Patients' perspectives on high-tech home care: a qualitative inquiry into the user-friendliness of four technologies

BACKGROUND: The delivery of technology-enhanced home care is growing in most industrialized countries. The objective of our study was to document, from the patient's perspective, how the level of user-friendliness of medical technology influences its integration into the private and social lives of patients. Understanding what makes a technology user-friendly should help improve the design of home care services. METHODS: Four home care interventions that are frequently used and vary in their technical and clinical features were selected: Antibiotic intravenous therapy, parenteral nutrition, peritoneal dialysis and oxygen therapy. Our qualitative study relied on the triangulation of three sources of data: 1) interviews with patients (n = 16); 2) interviews with carers (n = 6); and 3) direct observation of nursing visits of a different set of patients (n = 16). Participants of varying socioeconomic status were recruited through primary care organizations and hospitals that deliver home care within 100 km of Montreal, the largest urban area in the province of Quebec, Canada. RESULTS: The four interventions have both a negative and positive effect on patients' lives. These technologies were rarely perceived as user-friendly, and user-acceptance was closely linked to user-competence. Compared with acute I.V. patients, who tended to be passive, chronic patients seemed keener to master technical aspects. While some of the technical and human barriers were managed well in the home setting, engaging in the social world was more problematic. Most patients found it difficult to maintain a regular job because of the high frequency of treatment, while some carers found their autonomy and social lives restricted. Patients also tended to withdraw from social activities because of social stigmatization and technical barriers. CONCLUSIONS: While technology contributes to improving the patients' health, it also imposes significant constraints on their lives. Policies aimed at developing home care must clearly integrate principles and resources supporting the appropriate use of technology. Close monitoring of patients should be part of all technology-enhanced home care programs

Biological Effects of a De Novo Designed Myxoma Virus Peptide Analogue: Evaluation of Cytotoxicity on Tumor Cells

Not availabl

Structural and Functional Characterization of Mature Forms of Metalloprotease E495 from Arctic Sea-Ice Bacterium Pseudoalteromonas sp. SM495

E495 is the most abundant protease secreted by the Arctic sea-ice bacterium Pseudoalteromonas sp. SM495. As a thermolysin family metalloprotease, E495 was found to have multiple active forms in the culture of strain SM495. E495-M (containing only the catalytic domain) and E495-M-C1 (containing the catalytic domain and one PPC domain) were two stable mature forms, and E495-M-C1-C2 (containing the catalytic domain and two PPC domains) might be an intermediate. Compared to E495-M, E495-M-C1 had similar affinity and catalytic efficiency to oligopeptides, but higher affinity and catalytic efficiency to proteins. The PPC domains from E495 were expressed as GST-fused proteins. Both of the recombinant PPC domains were shown to have binding ability to proteins C-phycocyanin and casein, and domain PPC1 had higher affinity to C-phycocyanin than domain PPC2. These results indicated that the domain PPC1 in E495-M-C1 could be helpful in binding protein substrate, and therefore, improving the catalytic efficiency. Site-directed mutagenesis on the PPC domains showed that the conserved polar and aromatic residues, D26, D28, Y30, Y/W65, in the PPC domains played key roles in protein binding. Our study may shed light on the mechanism of organic nitrogen degradation in the Arctic sea ice

The Two-Domain LysX Protein of Mycobacterium tuberculosis Is Required for Production of Lysinylated Phosphatidylglycerol and Resistance to Cationic Antimicrobial Peptides

The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside derivatives, in addition to a single basic species, phosphatidylethanolamine. Here we demonstrate that an additional basic PL, lysinylated PG (L-PG), is a component of the PLs of Mtb H37Rv and that the lysX gene encoding the two-domain lysyl-transferase (mprF)-lysyl-tRNA synthetase (lysU) protein is responsible for L-PG production. The Mtb lysX mutant is sensitive to cationic antibiotics and peptides, shows increased association with lysosome-associated membrane protein–positive vesicles, and it exhibits altered membrane potential compared to wild type. A lysX complementing strain expressing the intact lysX gene, but not one expressing mprF alone, restored the production of L-PG and rescued the lysX mutant phenotypes, indicating that the expression of both proteins is required for LysX function. The lysX mutant also showed defective growth in mouse and guinea pig lungs and showed reduced pathology relative to wild type, indicating that LysX activity is required for full virulence. Together, our results suggest that LysX-mediated production of L-PG is necessary for the maintenance of optimal membrane integrity and for survival of the pathogen upon infection

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs

Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Stress, anxiety and depression can cause complex physiological and neuroendocrine changes, resulting in increased level of stress related hormone catecholamine, which may constitute a primary mechanism by which physiological factors impact gene expression in tumors. In the present study, we investigated the effects of catecholamine stimulation on MMP-7 expression in gastric cancer cells and elucidated the molecular mechanisms of the up-regulation of MMP-7 level by catecholamine through an adrenergic signaling pathway.</p> <p>Results</p> <p>Increased MMP-7 expression was identified at both mRNA and protein levels in the gastric cancer cells in response to isoproterenol stimulation. β2-AR antigonist effectively abrogated isoproterenol-induced MMP-7 expression. The activation of STAT3 and AP-1 was prominently induced by isoproterenol stimulation and AP-1 displayed a greater efficacy than STAT3 in isoproterenol-induced MMP-7 expression. Mutagenesis of three STAT3 binding sites in MMP-7 promoter failed to repress the transactivation of MMP-7 promoter and silencing STAT3 expression was not effective in preventing isoproterenol-induced MMP-7 expression. However, isoproterenol-induced MMP-7 promoter activities were completely disappeared when the AP-1 site was mutated. STAT3 and c-Jun could physically interact and bind to the AP-1 site, implicating that the interplay of both transcriptional factors on the AP-1 site is responsible for isoproterenol-stimulated MMP-7 expression in gastric cancer cells. The expression of MMP-7 in gastric cancer tissues was found to be at the site where β2-AR was overexpressed and the levels of MMP-7 and β2-AR were the highest in the metastatic locus of gastric cancer.</p> <p>Conclusions</p> <p>Up-regulation of MMP-7 expression through β2-AR-mediated signaling pathway is involved in invasion and metastasis of gastric cancer.</p

Reverse Effect of Mammalian Hypocalcemic Cortisol in Fish: Cortisol Stimulates Ca2+ Uptake via Glucocorticoid Receptor-Mediated Vitamin D3 Metabolism

Cortisol was reported to downregulate body-fluid Ca2+ levels in mammals but was proposed to show hypercalcemic effects in teleostean fish. Fish, unlike terrestrial vertebrates, obtain Ca2+ from the environment mainly via the gills and skin rather than by dietary means, and have to regulate the Ca2+ uptake functions to cope with fluctuating Ca2+ levels in aquatic environments. Cortisol was previously found to regulate Ca2+ uptake in fish; however, the molecular mechanism behind this is largely unclear. Zebrafish were used as a model to explore this issue. Acclimation to low-Ca2+ fresh water stimulated Ca2+ influx and expression of epithelial calcium channel (ecac), 11β-hydroxylase and the glucocorticoid receptor (gr). Exogenous cortisol increased Ca2+ influx and the expressions of ecac and hydroxysteroid 11-beta dehydrogenase 2 (hsd11b2), but downregulated 11β-hydroxylase and the gr with no effects on other Ca2+ transporters or the mineralocorticoid receptor (mr). Morpholino knockdown of the GR, but not the MR, was found to impair zebrafish Ca2+ uptake function by inhibiting the ecac expression. To further explore the regulatory mechanism of cortisol in Ca2+ uptake, the involvement of vitamin D3 was analyzed. Cortisol stimulated expressions of vitamin D-25hydroxylase (cyp27a1), cyp27a1 like (cyp27a1l), 1α-OHase (cyp27b1) at 3 dpf through GR, the first time to demonstrate the relationship between cortisol and vitamin D3 in fish. In conclusion, cortisol stimulates ecac expression to enhance Ca2+ uptake functions, and this control pathway is suggested to be mediated by the GR. Lastly, cortisol also could mediate vitamin D3 signaling to stimulate Ca2+ uptake in zebrafish