Differences in DNA repair capacity, cell death and transcriptional response after irradiation between a radiosensitive and a radioresistant cell line

Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24h after irradiation genes involved in "DNA damage response", "direct p53 effectors" and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols

Clinical decision making and mental health service use in people with severe mental illness across Europe

Objective: This study aims to explore relationships between preferred and experienced clinical decision making with service use, and associated costs, by people with severe mental illness. Methods: Prospective observational study of mental healthcare in six European countries: Germany, UK, Italy Hungary, Denmark and Switzerland. Patients (N = 588) and treating clinicians (N = 213) reported preferred and experienced decision making at baseline using the Clinical Decision Making Style Scale (CDMS) and the Clinical Decision Involvement and Satisfaction Scale (CDIS). Retrospective service use was assessed with the Client Socio-Demographic and Service Receipt Inventory (CSSRI-EU) at baseline and 12-month follow-up. Negative binomial regression analyses examined the effects of CDMS and CDIS on service use and inpatient costs at baseline and multilevel models examined these relationships over time. Results: At baseline, staff and patient preferences for active decision making and low patient satisfaction with experienced decisions were associated with longer hospital admissions and higher costs. Patient preferences for active decision making predicted increases in hospital admissions (b = .236, p =.043) over 12 months and cost increases were predicted by low patient satisfaction (b = 4803, p =.005). Decision making was unrelated to medication, outpatient, or community service use. Conclusions: Decision making is related to inpatient service use and associated costs by people with severe mental illness. A preference for shared decision making may reduce healthcare costs via a reduction in inpatient admissions. Patient satisfaction with decisions is a crucial predictor of healthcare costs; therefore, clinicians should maximize patient satisfaction with decision making

Helping alliance and unmet needs in routine care of people with severe mental illness across Europe: a prospective longitudinal multicenter study

The helping alliance (HA) refers to the collaborative bond between patient and therapist including shared goals and tasks. People with severe mental illness have a complex mixture of clinical and social needs. Using mixed-effects regression, this study examined in 588 people with severe mental illness whether an increase in the HA is associated with fewer unmet needs over time, and whether change in the HA precedes change in unmet needs. It was found that a reduction of unmet needs was slower in patients with higher HA (B=0.04, p<.0001) only for patient-rated measures. Improvement in both patient-rated and staff-rated HA over time was associated with fewer subsequent patient- (B=-0.10, p<0.0001) and staff-rated (B=-0.08, p=0.0175) unmet needs. With positive changes in the HA preceding fewer unmet needs, findings provide further evidence for a causal relationship between alliance and outcome in the treatment of people with severe mental illness

Clinical Decision Making and Outcome in Routine Care for People with Severe Mental Illness (CEDAR): Study protocol

BACKGROUND: A considerable amount of research has been conducted on clinical decision making (CDM) in short-term physical conditions. However, there is a lack of knowledge on CDM and its outcome in long-term illnesses, especially in care for people with severe mental illness. METHODS/DESIGN: The study entitled "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR) is carried out in six European countries (Denmark, Germany, Hungary, Italy, Switzerland and UK). First, CEDAR establishes a methodology to assess CDM in people with severe mental illness. Specific instruments are developed (and psychometric properties established) to measure CDM style, key elements of CDM in routine care, as well as CDM involvement and satisfaction from patient and therapist perspectives. Second, these instruments are being put to use in a multi-national prospective observational study (bimonthly assessments during a one-year observation period; N = 560). This study investigates the immediate, short- and long-term effect of CDM on crucial dimensions of clinical outcome (symptom level, quality of life, needs) by taking into account significant variables moderating the relationship between CDM and outcome. DISCUSSION: The results of this study will make possible to delineate quality indicators of CDM, as well as to specify prime areas for further improvement. Ingredients of best practice in CDM in the routine care for people with severe mental illness will be extracted and recommendations formulated. With its explicit focus on the patient role in CDM, CEDAR will also contribute to strengthening the service user perspective. This project will substantially add to improving the practice of CDM in mental health care across Europe. TRIAL REGISTER: ISRCTN75841675

Jovanka kommt an! Stadtgestaltung für einen inklusiven Campus Lichtwiese. Städtebaulicher Entwurf im Sommersemester 2017.

Der TU Darmstadt Campus Lichtwiese wird sich in den nächsten Jahrzehnten stark entwickeln. Zur Debatte stehen eines neues Mobilitätskonzept, die Neuordnung der Freiflächen und Nachverdichtung durch studentisches Wohnen. In Rahmen des Entwurfs sollen in Zusammenarbeit mit Studierenden mit eingeschränkter Mobilität, Seh- oder Höreinschränkung, und Newcomern in Darmstadt Konzepte entwickelt werden, die Zugänglichkeit und Aufenthaltsqualität des Campus (für eine der Gruppen) im Sinne des Universal Design und des Access for All erhöhen

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Can we learn from the ecology of the Bohemian gentian and save another closely related species of Gentianella?

Bohemian gentian (Gentianella praecox subsp. bohemica) is an endemic taxon that occurs on the Czech Massif and together with the Sturmian gentian (Gentianella obtusifolia subsp. sturmiana) are the only autumnal species of Gentianella with large flowers in central Europe. Both species have declined dramatically in both population size and numbers of populations. The Bohemian gentian rescue programme, which recommended appropriate management measures, was adopted in 2011. Here we study the ecology of this species, results of the rescue programme and explore the possibilities of using the experience resulting from this programme for improving the viability of the second species. Long-term monitoring of populations of the Bohemian gentian has shown that regular mowing or grazing together with careful litter removal and gap creation are necessary for its survival in the current climatic conditions. We found some ecological differences between these two closely related species of Gentianella. However, our empirical experience of the largest population of the Sturmian gentian at a site where it thrives, and general evidence that gaps are crucial for the successful establishment of Gentianella seedlings, indicate that regular mowing or grazing together with careful litter removal and creation of gaps, should also be recommended as in the case of the Bohemian gentian rescue programme. Artificial gaps are especially crucial for successful seedling regeneration in oligotrophic meadows with dense vegetation, where the last Sturmian gentian populations survive

Differences in DNA repair capacity, cell death and transcriptional response after irradiation between a radiosensitive and a radioresistant cell line

Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24h after irradiation genes involved in "DNA damage response", "direct p53 effectors" and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols

Can Heparin-Coated ECMO Cannulas Induce Thrombocytopenia in COVID-19 Patients?

Extracorporeal membrane oxygenation (ECMO) is often used in the management of COVID-19-related severe respiratory failure. We report the first case of a patient with COVID-19-related ARDS on ECMO support who developed symptoms of heparin-induced thrombocytopenia (HIT) in the absence of heparin therapy. A low platelet count of 61 G/L was accompanied by the presence of circulating HIT antibodies 12 days after ECMO initiation. Replacement of the ECMO system including cannulas resulted in the normalization of the platelet count. However, the clinical situation did not improve, and the patient died 9 days later. Careful consideration of anticoagulant therapy and ECMO circuit, as well as routine HIT antibody testing, may prevent a fatal course in ECMO-supported COVID-19 patients