Background: Aged long-term care receivers are affected by various adverse skin conditions like pressure ulcers, incontinence-associated dermatitis, dryness, intertrigo, and many more. Prevention of these skin problems and the provision of general hygiene and skin care activities are key areas of nursing practice. Numerous condition-specific guidelines are available and are implemented separately. On the other hand, there is huge overlap in terms of etiology, pathogenesis, and prevention of the skin conditions mentioned above. This leads to fragmented practice neglecting shared etiologies and prevention and treatment principles.
Methods: The overall aims of this trial are to test the feasibility and to estimate possible effects of the implementation of a comprehensive skin care and prevention strategy targeting main nursing-relevant skin problems at the same time. A two-arm cluster-randomized controlled trial will be performed in 20 nursing homes randomly selected from the population of nursing homes of the state of Berlin, comparing skin care according to the skin care and prevention strategy with standard skin care.
Discussion: It is expected that the implementation of this evidence-based skin care and prevention strategy will reduce the incidence of pressure ulcers, incontinence dermatitis, and other skin problems frequently related to care dependency. This trial will benefit individual patients and aged nursing home residents in general given the high prevalence and incidence of the addressed skin conditions. Findings of this exploratory trial may lay the foundation for a change in the development and evaluation of clinical standards and practices in general as it moves the perspective from individual conditions to a more comprehensive view on overlapping or coexisting health problems, in this case common skin conditions, in old-age long-term care receivers.View less
Place branding is seriously studied in various academic disciplines. Its impact on strategic development plays a vital role in processes of sustainable urban transformation. Place branding originated in tourism management and over time its research focus spilled over and evolved in environmental science, urban studies and public administration. Scholars and policy makers are currently faced with a myriad of concepts in place branding research, which show considerable overlap but should be carefully distinguished from each other. To increase our understanding of this body of research, this article observes a strong pattern of the concepts in use, in their references to location types (i.e., urban, city, destination, place) and broadcasting activities (branding, marketing, promotion). It builds on this observation by collecting studies from the Scopus database by location type and broadcasting activities (LT–BA) reference pairs and systematically analysing and reviewing these from 1980 to 2018. A total of 2665 articles and reviews were identified and analysed based on (1) occurrences per reference pair, (2) co-occurrences per reference pair, and (3) co-occurrences for each reference pair with other concepts. On that basis, the origin and evolution of the research field including multiple reference pairs in use is explored and described.View less
Oxytocin (OXT) is critically involved in the regulation of attachment and interpersonal function. In this study, emotional childrens movies were used to stimulate OXT secretion in patients with schizophrenia and healthy controls (HCs). Furthermore, associations of OXT levels with measures of attachment style (Psychosis Attachment Measure), childhood adversity (Childhood Trauma Questionnaire) and symptom severity [Positive and Negative Syndrome Scale (PANSS)] were considered. In 35 patients with schizophrenia and 35 matched HCs, radioimmunoassay with sample extraction was used to determine OXT plasma levels before and after viewing of movie scenes portraying emotional bonding and loss and compared to a non-emotional condition. Statistical analysis indicated lower baseline OXT levels in female patients than in all other groups. OXT reactivity during emotional movies was significantly higher in patients when compared to HCs. OXT reactivity during the control movie related to PANSS `general psychopathology. No significant associations appeared between baseline or induced OXT levels and other PANSS subscales, attachment style or childhood adversity in patients. Our findings suggest differences of baseline OXT and a higher OXT reactivity toward strong emotional stimuli in patients with schizophrenia, suggesting a role of OXT as a gender- and context-dependent modulator of socio-emotional function.View less
New inhibitors of tubulin polymerization and/or histone deacetylase (HDAC) activity were synthesized by attaching alkyl tethered hydroxamic acid appendages of varying length to oxazole-bridged combretastatin A-4 analogous caps. While their antiproliferative and microtubule disrupting effect was most pronounced for derivatives with short spacers, HDAC inhibition was strongest for those with longer spacers. These findings were further supported by computational methods such as structure-based docking experiments exploring the target interactions of the derivatives with varying linkers. For instance, compounds featuring short four-atom spacers between cap and hydroxamic acid inhibited the growth of various cancer cell lines and human endothelial hybrid cells with IC50 values in the low nanomolar range. In line with their ability to inhibit the microtubule assembly, four- and five-atom spacered hydroxamic acids caused an accumulation of 518A2 melanoma cells in G2/M phase, whereas a compound featuring a six-atom spacer and performing best in HDAC inhibition, induced a G1 arrest in these cells. All these beneficial anticancer activities together with their selectivity for cancer cells over non-malignant cells, point out the great potential of these novel pleiotropic HDAC and tubulin inhibitors as drug candidates for cancer therapy.View less
The globally rising incidences of multidrug-resistant (MDR) Pseudomonas aeruginosa (Psae) in humans and live-stock animals has prompted the World Health Organization to rate MDR Psae as serious threat for human health. Only little is known, however, regarding factors facilitating gastrointestinal Psae-acquisition by the vertebrate host and subsequently induced in fl ammatory sequelae. In the present study, we addressed whether subacute ileitis predisposed mice harboring a human gut microbiota for intestinal MDR Psae carriage and whether in fl ammatory responses might be induced following peroral challenge with the opportunistic pathogen. To accomplish this, secondary abiotic mice were associated with a human gut microbiota by fecal microbiota transplantation. Ten days later (i.e., on day 0), subacute ileitis was induced in human microbiota associated (hma) mice by peroral low-dose Toxoplasma gondii infection. On day 5 post-infection, mice were perorally challenged with 10(9) colony forming units of a clinical MDR Psae isolate by gavage and the fecal bacterial loads surveyed thereafter. Four days post-peroral challenge, only approximately one third of mice with a human gut microbiota and subacute ileitis harbored the opportunistic pathogen in the intestinal tract. Notably, the gut microbiota composition was virtually unaffected by the Psae-carriage status during subacute ileitis of hma mice. The Psae challenge resulted, however, in more pronounced intestinal epithelial apoptotic cell and T lymphocyte responses upon ileitis induction that were not restricted to the ileum, but also affected the large intestines. Higher Psae-induced abundances of T cells could additionally be observed in extra-intestinal compartments including liver, kidney, lung, and heart of hma mice with subacute ileitis. Furthermore, higher apoptotic cell numbers, but lower anti-in fl ammatory IL-10 concentrations were assessed in the liver of Psae as compared to mock treated mice with ileitis. Remarkably, Psae-challenge was accompanied by even more pronounced systemic secretion of pro-inflammatory cytokines such as TNF and IL-6 at day 9 post ileitis induction. In conclusion, whereas in one third of hma mice with subacute ileitis Psae could be isolated from the intestines upon peroral challenge, the opportunistic pathogen was responsible for inflammatory sequelae in intestinal, extra-intestinal, and even systemic compartments and thus worsened subacute ileitis outcome irrespective of the Psae-carrier status.View less
Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease of the mucous membranes, which can cause irreversible scarring and is discussed to be associated with cancer, if laminin-332-autoantibodies are present. MMP with severe ocular and laryngeal involvement is difficult to treat and can be treatment-refractory to conventional immunosuppressant therapy. A 67-year-old man with a history of prostate cancer presented to our clinic with sore throat, intraoral bullae, odynophagia, dysphonia, exertional dyspnea, and erosions of the glans penis. Clinical examination confirmed a laryngo-pharyngitis with involvement of the epiglottis and bilateral symblepharon. Diagnostics comprising multiple biopsies, direct and indirect immunofluorescence, serology analysis, and immunoblotting confirmed the diagnosis of a paraneoplastic MMP by showing a subepithelial split in histology and the presence of anti-laminin-332-antibodies. Despite combined systemic treatment with prednisolone and either dapsone or azathioprine, a progress of the disease occurred leading to severe ocular and laryngeal complications. Two month after rituximab treatment, complete disease control was achieved. This case report shows a severe ocular and life threatening laryngeal involvement of therapy-refractory paraneoplastic MMP highlighting the importance of interdisciplinary management and difficulty of diagnosing MMP despite repeated diagnostic testing.View less
Known human coronaviruses are believed to have originated in animals and made use of intermediate hosts for transmission to humans. The intermediate hosts of most of the human coronaviruses are known, but not for HCoV-NL63. This study aims to assess the possible role of some major domestic livestock species as intermediate hosts of HCoV-NL63. We developed a testing algorithm for high throughput screening of livestock sera with ELISA and confirmation with recombinant immunofluorescence assay testing for antibodies against HCoV-NL63 in livestock. Optimization of the ELISA showed a capability of the assay to significantly distinguish HCoV-NL63 from HCoV-229E (U = 27.50, p < 0.001) and HCoV-OC43 (U = 55.50, p < 0.001) in coronavirus-characterized sera. Evaluation of the assay with collected human samples showed no significant difference in mean optical density values of immunofluorescence-classified HCoV-NL63-positive and HCoV-NL63-negative samples (F (1, 215) = 0.437, p = 0.509). All the top 5% (n = 8) most reactive human samples tested by ELISA were HCoV-NL63 positive by immunofluorescence testing. In comparison, only a proportion (84%, n = 42) of the top 25% were positive by immunofluorescence testing, indicating an increased probability of the highly ELISA reactive samples testing positive by the immunofluorescence assay. None of the top 5% most ELISA reactive livestock samples were positive for HCoV-NL63-related viruses by immunofluorescence confirmation. Ghanaian domestic livestock are not likely intermediate hosts of HCoV-NL63-related coronaviruses.View less
CD4(+)CD25(+)FoxP3(+) human regulatory T-CELLS (T-REG) are promising candidates for reshaping undesired immunity/inflammation by adoptive cell transfer, yet their application is strongly dependent on robust assays testing their functionality. Several studies along with first clinical data indicate T-REG to be auspicious to use for future cell therapies, e.g., to induce tolerance after solid organ transplantation. To this end, T-REG suppressive capacity has to be thoroughly evaluated prior to any therapeutic application. A 7 h-protocol for the assessment of T-REG function by suppression of the early activation markers CD154 and CD69 on CD4(+)CD25(-) responder T-CELLS (T-RESP) upon polyclonal stimulation via alpha CD3/28-coated activating microbeads has previously been published. Even though this assay has since been applied by various groups, the protocol comes with a critical pitfall, which is yet not corrected by the journal of its original publication. Our results demonstrate that the observed decrease in activation marker frequency on T-RESP is due to competition for alpha CD3/28-coated microbeads as opposed to a T-REG-attributable effect and therefore the protocol cannot further be used as a diagnostic test to assess suppressive TREG function.View less
Although riboflavin (RF) belongs to the water-soluble vitamins of group B, its solubility is low. Therefore, the application of micro-formulations may help to overcome this limiting factor for the delivery of RF. In this study we immobilized RF in newly developed albumin submicron particles prepared using the Co-precipitation Crosslinking Dissolution technique (CCD-technique) of manganese chloride and sodium carbonate in the presence of human serum albumin (HSA) and RF. The resulting RF containing HSA particles (RF-HSA-MPs) showed a narrow size distribution in the range of 0.9 to 1 mu m, uniform peanut-like morphology, and a zeta-potential of -15 mV. In vitro release studies represented biphasic release profiles of RF in a phosphate buffered saline (PBS) pH 7.4 and a cell culture medium (RPMI) 1640 medium over a prolonged period. Hemolysis, platelet activation, and phagocytosis assays revealed a good hemocompatibility of RF-HSA-MPs.View less
With growing populations and climate change, assuring food and nutrition security is an increasingly challenging task. Climate smart and sustainable agriculture, that is, conceiving agriculture to be resistant and resilient to a changing climate while keeping it viable in the long term, is probably the best solution. The role of soil biota and particularly arbuscular mycorrhizal (AM) fungi in this new agriculture is believed to be of paramount importance. However, the large nutrient pools and the microbiota of subsoils are rarely considered in the equation. Here we explore the potential contributions of subsoil AM fungi to this agriculture and suggest future research goals that would allow us to maximize their benefits.View less
Sprouting angiogenesis is a necessary process in regeneration and development as well as in tumorigenesis. VEGF-A is the main pro-angiogenic chemoattractant and it can bind to the decoy receptor VEGFR1 or to VEGFR2 to induce sprouting. Active sprout cells express Dll4, which binds to Notch1 on neighboring cells, in turn inhibiting VEGFR2 expression. It is known that the balance between VEGFR2 and VEGFR1 determines tip selection and network architecture, however the quantitative interrelationship of the receptors and their interrelated balances, also with relation to Dll4-Notch1 signaling, remains yet largely unknown. Here, we present an agent-based computer model of sprouting angiogenesis, integrating VEGFR1 and VEGFR2 in a detailed model of cellular signaling. Our model reproduces experimental data on VEGFR1 knockout. We show that soluble VEGFR1 improves the efficiency of angiogenesis by directing sprouts away from existing cells over a wide range of parameters. Our analysis unravels the relevance of the stability of the active notch intracellular domain as a dominating hub in this regulatory network. Our analysis quantitatively dissects the regulatory interactions in sprouting angiogenesis. Because we use a detailed model of intracellular signaling, the results of our analysis are directly linked to biological entities. We provide our computational model and simulation engine for integration in complementary modeling approaches.View less
As in many countries, the numbers of older prisoners are rising in Germany, but scientific information on this group is scarce. For the current study, a survey was used that included all prison suicides in Germany between the years of 2000 and 2013. Suicide rates of the elderly prisoners exceeded the suicide rates of the general population and the same age group. We observed a continuous decrease in the suicide rate of elderly prisoners. When compared to the younger suicide victims in prison, significantly more elderly suicide victims were: female, of German nationality, remand prisoners, or serving a life sentence. In Germany, elderly prisoners are a vulnerable subpopulation of the prison population. Higher suicide rates than in the same age group in the general population indicate unmet needs regarding mental disorders and their specific treatment.View less
Introduction: The aim of this study is to describe the initial stages of the iterative and user-centered mobile mental health adaptation process of Step-by-Step (SbS), a modularized and originally web-based e-mental health intervention developed by the World Health Organization (WHO). Given the great need for improving the responsiveness and accessibility of health systems in host countries, the EU-funded STRENGTHS consortium studies the adaptation, implementation and scaling-up of SbS for Syrian refugees in Germany, Sweden and Egypt. Using early prototyping, usability testing and identification of barriers to implementation, the study demonstrates a user-centered process of contextual adaptation to the needs and expectations of Syrian refugees.
Materials and Methods: N = 128 adult Syrian refugees residing in Germany, Sweden and Egypt took part in qualitative assessments. Access, usage, and potential barriers regarding information and communication technologies (ICTs) were assessed in free list interviews. Interactive prototypes of the app were presented in key informant interviews and evaluated on usability, user experience and dissemination strategies. Focus groups were conducted to verify the results. The interview protocols were analyzed using inductive and deductive thematic analysis.
Results: The use of digital technologies was found to be widespread among Syrian refugees. Technical literacy and problems with accessing the internet were common barriers. The majority of the respondents reacted positively to the presented app prototypes, stressing the potential health impact of the intervention (n = 28; 78%), its flexibility and customizability (n = 19; 53%) as well as the easy learnability of the app (n = 12; 33%). Aesthetic components (n = 12; 33%) and the overall length and pace of the intervention sessions (n = 9; 25%) were criticized in regard to their negative impact on user motivation. Acceptability, credibility, and technical requirements were identified as main barriers to implementation.
Discussion: The study provided valuable guidance for adapting the app version of SbS and for mobile mental health adaptation in general. The findings underline the value of contextual adaptation with a focus on usability, user experience, and context specific dissemination strategies. Related factors such as access, acceptability and adherence have major implications for scaling-up digital interventions.View less
Objective: To test the hypothesis that olfactory (OF) and gustatory function (GF) is disturbed in patients with autoimmune encephalitides (AE).
Methods: The orthonasal OF was tested in 32 patients with AE and 32 age- and sex-matched healthy controls (HC) with the standardized Threshold Discrimination Identification (TDI) score. This validated olfactory testing method yields individual scores for olfactory threshold (T), odor discrimination (D), and identification (I), along with a composite TDI score. The GF was determined by the Taste Strip Test (TST).
Results: Overall, 24/32 (75%) of patients with AE, but none of 32 HC (p < 0.001) had olfactory dysfunction in TDI testing. The results of the threshold, discrimination and identification subtests were significantly reduced in patients with AE compared to HC (all p < 0.001). Assessed by TST, 5/19 (26.3%) of patients with AE, but none of 19 HC presented a significant limitation in GF (p < 0.001). The TDI score was correlated with the subjective estimation of the olfactory capacity on a visual analog scale (VAS; r(s) = 0.475, p = 0.008). Neither age, sex, modified Rankin Scale nor disease duration were associated with the composite TDI score.
Conclusions: This is the first study investigating OF and GF in AE patients. According to unblinded assessment, patients with AE have a reduced olfactory and gustatory capacity compared to HC, suggesting that olfactory and gustatory dysfunction are hitherto unrecognized symptoms in AE. Further studies with larger number of AE patients would be of interest to verify our results.View less
Background: We aimed to investigate the role of hypercoagulability on the risk of lifetime cardiovascular recurrences after myocardial infarction or ischaemic stroke.
Methods: Young women (< 50 years) with either myocardial infarction (n = 197) or ischaemic stroke (n = 107) were followed between 1995 and 2012 in the RATIO follow-up study. To determine whether hypercoagulability affects the risk or recurrence, a coagulation score based on acquired and inherited markers was compiled and used in a quartile analysis. Hazard ratios (HRs) obtained from Cox proportional models and adjusted for several cardiovascular risk factors were used to compare quartiles of the coagulation score for the risk of recurrence.
Results: During a median follow-up of 19 years, 59 cardiovascular recurrences occurred. In patients with myocardial infarction no association was found between a high prothrombotic score and recurrences (highest quartile vs lowest quartile HR 0.7, 95% CI, 0.3–1.8). Conversely, ischaemic stroke patients with a high prothrombotic score showed a doubling in risk of long-term cardiovascular recurrences (HR 1.9, 95% CI 0.6–6.3) compared with ischaemic stroke patients and low levels of the score, with a dose response relationship.
Conclusions: An increased coagulation tendency might be associated with long-term cardiovascular risk in women with ischaemic stroke, but not in women with myocardial infarction.View less
A long-standing position in philosophy, law, and theology is that a person can be held morally responsible for an action only if they had the freedom to choose and to act otherwise. Thus, many philosophers consider freedom to be a necessary condition for moral responsibility. However, empirical findings suggest that this assumption might not be in line with common sense thinking. For example, in a recent study we used surveys to show that – counter to positions held by many philosophers – lay people consider actions to be free when they are spontaneous rather than being based on reasons. In contrast, responsibility is often considered to require that someone has thought about the alternative options. In this study we used an online survey to directly test the degree to which lay judgements of freedom and responsibility match. Specifically, we tested whether manipulations of deliberation affect freedom and responsibility judgements in the same way. Furthermore, we also tested the dependency of these judgements on a person’s belief that their decision had consequences for their personal life. We found that deliberation had an opposite effect on freedom and responsibility judgements. People were considered more free when they acted spontaneously, whereas they were considered more responsible when they deliberated about their actions. These results seem to suggest that deliberating about reasons is crucially important for the lay concept of responsibility, while for the lay notion of freedom it is perceived to be detrimental. One way of interpreting our findings for the interdisciplinary debate on free will and responsibility could be to suggest that lay beliefs match the philosophical position of semi-compatibilism. Semi-compatibilists insist that the metaphysical debate on the nature of free will can be separated from the debate on conditions of responsible agency. According to our findings the beliefs of lay people are in line with views held by semi-compatibilists, even though we did not test whether they endorse that position explicitly.View less
Introduction: The improvement-or at least maintenance-of health-related quality of life (HRQoL) in children and adolescents is one of the main aims of chronic disease care. This study examines HRQoL of children and adolescents with three different chronic conditions (i.e., diabetes mellitus, asthma, juvenile arthritis) using the computer-adaptive test Kids-CAT, comprising five HRQoL domains: physical well-being, psychological well-being, parent relations, social support and peers, and school well-being. Further, associations between HRQoL and distinct clinical data and medical assessments are investigated to explore how much variability of the five domains can be explained by these variables. Methods: Cross-sectional data of the Kids-CAT study was analyzed. The Kids-CAT was used in two outpatient clinics in northern Germany gathering data on self-reported HRQoL in n = 309 children and adolescents aged 7-17 years. Additionally, general patient information, clinical data, and pediatrician-reported medical assessments were measured. Multiple regression analyses were conducted to explore associations between HRQoL and selected variables (i.e., disease duration, co-morbidity, disease control, overall health status). Results: Overall, self-reported HRQoL in all five domains were comparable to data of an age-and sex-matched reference population. Results of regression analyses indicated that the investigated variables only minimally explain variance in the five Kids-CAT domains. Sociodemographic, clinical data, and medical assessments explained 18.4% of the variance in physical well-being, 10.7% in psychological well-being, and <10% of the variance in parent relations, social support and peers, and school well-being. Conclusion: Sociodemographic data, disease duration, co-morbidity, and medical assessments, such as disease control or pediatrician-assessed overall health status show low association with HRQoL of children and adolescents with chronic conditions. Data on self-reported HRQoL delivers valuable information on children's well-being and can improve healthcare professionals' understanding of the subjective well-being of their young patients. The implementation of tools like the Kids-CAT can facilitate the identification of potential problem areas, which should enable healthcare professionals to better address specific healthcare needs. Clinical Trial Registration: identifier: DRKS00006326 (retrospectively registered); Date of registry: August 1st, 2014.View less
Scaffolds made of biodegradable biomaterials are widely used to guide bone regeneration. Commonly, in vitro assessment of scaffolds' osteogenesis potential has been performed predominantly in monoculture settings. Hence, this study evaluated the potential of an unstimulated, growth factor-free co-culture system comprised of osteoblasts (OB) and peripheral blood mononuclear cells (PBMC) over monoculture of OB as an in vitro platform for screening of bone regeneration potential of scaffolds. Particularly, this study focuses on the osteogenic differentiation and mineralized matrix formation aspects of cells. The study was performed using scaffolds fabricated by means of a melt electrowriting (MEW) technique made of medical-grade polycaprolactone (PCL), with or without a surface coating of calcium phosphate (CaP). Qualitative results, i.e., cell morphology by fluorescence imaging and matrix mineralization by von Kossa staining, indicated the differences in cell behaviours in response to scaffolds' biomaterial. However, no obvious differences were noted between OB and OB+PBMC groups. Hence, quantitative investigation, i.e., alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activities, and gene expression were quantitatively evaluated by reverse transcription-polymerase chain reaction (RT-qPCR), were evaluated only of PCL/CaP scaffolds cultured with OB+PBMC, while PCL/CaP scaffolds cultured with OB or PBMC acted as a control. Although this study showed no differences in terms of osteogenic differentiation and ECM mineralization, preliminary qualitative results indicate an obvious difference in the cell/non-mineralized ECM density between scaffolds cultured with OB or OB+PBMC that could be worth further investigation. Collectively, the unstimulated, growth factor-free co-culture (OB+PBMC) system presented in this study could be beneficial for the pre-screening of scaffolds' in vitro bone regeneration potential prior to validation in vivo.View less