Assessing the socio-economic and demographic impact on health-related quality of life: evidence from Greece

Objectives:  The impact of socioeconomic status on health has been extensively studied and studies have shown that low socio-economic status is related to lower values of various health and quality-of-health measures. The aim of this study was to assess the influence of demographic and socio-economic factors on health- related quality of life (HRQoL). Methods:  A cross-sectional study was carried out in 2003 using a representative sample of a Greek general population (n = 1007, 18+ years old), living in Athens area. Multivariate stepwise linear regression analyses were performed to investigate the influence of socio-demographic and economic variables on HRQoL, measured by eight scales of the SF-36. Interaction effects between socioeconomic status (SES) and demographic variables were also performed Results:  Females and elderly people were associated with impaired HRQoL in all SF-36 scales. Disadvantaged SES i. e. primary education and low total household income was related to important decline in HRQoL and a similar relation was identified among men and women. Only the interaction effects between age and SES was statistically significant for some SF-36 scales. Multiple regression analyses produced models explaining significant portions of the variance in SF-36 scales, especially physical functioning. Conclusions:  The analysis presented here gives evidence of a relationship existing between SES and HRQoL similar to what has been found elsewhere. In order to protect people from the damaging effects of poverty in health it is important to formulate health promotion educational programs or to direct policies to empower the disposable income etc. Helping people in disadvantaged SES to achieve the good health that people in more advantaged SES attained would help to prevent the widening of health inequalities. Submitted: 05 May 2008; revised: 13 November 2008, 23 March 2009; accepted: 26 March 2009     

MitoExtra SuperGen

SuperGen Inc is developing a cyclodextrin-based reformulation of mitomycin C (MitoExtra) for the potential treatment of gastic, pancreatic, breast lung and colorectal cancers. In April 2002, the NDA was pending approval from the US FDA after a March 2002 filing of a final response including data from a phase II trial [447618]. MitoExtra is a proprietary reformulation of the approved anticancer drug mitomycin C. SuperGen's reformulation is based on technology designed to improve the handling characteristics and safety profile of mitomycin C and other anticancer drugs by enhancing the drug's stability in solution form and 'shielding' it at the injection site [205482]. In a phase II study in patients with advanced solid tumors, MitoExtra showed no evidence of diminished efficacy or unexpected toxicity [447618]. In April 2000, SuperGen' was issued US-06048845, protecting the company's proprietary Extra technology platform [363494].     

Antioxidant responses following active and passive smoking of tobacco and electronic cigarettes

Context: It has been indicated that acute active and passive tobacco cigarette smoking may cause changes on redox status balance that may result in significant pathologies. However, no study has evaluated the effects of active and passive e-cigarette smoking on redox status of consumers.

Objective: To examine the acute effects of active and passive e-cigarette and tobacco cigarette smoking on selected redox status markers.

Methods: Using a randomized single-blind crossover design, 30 participants (15 smokers and 15 nonsmokers) were exposed to three different experimental conditions. Smokers underwent a control session, an active tobacco cigarette smoking session (smoked 2 cigarettes within 30-min) and an active e-cigarette smoking session (smoked a pre-determined number of puffs within 30-min using a liquid with 11?ng/ml nicotine). Similarly, nonsmokers underwent a control session, a passive tobacco cigarette smoking session (exposure of 1?h to 23?±?1?ppm of CO in a 60?m³ environmental chamber) and a passive e-cigarette smoking session (exposure of 1?h to air enriched with pre- determined number of puffs in a 60?m³ environmental chamber). Total antioxidant capacity (TAC), catalase activity (CAT) and reduced glutathione (GSH) were assessed in participants’ blood prior to, immediately after, and 1-h post-exposure.

Results: TAC, CAT and GSH remained similar to baseline levels immediately after and 1-h-post exposure (p?>?0.05) in all trials.

Conclusions: Tobacco and e-cigarette smoking exposure do not acutely alter the response of the antioxidant system, neither under active nor passive smoking conditions. Overall, there is not distinction between tobacco and e-cigarette active and passive smoking effects on specific redox status indices.     

Multi-walled carbon nanotubes induce T lymphocyte apoptosis

Carbon nanotubes are a man-made form of carbon that did not exist in our environment until very recently. Due to their unique chemical, physical, optical, and magnetic properties, carbon nanotubes have found many uses in industrial products and in the field of nanotechnology, including in nanomedicine. However, very little is yet known about the toxicity of carbon nanotubes. Here, we compare the toxicity of pristine and oxidized multi-walled carbon nanotubes on human T cells and find that the latter are more toxic and induce massive loss of cell viability through programmed cell death at doses of 400 microg/ml, which corresponds to approximately 10 million carbon nanotubes per cell. Pristine, hydrophobic, carbon nanotubes were less toxic and a 10-fold lower concentration of either carbon nanotube type were not nearly as toxic. Our results suggest that carbon nanotubes indeed can be very toxic at sufficiently high concentrations and that careful toxicity studies need to be undertaken particularly in conjunction with nanomedical applications of carbon nanotubes.     

Alternative payment and care‐delivery models in oncology: A systematic review

Rising US health care costs have led to the creation of alternative payment and care‐delivery models designed to maximize outcomes and/or minimize costs through changes in reimbursement and care delivery. The impact of these interventions in cancer care is unclear. This review was undertaken to describe the landscape of new alternative payment and care‐delivery models in cancer care. In this systematic review, 22 alternative payment and/or care‐delivery models in cancer care were identified. These included 6 bundled payments, 4 accountable care organizations, 9 patient‐centered medical homes, and 3 other interventions. Only 12 interventions reported outcomes; the majority (n = 7; 58%) improved value, 4 had no impact, and 1 reduced value, but only initially. Heterogeneity of outcomes precluded a meta‐analysis. Despite the growth in alternative payment and delivery models in cancer, there is limited evidence to evaluate their efficacy. Cancer 2018. © 2018 American Cancer Society.     

Imaging immune surveillance by T cells and NK cells

Summary: As T cells and natural killer (NK) cells survey the surface of other cells, cognate receptors and ligands are commonly organized into distinct micrometer‐scale domains at the intercellular contact, creating an immune or immunological synapse (IS). We aim to address the still unanswered questions of how this organization of proteins aids immune surveillance and how these domains are biophysically constructed. Molecular mechanisms for the formation of the IS include a role for the cytoskeleton, segregation of proteins according to the size of their extracellular domains, and association of proteins with lipid rafts. Towards understanding the function of the IS, it is instructive to compare and contrast the supramolecular organization of proteins at the inhibitory and activating NK cell IS with that at the activating T cell IS. Finally, it is essential to develop new technologies for probing molecular recognition at cell surfaces. Imaging parameters other than fluorescence intensity, such as the lifetime of the fluorophore's excited state, could be used to report on protein environments.     

Cell surface organization of stress-inducible proteins ULBP and MICA that stimulate human NK cells and T cells via NKG2D

Cell surface proteins major histocompatibility complex (MHC) class I-related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein-tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells.     

From Drug Screening to Target Deconvolution: a Target-Based Drug Discovery Pipeline Using Leishmania Casein Kinase 1 Isoform 2 To Identify Compounds with Antileishmanial Activity

Existing therapies for leishmaniases present significant limitations, such as toxic side effects, and are rendered inefficient by parasite resistance. It is of utmost importance to develop novel drugs targeting Leishmania that take these two limitations into consideration. We thus chose a target-based approach using an exoprotein kinase, Leishmania casein kinase 1.2 (LmCK1.2) that was recently shown to be essential for intracellular parasite survival and infectivity. We developed a four-step pipeline to identify novel selective antileishmanial compounds. In step 1, we screened 5,018 compounds from kinase-biased libraries with Leishmania and mammalian CK1 in order to identify hit compounds and assess their specificity. For step 2, we selected 88 compounds among those with the lowest 50% inhibitory concentration to test their biological activity on host-free parasites using a resazurin reduction assay and on intramacrophagic amastigotes using a high content phenotypic assay. Only 75 compounds showed antileishmanial activity and were retained for step 3 to evaluate their toxicity against mouse macrophages and human cell lines. The four compounds that displayed a selectivity index above 10 were then assessed for their affinity to LmCK1.2 using a target deconvolution strategy in step 4. Finally, we retained two compounds, PP2 and compound 42, for which LmCK1.2 seems to be the primary target. Using this four-step pipeline, we identify from several thousand molecules, two lead compounds with a selective antileishmanial activity.     

Angiotensin II up-regulates CX3CR1 expression in THP-1 monocytes: impact on vascular inflammation and atherogenesis

The potential regulatory effect of angiotensins on circulating mononuclear cell activation and migration has not yet been thoroughly evaluated. Using flow cytometry we assessed the possible effect of angiotensin I and II on the expression of CX3CR1 and a single representative of each major chemokine family (CCR5 and CXCR4) in THP-1 monocytes, Jurcat T lymphocytes and primary monocytes—isolated from healthy donors. Fluorescence intensity and the rate of chemokine-positive cells was measured in naïve cells and cells treated with angiotensin I and II. Neither angiotensin I nor angiotensin II exhibited any effect on fluorescence intensity and the rate of CX3CR1-, CCR5- and CXCR4-positive cells in primary peripheral blood mononuclear cells and Jurkat T cells. However, angiotensin II significantly increased the rate of CX3CR1-positive THP-1 cells. This effect was not attenuated by the pre-incubation of THP-1 cells with the AT-1 receptor blocker losartan, suggesting that this was not an AT-1-mediated effect. Angiotensin I and II had no effect on fluorescence intensity and the rate of CCR5- and CXCR4-positive THP-1 cells. In conclusion, angiotensin II increases the rate of CX3CR1-positive THP-1 cells. By extrapolating this in vitro observation to disease mechanisms, we speculate that angiotensin II induces up-regulation of CX3CR1 and promotes firm adhesion of circulation CX3CR1-positive monocytes on CX3CL1 expressing endothelial cells inducing vascular inflammation and atherogenesis.     

Novel methodology to characterize electromagnetic exposure of the brain

Due to the greatly non-uniform field distribution induced in brain tissues by radio frequency electromagnetic sources, the exposure of anatomical and functional regions of the brain may be a key issue in interpreting laboratory findings and epidemiological studies concerning endpoints related to the central nervous system. This paper introduces the Talairach atlas in characterization of the electromagnetic exposure of the brain. A hierarchical labeling scheme is mapped onto high-resolution human models. This procedure is fully automatic and allows identification of over a thousand different sites all over the brain. The electromagnetic absorption can then be extracted and interpreted in every region or combination of regions in the brain, depending on the characterization goals. The application examples show how this methodology enhances the dosimetry assessment of the brain based on results obtained by either finite difference time domain simulations or measurements delivered by test compliance dosimetry systems. Applications include, among others, the detailed dosimetric analysis of the exposure of the brain during cell phone use, improved design of exposure setups for human studies or medical diagnostic and therapeutic devices using electromagnetic fields or ultrasound.