Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis.

We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analysed samples of sepsis-suspected patients (N=20) and age-spanning healthy controls (N=12), using flow cytometry-based assays. We measured inflammatory markers from plasma fractions, and immunophenotyped freshly isolated unfixed PBMCs for leukocytes subsets representation and expression of activation markers, including chemokine receptors.

Best practices for user consultation in flow cytometry shared resource laboratories.

This "Best Practices in User Consultation" article is the result of a 2022 International Society for the Advancement of Cytometry (ISAC) membership survey that collected valuable insights from the shared research laboratory (SRL) community and of a group discussion at the CYTO 2022 workshop of the same name. One key takeaway is the importance of initiating a consultation at the outset of a flow cytometry project, particularly for trainees. This approach enables the improvement and standardization of every step, from planning experiments to interpreting data.

Endosomal cargo recycling mediated by Gpa1 and phosphatidylinositol 3-kinase is inhibited by glucose starvation.

Cell surface protein trafficking is regulated in response to nutrient availability, with multiple pathways directing surface membrane proteins to the lysosome for degradation in response to suboptimal extracellular nutrients. Internalized protein and lipid cargoes recycle back to the surface efficiently in glucose-replete conditions, but this trafficking is attenuated following glucose starvation. We find that cells with either reduced or hyperactive phosphatidylinositol 3-kinase (PI3K) activity are defective for endosome to surface recycling.

The Rpd3-Complex Regulates Expression of Multiple Cell Surface Recycling Factors in Yeast.

Intracellular trafficking pathways control residency and bioactivity of integral membrane proteins at the cell surface. Upon internalisation, surface cargo proteins can be delivered back to the plasma membrane via endosomal recycling pathways. Recycling is thought to be controlled at the metabolic and transcriptional level, but such mechanisms are not fully understood.

Bone marrow remodeling supports hematopoiesis in response to immune thrombocytopenia progression in mice.

Immune thrombocytopenia (ITP) is an acquired autoimmune condition characterized by both reduced platelet production and the destruction of functionally normal platelets by sustained attack from the immune system. However, the effect of prolonged ITP on the more immature hematopoietic progenitors remains an open area of investigation. By using a murine in vivo model of extended ITP, we revealed that ITP progression drives considerable progenitor expansion and bone marrow (BM) remodeling.

Cytotoxic (,-1,3,5-triaminocyclohexane)ruthenium(II)-diphosphine complexes; evidence for covalent binding intercalation with DNA.

We report cytotoxic ruthenium(ii) complexes of the general formula [RuCl(cis-tach)(diphosphine)]+ (cis-tach = cis-cis-1,3,5-triaminocyclohexane) that have been characterised by 1H, 13C and 31P{1H} NMR spectroscopy, mass spectrometry, X-ray crystallography and elemental analysis. The kinetics of aquation and stability of the active species have been studied, showing that the chlorido ligand is substituted by water at 298 K with first order rate constants of 10-2-10-3 s-1, ideal for potential clinical use as anti-tumour agents. Strong interactions with biologically relevant duplex and quadruplex DNA models correlate with the activity observed with A549, A2780 and 293T cell lines, and the degree of activity was found to be sensitive to the chelating diphosphine ligand.

PRMT7 regulates RNA-binding capacity and protein stability in Leishmania parasites.

RNA binding proteins (RBPs) are the primary gene regulators in kinetoplastids as transcriptional control is nearly absent, making Leishmania an exceptional model for investigating methylation of non-histone substrates. Arginine methylation is an evolutionarily conserved protein modification catalyzed by Protein aRginine Methyl Transferases (PRMTs). The chromatin modifier PRMT7 is the only Type III PRMT found in higher eukaryotes and a restricted number of unicellular eukaryotes.

Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.

Background: Phospholipases D1 and D2 (PLD1/2) are implicated in tumorigenesis through their generation of the signalling lipid phosphatidic acid and its downstream effects. Inhibition of PLD1 blocks prostate cell growth and colony formation. Here a role for PLD2 in prostate cancer (PCa), the major cancer of men in the western world, is examined.

Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo-controlled trial.

Aims: Morphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost-effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo.

Palliative care for people living with heart failure: European Association for Palliative Care Task Force expert position statement.

Contrary to common perception, modern palliative care (PC) is applicable to all people with an incurable disease, not only cancer. PC is appropriate at every stage of disease progression, when PC needs emerge. These needs can be of physical, emotional, social, or spiritual nature.

Does advance care planning in addition to usual care reduce hospitalisation for patients with advanced heart failure: A systematic review and narrative synthesis.

Background: People with advanced heart failure have repeated hospital admissions. Advance care planning can support patient preferences, but studies in people with heart failure have not been assessed.

Aim: To evaluate the literature regarding advance care planning in heart failure.

Which patients with heart failure should receive specialist palliative care?

Aims: We investigated which patients with heart failure (HF) should receive specialist palliative care (SPC) by first creating a definition of need for SPC in patients hospitalised with HF using patient-reported outcome measures (PROMs) and then testing this definition using the outcome of days alive and out of hospital (DAOH). We also evaluated which baseline variables predicted need for SPC and whether those with this need received SPC.

Methods And Results: PROMs assessing quality of life (QoL), symptoms, and mood were administered at baseline and every 4 months.

Thymic B Cell-Mediated Attack of Thymic Stroma Precedes Type 1 Diabetes Development.

Type 1 diabetes (T1D) results from a coordinated autoimmune attack of insulin producing beta cells in the pancreas by the innate and adaptive immune systems, beta cell death being predominantly T cell-mediated. In addition to T cells, peripheral B cells are important in T1D progression. The thymus of mice and man also contains B cells, and lately they have been linked to central tolerance of T cells.

The feasibility of a randomised controlled trial to compare the cost-effectiveness of palliative cardiology or usual care in people with advanced heart failure: Two exploratory prospective cohorts.

Background:: The effectiveness of cardiology-led palliative care is unknown; we have insufficient information to conduct a full trial.

Aim:: To assess the feasibility (recruitment/retention, data quality, variability/sample size estimation, safety) of a clinical trial of palliative cardiology effectiveness.

Design:: Non-randomised feasibility.

Cardiovascular implanted electronic devices in people towards the end of life, during cardiopulmonary resuscitation and after death: guidance from the Resuscitation Council (UK), British Cardiovascular Society and National Council for Palliative Care.

The Resuscitation Council (UK), the British Cardiovascular Society (including the British Heart Rhythm Society and the British Society for Heart Failure) and the National Council for Palliative Care recognise the importance of providing clear and consistent guidance on management of cardiovascular implanted electronic devices (CIEDs) towards the end of life, during cardiorespiratory arrest and after death. This document has been developed to provide guidance for the full range of healthcare professionals who may encounter people with CIEDs in the situations described and for healthcare managers and commissioners. The authors recognise that some patients and people close to patients may also wish to refer to this document.

Phase 2 Randomised Controlled Trial and Feasibility Study of Future Care Planning in Patients with Advanced Heart Disease.

Future Care Planning (FCP) rarely occurs in patients with heart disease until close to death by which time the potential benefits are lost. We assessed the feasibility, acceptability and tested a design of a randomised trial evaluating the impact of FCP in patients and carers. 50 patients hospitalised with acute heart failure or acute coronary syndrome and with predicted 12 month mortality risk of >20% were randomly allocated to FCP or usual care for 12 weeks upon discharge and then crossed-over for the next 12 weeks.

Quantification of proteins by flow cytometry: Quantification of human hepatic transporter P-gp and OATP1B1 using flow cytometry and mass spectrometry.

Flow cytometry is a powerful tool for the quantitation of fluorescence and is proven to be able to correlate the fluorescence intensity to the number of protein on cells surface. Mass spectroscopy can also be used to determine the number of proteins per cell. Here we have developed two methods, using flow cytometry and mass spectroscopy to quantify number of transporters in human cells.

Palliative care needs in patients hospitalized with heart failure (PCHF) study: rationale and design.

Aims: The primary aim of this study is to provide data to inform the design of a randomized controlled clinical trial (RCT) of a palliative care (PC) intervention in heart failure (HF). We will identify an appropriate study population with a high prevalence of PC needs defined using quantifiable measures. We will also identify which components a specific and targeted PC intervention in HF should include and attempt to define the most relevant trial outcomes.

Future Care Planning for patients approaching end-of-life with advanced heart disease: an interview study with patients, carers and healthcare professionals exploring the content, rationale and design of a randomised clinical trial.

Objective: To explore the optimal content and design of a clinical trial of an end-of-life intervention for advanced heart disease with patients, carers and healthcare professionals.

Design: Qualitative interview and focus group study.

Setting: Community and hospital-based focus groups and interviews.

Clearing up the signal: spectral imaging and linear unmixing in fluorescence microscopy.

The ongoing progress in fluorescence labeling and in microscope instrumentation allows the generation and the imaging of complex biological samples that contain increasing numbers of fluorophores. For the correct quantitative analysis of datasets with multiple fluorescence channels, it is essential that the signals of the different fluorophores are reliably separated. Due to the width of fluorescence spectra, this cannot always be achieved using the fluorescence filters in the microscope.

Palliative care for people with heart failure: summary of current evidence and future direction.

Background: Heart failure is a common condition with a significant physical and psychological burden for patients and their families. The need for supportive and palliative care: It is well recognised that palliative care is important in patients with advanced heart failure.

What Is Known: Heart failure patients have limited access to palliative care services.

The stochastic silencing phenotype of Arabidopsis morc6 mutants reveals a role in efficient RNA-directed DNA methylation.

The RNA-directed DNA methylation (RdDM) pathway is of central importance to the initiation and maintenance of transcriptional gene silencing in plants. DNA methylation is directed to target sequences by a mechanism that involves production of small RNAs by RNA polymerase IV and long non-coding RNAs by RNA polymerase V. DNA methylation then leads to recruitment of histone-modifying enzymes, followed by establishment of a silenced chromatin state.

ICDs in end-stage heart failure.

Implantable cardioverter defibrillators (ICDs) reduce mortality in selected patients with chronic heart failure but prognostic benefit is likely to attenuate with progression to end-stage heart failure. The incidence of multiple futile ICD shocks before death is uncertain. Only individual patients, supported by their healthcare professionals, can decide when ICD therapy becomes futile in end-stage heart failure.