Organizational issues and major problems of palliative care concerning treatment of end-stage renal disease in Polish residential hospices and hospital- -based palliative medicine wards

Copyright © Via Medica. Background. Patients diagnosed with end-stage renal disease experience a significant level of symptom burden, including pain, nausea and vomiting, inability to urinate, fatigue etc. At this point in disease progression, it is important to establish what types and choices of therapy are most suitable for these patients, in particular, the value of continuing dialysis treatment. Material and methods. A self-administered questionnaire was distributed among Polish residential hospices and hospital based palliative medicine wards. All responses obtained underwent statistical analysis using Pearson's Chi Square test. Results. Permanent palliative care facilities, from which 73 out of 166 registered in Poland, took part in the survey. ESRD patients were identified to be cared by 81% of the aforementioned institutions. The most common treatment approach for these patients was highlighted as conservative treatment (68%), followed by hemodialysis (47%), whereas merely 11% provided peritoneal dialysis. Differences between facilities were identified relating to therapeutic recommendations for terminal ESRD patients with residential hospices more likely to recommend dialysis in conjunction with palliative care, whereas palliative wards advocated a withdrawal from dialysis followed by the initiation of palliative care. Conclusion. All surveyed facilities considered ESRD patients eligible for guaranteed hospice and palliative care services. However, certain changes are needed to improve care for ESRD patients, including: The development of collaborative partnerships between hospices, dialysis centers and nephrologists, development of guidelines for withdrawing dialysis and applying conservative treatment, introducing better renal-based training for medical personnel as well as the introduction of transparency within rules relating to the financing of these services

Elements for European logistics policy - A discussion paper

Following a Finnish initiative the European Commission is preparing a communication on logistics in 2006. To support the preparations Finland arranged the so called EULOC-process in which logistics experts from different countries were invited to participate. First, an industry foresight of European logistics in 2015 was created. Next, the mission, vision and policy priorities of the European logistics policy were discussed. The mission for European logistics policy was created from the viewpoint of citizens, companies, states and Europe. Seven vision elements were created. The driving visions are “Seamless systems” and “Intelligent regulation”. The guiding and enabling visions are “Resources” and “Cost efficiency”. The outcome visions are “Europe’s competitiveness”, “Equal business opportunity” and “Sustainability”. According to the experts’ views the priority areas of European logistics policy are Infrastructure – Seamless systems require investments Research, development and training – Strengthen the competitiveness of the European Union Enterprises – The reinforcement of logistic industry Regulation – Innovative and intelligent Cost Efficiency – Effective logistics Sustainability – From environmental, social and economic viewpoint, a must in modern logistics Co-Operation – A strategic issue in network society Public-Private Partnership – Agile solutions for investments

An Essential Role for the Proximal but Not the Distal Cytoplasmic Tail of Glycoprotein M in Murid Herpesvirus 4 Infection

Murid herpesvirus-4 (MuHV-4) provides a tractable model with which to define common, conserved features of gamma-herpesvirus biology. The multi-membrane spanning glycoprotein M (gM) is one of only 4 glycoproteins that are essential for MuHV-4 lytic replication. gM binds to gN and is thought to function mainly secondary envelopment and virion egress, for which several predicted trafficking motifs in its C-terminal cytoplasmic tail could be important. We tested the contribution of the gM cytoplasmic tail to MuHV-4 lytic replication by making recombinant viruses with varying C-terminal deletions. Removing an acidic cluster and a distal YXXΦ motif altered the capsid distribution somewhat in infected cells but had little effect on virus replication, either in vitro or in vivo. In contrast, removing a proximal YXXΦ motif as well completely prevented productive replication. gM was still expressed, but unlike its longer forms showed only limited colocalization with co-transfected gN, and in the context of whole virus appeared to support gN expression less well. We conclude that some elements of the gM cytoplasmic tail are dispensible for MuHV-4 replication, but the tail as a whole is not

Understanding the role of hospice pharmacists: a qualitative study

Background Pharmacists are important members of multidisciplinary teams but, despite surveys of provision, the role of the hospice pharmacist is not well described. Objective To explore the role of the hospice pharmacist and identify barriers and facilitators to the role. Setting Hospices offering in-patient services caring for adults towards the end of life in one geographical area of northern England. Method Pharmacists providing services to hospices were invited to take part in qualitative semi-structured interviews asking about experience, patient contact, team working and barriers and facilitators to the role. These were recorded verbatim and data were analysed thematically using framework analysis. Main outcome measure The hospice pharmacist’s perceptions of their role and barriers and facilitators to it. Results Fifteen pharmacists took part. Two themes and ten subthemes were identified focused on tasks and communication. Practise was varied and time limited the quantity and depth of services carried out but was often spent navigating complex drug supply routes. Participants found methods of communication suited to the hours they spent in the hospice although communication of data was a barrier to effective clinical service provision. Participants identified the need for appropriate training and standards of practice for hospice pharmacists would enable better use of their skills. Conclusion Barriers to the role of hospice pharmacist include time, access to role specific training, access to clinical information and complex medicines supply chains. The role would benefit from definition to ensure that hospices are able to use hospice pharmacists to their greatest potential

EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner

Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion