Determinants of out-of-hours service users' potentially inappropriate referral or non-referral to an emergency department: a retrospective cohort study in a local health authority, Veneto Region, Italy

BACKGROUND: A growing presence of inappropriate patients has been recognised as one of the main factors influencing emergency department (ED) overcrowding, which is a very widespread problem all over the world. On the other hand, out-of-hours (OOH) physicians must avoid delaying the diagnostic and therapeutic course of patients with urgent medical conditions. The aim of this study was to analyse the appropriateness of patient management by OOH services, in terms of their potentially inappropriate referral or non-referral of non-emergency cases to the ED. METHODS: This was an observational retrospective cohort study based on data collected in 2011 by the local health authority No. 4 in the Veneto Region (Italy). After distinguishing between patients contacting the OOH service who were or were not referred to the ED, and checking for patients actually presenting to the ED within 24\u2005hours thereafter, these patients' medical management was judged as potentially appropriate or inappropriate. RESULTS: The analysis considered 22\u2005662 OOH service contacts recorded in 2011. The cases of potentially inappropriate non-referral to the ED were 392 (1.7% of all contacts), as opposed to 1207 potentially inappropriate referrals (5.3% of all contacts). Age, nationality, type of disease and type of intervention by the OOH service were the main variables associated with the appropriateness of patient management. CONCLUSIONS: These findings may be useful for pinpointing the factors associated with a potentially inappropriate patient management by OOH services and thus contribute to improving the deployment of healthcare and the quality of care delivered by OOH services

Comparative analysis of the human hepatic and adipose tissue transcriptomes during LPS-induced inflammation leads to the identification of differential biological pathways and candidate biomarkers

<p>Abstract</p> <p>Background</p> <p>Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. We induced inflammation in adipose and liver tissues <it>in vitro </it>in order to mimic inflammation <it>in vivo </it>with the aim to identify tissue-specific processes implicated in IR and to find biomarkers indicative for tissue-specific IR.</p> <p>Methods</p> <p>Human adipose and liver tissues were cultured in the absence or presence of LPS and DNA Microarray Technology was applied for their transcriptome analysis. Gene Ontology (GO), gene functional analysis, and prediction of genes encoding for secretome were performed using publicly available bioinformatics tools (DAVID, STRING, SecretomeP). The transcriptome data were validated by proteomics analysis of the inflamed adipose tissue secretome.</p> <p>Results</p> <p>LPS treatment significantly affected 667 and 483 genes in adipose and liver tissues respectively. The GO analysis revealed that during inflammation adipose tissue, compared to liver tissue, had more significantly upregulated genes, GO terms, and functional clusters related to inflammation and angiogenesis. The secretome prediction led to identification of 399 and 236 genes in adipose and liver tissue respectively. The secretomes of both tissues shared 66 genes and the remaining genes were the differential candidate biomarkers indicative for inflamed adipose or liver tissue. The transcriptome data of the inflamed adipose tissue secretome showed excellent correlation with the proteomics data.</p> <p>Conclusions</p> <p>The higher number of altered proinflammatory genes, GO processes, and genes encoding for secretome during inflammation in adipose tissue compared to liver tissue, suggests that adipose tissue is the major organ contributing to the development of systemic inflammation observed in IR. The identified tissue-specific functional clusters and biomarkers might be used in a strategy for the development of tissue-targeted treatment of insulin resistance in patients.</p

Role of Myosin Va in the Plasticity of the Vertebrate Neuromuscular Junction In Vivo

Background: Myosin Va is a motor protein involved in vesicular transport and its absence leads to movement disorders in humans (Griscelli and Elejalde syndromes) and rodents (e.g. dilute lethal phenotype in mice). We examined the role of myosin Va in the postsynaptic plasticity of the vertebrate neuromuscular junction (NMJ). Methodology/Principal Findings: Dilute lethal mice showed a good correlation between the propensity for seizures, and fragmentation and size reduction of NMJs. In an aneural C2C12 myoblast cell culture, expression of a dominant-negative fragment of myosin Va led to the accumulation of punctate structures containing the NMJ marker protein, rapsyn-GFP, in perinuclear clusters. In mouse hindlimb muscle, endogenous myosin Va co-precipitated with surface-exposed or internalised acetylcholine receptors and was markedly enriched in close proximity to the NMJ upon immunofluorescence. In vivo microscopy of exogenous full length myosin Va as well as a cargo-binding fragment of myosin Va showed localisation to the NMJ in wildtype mouse muscles. Furthermore, local interference with myosin Va function in live wildtype mouse muscles led to fragmentation and size reduction of NMJs, exclusion of rapsyn-GFP from NMJs, reduced persistence of acetylcholine receptors in NMJs and an increased amount of punctate structures bearing internalised NMJ proteins. Conclusions/Significance: In summary, our data show a crucial role of myosin Va for the plasticity of live vertebrate neuromuscular junctions and suggest its involvement in the recycling of internalised acetylcholine receptors back to th

A single point mutation (E166Q) prevents dicyclohexylcarbodiimide binding to the photosystem II subunit CP29

Energy-dependent quenching of chlorophyll fluorescence (qE) reflects the action of a powerful mechanism of protection from photoinhibition in which the low pH in the chloroplast lumen induces dissipation of excess excitation energy. Dicyclohexylcarbodiimide (DCCD), a protein-modifying agent, is a powerful inhibitor of qE and has been shown to react with acidic residues, in a hydrophobic environment, involved in proton translocation. The CP29 subunit of photosystem II has been proposed to be the site of qE quenching and shown to bind DCCD. We have hypothesised, on the basis of the CP29 protein sequence and of the structure of light-harvesting complex II protein, that glutamic acid 166 is the DCCD binding site. In this study, we have produced recombinant proteins either with wild-type sequence or carrying a mutation on the 166 position. We show that the mutant protein does not bind DCCD. This identifies E166 as the site whose protonation may lead to a conformational change triggering qE

Socio-demographic factors and processes associated with stages of change for smoking cessation in pregnant versus non-pregnant women.

BACKGROUND: The tobacco control community assumes that the most effective interventions are personalized. Nevertheless, little attention is paid to understanding differences between pregnant and non-pregnant European women in terms of the social factors that influence tobacco use and the processes of change used to quit smoking. METHODS: The study consecutively enrolled 177 pregnant women who acknowledged smoking the year before pregnancy and 177 non-pregnant women who acknowledged smoking the year before their clinic visit for a Pap test. RESULTS: With respect to socio-demographic factors, the stages of change in pregnant women were associated with level of education, marital status, and the presence of roommates, partners and friends who smoke. In pregnant women, there was no statistically significant difference in the processes used to stop smoking among the stages of change. Furthermore, behavioral processes were higher in non-pregnant women than in pregnant women, and the difference was statistically significant in the advanced stages of behavioral change. Both pregnant and non-pregnant women showed higher levels of acceptance towards smoking in the earlier stages of change, but the acceptability of smoking in the pre-contemplative stage was higher in non-pregnant women. Greater craving was detected in non-pregnant vs. pregnant women at all stages and reached a statistically significant level at the pre-contemplative stage. CONCLUSION: Pregnancy is a favorable time to stop smoking since pregnant women are more likely to be in an advanced stage of behavioral change. Pregnant and non-pregnant women are distinct populations in the types and processes of change involved in smoking cessation. The intervention programs to promote smoking cessation and prevent relapses will need to take these differences into account

A small-scale pilot plant using an oxygen-reducing gas-diffusion electrode for hydrogen peroxide electrosynthesis

A pilot plant for electro-generation of hydrogen peroxide using an oxygen-reducing gas-diffusion electrode (GDE) was built and a mathematical model was developed to simulate the overall system. The electrode was made of a web coated with layers of VULCAN XC-72 Carbon catalyst on both sides of the assembly and a coating of SAB (Shawinigan Acetylene Black) on the gas-side. Electrolyses were carried out in galvanostatic mode, using catholyte consisting of 0.07 M NaCl solution, pH 2.7 and adopting a batch recycle mode of operation. Mathematical analysis was based on a three-phase model, and simulated the evolution of hydrogen peroxide concentration profiles in liquid-filled pores. Various models were developed to represent the behaviour of the cathode compartment in the electrochemical cell. The result is a tool which shows how hydrodynamics affect the performance of the overall system. Hydrogen peroxide production achieved during electrolysis can be calculated by means of this tool. Comparison of numerical simulations against experimental data validated the model developed in this study

Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia.

According to experimental models suggesting that overproduction of oxygen free-radicals may occur when the electron transport in the respiratory chain is impaired, we searched for in vivo biological markers of oxidative stress in 11 patients affected by histologically proven mitochondrial myopathy with progressive external ophthalmoplegia (PEO) and partial cytochrome c oxidase deficiency in muscle fibres. Six of the patients carried large-scale deletions of mitochondrial DNA. Biochemical assays included the determination of plasma and erythrocyte reduced glutathione (GSH) concentration, plasma malondialdehyde, fluorescent adducts of aldehydes with plasma proteins, and serum level of lipid peroxides. In patients with PEO the mean values of lipid peroxides and of the fluorescent adducts of aldehydes with plasma proteins were significantly higher with respect to normal controls, while the mean values of plasma and erythrocyte GSH concentration were significantly lower. The reported data indicate an increase of lipid peroxidation indexes along with the reduction of one of the most important antioxidant systems and suggest the hypothesis that overproduction of reduced oxygen species might be an adjunctive cause of cell damage in mitochondrial myopathies and encephalomyopathies associated with defects of oxidative phosphorylation

Stimulation of P2 receptors causes release of IL-1\u3b2-loaded microvesicles from human dendritic cells1

Dendritic cells (DCs) are professional antigen-presenting cells that initiate the immune response by activating T lymphocytes. DCs express plasma membrane receptors for extracellular nucleotides named P2 receptors (P2Rs). Stimulation of P2Rs in these cells is known to cause chemotaxis, cytokine release, and cell death and to modulate LPS-dependent differentiation. Here we show that stimulation of the P2X(7) receptor subtype (P2X(7)R) causes fast microvesicle shedding from DC plasma membrane. Vesicle release occurs from both immature and mature DCs; however, only vesicles from mature DCs, due to their previous exposure to LPS, contain IL-1beta. Microvesicles, whether from immature or mature DCs, also contain caspase-1 and -3 and cathepsin D. They also express the P2X(7)R in addition to other P2Rs and known markers of immune cells such as major histocompatibility complex II (MHC II) and CD39. Activation of the P2X(7)R by extracellular ATP causes IL-1beta release from the vesicle lumen. Previous studies demonstrated that high extracellular K(+) inhibits IL-1beta processing and release; here we show that high ionic strength reduces microvesicle shedding when compared with a low ionic strength medium but strongly increases microvesicle IL-1beta loading