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Self-administration of antibiotics using elastomeric pumps has become the most frequently used treatment modality at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne. However, it remains unknown how comfortable patients feel using this mode of treatment. A questionnaire was offered to all patients treated at the OPAT unit between June 2014 and December 2015. The questionnaire was distributed to 188 patients and 112 questionnaires were returned. Seventy-one patients were treated by self-administration, 21 attended the OPAT unit on a daily basis, and 20 received their antibiotics from home-care nurses. Overall, 83-97% of the patients gave the highest possible scores to the four items evaluating their global satisfaction. Subjects treated by self-administration gave a significantly better rating to 6 of the 17 semi-quantitative questions than the patients treated at the OPAT unit or by home-care nurses. There was no item which was more poorly rated by patients treated by self-administered OPAT than by the other treatment groups. In conclusion satisfaction was high in all patients treated by OPAT. The particularly high satisfaction of patients treated by self-administration of antibiotics with elastomeric pumps suggests that a significant number of patients are happy to take over some responsibility for their treatment. Patients' capacity to appropriate their care themselves should not be underestimated by health care professionals. [ABSTRACT FROM AUTHOR]

Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment, but no formal OPAT unit existed in Switzerland until recently. In December 2013 an OPAT unit was established at Lausanne University Hospital. We review here the experience of this new OPAT unit after 18 months of activity. Patient characteristics, clinical activities and outcomes were recorded prospectively. Need and acceptance was evaluated as number of OPAT courses administered and number of patients refusing OPAT. Safety and efficacy were evaluated as: (1) adverse events linked to antimicrobials and catheters, (2) re-admission to hospital, (3) rate of treatment failures and (4) mortality. Over 18 months, 179 courses of OPAT were administered. Acceptance was high with only four patients refusing OPAT. Urinary tract infections with resistant bacteria and musculoskeletal infections were the most common diagnoses. Self-administration of antibiotics using elastomeric pumps became rapidly the most frequently used approach. Sixteen patients presented with adverse events linked to antimicrobials and catheters. OPAT-related readmissions occurred in nine patients. The overall cure rate was 94 %. This study shows that OPAT is very well accepted by patients and medical staff, even in a setting which has not used this type of treatment approach until now. Self-administration using elastomeric pumps proved to be particularly useful, safe and efficient. OPAT offers a good alternative to hospitalisation for patients presenting with infections due to resistant bacteria that cannot be treated orally anymore and for difficult to treat infections. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transition (EMT) is closely linked to conversion of early-stage tumours into invasive malignancies. Many signalling pathways are involved in EMT, but the key regulatory kinases in this important process have not been clearly identified. Protein kinase CK2 is a multi-subunit protein kinase, which, when overexpressed, has been linked to disease progression and poor prognosis in various cancers. Specifically, overexpression of CK2α in human breast cancers is correlated with metastatic risk. In this article, we show that an imbalance of CK2 subunits reflected by a decrease in the CK2β regulatory subunit in a subset of breast tumour samples is correlated with induction of EMT-related markers. CK2β-depleted epithelial cells displayed EMT-like morphological changes, enhanced migration, and anchorage-independent growth, all of which require Snail1 induction. In epithelial cells, Snail1 stability is negatively regulated by CK2 and GSK3β through synergistic hierarchal phosphorylation. This process depends strongly on CK2β, thus confirming that CK2 functions upstream of Snail1. In primary breast tumours, CK2β underexpression also correlates strongly with expression of EMT markers, emphasizing the link between asymmetric expression of CK2 subunits and EMT in vivo. Our results therefore highlight the importance of CK2β in controlling epithelial cell plasticity. They show that CK2 holoenzyme activity is essential to suppress EMT, and that it contributes to maintaining a normal epithelial morphology. This study also suggests that unbalanced expression of CK2 subunits may drive EMT, thereby contributing to tumour progression. [ABSTRACT FROM AUTHOR]

Protein kinase CK2 targets a vast array of substrates located in a number of cellular compartments, making the challenge of discriminating among these substrates a daunting task. However, as a signaling protein, CK2 could be targeted to different cellular compartments in response to various stress stimuli such as heat shock, UV irradiation, hypoxia, DNA damage and viral infections. This review will be focused on the evidence that the dynamic association of CK2 subunits and the substrate-dependent subcellular targeting of the enzyme are a likely point of regulation in response to a variety of signaling events. We propose that in addition to enzymatic substrate recognition, regulated CK2 localization to specific compartments should help to provide the exquisite specificity required for robust signal transduction. [ABSTRACT FROM AUTHOR]

Based on the perturbation of its expression in human cancers and on its involvement in transformation and tumorigenesis, protein kinase CK2 has recently attracted attention as a potential therapeutic target. To assess the value of CK2 as a target for antiproliferative strategies, we have initiated a program aiming to develop inhibitors targeting specifically the regulatory CK2β subunit. Here, we use a two-hybrid approach to isolate from combinatorial libraries, peptide aptamers that specifically interact with CK2β. One of these (P1), which has significant sequence homology to the cytomegalovirus IE2 protein, binds with high affinity to the N-terminal domain of CK2β without disrupting the formation of the CK2 holoenzyme. Expression of green fluorescent protein (GFP)-P1 in different mammalian cell lines activates p53 phosphorylation on serine 15, induces an upregulation of p21 and the release of the Cyt-C and apoptosis-inducing factor proapoptotic proteins triggering caspase-dependent and caspase-independent apoptosis. GFP-P1-induced apoptosis is associated with a p53-dependent pathway as cell death was abrogated in p53 knocked out cells. In summary, our data show that genetically selected peptide aptamers that specifically target CK2β can induce apoptosis in mammalian cells through the recruitment of a p53-dependent apoptosis pathway. They also emphasize the critical role of CK2β for cell survival and might allow the design of novel proapoptotic agents targeting this protein.Oncogene (2006) 25, 7343–7353. doi:10.1038/sj.onc.1209722; published online 5 June 2006 [ABSTRACT FROM AUTHOR]

In a previous report, we documented that a major portion of the nuclear protein kinase CK2α (CK2α) subunit does not form heterooligomeric structures with the β subunit, but it binds tightly to nuclear structures in an epithelial Chironomus cell line [1]. We report here that the CK2α, but not β, subunit is co-localized with productively transcribing RNA polymerase II (pol II) on polytene chromosomes of Chironomus salivary gland cells. Likewise, the RAP74 subunit of TFIIF, a potential substrate for CK2, is co-localized with pol II. The occupancies of chromosomes with the CK2α and RAP74 subunits are sensitive to DRB, an inhibitor of pol II-based transcription and the activity of CK2 and pol II carboxyl-terminal kinases. DRB alters the chromosomal distribution of the CK2α and RAP74 subunits: there is a time-dependent clearance from the chromosomes of CK2α and RAP74 subunits, which coincides in time the completion and release of preinitiated transcripts after addition of DRB. The results suggest that both the CK2α and RAP74 subunits travel with the elongating pol II molecules along the DNA template during the entire transcription cycle. No detectable re-association of CK2α and RAP74 with the promoters takes, however, place after the completion of the preinitiated transcripts in the presence of DRB. In contrast, the binding of hypophosporylated pol II and TFIIH to the active gene loci is not abolished by the DRB regimen. Our data are consistent with the possibility that in living Chironomus salivary gland cells, DRB interferes with the recruitment of TFIIF, but not of TFIIH, to the promoter by interference with the activity of the CK2α subunit enzyme and phosphorylation of RAP74 and thereby DRB blocks transcription initiation. [ABSTRACT FROM AUTHOR]

The inclusive production of γ's and π's in K p-interactions at 32 GeV/c is studied. About 30.000 γ's coming from a Mirabelle bubble chamber experiment with a sensitivity of 6.5 ev/μb have been used for the analysis. Inclusive and topological cross sections of γ's are measured. The γ invariant differential distributions and their scaling properties are investigated. The inclusive cross section of π-production is determined and the π invariant differential distributions are evaluated and compared to those of π. [ABSTRACT FROM AUTHOR]

Longitudinal correlations between pions inclusively produced in the target and beam fragmentation regions are studied in a K p bubble chamber experiment at 32 GeV/c with a sensitivity of about 6.7 ev/μb. It was found that the $${{\tilde x_2 = x_2 } \mathord{\left/ {\vphantom {{\tilde x_2 = x_2 } {(1 - \left| {x_1 } \right|)}}} \right. \kern-\nulldelimiterspace} {(1 - \left| {x_1 } \right|)}}$$ distributions of charged pions with momentum fraction in the proton hemisphere with respect to a charged 'trigger' pion with momentum fraction x do not show scaling, that those of the associated π/π do not compare to K p interactions and give indications for quark annihilation. The invariant two- and three pion longitudinal C.M. distributions show significant deviations from the naive quark recombination picture. Distinct long-range correlations observed between π s from the proton fragmentation region and π s from the K fragmentation region could imply contributions from quark exchange or quark annihilation mechanisms in K p interactions at 32 GeV/c. [ABSTRACT FROM AUTHOR]

New data on the inclusive production of the non-strange resonances ϱ(770), ω(783), ϕ(1020) and f(1270) in K p interactions at 32 GeV/c are presented. The inclusive production cross sections are equal to (4.32±0.72) mb, (3.7±1.4) mb, (0.65±0.10) mb and (0.91±0.35) mb respectively. Estimates of the topological cross sections are also obtained. The invariant and non-invariant x-distributions for the vector mesons ϱ and ϕ indicate the prevalence of forward resonance production in the c.m. system. For the tensor f-meson the rapidity and x-distributions are presented. The t′-distributions for ϱ, ϕ, and f have exponential slopes of 0.6±0.1 GeV, 1.2±0.2 GeV, and 0.8±0.5 GeV respectively. The exponential slope of p-distribution of the f-meson is equal to (2.3±0.5) GeV. [ABSTRACT FROM AUTHOR]

The inclusive production of neutral kaons in K p interactions at 32 GeV/ c is studied in final states with one, two and three strange particles ( K or Λ). Inclusive and topological cross sections are obtained and their energy dependence discussed by comparison with lower energy data. The invariant differential cross sections of neutral kaons are studied as a function of Feynman x, the c.m. rapidity and the transverse momentum, and a comparison is made with data at 14.3 GeV/ c. Invariant x-distributions are obtained separately for 'indirect' neutral kaons from $$\bar K*(890)$$ decays and for 'prompt' kaons. We also discuss the possibility of connecting quark structure functions with hadron fragmentation spectra at this c.m. energy $$\sqrt s \simeq 8 GeV$$ . [ABSTRACT FROM AUTHOR]

We present final results on the inclusive production of the $$\bar K^{*0} (890)$$ , K(890), K(890), K(890), K(1420), and $$\bar K^{*0} (1420)$$ resonances in K p interactions at 32 GeV/ c. Total cross sections and invariant x-distributions are determined. Inclusive cross sections of $$\bar K^{*\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{o} } (890)$$ amount to ≃4 mb each, of $$\bar K^{*\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{o} } (1420)$$ to ≃1 mb and of K(890) to ≃0.8 mb. These values are in agreement with additive quark model predictions. All strangeness S=−1 resonances are predominantly produced in the forward hemisphere, the tensor mesons being more peripherally produced than the vector ones. The $$\bar K^{*\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{o} } (890)$$ density matrix elements and t-distributions are obtained. The unnatural spin-parity exchange contribution to inclusive $$\bar K^{*\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{o} } (890)$$ production amounts to ≳60% at | t|<0.4 GeV and decreases with increasing | t|. Whenever relevant, a comparison is also made with available data at other energies. [ABSTRACT FROM AUTHOR]

Total and semi-inclusive cross sections, longitudinal and transverse momentum distributions and spin density matrix elements of the K(892) and K(892) produced in the inclusive reactions K p→ K(892)+ X and K p→ K(892)+ X at 32 GeV/ c are studied in detail. The inclusive spectra of the K(892) and their decay products are compared with pion and neutral kaon production. The K(892) and K(892) are dominantly produced by kaon fragmentation processes. The dependence of average transverse momentum < p> vs. x for resonances has been investigated for the first time. [ABSTRACT FROM AUTHOR]

Final data on topological cross sections are presented. Inclusive single particle distributions for the reactions K p→ π X at 32 GeV/ c are discussed and compared with data at lower energies. Early scaling in the fragmentation regions is confirmed, while cross sections in th central region continue to rise with energy even faster than in pp interactions. The x-and p-dependence of the π/π ratio in K p interactions is discussed and a comparison of reactions K p→ π X and K p→ π X at 32 GeV/ c is made in the context of constituent models. We also present transverse momentum distributions, show prominent seagull effects and study how they are influenced by resonance production. [ABSTRACT FROM AUTHOR]

Antilambda production is studied in K p interactions at 32 GeV/ c. Both total and differential cross sections are presented. The inclusive $$\bar \Lambda $$ production cross section amounts to 109±7 μb. A remarkable energy dependence is observed, σ( $$\bar \Lambda $$ ) increasing by a factor of four between 14.3 and 32 GeV/ c. The p distribution exhibits an exponential fall-off with a slope of 3.3±0.2 (GeV/ c). Most of the $$\bar \Lambda $$ 's are emitted in the forward hemisphere. The invariant x distribution increases between 14.3 and 32 GeV/ c. Data are presented for $$\bar \Lambda $$ production in K p→Λ $$\bar \Lambda $$ + X K p→ $$\bar \Lambda $$ K+ X, and K p→ $$\bar \Lambda $$ p+ X. [ABSTRACT FROM AUTHOR]

Data on Λ and $$\bar \Lambda $$ polarization in K p interactions at 32 GeV/c are presented. A comparison is made between the results of these two experiments as well as with the data at lower energies. The contribution of the different production mechanisms to the Λ( $$\bar \Lambda $$ ) polarization are discussed. [ABSTRACT FROM AUTHOR]