A survey to ascertain peer support models available in Head and Neck cancer across the United Kingdom.

In cancers and chronic conditions, peer support (PS) has been shown to improve quality of life (QOL) and provide an important coping mechanism for patients, however there is little evidence for this intervention in Head and Neck cancer (HNC). Peer support allows individuals to come together and share information, encouragement, and experiences. It is delivered in a variety of ways including one-to-one, online, and support groups. There is limited literature regarding the timing, barriers, and types of PS available for individuals with HNC across the United Kingdom (UK). The aim of this project was to survey healthcare professionals with respect to their experience regarding types, timings, and barriers to PS in HNC. The survey was developed based on the literature, feedback and advice from a HNC patient research group and healthcare professionals. It was conducted online and consisted of twelve questions. Eighty-eight individuals responded covering twenty-four of twenty-six cancer alliances across the UK. Three main themes with subthemes were identified: patient barriers (emotional barriers and patient limitations), organisational barriers (administrative problems, limited time and resources and COVID-19), and staff barriers (lack of departmental support, concerns with PS and matching and timing of support). The survey demonstrated the different types of PS available across the UK and the barriers faced when implementing this support. It highlighted the complexity of being able to satisfactorily deliver appropriate and effective PS in HNC and the challenges involved.

Prevalence of Helicobacter pylori positivity in patients undergoing percutaneous coronary intervention.

BACKGROUND: The adverse effect of haemorrhagic complications after percutaneous coronary intervention (PCI) on outcome is well established with Helicobacter pylori infection known to be an important precipitant of peptic ulcer disease in patients receiving non-steroidal anti-inflammatory drug therapy. The prevalence of H. pylori positivity in patients undergoing PCI and receiving subsequent antiplatelet therapy is unknown. AIMS: We sought to determine the prevalence and features associated with H. pylori positivity in patients undergoing PCI. METHODS: All patients undergoing PCI between August 2008 and April 2009 were identified and assessed for H. pylori positivity with serological status determined by using a commercially supplied enzyme-linked immunosorbent assay. RESULTS: A total of 245 patients undergoing PCI during the study period had samples obtained for H. pylori serology. Of these, 91 were positive for H. pylori serology (37%) and 148 were negative (60%) with six samples being equivocal (3%). Of those patients positive for H. pylori, 75% were on agents at admission known to promote or precipitate gastrointestinal haemorrhage. Patients positive for H. pylori tended to be older, with increased creatinine and more likely to be receiving proton pump inhibitor therapy. CONCLUSIONS: In an unselected cohort of patients undergoing PCI in a single centre, we detected a prevalence of H. pylori positivity in 37% of patients; this denotes a potentially treatable precipitant of haemorrhage in a considerable portion of patients receiving dual antiplatelet therapy after PCI. Further prospective study is required to determine if the presence of H. pylori positivity is associated with adverse events in terms of gastrointestinal and cardiac outcomes.

Case report: prehospital use of intranasal ketamine for paediatric burn injury.

In this study, the administration of an intravenous ketamine formulation to the nasal mucosa of a paediatric burn victim is described in the prehospital environment. Effective analgesia was achieved without the need for vascular or osseous access. Intranasal ketamine has been previously described for chronic pain and anaesthetic premedication. This case highlights its potential as an option for prehospital analgesia.

Open-cellular organic semiconductor thin films by vertical co-deposition using sub-100 nm nanosphere templates.

Vertical co-deposition of sub-100 nm polystyrene sphere templates with water-soluble small molecule or polymeric semiconductors, followed by solvent vapour assisted sphere removal, is shown to be an excellent method for generating porous large area organic semiconductor thin films with sub-100 nm open-cellular networks, with numerous potential applications in areas such as sensing and photovoltaics.

Charge transfer between acenes and PbS nanocrystals.

Organic-inorganic hybrid heterojunctions have potential as the basis for future photovoltaic devices. Herein, we report the results of investigations exploring the possibility of using pentacene and tetracene as photoelectron donors in conjunction with PbS nanocrystals (PbS-NCs). Photoinduced charge transfer was probed using external quantum efficiency measurements on acene:PbS-NC hybrid photovoltaic devices in conjunction with photoluminescence studies of the corresponding bilayer films. It is shown that photoelectron transfer from pentacene to the PbS-NCs is inefficient as compared to that between tetracene and PbS-NCs. The latter case can be rationalized in terms of the energy level alignment at the heterojunction assuming a common vacuum level. However, in the case of pentacene:PbS-NC junctions an interfacial energy level shift must be considered in order to explain the observations.

The fabrication and analysis of a PbS nanocrystal:C(60) bilayer hybrid photovoltaic system.

A near-infrared sensitive hybrid photovoltaic system between PbS nanocrystals (PbS-NCs) and C(60) is demonstrated. Up to 0.44% power conversion efficiency is obtained under AM1.5G with a short circuit current density (J(sc)) of 5 mA cm(-2) when the PbS-NC layer is treated in anhydrous methanol. The observed J(sc) is found be approximately one-third of the maximum expected from this hybrid configuration, indicating the potential for further optimization. Crucial for device operation, a smooth film of nanocrystals is seen to form on the hole transporting poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) layer deposited on the transparent electrode, facilitated through an ionic interaction between nanocrystal capping ligands and the PEDOT:PSS. The formation of the open circuit voltage in this system is seen to be influenced by an interfacial dipole formed at the hole-extracting electrode, providing insights for further optimization.

The secreted Dictyostelium protein CfaD is a chalone.

Dictyostelium discoideum cells secrete CfaD, a protein that is similar to cathepsin proteases. Cells that lack cfaD proliferate faster and reach a higher stationary-phase density than wild-type cells, whereas cells that overexpress CfaD proliferate slowly and reach the stationary phase when at a low density. On a per-nucleus basis, CfaD affects proliferation but not growth. The drawback of not having CfaD is a reduced spore viability. Recombinant CfaD has no detectable protease activity but, when added to cells, inhibits the proliferation of wild-type and cfaD(-) cells. The secreted protein AprA also inhibits proliferation. AprA is necessary for the effect of CfaD on proliferation. Molecular-sieve chromatography indicates that in conditioned growth medium, the 60 kDa CfaD is part of a approximately 150 kDa complex, and both chromatography and pull-down assays suggest that CfaD interacts with AprA. These results suggest that two interacting proteins may function together as a chalone signal in a negative feedback loop that slows Dictyostelium cell proliferation.

A cell number-counting factor regulates levels of a novel protein, SslA, as part of a group size regulation mechanism in Dictyostelium.

Developing Dictyostelium cells form aggregation streams that break into groups of approximately 2 x 10(4) cells. The breakup and subsequent group size are regulated by a secreted multisubunit counting factor (CF). To elucidate how CF regulates group size, we isolated second-site suppressors of smlA(-), a transformant that forms small groups due to oversecretion of CF. smlA(-) sslA1(CR11) cells form roughly wild-type-size groups due to an insertion in the beginning of the coding region of sslA1, one of two highly similar genes encoding a novel protein. The insertion increases levels of SslA. In wild-type cells, the sslA1(CR11) mutation forms abnormally large groups. Reducing SslA levels by antisense causes the formation of smaller groups. The sslA(CR11) mutation does not affect the extracellular accumulation of CF activity or the CF components countin and CF50, suggesting that SslA does not regulate CF secretion. However, CF represses levels of SslA. Wild-type cells starved in the presence of smlA(-) cells, recombinant countin, or recombinant CF50 form smaller groups, whereas sslA1(CR11) cells appear to be insensitive to the presence of smlA(-) cells, countin, or CF50, suggesting that the sslA1(CR11) insertion affects CF signal transduction. We previously found that CF reduces intracellular glucose levels. sslA(CR11) does not significantly affect glucose levels, while glucose increases SslA levels. Together, the data suggest that SslA is a novel protein involved in part of a signal transduction pathway regulating group size.

A 60-kilodalton protein component of the counting factor complex regulates group size in Dictyostelium discoideum.

Much remains to be understood about how a group of cells or a tissue senses and regulates its size. Dictyostelium discoideum cells sense and regulate the size of groups and fruiting bodies using a secreted 450-kDa complex of proteins called counting factor (CF). Low levels of CF result in large groups, and high levels of CF result in small groups. We previously found three components of CF (D. A. Brock and R. H. Gomer, Genes Dev. 13:1960-1969, 1999; D. A. Brock, R. D. Hatton, D.-V. Giurgiutiu, B. Scott, R. Ammann, and R. H. Gomer, Development 129:3657-3668, 2002; and D. A. Brock, R. D. Hatton, D.-V. Giurgiutiu, B. Scott, W. Jang, R. Ammann, and R. H. Gomer, Eukaryot. Cell 2:788-797, 2003). We describe here a fourth component, CF60. CF60 has similarity to acid phosphatases, although it has very little, if any, acid phosphatase activity. CF60 is secreted by starving cells and is lost from the 450-kDa CF when a different CF component, CF50, is absent. Although we were unable to obtain cells lacking CF60, decreasing CF60 levels by antisense resulted in large groups, and overexpressing CF60 resulted in small groups. When added to wild-type cells, conditioned starvation medium from CF60 overexpressor cells as well as recombinant CF60 caused the formation of small groups. The ability of recombinant CF60 to decrease group size did not require the presence of the CF component CF45-1 or countin but did require the presence of CF50. Recombinant CF60 does not have acid phosphatase activity, indicating that the CF60 bioactivity is not due to a phosphatase activity. Together, the data suggest that CF60 is a component of CF, and thus this secreted signal has four different protein components.

Volumetric analysis of a specific language region - the planum temporale.

Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.

A cell number counting factor regulates Akt/protein kinase B to regulate Dictyostelium discoideum group size.

Little is known about how individual cells can organize themselves to form structures of a given size. During development, Dictyostelium discoideum aggregates in dendritic streams and forms groups of approximately 20,000 cells. D. discoideum regulates group size by secreting and simultaneously sensing a multiprotein complex called counting factor (CF). If there are too many cells in a stream, the associated high concentration of CF will decrease cell-cell adhesion and increase cell motility, causing aggregation streams to break up. The pulses of cyclic AMP (cAMP) that mediate aggregation cause a transient translocation of Akt/protein kinase B (Akt/PKB) to the leading edge of the plasma membrane and a concomitant activation of the kinase activity, which in turn stimulates motility. We found that countin- cells (which lack bioactive CF) and wild-type cells starved in the presence of anticountin antibodies (which block CF activity) showed a decreased level of cAMP-stimulated Akt/PKB membrane translocation and kinase activity compared to parental wild-type cells. Recombinant countin has the bioactivity of CF, and a 1-min treatment of cells with recombinant countin potentiated Akt/PKB translocation to membranes and Akt/PKB activity. Western blotting of total cell lysates indicated that countin does not affect the total level of Akt/PKB. Fluorescence microscopy of cells expressing an Akt/PKB pleckstrin homology domain-green fluorescent protein (PH-GFP) fusion protein indicated that recombinant countin and anti-countin antibodies do not obviously alter the distribution of Akt/PKB PH-GFP when it translocates to the membrane. Our data indicate that CF increases motility by potentiating the cAMP-stimulated activation and translocation of Akt/PKB.

Improved tolerance to missing data in myocardial perfusion SPET using OSEM reconstruction.

When projection data are incomplete for various technical reasons, artefacts may occur in the reconstructed images. This study examines whether an iterative reconstruction method, the ordered subsets implementation of the EM algorithm (OSEM), can improve reconstruction and minimise the artefacts compared to filtered back-projection (FBP). We varied the number and location of projections removed to investigate when significant artefacts occur, and whether diagnosis is affected. Phantom studies were analysed with sequential orthogonal pairs of projection angles removed (as would typically occur when either data loss or severe motion is detected during acquisition with a right-angled, dual-head cardiac single-photon emission tomography system) and reconstructed with both FBP and OSEM. Twelve normal myocardial perfusion studies were also assessed to study the effect of missing projections on clinical diagnosis. Differences between reconstructions with intact versus missing data were measured. Also, reconstructed images were clinically assessed and scored on a five-point scale based on whether the artefacts would alter clinical interpretation. Although both reconstruction methods showed artefacts, the absolute differences between reconstructed phantom data with intact and missing projection sets were significantly greater (P<0.005) for FBP than for OSEM for all numbers of missing projections. The clinical data showed similar differences between FBP and OSEM reconstructions. The three observers noted superiority of OSEM compared to FBP, with reduced incidence of clinically significant artefacts. However, neither reconstruction method could tolerate six or more missing pairs from 32 projections. There was no significant dependence on the angular location of missing projections. In the absence of any attempt to correct for missing projections, OSEM reduced the influence of artefacts compared to FBP.

Disruption of aldehyde reductase increases group size in dictyostelium.

Developing Dictyostelium cells form structures containing approximately 20,000 cells. The size regulation mechanism involves a secreted counting factor (CF) repressing cytosolic glucose levels. Glucose or a glucose metabolite affects cell-cell adhesion and motility; these in turn affect whether a group stays together, loses cells, or even breaks up. NADPH-coupled aldehyde reductase reduces a wide variety of aldehydes to the corresponding alcohols, including converting glucose to sorbitol. The levels of this enzyme previously appeared to be regulated by CF. We find that disrupting alrA, the gene encoding aldehyde reductase, results in the loss of alrA mRNA and AlrA protein and a decrease in the ability of cell lysates to reduce both glyceraldehyde and glucose in an NADPH-coupled reaction. Counterintuitively, alrA- cells grow normally and have decreased glucose levels compared with parental cells. The alrA- cells form long unbroken streams and huge groups. Expression of AlrA in alrA- cells causes cells to form normal fruiting bodies, indicating that AlrA affects group size. alrA- cells have normal adhesion but a reduced motility, and computer simulations suggest that this could indeed result in the formation of large groups. alrA- cells secrete low levels of countin and CF50, two components of CF, and this could partially account for why alrA- cells form large groups. alrA- cells are responsive to CF and are partially responsive to recombinant countin and CF50, suggesting that disrupting alrA inhibits but does not completely block the CF signal transduction pathway. Gas chromatography/mass spectroscopy indicates that the concentrations of several metabolites are altered in alrA- cells, suggesting that the Dictyostelium aldehyde reductase affects several metabolic pathways in addition to converting glucose to sorbitol. Together, our data suggest that disrupting alrA affects CF secretion, causes many effects on cellular metabolism, and has a major effect on group size.

CF45-1, a secreted protein which participates in Dictyostelium group size regulation.

Developing Dictyostelium cells aggregate to form fruiting bodies containing typically 2 x 10(4) cells. To prevent the formation of an excessively large fruiting body, streams of aggregating cells break up into groups if there are too many cells. The breakup is regulated by a secreted complex of polypeptides called counting factor (CF). Countin and CF50 are two of the components of CF. Disrupting the expression of either of these proteins results in cells secreting very little detectable CF activity, and as a result, aggregation streams remain intact and form large fruiting bodies, which invariably collapse. We find that disrupting the gene encoding a third protein present in crude CF, CF45-1, also results in the formation of large groups when cells are grown with bacteria on agar plates and then starve. However, unlike countin(-) and cf50(-) cells, cf45-1(-) cells sometimes form smaller groups than wild-type cells when the cells are starved on filter pads. The predicted amino acid sequence of CF45-1 has some similarity to that of lysozyme, but recombinant CF45-1 has no detectable lysozyme activity. In the exudates from starved cells, CF45-1 is present in a approximately 450-kDa fraction that also contains countin and CF50, suggesting that it is part of a complex. Recombinant CF45-1 decreases group size in colonies of cf45-1(-) cells with a 50% effective concentration (EC(50)) of approximately 8 ng/ml and in colonies of wild-type and cf50(-) cells with an EC(50) of approximately 40 ng/ml. Like countin(-) and cf50(-) cells, cf45-1(-) cells have high levels of cytosolic glucose, high cell-cell adhesion, and low cell motility. Together, the data suggest that CF45-1 participates in group size regulation in Dictyostelium.

Artifactually low glycated haemoglobin in a patient with severe hypertriglyceridaemia.

This report describes a case of artifactually low glycated haemoglobin (Hb) in a patient with type II diabetes and severe hypertriglyceridaemia. The effect of hypertriglyceridaemia on glycated Hb determination using the Abbott Vision method was investigated in a series of patients with diabetes. The interference of triglycerides in glycated Hb assays was also investigated by two other methods, the Beckman Synchron CX4 delta immunoturbidimetric method, and the Primus affinity chromatography high performance liquid chromatography assay.

The different components of a multisubunit cell number-counting factor have both unique and overlapping functions.

Dictyostelium aggregation streams break up into groups of 10(3) to 2 x 10(4) cells. The cells sense the number of cells in a stream or group by the level of a secreted counting factor (CF). CF is a complex of at least 5 polypeptides. When the gene encoding countin (one of the CF polypeptides) was disrupted, the cells could not sense each other's presence, resulting in non-breaking streams that coalesced into abnormally large groups. To understand the function of the components of CF, we have isolated cDNA sequences encoding a second component of CF, CF50. CF50 is 30% identical to lysozyme (but has very little lysozyme activity) and contains distinctive serine-glycine motifs. Transformants with a disrupted cf50 gene, like countin(-) cells, form abnormally large groups. Addition of recombinant CF50 protein to developing cf50(-) cells rescues their phenotype by decreasing group size. Abnormalities seen in aggregating countin(-) cells (such as high cell-cell adhesion and low motility) are also observed in the cf50(-) cells. Western blot analysis of conditioned medium sieve column fractions showed that the CF50 protein is present in the same fraction as the 450 kDa CF complex. In the absence of CF50, secreted countin is degraded, suggesting that one function of CF50 may be to protect countin from degradation. However, unlike countin(-) cells, cf50(-) cells differentiate into an abnormally high percentage of cells expressing SP70 (a marker expressed in a subset of prespore cells), and this difference can be rescued by exposing cells to recombinant CF50. These observations indicate that unlike other known multisubunit factors, CF contains subunits with both overlapping and unique properties.

ABC transporters required for endocytosis and endosomal pH regulation in Dictyostelium.

In Dictyostelium, the RtoA protein links both initial cell-type choice and physiological state to cell-cycle phase. rtoA- cells (containing a disruption of the rtoA gene) generally do not develop past the mound stage, and have an abnormal ratio of prestalk and prespore cells. RtoA is also involved in fusion of endocytic/exocytic vesicles. Cells lacking RtoA, although having a normal endocytosis rate, have a decreased exocytosis rate and endosomes with abnormally low pHs. RtoA levels vary during the cell cycle, causing a cell-cycle-dependent modulation of parameters such as cytosolic pH (Brazill et al., 2000). To uncover other genes involved in the RtoA-mediated differentiation, we identified genetic suppressors of rtoA. One of these suppressors disrupted two genes, mdrA1 and mdrA2, a tandem duplication encoding two members of the ATP binding cassette (ABC) transporter superfamily. Disruption of mdrA1/mdrA2 results in release from the developmental block and suppression of the defect in initial cell type choice caused by loss of the rtoA gene. However, this is not accomplished by re-establishing the link between cell type choice and cell cycle phase. MdrA1 protein is localized to the endosome. mdrA1- /mdrA2- cells (containing a disruption of these genes) have an endocytosis rate roughly 70% that of wild-type or rtoA- cells, whereas mdrA1- /mdrA2- /rtoA- cells have an endocytosis rate roughly 20% that of wild-type. The exocytosis rates of mdrA1- /mdrA2- and mdrA1- /mdrA2- /rtoA- are roughly that of wild-type. mdrA1- /mdrA2- endosomes have an unusually high pH, whereas mdrA1- /mdrA2- /rtoA- endosomes have an almost normal pH. The ability of mdrA1/mdrA2 disruption to rescue the cell-type proportion, developmental defects, and endosomal pH defects caused by rtoA disruption, and the ability of rtoA disruption to exacerbate the endocytosis defects caused by mdrA1/mdrA2 disruption, suggest a genetic interaction between rtoA, mdrA1 and mdrA2.

Antiepileptic hypersensitivity syndrome in children.

OBJECTIVE: To assess clinical features and outcomes of childhood antiepileptic hypersensitivity syndrome (AHS). AHS is an idiosyncratic reaction to aromatic anticonvulsants that can result in severe multiorgan dysfunction and death. METHODS: Children with suspected AHS (fever, rash, lymphadenopathy, liver dysfunction) were identified by an in-house computerized adverse drug event reporting system. The medical charts of children with suspected AHS were reviewed. A MEDLINE search (from 1966 to October 1999) was performed using the term antiepileptic hypersensitivity syndrome. RESULTS: Fourteen of 36 children who experienced a rash, urticaria, pruritus, fever, or hepatotoxicity associated with aromatic anticonvulsants met the criteria for AHS (mean age 10.4 +/- 6.5 y; males to females 8:6, white to African-American to biracial 10:3:1). Eight patients were receiving phenytoin, six carbamazepine, and four phenobarbital alone or in combination. The mean time from exposure to development of symptoms was 23.0 +/- 14.8 days. In addition to rash and fever (present in all patients by definition), other common features of AHS were lymphocytosis (71.4%), elevated erythrocyte sedimentation rate (64.3%), elevated aminotransferases (64.3%), lymphadenopathy (57.1%), eosinophilia (42.8%, coagulopathy (42.8%), leukocytosis (35.7%), leukopenia (35.7%), hyperbilirubinemia (35.7%), and nephritis (7.1%). All children recovered except one, who died from complications of liver failure. Clinical outcome was simimlar between children who received systemic steroid therapy (n=5) and those who did not. Antiepileptics producing AHS were discontinued in all patients. CONCLUSIONS: AHS can be fatal in children if not promptly recognized. Fever, rash, and hepatotoxicity should serve as presumptive evidence for AHS, which requires immediate discontinuation of an offending anticonvulsant.

Differential expression of Fas ligand in Th1 and Th2 cells is regulated by early growth response gene and NF-AT family members.

Inducible expression of Fas ligand (CD95 ligand) by activated T cells and the resulting apoptosis of CD95-bearing cells is a critical component of peripheral T cell homeostasis and cytotoxic effector mechanisms. Transcriptional control of the expression of Fas ligand has been attributed to a number of factors, including early growth response gene 2 (Egr2), Egr3, Sp1, and NF-AT, although a direct contribution of NF-AT is controversial. The present study confirms a role for Egr factors and indicates that NF-AT is essential for optimal expression of murine Fas ligand through a direct interaction with an NF-AT consensus element. The role of these factors was further defined by studying the differential expression of Fas ligand in Th1 and Th2 lines derived from DO11.10 TCR transgenic mice. EMSA analyses of a composite Egr/NF-AT site showed recruitment of Sp1 to this site in Th2 cells, but not in Th1 cells. Furthermore, gel-shift analyses demonstrated the binding of Egr1, 2, and 3 in Th2 cells and Egr1 and 2, but not Egr3 in Th1 cells at a known Egr site. Northern analysis corroborated the lack of Egr3 in Th1 cells. Differential usage of these transcription factors by Th1 and Th2 cells suggests a potential mechanism underlying the differential expression of Fas ligand by distinct T cell lineages.