The evolution of the cytoskeleton

The cytoskeleton is a system of intracellular filaments crucial for cell shape, division, and function in all three domains of life. The simple cytoskeletons of prokaryotes show surprising plasticity in composition, with none of the core filament-forming proteins conserved in all lineages. In contrast, eukaryotic cytoskeletal function has been hugely elaborated by the addition of accessory proteins and extensive gene duplication and specialization. Much of this complexity evolved before the last common ancestor of eukaryotes. The distribution of cytoskeletal filaments puts constraints on the likely prokaryotic line that made this leap of eukaryogenesis

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Electronic Implementation of Integrated End-of-life Care: A Local Approach

Introduction: The Liverpool Care Pathway for the Dying Patient is an instrument to deliver integrated care for patients in their last hours of life. Originally a paper-based system, this study investigates the feasibility of an electronic version.  Methods: An electronic Liverpool Care Pathway was implemented in a specialized palliative care unit of a German university hospital. Its use is exemplified by means of auditing and analysis of the proportion of recorded items.  Results: In the years 2013 and 2014 the electronic Liverpool Care Pathway was used for the care of 159 patients. The uptake of the instrument was high (67%). Most items were recorded. Apart from a high usability, the fast data retrieval allows fast analysis for auditing and research.  Conclusions and discussion: The electronic instrument is feasible in a computerized ward and has strong advantages for retrospective analysis.  Trial registration: Internal Clinical Trial Register of the Medical Faculty, Heinrich Heine University Düsseldorf, No. 2015124683 (7 December 2015)

Caring for patients during voluntarily stopping of eating and drinking (VSED): experiences of a palliative care team in Germany

Abstract Background Health-care professionals are confronted with patients who wish to end their lives through voluntarily stopping eating and drinking (VSED). During VSED, symptoms such as agitation, thirst or psychological distress may arise, thus making close medical accompaniment necessary. Dealing with these symptoms can put a high burden on palliative care teams. Furthermore, divergent perceptions of the ethical classification of VSED may lead to moral distress. The aim of this study was to assess the influence of experience gained over time on the burden of palliative care professionals while accompanying patients during VSED and to assess the perceptions of coping strategies. Methods This is a prospective single-centre study conducted at the Interdisciplinary Centre for Palliative Care at University Hospital Duesseldorf, Germany. At two points in time (T1, T2) one year apart, team members of all professions who were actively involved in the accompaniment were eligible to complete a pretested questionnaire. Results Team members perceived the symptom complex of psychological distress, anxiety, and agitation to be the most burdensome symptoms for the patients (T1: 28/49, 57.1%; T2: 33/59, 55.9%). Thirst was the second most observed symptom (T1: 17/49, 34.7%, T2: 19/59, 32.2%). These were also the most burdensome symptoms for individual team members. Most team members found there were no general moral concerns. There was a decrease in the perceived importance of support strategies such as ethical counselling (85.7% versus 63.6%). Conclusions Accompanying patients during VSED is a challenge for health-care professionals. When comparing T2 to T1, less emphasis lies on the importance of ethical counselling or psychiatric assessment to build a foundation for the accompaniment. Moral and ethical concerns seem to play a minor role. More in-depth studies covering a bigger sample size as well as qualitative studies are needed

Specialist Palliative Care Consultations in COVID-19 Patients in the ICU—A Retrospective Analysis of Patient Characteristics and Symptoms at a German University Hospital

COVID-19 patients who may require invasive therapeutic procedures such as extracorporeal membrane oxygenation (ECMO) have high symptom burden and in-hospital mortality. In addition, awake patients on ECMO are new in the intensive care unit (ICU) setting. Inpatient specialist palliative care (sPC) provides support such as symptom control on a physical, psychosocial and spiritual level. The field of sPC in COVID-19 patients is still new and important to investigate. We aim to analyze sPC of COVID-19 patients in the ICU with regard to patient characteristics and symptoms from a palliative care perspective. We conducted a retrospective analysis (03/2020–04/2021) and identified 51 ICU patients receiving sPC. The statistical analysis included descriptive statistics and comparisons of symptoms. The first sPC contact of patients (mean age 69.5 years, 62.7% male) was around 14 days after COVID-19 confirmation, and 43% were treated with ECMO therapy. The baseline symptom burden was high with a focus on weakness (100%), tiredness (98%), dyspnea (96%) and family burden (92%). The symptom intensity significantly decreased during the time period of sPC and COVID-19 treatment (t(99) = 3.119, p = 0.003, d = 0.437). These results help intensivists and sPC clinicians to identify symptoms and the need for sPC in COVID-19 patients. However, studies with prospective and controlled designs need to follow