Inpatient costs, mortality and 30-day re-admission in patients with central-line-associated bloodstream infections

AbstractPrevious work has suggested that central-line-associated bloodstream infection (CLABSI) is associated with increased costs and risk of mortality; however, no studies have looked at both total and variable costs, and information on outcomes outside of the intensive-care unit (ICU) is sparse. The aim of this study was to determine the excess in-hospital mortality and costs attributable to CLABSI in ICU and non-ICU patients. We conducted a retrospective cohort and cost-of-illness study from the hospital perspective of 398 patients at a tertiary-care academic medical centre from 1 January 2008 to 31 December 2010. All CLABSI patients and a simple random sample drawn from a list of all central lines inserted during the study period were included. Generalized linear models with log link and gamma distribution were used to model costs as a function of CLABSI and important covariates. Costs were adjusted to 2010 US dollars by use of the personal consumption expenditures for medical care index. We used multivariable logistic regression to identify independent predictors of in-hospital mortality. Among both ICU and non-ICU patients, adjusted variable costs for patients with CLABSI were c. $32 000 (2010 US dollars) higher on average than for patients without CLABSI. After we controlled for severity of illness and other healthcare-associated infections, CLABSI was associated with a 2.27-fold (95% CI 1.15–4.46) increased risk of mortality. Other healthcare-associated infections were also significantly associated with greater costs and mortality. Overall, CLABSI was associated with significantly higher adjusted in-hospital mortality and total and variable costs than those for patients without CLABSI

Calnexin, an ER-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. METHODS: The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. RESULTS: There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. CONCLUSION: Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies

Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

Polarization instabilities in a two-photon laser

We describe the operating characteristics of a new type of quantum oscillator that is based on a two-photon stimulated emission process. This two-photon laser consists of spin-polarized and laser-driven $^{39}$K atoms placed in a high-finesse transverse-mode-degenerate optical resonator, and produces a beam with a power of $\sim$0.2 $\mu$W at a wavelength of 770 nm. We observe complex dynamical instabilities of the state of polarization of the two-photon laser, which are made possible by the atomic Zeeman degeneracy. We conjecture that the laser could emit polarization-entangled twin beams if this degeneracy is lifted.Comment: Accepted by Physical Review Letters. REVTeX 4 pages, 4 EPS figure

A quantitative PCR method to quantify ruminant DNA in porcine crude heparin

Heparin is a well-known glycosaminoglycan extracted from porcine intestines. Increased vigilance for transmissible spongiform encephalopathy in animal-derived pharmaceuticals requires methods to prevent the introduction of heparin from ruminants into the supply chain. The sensitivity, specificity, and precision of the quantitative polymerase chain reaction (PCR) make it a superior analytical platform for screening heparin raw material for bovine-, ovine-, and caprine-derived material. A quantitative PCR probe and primer set homologous to the ruminant Bov-A2 short interspersed nuclear element (SINE) locus (Mendoza-Romero et al. J. Food Prot. 67:550–554, 2004) demonstrated nearly equivalent affinities for bovine, ovine, and caprine DNA targets, while exhibiting no cross-reactivity with porcine DNA in the quantitative PCR method. A second PCR primer and probe set, specific for the porcine PRE1 SINE sequence, was also developed to quantify the background porcine DNA level. DNA extraction and purification was not necessary for analysis of the raw heparin samples, although digestion of the sample with heparinase was employed. The method exhibits a quantitation range of 0.3–3,000 ppm ruminant DNA in heparin. Validation parameters of the method included accuracy, repeatability, precision, specificity, range, quantitation limit, and linearity

Irradiation leads to apoptosis of Kupffer cells by a Hsp27-dependant pathway followed by release of TNF-α

In a previous publication, we were able to show that irradiation of Kupffer cells, the liver resident macrophages, leads to an increased TNF-α concentration in the culture medium. The pathomechanisms underlying this phenomenon, however, remained to be elucidated. Here, we show that following irradiation of Kupffer cells, the apoptosis rate increased drastically within 48 h. At the same time, the total TNF-α concentration in cell lysates of Kupffer cells attached to the culture plate decreased. However, normalization of the TNF-α concentration with respect to cell number revealed that TNF-α concentration per attached cell remained constant during the observation period. Western blot analysis showed that heat shock protein 27 (Hsp27) is strongly downregulated and bax is upregulated in irradiated Kupffer cells as compared to sham-irradiated cells. Overexpression of Hsp27 in Kupffer cells was shown to prevent the effect of irradiation on bax expression, apoptosis and, at the same time, on increase of TNF-α concentration in the Kupffer cell medium. We conclude that irradiation of Kupffer cells leads to apoptosis because of downregulation of Hsp27 and consecutive upregulation of bax expression. Furthermore, we suggest that apoptosis of Kupffer cells leads to an increase of TNF-α concentration in the culture medium which may be due to cell death rather than active release or synthesis

Search for the lepton-family-number nonconserving decay \mu -> e + \gamma

The MEGA experiment, which searched for the muon- and electron-number violating decay \mu -> e + \gamma, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio of \mu -> e + \gamma) < 1.2 x 10^{-11} was obtained

Two step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate

Cerebral ischemia and excitotoxic injury induce transient or permanent bioenergetic failure, and may result in neuronal apoptosis or necrosis. We have previously shown that ATP depletion and activation of AMP-activated protein kinase (AMPK) during excitotoxic injury induces neuronal apoptosis by transcription of the proapoptotic BH3 only protein, Bim. AMPK, however, also exerts pro-survival functions in neurons. The molecular switches that determine these differential outcomes are not well understood. Using an approach combining biochemistry, single cell imaging and computational modeling, we here demonstrate that excitotoxic injury activated the bim promoter in a FOXO3-dependent manner. The activation of AMPK reduced AKT activation, and led to dephosphorylation and nuclear translocation of FOXO3. Subsequent mutation studies indicated that bim gene activation during excitotoxic injury required direct FOXO3 phosphorylation by AMPK in the nucleus as a second activation step. Inhibition of this phosphorylation prevented Bim expression and protected neurons against excitotoxic and oxygen/glucose deprivation-induced injury. Systems analysis and computational modeling revealed that these two activation steps defined a coherent feedforward loop; a network motif capable of filtering any effects of short-term AMPK activation on bim gene induction. This may prevent unwanted AMPK-mediated Bim expression and apoptosis during transient or physiological bioenergetic stress

Stakeholder involvement in systematic reviews:a scoping review

Abstract Background There is increasing recognition that it is good practice to involve stakeholders (meaning patients, the public, health professionals and others) in systematic reviews, but limited evidence about how best to do this. We aimed to document the evidence-base relating to stakeholder involvement in systematic reviews and to use this evidence to describe how stakeholders have been involved in systematic reviews. Methods We carried out a scoping review, following a published protocol. We searched multiple electronic databases (2010–2016), using a stepwise searching approach, supplemented with hand searching. Two authors independently screened and discussed the first 500 abstracts and, after clarifying selection criteria, screened a further 500. Agreement on screening decisions was 97%, so screening was done by one reviewer only. Pre-planned data extraction was completed, and the comprehensiveness of the description of methods of involvement judged. Additional data extraction was completed for papers judged to have most comprehensive descriptions. Three stakeholder representatives were co-authors for this systematic review. Results We included 291 papers in which stakeholders were involved in a systematic review. Thirty percent involved patients and/or carers. Thirty-two percent were from the USA, 26% from the UK and 10% from Canada. Ten percent (32 reviews) were judged to provide a comprehensive description of methods of involving stakeholders. Sixty-nine percent (22/32) personally invited people to be involved; 22% (7/32) advertised opportunities to the general population. Eighty-one percent (26/32) had between 1 and 20 face-to-face meetings, with 83% of these holding ≤ 4 meetings. Meetings lasted 1 h to ½ day. Nineteen percent (6/32) used a Delphi method, most often involving three electronic rounds. Details of ethical approval were reported by 10/32. Expenses were reported to be paid to people involved in 8/32 systematic reviews. Discussion/conclusion We identified a relatively large number (291) of papers reporting stakeholder involvement in systematic reviews, but the quality of reporting was generally very poor. Information from a subset of papers judged to provide the best descriptions of stakeholder involvement in systematic reviews provide examples of different ways in which stakeholders have been involved in systematic reviews. These examples arguably currently provide the best available information to inform and guide decisions around the planning of stakeholder involvement within future systematic reviews. This evidence has been used to develop online learning resources. Systematic review registration The protocol for this systematic review was published on 21 April 2017. Publication reference: Pollock A, Campbell P, Struthers C, Synnot A, Nunn J, Hill S, Goodare H, Watts C, Morley R: Stakeholder involvement in systematic reviews: a protocol for a systematic review of methods, outcomes and effects. Research Involvement and Engagement 2017, 3:9. https://doi.org/10.1186/s40900-017-0060-4

INS-1 Cells Undergoing Caspase-Dependent Apoptosis Enhance the Regenerative Capacity of Neighboring Cells

Our results suggest that apoptosing INS-1 cells shed microparticles that may stimulate PSP/reg induction in neighboring cells, a mechanism that may facilitate the recovery of β-cell mass in HNF1A-MODY