQualiDe cohorts. Participants Older adults (N = 3497) with mean age 79.8 years, 67.2% female. Measurements Standardized interviews and questionnaires were used to assess self-reported HI and VI at baseline and all-cause dementia in 9 follow-ups, spanning over 20 years. Methods Competing risk regression models were conducted to test the main and interaction effects of HI and VI on dementia incidence, adjusting for established risk factors of dementia and accumulated mortality. Results HI and VI at baseline were reported by 30.3% and 16.6% of individuals, respectively. Adjusting for baseline information on sociodemographics, substance use, cognitive functioning and morbidity, and controlling for accumulated mortality risk, HI (sHR 1.16, 95% CI 1.04–1.30, p = 0.011) but not VI (sHR 1.07, 95% CI 0.90–1.28, p = 0.462) was significantly associated with incident dementia. There was no interaction between HI and VI (sHR 1.09, 95% CI 0.81–1.46, p = 0.567). Conclusions Hearing impairment is associated with an increased incidence of all-cause dementia in older adults. There is no excess risk or risk compensation through the additional presence or absence of visual impairment. Early prevention measures for hearing impairment might help to reduce the long-term risk of dementia

The Role of Social Isolation and the Development of Depression: A Comparison of the Widowed and Married Oldest Old in Germany

Widowhood is common in old age, can be accompanied by serious health consequences and is often linked to substantial changes in social network. Little is known about the impact of social isolation on the development of depressive symptoms over time taking widowhood into account. We provide results from the follow-up 5 to follow-up 9 from the longitudinal study AgeCoDe and its follow-up study AgeQualiDe. Depression was measured with GDS-15 and social isolation was assessed using the Lubben Social Network Scale (LSNS-6). The group was aligned of married and widowed people in old age and education through entropy balancing. Linear mixed models were used to examine the frequency of occurrence of depressive symptoms for widowed and married elderly people depending on the risk of social isolation. Our study shows that widowhood alone does not lead to an increased occurrence of depressive symptoms. However, "widowed oldest old", who are also at risk of social isolation, have significantly more depressive symptoms than those without risk. In the group of "married oldest old", women have significantly more depressive symptoms than men, but isolated and non-isolated do not differ. Especially for people who have lost a spouse, the social network changes significantly and increases the risk for social isolation. This represents a risk factor for the occurrence of depressive symptoms

ETMR-05: Single-cell transcriptomics of ETMR reveals developmental cellular programs and tumor-pericyte communications in the microenvironment [Abstract]

BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) are pediatric brain tumors bearing a grim prognosis, despite intensive multimodal therapeutic approaches. Insights into cellular heterogeneity and cellular communication of tumor cells with cells of the tumor microenvironment (TME), by applying single-cell (sc) techniques, potentially identify mechanisms of therapy resistance and target-directed treatment approaches. MATERIAL AND METHODS: To explore ETMR cell diversity, we used single-cell RNA sequencing (scRNA-seq) in human (n=2) and murine ETMR (transgenic mode; n=4) samples, spatial transcriptomics, 2D and 3D cultures (including co-cultures with TME cells), multiplex immunohistochemistry and drug screens. RESULTS: ETMR microenvironment is composed of tumor and non-tumor cell types. The ETMR malignant compartment harbour cells representing distinct transcriptional metaprograms, (NSC-like, NProg-like and Neuroblast-like), mirroring embryonic neurogenic cell states and fuelled by neurogenic pathways (WNT, SHH, Hippo). The ETMR TME is composed of oligodendrocyte and neuronal progenitor cells, neuroblasts, microglia, and pericytes. Tumor-specific ligand-receptor interaction analysis showed enrichment of intercellular communication between NProg-like ETMR cells and pericytes (PC). Functional network analyses reveal ETMR-PC interactions related to stem-cell signalling and extracellular matrix (ECM) organization, involving factors of the WNT, BMP, and CxCl12 networks. Results from ETMR-PC co-culture and spatial transcriptomics pointed to a pivotal role of pericytes in keeping ETMR in a germinal neurogenic state, enriched in stem-cell signalling. Drug screening considering cellular heterogeneity and cellular communication suggested novel therapeutic approaches. CONCLUSION: ETMR demonstrated diversity in the microenvironment, with enrichment of cell-cell communications with pericytes, supporting stem-cell signalling and interfering in the organization of the tumor extracellular matrix. Targeting ETMR-PC interactions might bring new opportunities for target-directed therapy

Effects of general practitioner training and family support services on the care of home-dwelling dementia patients - Results of a controlled cluster-randomized study

<p>Abstract</p> <p>Background</p> <p>More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. <it>Objective: </it>To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups.</p> <p>Method</p> <p>129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling (in Arm B one year after baseline, in Arm C at baseline) were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services.</p> <p>Results</p> <p>The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing.</p> <p>Conclusion</p> <p>Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Prevalence of Anxiety Symptoms and Their Association With Loss Experience in a Large Cohort Sample of the Oldest-Old. Results of the AgeCoDe/AgeQualiDe Study

Background: Anxiety in adults is a common mental health problem. However, studies on anxiety in the oldest-old are lacking. We sought to identify the age- and gender-specific prevalence of anxiety symptoms in a large sample of general practice patients. Furthermore, we investigated relevant associations of anxiety specifically with respect to recent experience of loss.Methods: Based on the German Study on Ageing, Cognition and Dementia in general practice patients, a sample of 897 patients aged 82 years and older was assessed. Anxiety was assessed using the short form of the Geriatric Anxiety Inventory (GAI-SF). For the assessment of loss, patients were asked whether there were cases of death in their closer social environment since the last assessment. Descriptive and logistic regression analyses were run.Results: Of the oldest-old individuals (aged 82+ years, mean age: 86.8), 14.5% (95% CI 12.4–16.8) suffered from anxiety symptoms. Highest prevalence rates were found for 82- to 85-year-old women (17.2%, 95% CI 12.6–22.1) and for 86- to 90-year-old patients (both sexes) in general (15.9%, 95% CI 12.6–19.2). Older individuals who experienced cases of death in their close social environment within the last 18 months had almost twice the odds [odds ratio (OR) 1.91, 95% confidence interval (CI) 1.15–3.17] of reporting anxiety compared to those without a recent loss. As expected, depression and impaired cognitive status were associated with the presence of anxiety symptoms. No relation was found between social network, gender, age, frailty, or physical illness and anxiety in regression analysis.Conclusions: This study provides for the first time age- and gender-specific prevalence rates of anxiety symptoms and associated risk factors among a large population-based sample of oldest-old primary care attenders. Anxiety is highly prevalent in individuals aged 82 years and older. Depression, impaired cognitive status, and recent experience of loss are associated with late-life anxiety. Our findings support the idea that recent experience of loss should be taken seriously in the context of clinical practice with respect to diagnosing and treating anxiety in old age