The in vivo effects of PIXY321 therapy on human monocyte activity

In this report we describe the time-dependent effects of PIXY321 (a synthetic hybrid cytokine) treatment (500 and 750 micrograms/m2/day for 14 days) on six sarcoma patients. Blood was taken prior to PIXY321 injection (day 0), on days 1, 7, and 14 of treatment, and 7 days posttreatment (day 21). The number of isolated monocytes quadrupuled by day 7 and sustained a significant increase through day 14. There were significant increases in the percentage of circulating monocytes relative to total mononuclear cells on days 1 and 7 of therapy. There were no significant changes in monocyte cell surface antigens (15 checked), suggesting that the increase in monocyte numbers was not due to increased numbers of immature monocytes. The basal activity of the monocytes was not markedly altered during treatment; however, they were primed for significantly increased phorbol 12,13-dibutyrate-stimulated superoxide anion production and endotoxin-stimulated release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) on days of 1 and 7 of therapy. There was a significant increase of IL-1 beta mRNA levels (unstimulated cells) on days 1 and 7, but TNF-alpha mRNA levels increased significantly on day 1 only. Consistent with the increase in superoxide anion production, there were increases in monocyte protein kinase C (PKC) levels on all days of therapy. There was a significant increase in PKCII beta mRNA only on the first day of treatment. All significant changes in monocyte number and function produced by PIXY321 infusion were reversible, as there were no sustained effects on day 21 (7 days after therapy). These results indicate that the effects of PIXY321 may be mediated through up-regulation of PKC resulting in monocytes primed for increased functional activity in response to an appropriate second stimulus.     

Psychosocial status of children with diabetes in the first 2 years after diagnosis

OBJECTIVE: The purpose of this study was to determine the pattern of adjustment over time of a cohort of children with newly diagnosed diabetes compared with a cohort of peer-selected children without diabetes over the first 2 years after the diagnosis of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Children (n = 89 with IDDM, n = 53 without IDDM) ages 8-14 years were studied with the Children's Depression Inventory, State-Trait Anxiety Inventory for Children, Child and Adolescent Adjustment Profile, Self-Perception Profile for Children, and a general health scale. Initial data were collected within 6 weeks of the diagnosis of IDDM and at 3, 6, 12, and 24 months thereafter. RESULTS: There were no demographic differences between the two groups. Initially, children with diabetes were more depressed, more dependent, and more withdrawn than their peers. By 1 year postdiagnosis, there were no significant differences in psychosocial status between the two groups. By 2 years postdiagnosis, depression, dependency, and withdrawal were significantly higher in children with diabetes than in their peers without IDDM. Self-perceived competence remained similar between the two groups at all time points. CONCLUSIONS: After an initial period of adjustment, children with IDDM have equivalent psychosocial status to children without IDDM, but by 2 years after diagnosis, they have experienced twice the amount of depression and adjustment problems as their peers. Interventions should be aimed at this critical period between 1 and 2 years postdiagnosis.     

Growth and characterization of (111)B InGaAs/GaAs multi-quantum well PIN diode structures

High quality piezoelectric strained InGaAs/GaAs multi-quantum well structures on (111)B GaAs substrates have been grown by solid-source molecular beam epitaxy in a PIN configuration. 10K photoluminescence (PL) shows narrow peaks with widths as low as 3 meV for a 25-period structure while room temperature (RT) PL shows several higher order peaks, normally forbidden, indicating breaking of inversion symmetry by the piezoelectric field. Furthermore, both the 10K PL peak position and the form of the RT PL spectra depend on the number of quantum wells within the intrinsic region, suggesting that the electric-field distribution is altered thereby. Diodes fabricated from these structures had sharp avalanche breakdown voltages (V_bd) and leakage currents as low as 8 × 10⁻⁶ A/cm² at 0.95 V_bd, indicating quality as high as in (100) devices. On leave from: Department de Ingeniera Electronica, Universidad Politecnica de Madrid, Madrid, Spain.     

High pressure areas

The study highlighted the extent of occupational distress in a group of nurses in an NHS hospital trust. The levels of distress were similar across settings and similar to levels identified in current NHS-wide studies. Levels of work pressure and emotional exhaustion were higher than previous UK norms. High levels of distress were associated with younger age, high work pressure and low social support. For general mental well-being individual factors, such as satisfaction with social support, were more predictive than organisational factors. For work-specific distress, factors in the work environment, such as work pressure, patient contact and task orientation, were more important. Strategies for addressing the needs identified were reviewed and are now being implemented.     

Effect on cell kill of addition of multidrug resistance modifiers cyclosporin A and PSC 833 to cytotoxic agents in acute myeloid leukaemia

Multidrug resistance (MDR) mediated by the drug efflux pump P-glycoprotein (Pgp), may cause remission failure and relapse in patients with acute myeloid leukaemia (AML) by extruding cytotoxic agents such as anthracyclines from leukaemic cells thus allowing them to survive. Cell line data suggest that reversal of MDR is possible using modifying drugs such as cyclosporin A (CSA) and its analogue PSC 833. We have investigated the effects on cell kill of the addition of CSA and PSC 833 to daunorubicin, idarubicin, mitozantrone, etoposide and cytarabine in 52 fresh cell samples from AML patients using an MTT assay. Pgp status was determined by using monoclonal antibodies JSB-1 and MRK-16 and by assessment of rhodamine efflux. Although overall each cytotoxic-modifier combination produced significant improvements in cell kill compared to cytotoxic alone (P values ranged from P < 0.001 to P = 0.017), modifiers also produced significant cytotoxicity in their own right, and no consistent difference was seen between responses in Pgp-positive and negative groups. Up to one in three Pgp-positive samples failed to show any improvement in cell kill with the addition of CSA or PSC 833, possibly owing to co-expression of alternative resistance mechanisms not affected by the MDR modifiers. The best responses were seen when PSC 833 was added to idarubicin, with 7 out of 22 Pgp-positive cases (32%) showing five-fold improvements in cell kill or better compared to idarubicin alone. Comparison of equimolar concentrations of the two modifiers in the Pgp positive group failed to show a significant difference in cell kill, though PSC 833 was markedly superior to CSA in a minority of highly responsive samples which demonstrated clear evidence of MDR reversal. Our in vitro data suggest that MDR modifiers such as CSA and PSC 833 could play an important role in the therapy of AML and indicate the need for prospective randomised trials to assess their clinical efficacy.     

Psychological and emotional effects of the use of oral baclofen: a preliminary study

Spasticity is a common problem following spinal cord injury. The drug of choice to control spasms is baclofen. There would appear to be no reported studies which have evaluated the psychological and emotional effect of this drug. This preliminary study investigated a number of such effects, including depression, anxiety and general mood state. First, we examined 10 subjects before and during the administration of baclofen. They were then compared to a control group of 12 subjects. A second cohort of 12 subjects taking baclofen were compared to a control group of nine subjects at a specific time after injury. Results indicated that whilst some significant differences were found, suggesting an increase in fatigue with use of baclofen, no major adverse psychological effects were noted. The implications of these results were discussed and suggestions for further research were highlighted.     

Electric field driven addressing of ATPS droplets in microfluidic chips

The possibility of controlled droplet motion (droplet addressing) mediated by DC electric field in aqueous two-phase systems (ATPS) is here reported for the first time. Three ATPS of polyethylene glycol (PEG)/salt type, namely PEG/phosphate, PEG/sulphate, and PEG/carbonate, were selected for this study. We observed fast motion of salty droplets dispersed in PEG continuous phase induced by electric field of relative low strength. Hence, three fluidic systems with separated electrode chambers for the evaluation of electrophoretic mobilities and for addressing experiments were fabricated. Electrophoretic mobilities of salty droplets always exceeded the value of \(1\times 10^{-7}\, \hbox {m}^2\hbox {V}^{-1}\hbox {s}^{-1}\), which is about by one magnitude higher value than those typically measured in water–oil droplet systems. The electrophoretic mobilities in systems with free surface are the same or even smaller than in closed microfluidic structures, which is accounted mainly to the fact that a significant part of salty droplets is exposed to air and does not contribute to droplet forcing. Series of addressing and merging experiments in a microfluidic chip shows that DC electric field can be used as a powerful tool for smart manipulation of droplets in microfluidic systems with PEG/salt ATPS.     

Reusable Cellulose‐Based Hydrogel Sticker Film Applied as Gate Dielectric in Paper Electrolyte‐Gated Transistors

A new concept for reusable eco‐friendly hydrogel electrolytes based on cellulose is introduced. The reported electrolytes are designed and engineered through a simple, fast, low‐cost, and eco‐friendly dissolution method of microcrystalline cellulose at low temperature using an aqueous LiOH/urea solvent system. The cellulose solution is combined with carboxymethyl cellulose, followed by the regeneration and simultaneous ion incorporation. The produced free standing cellulose‐based electrolyte films exhibit interesting properties for application in flexible electrochemical devices, such as biosensors or electrolyte‐gated transistors (EGTs), because of their high specific capacitances (4–5 µF cm^?2), transparency, and flexibility. Indium–gallium–zinc‐oxide EGTs on glass with laminated cellulose‐based hydrogel electrolytes (CHEs) as the gate dielectric are produced presenting a low working voltage (<2 V), showing an on–off current ratio (I _on/off) of 10⁶, a subthreshold swing lower than 0.2 V dec^?1, and saturation mobility (μ_Sat) reaching 26 cm² V^?1 s^?1. The flexible CHE‐gated transistors on paper are also demonstrated, which operate at switching frequencies up to 100 Hz. Combining the flexibility of the EGTs on paper with the reusability of the developed CHEs is a breakthrough toward biodegradable advanced functional materials allied with disposable/recyclable and low‐cost electronic devices.     

Adsorption of Naphthol Green B on unburned carbon: 2-and 3-parameter linear and non-linear equilibrium modelling

The study deals with adsorption of Naphthol Green B on two unburned carbons and the parent coal,from which the UCs have been created in a fluidised-bed power station.Particular attention has been paid to the adsorption equilibrium modelling:experimental data has been analysed using 2-parameter(Langmuir,Freundlich) and3-parameter(Redlich-Peterson) isotherms — both linear and non-linear regressions have been used for the estimation of the isotherm parameters.In the case of both UCs,the Langmuir isotherm model provides the worst fit,whereas 2-parameter Freundlich and 3-parameter Redlich-Peterson models are both good,from which 3-parameter Redlich-Peterson isotherm provides slightly better results(despite the penalty used for the higher number of parameters).In the case of both UCs,the linear regression of Freundlich and Redlich-Peterson models provides good results(comparable with non-linear regressions).Unlike both UCs,the best fit of the experimental data from the adsorption on the coal has been achieved by the Langmuir isotherm model.The results based on the Freundlich or Redlich-Peterson model were(in this case) somewhat worse.