bluuebunny/crossref_metadata_2025 huggingface dataset:
Nursing knowledge of hepatitis – 25 years later
Authors: MacLean Alison , Angus Neil J , Evans Roger , Hay Andrew J , Ho-Yen Darrel O
Published: November 2011

This is a survey of nurses’ and nursing students’ knowledge about hepatitis A and B and the results are compared with a similar survey of 25 years ago. Questionnaires were given to registered nurses, healthcare assistants and first and third year student nurses during May 2009. In 2009, more participants knew about the transmission of hepatitis B compared with those in 1984. However, in 1984 and 2009, there was ignorance about hepatitis B’s long incubation period and faecal-oral transmission of hepatitis A. Third year students demonstrated better understanding than first years in their knowledge of hepatitis A, B and C. It is encouraging that there has been an increase in the knowledge about hepatitis B transmission. Knowledge about hepatitis A remains poor and it is still being confused with hepatitis B. The overall knowledge about the hepatic viruses remains low and highlights an educational need among today’s nurses.
Assembling geographical knowledges of changing worlds
Authors: McGuirk Pauline
Published: November 2011

This piece is sympathetic to the critical questions and epistemological arguments Larner (2011) presents for the current conjuncture of global transformations. I mobilize Larner’s arguments for process-oriented assemblage thinking and apply them to the particular conjuncture through which one of these transformations – climate change – is being problematized in the Australian empirical context, and its connection to existing and emergent institutional and political formations and knowledge practices. I also point to emergent process-oriented, situated scholarly accounts of climate change in Australia and their potential to expand the contestable spaces whereby alternative politicizations and alternative political and institutional forms might be imagined and enacted. In closing, I reflect on the connection between situated accounts, such as these, and the potential performative effects of situated theorizing.
Stage IV sarcoidosis: comparison of survival with the general population and causes of death
Authors: Nardi A. , Brillet P-Y. , Letoumelin P. , Girard F. , Brauner M. , Uzunhan Y. , Naccache J-M. , Valeyre D. , Nunes H.
Published: November 2011

The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications.

This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean±sdage 48.1±12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan–Meier method and compared using the log-rank test.

During the follow-up period (7.1±4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p=0.013). 16 (11.3%) patients died from the following causes: refractory PH (n=5), chronic respiratory insufficiency (n=4), acute respiratory insufficiency (n=2), haemoptysis due to aspergilloma (n=1), heart sarcoidosis (n=1), nocardiosis (n=1) and unknown causes (n=2).

Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.
Community-associated Methicillin-resistant Staphylococcus aureusBacteremia and Endocarditis among HIV Patients: A cohort study
Authors: Furuno Jon P , Johnson Jennifer K , Schweizer Marin L , Uche Anayochukwu , Stine Oscar C , Shurland Simone M , Forrest Graeme N
Published: November 2011

Background

HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) among HIV-infected patients withS. aureusbloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population.

Methods

All adult HIV-infected patients with documentedS. aureusbacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors forS. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use.

Results

Among 131 episodes ofS. aureusbacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality.

Conclusions

CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes.
Clinical implication of HLA class I expression in breast cancer
Authors: Kaneko Koichi , Ishigami Sumiya , Kijima Yuko , Funasako Yawara , Hirata Munetsugu , Okumura Hiroshi , Shinchi Hiroyuki , Koriyama Chihaya , Ueno Shinichi , Yoshinaka Heiji , Natsugoe Shoji
Published: November 2011

Background

Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified.

Methods

A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed.

Results

The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval.

Conclusion

The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.
Problematic Internet use in Chinese adolescents and its relation to psychosomatic symptoms and life satisfaction
Authors: Cao Hui , Sun Ying , Wan Yuhui , Hao Jiahu , Tao Fangbiao
Published: November 2011

Background

Problematic Internet use (PIU) is a growing problem in Chinese adolescents. Little is known about associations of PIU with physical and psychological health. This study was designed to investigate the prevalence of PIU and to test the relationships between PIU and psychosomatic symptoms and life satisfaction among adolescents in mainland China.

Methods

A cross-sectional survey was conducted comprising a large representative sample of 17 599 students in eight cities of China. PIU was assessed by the 20-item Young Internet Addiction Test (YIAT). The Multidimensional Sub-health Questionnaire of Adolescents and the Multidimensional Students' Life Satisfaction Scale were administered to obtain information on psychosomatic symptoms and life satisfaction. Demographics and Internet usage patterns were also collected. Logistic regression was used to assess the effects of PIU on psychosomatic symptoms and life satisfaction.

Results

Approximately 8.1% of subjects showed PIU. Adolescents with PIU were associated with males, high school students, urban, eastern and western areas, upper self-report family economy, service type mostly used for entertainment and relieving loneliness and more frequency of Internet use. Compared with normal Internet users, adolescents with PIU were more likely to suffer from psychosomatic symptoms (P < 0.001), including lack of physical energy (P < 0.001), physiological dysfunction (P < 0.001), weakened immunity (P < 0.001), emotional symptoms (P < 0.001), behavioural symptoms (P < 0.001) and social adaptation problems (P < 0.001). Adolescents with PIU had lower scores on total and all dimensions of life satisfaction (all P < 0.001). Adjusted for the demographic and Internet-related factors, there was positive significant relationship between PIU and psychosomatic symptoms, but negatively related to life satisfaction.

Conclusions

PIU is common among Chinese students, and PIU was significantly associated with psychosomatic symptoms and life satisfaction. Effective measures are needed to prevent the spread of this problem and interventions to prevent the effects of PIU on psychosomatic symptoms and life satisfaction should be conducted as early as possible.
Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) is a potential tumour suppressor in prostate cancer and is frequently silenced by promoter methylation
Authors: Ummanni Ramesh , Jost Edgar , Braig Melanie , Lohmann Frithjof , Mundt Frederike , Barett Christine , Schlomm Thorsten , Sauter Guido , Senff Tina , Bokemeyer Carsten , Sültmann Holger , Meyer-Schwesinger Catherine , Brümmendorf Tim H , Balabanov Stefan
Published: November 2011

Background

We have previously reported significant downregulation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in prostate cancer (PCa) compared to the surrounding benign tissue. UCHL1 plays an important role in ubiquitin system and different cellular processes such as cell proliferation and differentiation. We now show that the underlying mechanism of UCHL1 downregulation in PCa is linked to its promoter hypermethylation. Furthermore, we present evidences that UCHL1 expression can affect the behavior of prostate cancer cells in different ways.

Results

Methylation specific PCR analysis results showed a highly methylated promoter region for UCHL1 in 90% (18/20) of tumor tissue compared to 15% (3/20) of normal tissues from PCa patients. Pyrosequencing results confirmed a mean methylation of 41.4% in PCa whereas only 8.6% in normal tissues. To conduct functional analysis of UCHL1 in PCa, UCHL1 is overexpressed in LNCaP cells whose UCHL1 expression is normally suppressed by promoter methylation and found that UCHL1 has the ability to decrease the rate of cell proliferation and suppresses anchorage-independent growth of these cells. In further analysis, we found evidence that exogenous expression of UCHL1 suppress LNCaP cells growth probably via p53-mediated inhibition of Akt/PKB phosphorylation and also via accumulation of p27kip1 a cyclin dependant kinase inhibitor of cell cycle regulating proteins. Notably, we also observed that exogenous expression of UCHL1 induced a senescent phenotype that was detected by using the SA-ß-gal assay and might be due to increased p14ARF, p53, p27kip1 and decreased MDM2.

Conclusion

From these results, we propose that UCHL1 downregulation via promoter hypermethylation plays an important role in various molecular aspects of PCa biology, such as morphological diversification and regulation of proliferation.
Comparison of nanoparticle-mediated transfection methods for DNA expression plasmids: efficiency and cytotoxicity
Authors: Durán María Carolina , Willenbrock Saskia , Barchanski Annette , Müller Jessika-M V , Maiolini Arianna , Soller Jan T , Barcikowski Stephan , Nolte Ingo , Feige Karsten , Murua Escobar Hugo
Published: November 2011

Background

Reproducibly high transfection rates with low methodology-induced cytotoxic side effects are essential to attain the required effect on targeted cells when exogenous DNA is transfected. Different approaches and modifications such as the use of nanoparticles (NPs) are being evaluated to increase transfection efficiencies. Several studies have focused on the attained transfection efficiency after NP-mediated approaches. However, data comparing toxicity of these novel approaches with conventional methods is still rare.

Transfection efficiency and methodology-induced cytotoxicity were analysed after transfection with different NP-mediated and conventional approaches. Two eukaryotic DNA-expression-plasmids were used to transfect the mammalian cell line MTH53A applying six different transfection protocols: conventional transfection reagent (FuGENE HD, FHD), FHD in combination with two different sizes of stabilizer-free laser-generated AuNPs (PLAL-AuNPs_S1,_S2), FHD and commercially available AuNPs (Plano-AuNP), and two magnetic transfection protocols. 24 h post transfection efficiency of each protocol was analysed using fluorescence microscopy and GFP-based flow cytometry. Toxicity was assessed measuring cell proliferation and percentage of propidium iodide (PI%) positive cells. Expression of the respective recombinant proteins was evaluated by immunofluorescence.

Results

The addition of AuNPs to the transfection protocols significantly increased transfection efficiency in the pIRES-hrGFPII-eIL-12transfections (FHD: 16%; AuNPs mean: 28%), whereas the magnet-assisted protocols did not increase efficiency. Ligand-free PLAL-AuNPs had no significant cytotoxic effect, while the ligand-stabilized Plano-AuNPs induced a significant increase in the PI% and lower cell proliferation. For pIRES-hrGFPII-rHMGB1transfections significantly higher transfection efficiency was observed with PLAL-AuNPs (FHD: 31%; PLAL-AuNPs_S1: 46%; PLAL-AuNPs_S2: 50%), while the magnet-assisted transfection led to significantly lower efficiencies than the FHD protocol. With PLAL-AuNPs_S1 and _S2 the PI% was significantly higher, yet no consistent effect of these NPs on cell proliferation was observed. The magnet-assisted protocols were least effective, but did result in the lowest cytotoxic effect.

Conclusions

This study demonstrated that transfection efficiency of DNA-expression-plasmids was significantly improved by the addition of AuNPs. In some combinations the respective cytotoxicity was increased depending on the type of the applied AuNPs and the transfected DNA construct. Consequently, our results indicate that for routine use of these AuNPs the specific nanoparticle formulation and DNA construct combination has to be considered.
Approximating fixed points for nonself mappings in CAT(0) spaces
Authors: Razani Abdolrahman , Shabani Saeed
Published: November 2011

Suppose K is a nonempty closed convex subset of a complete CAT(0) space X with the nearest point projection P from X onto K. Let T : K → X be a nonself mapping, satisfying Condition (E) with F(T): = {x ∈ K : Tx = x} ≠ ∅. Suppose {x
n
} is generated iteratively by x1 ∈ K, x
n
+1 = P ((1 - α
n
)x
n
⊕ α
n
TP [(1 - β
n
)x
n
⊕ β
n
Tx
n
]),n ≥ 1, where {α
n
} and {β
n
} are real sequences in [ε, 1 - ε] for some ε ∈ (0, 1). Then, {x
n
} Δ-converges to some point x⋆ in F(T). This extends a result of Laowang and Panyanak [Fixed Point Theory Appl. 367274, 11 (2010)] for nonself mappings satisfying Condition (E).
Phase-Specific Plasticity of Synaptic Structures in the Somatosensory Cortex of Living Mice during Neuropathic Pain
Authors: Kim Sun Kwang , Kato Go , Ishikawa Tatsuya , Nabekura Junichi
Published: November 2011

Background:

Postsynaptic dendritic spines in the cortex are highly dynamic, showing rapid morphological changes including elongation/retraction and formation/elimination in response to altered sensory input or neuronal activity, which achieves experience/activity-dependent cortical circuit rewiring. Our previous long-term in vivo two-photon imaging study revealed that spine turnover in the mouse primary somatosensory (S1) cortex markedly increased in an early development phase of neuropathic pain, but was restored in a late maintenance phase of neuropathic pain. However, it remains unknown how spine morphology is altered preceding turnover change and whether gain and loss of presynaptic boutons are changed during neuropathic pain.

Findings:

Here we used short-term (2-hour) and long-term (2-week) time-lapse in vivo two-photon imaging of individual spines and boutons in the S1 cortical layer 1 of the transgenic mice expressing GFP in pyramidal neurons following partial sciatic nerve ligation (PSL). We found in the short-term imaging that spine motility (A length per 30 min) significantly increased in the development phase of neuropathic pain, but returned to the baseline in the maintenance phase. Moreover, the proportion of immature (thin) and mature (mushroom) spines increased and decreased, respectively, only in the development phase. Long-term imaging data showed that formation and elimination of boutons moderately increased and decreased, respectively, during the first 3 days following PSL and was subsequently restored.

Conclusions:

Our results indicate that the S1 synaptic structures are rapidly destabilized and rearranged following PSL and subsequently stabilized in the maintenance phase of neuropathic pain, suggesting a novel therapeutic target in intractable chronic pain.
Mucins Differently Expressed in Various Ampullary Adenocarcinomas
Authors: Wang Tao , Liang Ye M , Hu Peng , Cheng Yu F
Published: November 2011

Background

We investigated the occurrence and clinical significance of mucin expression in ampullary adenocarcinoma.

Methods

We retrospectively analyzed clinical, pathological, and survival data from 74 ampullary adenocarcinoma patients who received radical operation from January 2004 to November 2006.

Results

The tumors were located in the lower end of the common bile duct (46%), papillary duodenum (42%), and ampullary duodenum (12%), and expressed MUC1 (72%), MUC2 (20%), MUC5AC (43%), and MUC6 (27%). Expression of MUC1 was associated with tumor differentiation (OR: 4.71, 95% CI: 1.26, 17.66, P = 0.021). Expression of MUC5AC was associated with age (OR: 1.07, 95% CI: 1.11, 1.14, P = 0.026) and less vessel invasion(OR: 0.14, 95% CI: 0.03, 0.72, P = 0.019). The survival rates were not significantly different when patients had or had no expression of MUC1, MUC2, MUC5AC, or MUC6 in tumor. Patients with tumors positive for MUC5AC in the papillary duodenum had worse survival than those with tumors negative for MUC5AC (P = 0.044).

Conclusions

Expression of MUC1 was high (72%) in ampullary adenocarcinoma, while expressions of MUC2, MUC5AC, and MUC6 were lower. Mucins are useful markers to diagnose and identify ampullary adenocarcinoma, particularly in determining the degree of malignancy of ampullary adenocarcinoma.
The logic layout of the TOL network of Pseudomonas putida pWW0 plasmid stems from a metabolic amplifier motif (MAM) that optimizes biodegradation of m-xylene
Authors: Silva-Rocha Rafael , de Jong Hidde , Tamames Javier , de Lorenzo Víctor
Published: November 2011

Background

The genetic network of the TOL plasmid pWW0 of the soil bacterium Pseudomonas putida mt-2 for catabolism of m-xylene is an archetypal model for environmental biodegradation of aromatic pollutants. Although nearly every metabolic and transcriptional component of this regulatory system is known to an extraordinary molecular detail, the complexity of its architecture is still perplexing. To gain an insight into the inner layout of this network a logic model of the TOL system was implemented, simulated and experimentally validated. This analysis made sense of the specific regulatory topology out on the basis of an unprecedented network motif around which the entire genetic circuit for m-xylene catabolism gravitates.

Results

The most salient feature of the whole TOL regulatory network is the control exerted by two distinct but still intertwined regulators (XylR and XylS) on expression of two separated catabolic operons (upper and lower) for catabolism of m-xylene. Following model reduction, a minimal modular circuit composed by five basic variables appeared to suffice for fully describing the operation of the entire system. In silico simulation of the effect of various perturbations were compared with experimental data in which specific portions of the network were activated with selected inducers: m-xylene, o-xylene, 3-methylbenzylalcohol and 3-methylbenzoate. The results accredited the ability of the model to faithfully describe network dynamics. This analysis revealed that the entire regulatory structure of the TOL system enables the action an unprecedented metabolic amplifier motif (MAM). This motif synchronizes expression of the upper and lower portions of a very long metabolic system when cells face the head pathway substrate, m-xylene.

Conclusion

Logic modeling of the TOL circuit accounted for the intricate regulatory topology of this otherwise simple metabolic device. The found MAM appears to ensure a simultaneous expression of the upper and lower segments of the m-xylene catabolic route that would be difficult to bring about with a standard substrate-responsive single promoter. Furthermore, it is plausible that the MAM helps to avoid biochemical conflicts between competing plasmid-encoded and chromosomally-encoded pathways in this bacterium.
A new baseline for fascioliasis in Venezuela: lymnaeid vectors ascertained by DNA sequencing and analysis of their relationships with human and animal infection
Authors: Bargues M Dolores , González L Carolina , Artigas Patricio , Mas-Coma Santiago
Published: November 2011

Background

Human and animal fascioliasis poses serious public health problems in South America. In Venezuela, livestock infection represents an important veterinary problem whereas there appear to be few human cases reported, most of which are passively detected in health centres. However, results of recent surveys suggest that the situation may be underestimated in particular areas. To obtain a baseline for future fascioliasis assessment, studies were undertaken by means of rDNA ITS-2 and ITS-1 and mtDNAcox1 sequencing to clarify the specific status of Venezuelan lymnaeids, their geographical distribution and fascioliasis transmission capacity, by comparison with other American countries and other continents.

Results

Results obtained completely change the lymnaeid scenario known so far. The relatively rich lymnaeid fauna of Venezuela has been proven to include (i)Lymnaea meridensisandL. neotropicaas the only native members, (ii)L. cubensisandPseudosuccinea columellaintroduced from the Caribbean area, and (iii)Galba truncatulaandL. schirazensisintroduced from the Old World. The absence of representatives of the stagnicoline andRadixgroups is remarkable. Four species are fascioliasis vectors:G. truncatula,L. cubensisandL. neotropica, which have the capacity to give rise to human endemic areas, andP. columella, which is a source of animal infection and is responsible for the spread of disease. Vector capacity in the apparently highland endemicL. meridensisis to be confimed, although may be expected given its phylogenetic relationships. Similarly as elsewhere, the non-transmittingL. schirazensishas been confused withL. cubensis, also withG. truncatulaand possibly withL. neotropica.

Conclusions

The new scenario leads to the re-opening of many disease aspects. In Venezuela, altitude appears to be the main factor influencing fascioliasis distribution. Human infection shows an altitude pattern similar to other Andean countries, although a differing highland/lowland impact on animal infection does not appear evident. The overlap ofG. truncatula,L. cubensisand probably alsoL. neotropicain temperate and cold zones suggests a higher risk for human infection in mid and high altitude areas. A lymnaeid species mapping by means of DNA markers becomes a priority to determine human and animal fascioliasis distribution in Venezuela, owing to the importance of lymnaeid vectors in defining transmission and epidemiological patterns.
Risk of allergic reactions to wine, in milk, egg and fish‐allergic patients
Authors: Vassilopoulou Emilia , Karathanos Athanassios , Siragakis George , Giavi Stavroula , Sinaniotis Athanassios , Douladiris Nikolaos , Fernandez‐Rivas Montserrat , Clausen Michael , Papadopoulos Nikolaos G
Published: November 2011

Background

European legislators and wine producers still debate on the requirement for labeling of wines fined with potentially allergenic food proteins (casein, egg white or fish‐derived isinglass). We investigated whether wines fined with known concentrations of these proteins have the potential to provoke clinical allergic reactions in relevant patients.

Methods

In‐house wines were produced for the study, fined with different concentrations of casein (n = 7), egg albumin (n = 1) and isinglass (n = 3). ELISA and PCR kits specific for the respective proteins were used to identify the fining agents. Skin prick tests and basophil activation tests were performed in patients with confirmed IgE‐mediated relevant food allergies (n = 24). A wine consumption questionnaire and detailed history on possible reactions to wine was obtained in a multinational cohort of milk, egg or fish allergic patients (n = 53) and patients allergic to irrelevant foods as controls (n = 13).

Results

Fining agents were not detectable in wines with the available laboratory methods. Nevertheless, positive skin prick test reactions and basophil activation to the relevant wines were observed in the majority of patients with allergy to milk, egg or fish, correlating with the concentration of the fining agent. Among patients consuming wine, reported reactions were few and mild and similar with the ones reported from the control group.

Conclusion

Casein, isinglass or egg, remaining in traces in wine after fining, present a very low risk for the respective food allergic consumers. Physician and patient awareness campaigns may be more suitable than generalized labeling to address this issue, as the latter may have negative impact on both non‐allergic and allergic consumers.
Postextubation dysphagia is persistent and associated with poor outcomes in survivors of critical illness
Authors: Macht Madison , Wimbish Tim , Clark Brendan J , Benson Alexander B , Burnham Ellen L , Williams André , Moss Marc
Published: November 2011

Introduction

Dysphagia is common among survivors of critical illness who required mechanical ventilation during treatment. The risk factors associated with the development of postextubation dysphagia, and the effects of dysphagia on patient outcomes, have been relatively unexplored.

Methods

We conducted a retrospective, observational cohort study from 2008 to 2010 of all patients over 17 years of age admitted to a university hospital ICU who required mechanical ventilation and subsequently received a bedside swallow evaluation (BSE) by a speech pathologist.

Results

A BSE was performed after mechanical ventilation in 25% (630 of 2,484) of all patients. After we excluded patients with stroke and/or neuromuscular disease, our study sample size was 446 patients. We found that dysphagia was present in 84% of patients (n = 374) and classified dysphagia as absent, mild, moderate or severe in 16% (n = 72), 44% (n = 195), 23% (n = 103) and 17% (n = 76), respectively. In univariate analyses, we found that statistically significant risk factors for severe dysphagia included long duration of mechanical ventilation and reintubation. In multivariate analysis, after adjusting for age, gender and severity of illness, we found that mechanical ventilation for more than seven days remained independently associated with moderate or severe dysphagia (adjusted odds ratio (AOR) = 2.84 [interquartile range (IQR) = 1.78 to 4.56]; P < 0.01). The presence of severe postextubation dysphagia was significantly associated with poor patient outcomes, including pneumonia, reintubation, in-hospital mortality, hospital length of stay, discharge status and surgical placement of feeding tubes. In multivariate analysis, we found that the presence of moderate or severe dysphagia was independently associated with the composite outcome of pneumonia, reintubation and death (AOR = 3.31 [IQR = 1.89 to 5.90]; P < 0.01).

Conclusions

In a large cohort of critically ill patients, long duration of mechanical ventilation was independently associated with postextubation dysphagia, and the development of postextubation dysphagia was independently associated with poor patient outcomes.
Strain-dependent induction of neutrophil histamine production and cell death byPseudomonas aeruginosa
Authors: Xu Xiang , Zhang Hong , Song Yuanlin , Lynch Susan V , Lowell Clifford A , Wiener-Kronish Jeanine P , Caughey George H
Published: November 2011

Airway diseases often feature persistent neutrophilic inflammation and infection. In cystic fibrosis bronchitis, for example, Pseudomonas aeruginosa is isolated frequently. Previously, this laboratory revealed that neutrophils become major sources of histamine in mice with tracheobronchitis caused by the wall-less bacterium Mycoplasma pulmonis. To test the hypothesis that more-broadly pathogenic P. aeruginosa (which expresses cell wall-associated LPS and novel toxins) has similar effects, we incubated naïve mouse neutrophils with two strains of P. aeruginosa. Strain PAO1 greatly increased neutrophil histamine content and secretion, whereas strain PA103 depressed histamine production by killing neutrophils. The histamine-stimulating capacity of PAO1, but not PA103-mediated toxicity, persisted in heat-killed organisms. In PAO1-infected mice, lung and neutrophil histamine content increased. However, PAO1 did not alter production by mast cells (classical histamine reservoirs), which also resisted PA103 toxicity. To explore mechanisms of neutrophil-selective induction, we measured changes in mRNA encoding histidine decarboxylase (rate-limiting for histamine synthesis), probed involvement of endotoxin-TLR pathways in Myd88-deficient neutrophils, and examined contributions of pyocyanin and exotoxins. Results revealed that PAO1 increased histamine production by up-regulating histidine decarboxylase mRNA via pathways largely independent of TLR, pyocyanin, and type III secretion system exotoxins. PAO1 also increased histidine decarboxylase mRNA in neutrophils purified from infected lung. Stimulation required direct contact with neutrophils and was blocked by phagocytosis inhibitor cytochalasin D. In summary, Pseudomonas-augmented histamine production by neutrophils is strain-dependent in vitro and likely mediated by up-regulation of histidine decarboxylase. These findings raise the possibility that Pseudomonas-stimulated neutrophils can enhance airway inflammation by producing histamine.
Identical Gene Regulation Patterns of T3 and Selective Thyroid Hormone Receptor Modulator GC-1
Authors: Yuan Chaoshen , Lin Jean Z.H. , Sieglaff Douglas H. , Ayers Steven D. , DeNoto-Reynolds Frances , Baxter John D. , Webb Paul
Published: November 2011

Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRM) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver, and insulin resistance in preclinical animal models. STRM differ from native TH in preferential binding to the TRβ subtype vs. TRα, increased uptake into liver, and reduced uptake into other tissues. However, selective modulators of other nuclear receptors exhibit important gene-selective actions, which are attributed to differential effects on receptor conformation and dynamics and can have profound influences in animals and humans. Although there are suggestions that STRM may exhibit such gene-specific actions, the extent to which they are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, T3, and the prototype STRM GC-1 induce identical gene sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TRβ, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency vs. T3, at angiopoietin-like factor 4 in HepG2. Investigation of the latter effect confirms that GC-1 acts through TRβ to directly induce this gene but this gene-selective activity is not related to unusual T3-response element sequence, unlike previously documented promoter-selective STRM actions. Our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRM will be subtle and rare.
Constitutive Activation of IKKβ in Adipose Tissue Prevents Diet-Induced Obesity in Mice
Authors: Jiao Ping , Feng Bin , Ma Jie , Nie Yaohui , Paul Erin , Li Yujie , Xu Haiyan
Published: November 2011

The IκB kinase β (IKKβ) is a master kinase involved in obesity-related inflammation and insulin resistance through nuclear factor κB dependent and independent pathways. However, the effect of IKKβ activation in adipose tissue, the organ critical for storage of excessive energy and initiation of inflammatory responses in the context of obesity, on systemic insulin sensitivity and metabolism, has not been investigated. In our study, we found that mice overexpressing the constitutively active IKKβ in adipose tissue under the control of murine adipocyte fatty acid binding protein (aP2) promoter were protected from age-related and diet-induced body weight gains, despite increased food intake. The aP2-IKKβ SE mice have significantly reduced weights in all white adipose tissue depots and reduced triglyceride contents in adipose tissue, liver, and muscle. Despite increased systemic and tissue inflammation, aP2-IKKβ SE mice displayed decreased blood glucose levels, improved glucose, and insulin tolerance. This may be at least partially attributable to increased energy expenditure. Histological analysis revealed presence of many small adipocytes in white adipose tissue of aP2-IKKβ SE mice fed on high-fat diet. Furthermore, transgenic expression of IKKβ in adipose tissue improved high-fat diet-induced hepatosteatosis. Collectively, increased energy expenditure and reduced plasma free fatty acid levels may contribute to enhanced systemic insulin sensitivity in aP2-IKKβ SE mice. Our study demonstrates that presence of inflammation in adipose tissue before the development of obesity has beneficial effect on metabolism.
11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in Mice
Authors: Coutinho Agnes E. , Gray Mohini , Brownstein David G. , Salter Donald M. , Sawatzky Deborah A. , Clay Spike , Gilmour James S. , Seckl Jonathan R. , Savill John S. , Chapman Karen E.
Published: November 2011

Glucocorticoids profoundly influence immune responses, and synthetic glucocorticoids are widely used clinically for their potent antiinflammatory effects. Endogenous glucocorticoid action is modulated by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). In vivo, 11β-HSD1 catalyzes the reduction of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, thereby increasing intracellular glucocorticoid levels. 11β-HSD2 catalyzes the reverse reaction, inactivating intracellular glucocorticoids. Both enzymes have been postulated to modulate inflammatory responses. In the K/BxN serum transfer model of arthritis, 11β-HSD1-deficient mice showed earlier onset and slower resolution of inflammation than wild-type controls, with greater exostoses in periarticular bone and, uniquely, ganglion cysts, consistent with greater inflammation. In contrast, K/BxN serum arthritis was unaffected by 11β-HSD2 deficiency. In a distinct model of inflammation, thioglycollate-induced sterile peritonitis, 11β-HSD1-deficient mice had more inflammatory cells in the peritoneum, but again 11β-HSD2-deficient mice did not differ from controls. Additionally, compared with control mice, 11β-HSD1-deficient mice showed greater numbers of inflammatory cells in pleural lavages in carrageenan-induced pleurisy with lung pathology consistent with slower resolution. These data suggest that 11β-HSD1 limits acute inflammation. In contrast, 11β-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11β-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy.
Evolutionary History and Functional Characterization of the Amphibian Xenosensor CAR
Authors: Mathäs Marianne , Burk Oliver , Qiu Huan , Nußhag Christian , Gödtel-Armbrust Ute , Baranyai Dorothea , Deng Shiwei , Römer Kristin , Nem Dieudonné , Windshügel Björn , Wojnowski Leszek
Published: November 2011

The xenosensing constitutive androstane receptor (CAR) is widely considered to have arisen in early mammals via duplication of the pregnane X receptor (PXR). We report that CAR emerged together with PXR and the vitamin D receptor from an ancestral NR1I gene already in early vertebrates, as a result of whole-genome duplications. CAR genes were subsequently lost from the fish lineage, but they are conserved in all taxa of land vertebrates. This contrasts with PXR, which is found in most fish species, whereas it is lost from Sauropsida (reptiles and birds) and plays a role unrelated to xenosensing in Xenopus. This role is fulfilled in Xenopus by CAR, which exhibits low basal activity and pronounced responsiveness to activators such as drugs and steroids, altogether resembling mammalian PXR. The constitutive activity typical for mammalian CAR emerged first in Sauropsida, and it is thus common to all fully terrestrial land vertebrates (Amniota). The constitutive activity can be achieved by humanizing just two amino acids of the Xenopus CAR. Taken together, our results provide a comprehensive reconstruction of the evolutionary history of the NR1I subfamily of nuclear receptors. They identify CAR as the more conserved and remarkably plastic NR1I xenosensor in land vertebrates. Nonmammalian CAR should help to dissect the specific functions of PXR and CAR in the metabolism of xeno- and endobiotics in humans. Xenopus CAR is a first reported amphibian xenosensor, which opens the way to toxicogenomic and bioaugmentation studies in this critically endangered taxon of land vertebrates.
Neuronal correlates of a preference for leading signals in the synchronizing bushcricketMecopoda elongata(Orthoptera, Tettigoniidae)
Authors: Siegert M. E. , Römer H. , Hashim R. , Hartbauer M.
Published: November 2011

Acoustically interacting males of the tropical katydid Mecopoda elongata synchronize their chirps imperfectly, so that one male calls consistently earlier in time than the other. In choice situations, females prefer the leader signal, and it has been suggested that a neuronal mechanism based on directional hearing may be responsible for the asymmetric, stronger representation of the leader signal in receivers. Here, we investigated the potential mechanism in a pair of interneurons (TN1 neuron) of the afferent auditory pathway, known for its contralateral inhibitory input in directional hearing. In this interneuron, conspecific signals are reliably encoded under natural conditions, despite high background noise levels. Unilateral presentations of a conspecific chirp elicited a TN1 response where each suprathreshold syllable in the chirp was reliably copied in a phase-locked fashion. Two identical chirps broadcast with a 180 deg spatial separation resulted in a strong suppression of the response to the follower signal, when the time delay was 20 ms or more. Muting the ear on the leader side fully restored the response to the follower signal compared with unilateral controls. Time–intensity trading experiments, in which the disadvantage of the follower signal was traded against higher sound pressure levels, demonstrated the dominating influence of signal timing on the TN1 response, and this was especially pronounced at higher sound levels of the leader. These results support the hypothesis that the female preference for leader signals in M. elongata is the outcome of a sensory mechanism that originally evolved for directional hearing.
Associative learning between odorants and mechanosensory punishment in larval Drosophila
Authors: Eschbach Claire , Cano Carmen , Haberkern Hannah , Schraut Karla , Guan Chonglin , Triphan Tilman , Gerber Bertram
Published: November 2011

We tested whether Drosophila larvae can associate odours with a mechanosensory disturbance as a punishment, using substrate vibration conveyed by a loudspeaker (buzz: ). One odour (A) was presented with the buzz, while another odour (B) was presented without the buzz (A/B training). Then, animals were offered the choice between A and B. After reciprocal training (A/B), a second experimental group was tested in the same way. We found that larvae show conditioned escape from the previously punished odour. We further report an increase of associative performance scores with the number of punishments, and an increase according to the number of training cycles. Within the range tested (between 50 and 200 Hz), however, the pitch of the buzz does not apparently impact associative success. Last, but not least, we characterized odour–buzz memories with regard to the conditions under which they are behaviourally expressed – or not. In accordance with what has previously been found for associative learning between odours and bad taste (such as high concentration salt or quinine), we report that conditioned escape after odour–buzz learning is disabled if escape is not warranted, i.e. if no punishment to escape from is present during testing. Together with the already established paradigms for the association of odour and bad taste, the present assay offers the prospect of analysing how a relatively simple brain orchestrates memory and behaviour with regard to different kinds of ‘bad’ events.
IRS and TOR nutrient-signaling pathways act via juvenile hormone to influence honey bee caste fate
Authors: Mutti Navdeep S. , Dolezal Adam G. , Wolschin Florian , Mutti Jasdeep S. , Gill Kulvinder S. , Amdam Gro V.
Published: November 2011

Regardless of genetic makeup, a female honey bee becomes a queen or worker depending on the food she receives as a larva. For decades, it has been known that nutrition and juvenile hormone (JH) signaling determine the caste fate of the individual bee. However, it is still largely unclear how these factors are connected. To address this question, we suppressed nutrient sensing by RNA interference (RNAi)-mediated gene knockdown of IRS (insulin receptor substrate) and TOR (target of rapamycin) in larvae reared on queen diet. The treatments affected several layers of organismal organization that could play a role in the response to differential nutrition between castes. These include transcript profiles, proteomic patterns, lipid levels, DNA methylation response and morphological features. Most importantly, gene knockdown abolished a JH peak that signals queen development and resulted in a worker phenotype. Application of JH rescued the queen phenotype in either knockdown, which demonstrates that the larval response to JH remains intact and can drive normal developmental plasticity even when IRS or TOR transcript levels are reduced. We discuss our results in the context of other recent findings on honey bee caste and development and propose that IRS is an alternative substrate for the Egfr (epidermal growth factor receptor) in honey bees. Overall, our study describes how the interplay of nutritional and hormonal signals affects many levels of organismal organization to build different phenotypes from identical genotypes.
Clavulanic Acid Adsorption Studies in Zeolites
Authors: Forte Marcus Bruno Soares , Rodrigues Maria Isabel , Filho Francisco Maugeri
Published: November 2011

Zeolites are crystalline inorganic solids containing aluminium, silicon and oxygen arranged in a highly regular structure, and they are usually used in separation processes. In this study, zeolites have been shown to act as adsorbents for clavulanic acid. Ion exchange with different compensating cations (Na+, K+, Ca2+, Ba2+, Mg2+, Sr2+) was used to modify the natural zeolite (NZ) and the synthetic faujasite (13X). Kinetic analysis of the adsorption of clavulanic acid indicated that the 13X-Na zeolite was the most appropriate for this purpose. Under equilibrium conditions, the retention by this zeolite was about 17.4% (C*/C0 = 0.826), with the amount of clavulanic acid adsorbed relative to the amount of zeolite employed (q*) being ca. 0.5 mg/g. The 13X-Na zeolite was characterized in terms of its Si/Al ratio (1.5), density (dz = 2.248 g/cm3), superficial area (SBET = 444.860 m2/g), total pore volume (Vpore = 0.308 cm3/g), micropore volume (Vmicro = 0.203 cm3/g) and particle porosity (εp = 0.69). Adsorption isotherms at 10, 15 and 20 °C were constructed using 13X-Na zeolite and solutions of pure clavulanic acid; these demonstrated that the lower the temperature, the higher the amount of clavulanic acid adsorbed.
Will Gamify Those Processes. The Art of Innovation in the Public Sector
Authors: Michaelides Dimis
Published: November 2011

The Art of Innovation model posits that it is possible to make uncreative organizations creative and creative organizations more so. To succeed, leaders must work on a set of innovation drivers to develop the SOURCES of creativity (Talent, Energy, Method); establish a STRUCTURE for innovation (Individual, Team, Target, System) and shape a CULTURE that promotes innovation (Ideas, Freedom, Engagement, Humor, Risk) [1]. This approach is as valid for public as it is for private organizations. There are however some differences between private and public sector. First, while innovation has clear value-adding potential for the public sector, there is no competitive impetus to innovate and the temptation to leave things as they are is larger. Second, certain innovation drivers when implemented in the public sector may require a different approach from the private sector. Target, for example asks where the organization is situated on the innovation "continuum" and ideas such as radical innovation and differentiation may be quite alien to the public sector. This should not however stop government from pursuing continuous improvement and assigning innovation objectives clearly to each and every department, team and individual. Freedom too is often stifled by outdated regulations or legislation that may be hard to change. And Risk, while always controversial, is more so in government where civil servants are often criticized by their (changing) political bosses obliging them to resort to unproductive risk avoidance.