bluuebunny/crossref_metadata_2025_split huggingface dataset:
KKL-35 Exhibits Potent Antibiotic Activity against Legionella Species Independently of
trans
-Translation Inhibition
Authors: Brunel Romain , Descours Ghislaine , Durieux Isabelle , Doublet Patricia , Jarraud Sophie , Charpentier Xavier 
Published: November 2017

ABSTRACT

trans
-Translation is a ribosome-rescue system that is ubiquitous in bacteria. Small molecules defining a new family of oxadiazole compounds that inhibit
trans
-translation have been found to have broad-spectrum antibiotic activity. We sought to determine the activity of KKL-35, a potent member of the oxadiazole family, against the human pathogen
Legionella pneumophila
and other related species that can also cause Legionnaires' disease (LD). Consistent with the essential nature of
trans
-translation in
L. pneumophila
, KKL-35 inhibited the growth of all tested strains at submicromolar concentrations. KKL-35 was also active against other LD-causing
Legionella
species. KKL-35 remained equally active against
L. pneumophila
mutants that have evolved resistance to macrolides. KKL-35 inhibited the multiplication of
L. pneumophila
in human macrophages at several stages of infection. No resistant mutants could be obtained, even during extended and chronic exposure. Surprisingly, KKL-35 was not synergistic with other ribosome-targeting antibiotics and did not induce the filamentation phenotype observed in cells defective for
trans
-translation. Importantly, KKL-35 remained active against
L. pneumophila
mutants expressing an alternate ribosome-rescue system and lacking transfer-messenger RNA, the essential component of
trans
-translation. These results indicate that the antibiotic activity of KKL-35 is not related to the specific inhibition of
trans
-translation and its mode of action remains to be identified. In conclusion, KKL-35 is an effective antibacterial agent against the intracellular pathogen
L. pneumophila
with no detectable resistance development. However, further studies are needed to better understand its mechanism of action and to assess further the potential of oxadiazoles in treatment.
High-Dose Daptomycin Is Effective as an Antibiotic Lock Therapy in a Rabbit Model of Staphylococcus epidermidis Catheter-Related Infection
Authors: Basas Jana , Palau Marta , Ratia Carlos , del Pozo José L. , Martín-Gómez María Teresa , Gomis Xavier , Torrents Eduard , Almirante Benito , Gavaldà Joan 
Published: November 2017

ABSTRACT
Long-term catheter-related bloodstream infections (CRBSIs) involving coagulase-negative staphylococci are associated with poor patient outcomes, increased hospitalization, and high treatment costs. The use of vancomycin lock therapy has been an important step forward in treatment of these biofilms, although failures occur in 20% of patients. In this study, we report that a high dose of daptomycin lock therapy may offer a therapeutic advantage for these CRBSIs in just 24 h of treatment.
Combination Antibiotic Exposure Selectively Alters the Development of Vancomycin Intermediate Resistance in Staphylococcus aureus
Authors: Zheng Xuting , Berti Andrew D. , McCrone Sue , Roch Melanie , Rosato Adriana E. , Rose Warren E. , Chen Baiyi 
Published: November 2017

ABSTRACT

Invasive methicillin-resistant
Staphylococcus aureus
(MRSA) treated with vancomycin (VAN) is associated with reduced VAN susceptibility and treatment failure. VAN combination therapy is one strategy to improve response, but comprehensive assessments of combinations to prevent resistance are limited. This study identifies optimal combinations to prevent the emergence of VAN-intermediate
Staphylococcus aureus
(VISA). Two standard MRSA and two heterogeneous VISA (hVISA) strains were exposed for 28 days
in vitro
to VAN alone, VAN with cefazolin (CFZ), fosfomycin, gentamicin, meropenem, rifampin, piperacillin-tazobactam (TZP), or trimethoprim-sulfamethoxazole. In addition to VAN susceptibility testing, cell wall thickness (CWT), carotenoid content, and membrane fluidity were determined for Mu3. VAN plus any β-lactam limited the VAN MIC increase to 1 to 4 mg/liter throughout the 28-day exposure, with CFZ and TZP being the most effective agents (VAN MIC = 1 to 2 mg/liter). Similar MIC trends occurred with the lipo-/glycopeptide agents daptomycin and telavancin, where β-lactam combinations with VAN prevented MIC increases to these agents as well. Combinations with non-β-lactams were ineffective in preventing VAN MIC increases with VAN MICs of 4 to 16 mg/liter emerging during weeks 2 to 4 of treatment. VAN plus β-lactam decreased CWT significantly, whereas VAN plus other antibiotics significantly increased the CWT. No correlation was observed between carotenoid content or membrane fluidity and antibiotic exposure. Only the combination exposures of VAN plus β-lactam suppress the development of VISA. Rational selection of VAN plus β-lactam should be further explored as a long-term combination treatment of MRSA infections due to their ability to suppress VAN resistance.
Whole-Genome Characterization of Bacillus cereus Associated with Specific Disease Manifestations
Authors: Chang T. , Rosch J. W. , Gu Z. , Hakim H. , Hewitt C. , Gaur A. , Wu G. , Hayden R. T. 
Published: November 2017

ABSTRACT

Bacillus cereus
remains an important cause of infections, particularly in immunocompromised hosts. While typically associated with enteric infections, disease manifestations can be quite diverse and include skin infections, bacteremia, pneumonia, and meningitis. Whether there are any genetic correlates of bacterial strains with particular clinical manifestations remains unknown. To address this gap in understanding, we undertook whole-genome analysis of
B. cereus
strains isolated from patients with a range of disease manifestations, including noninvasive colonizing disease, superficial skin infections, and invasive bacteremia. Interestingly, strains involved in skin infection tended to form a distinct genetic cluster compared to isolates associated with invasive disease. Other disease manifestations, despite not being exclusively clustered, nonetheless had unique genetic features. The unique features associated with the specific types of infections ranged from traditional virulence determinants to metabolic pathways and gene regulators. These data represent the largest genetic analysis to date of pathogenic
B. cereus
isolates with associated clinical parameters.
Do emotions related to alcohol consumption differ by alcohol type? An international cross-sectional survey of emotions associated with alcohol consumption and influence on drink choice in different settings
Authors: Ashton Kathryn , Bellis Mark A , Davies Alisha R , Hughes Karen , Winstock Adam 
Published: November 2017

ObjectivesTo examine the emotions associated with drinking different types of alcohol, explore whether these emotions differ by sociodemographics and alcohol dependency and whether the emotions associated with different drink types influence people’s choice of drinks in different settings.DesignInternational cross-sectional opportunistic survey (Global Drug Survey) using an online anonymous questionnaire in 11 languages promoted through newspapers, magazines and social media from November 2015 to January 2016.Study populationIndividuals aged 18–34 years who reported consumption of beer, spirits, red and white wine in the previous 12 months and were resident in countries with more than 200 respondents (n=21 countries; 29 836 respondents).Main outcome measuresPositive and negative emotions associated with consumption of different alcoholic beverages (energised, relaxed, sexy, confident, tired, aggressive, ill, restless and tearful) over the past 12 months in different settings.ResultsAlcoholic beverages vary in the types of emotions individuals report they elicit, with spirits more frequently eliciting emotional changes of all types. Overall 29.8% of respondents reported feeling aggressive when drinking spirits, compared with only 7.1% when drinking red wine (p<0.001). Women more frequently reported feeling all emotions when drinking alcohol, apart from feelings of aggression. Respondents’ level of alcohol dependency was strongly associated with feeling all emotions, with the likelihood of aggression being significantly higher in possible dependent versus low risk drinkers (adjusted OR 6.4; 95% CI 5.79 to 7.09; p<0.001). The odds of feeling the majority of positive and negative emotions also remained highest among dependent drinkers irrespective of setting.ConclusionUnderstanding emotions associated with alcohol consumption is imperative to addressing alcohol misuse, providing insight into what emotions influence drink choice between different groups in the population. The differences identified between sociodemographic groups and influences on drink choice within different settings will aid future public health practice to further comprehend individuals’ drinking patterns and influence behaviour change.
South Atlantic Perspectives on the Future International Legally Binding Instrument under the losc on Conservation and Sustainable Use of bbnj
Authors: Ribeiro Marta Chantal 
Published: November 2017

Abstract
The article focuses on the ocean governance systems of the South Atlantic Ocean aiming to contribute to the on-going debate concerning the development of an international legally binding instrument (ilbi) under the un Convention on the Law of the Sea on conservation and sustainable use of marine biodiversity beyond national jurisdiction (bbnj). For this purpose, a broad definition of South Atlantic Ocean has been adopted. The regional treaties and global initiatives relevant for the area are analysed in the context of discussions addressing bbnj. It also evaluated the importance of submissions to the Commission on the Limits of the Continental Shelf concerning the region. The main conclusion is that an ilbi is needed to supplement non-existent or insufficient ocean governance systems in the region and to strengthen and foster the progress of the regional ocean’s governance framework, provided that crucial factors such as transfer of technology and capacity-building are adequately addressed.
Regional Management of Areas beyond National Jurisdiction in the Western Indian Ocean: State of Play and Possible Ways Forward
Authors: Wright Glen , Rochette Julien 
Published: November 2017

Abstract
In recent years, the international community has become increasingly aware of the growing threats to marine biodiversity in areas beyond national jurisdiction (abnj), and international discussions on a new international legally binding are underway. In parallel, some States, through regional organisations, have progressively extended their activities into abnj, particularly through the development of area-based management tools (abmts). In this article, we consider how actors in the Western Indian Ocean (wio) might engage in abnj governance. In particular, we develop some possible scenarios for developing abmts in the wio, including through the development of fisheries closures, the establishment of marine protected areas (mpas), and the adoption of abmts under the auspices of relevant international organisations. We conclude that while the wio is currently not the most advanced region in terms of ongoing efforts to improve the governance of abnj, there are already some positive signals and promising options for the future.
Strengthening Governance Frameworks for Conservation and Sustainable Use of Marine Biodiversity in Areas beyond National Jurisdiction: Southern Hemisphere Perspectives
Authors: Warner Robin 
Published: November 2017

Abstract
The southern hemisphere is dominated by oceanic influences with 80% of its surface area consisting of ocean space. It hosts abundant marine biodiversity, which is under increasing pressure from activities such as fisheries and shipping as well as multiple sources of marine pollution and climate change impacts. The process initiated by the un General Assembly Resolution 69/292 to develop the elements of an international legally binding instrument (ilbi) for conservation and sustainable use of marine biodiversity in areas beyond national jurisdiction has the potential to contribute to a more integrated and cross-sectoral system of oceans governance at a global and regional scale. This article examines key features of the existing global and regional ocean governance framework in the southern hemisphere and how the anticipated ilbi might relate to existing ocean governance frameworks.
Validating the use of brain volume cutoffs to identify clinically relevant atrophy in RRMS
Authors: Bovis Francesca , De Stefano Nicola , Steinerman Joshua R , Knappertz Volker , Sormani Maria Pia 
Published: November 2017

Background: Baseline brain volume (BV) is predictive at a group level but is difficult to interpret at the single patient level. Objective: To validate BV cutoffs able to identify clinically relevant atrophy in relapsing–remitting multiple sclerosis (RRMS) patients. Methods: The expected normalized brain volume (NBV) for each patient was calculated using RRMS patients from two phase III clinical trials, applying a linear formula developed on the baseline variable of an independent data set. The difference between these expected NBV values and those actually observed was calculated and used to categorize the patients in the low-NBV, medium-NBV, and high-NBV groups. Results: The 2-year probability of 3-month confirmed disability worsening was significantly associated with the NBV categorization ( p = 0.006), after adjusting for treatment effect. Taking the high-NBV group as a reference, the hazard ratios for the medium-NBV and low-NBV groups were 1.22 (95% confidence interval (CI): 0.85–1.76, p = 0.27) and 1.69 (95% CI: 1.11–2.57, p = 0.01), respectively. Conclusion: This study validates the use of BV cutoffs to identify clinically relevant atrophy in RRMS study by showing that the three groups classified according to the baseline NBV adjusted for the other prognostic variables have a significant prognostic impact on the risk of disability progression.
Cardiovascular disease predictors and adipose tissue macrophage polarization: Is there a link?
Authors: Kralova Lesna Ivana , Petras Marek , Cejkova Sona , Kralova Anna , Fronek Jiri , Janousek Libor , Thieme Filip , Tyll Tomas , Poledne Rudolf 
Published: November 2017

Background The risk of cardiovascular disease is closely connected to adipose tissue inflammation. The links between cardiovascular risk predictors and pro and anti-inflammatory macrophages in human adipose tissue were analysed to gain an insight into the pathophysiology of cardiovascular disease. Design Subcutaneous and visceral adipose tissues were obtained from 79 subjects, 52 living kidney donors (during nephrectomy) and 27 patients with peripheral artery disease (during arterial tree reconstruction). Methods Macrophage subsets were isolated from adipose tissues and analysed by flow cytometry using CD14, CD16, CD36 and CD163 monoclonal antibodies. The mutually adjusted differences of phagocytic pro-inflammatory (CD14 + CD16 + CD36high), anti-inflammatory (CD14 + CD16-CD163+) and transitional subsets of macrophages were analysed in relation to cardiovascular predictors (sex, age, body mass index, smoking, hypercholesterolaemia, hypertension and statin treatment). Results Age, male sex and hypercholesterolaemia were closely positively associated with the phagocytic pro-inflammatory macrophage subset in visceral adipose tissues. Interestingly, the proportion of phagocytic pro-inflammatory macrophages was relevantly decreased by statin therapy. A strong positive association of body mass index to the phagocytic pro-inflammatory subset was found in subcutaneous adipose tissues only. A minor transitional subpopulation, CD14 + CD16 + CD36lowCD163+, increased with age in both adipose tissues. This transitional subpopulation was also negatively associated with obesity and hypercholesterolaemia in visceral adipose tissues. Conclusion An effect of cardiovascular risk predictors on adipose tissue macrophage subpopulations was revealed. Interestingly, while age, male sex and hypercholesterolaemia were connected with the pro-inflammatory macrophage subpopulation in visceral adipose tissues, body mass index had a prominent effect in subcutaneous adipose tissues only. A decreasing effect of statins on these pro-inflammatory macrophages was documented.
Microbiology and antibiotic susceptibility patterns in spontaneous bacterial peritonitis: A study of two Dutch cohorts at a 10‐year interval
Authors: Oey Rosalie C , de Man Robert A , Erler Nicole S , Verbon Annelies , van Buuren Henk R 
Published: November 2017

BackgroundRecent investigations suggest an increasing prevalence of Gram‐positive and antibiotic‐resistant bacteria causing spontaneous bacterial peritonitis (SBP), probably related to changes in antibiotic prescription patterns, in particular more widespread and long‐term use of antibiotic prophylaxis with quinolones.ObjectiveThe primary objective of this study was to assess potential changes in the microbiology of SBP in two patient cohorts studied at a 10‐year interval. Further aims were to study prognostic factors and outcome of SBP.MethodsA retrospective double‐cohort study, including all ascitic cultures from patients with cirrhosis obtained 2003–2005 and 2013–2014, was conducted.ResultsIn total 312 patients were included, 125 patients in the first and 187 patients in the second cohort. SBP was diagnosed in 132 of 840 analyzed ascitic fluid samples; 62 samples were culture positive. An increase of Gram‐positive bacterial isolates was noted from 26% to 46% between cohorts (p = 0.122). The prevalence of multidrug‐antibiotic–resistant pathogens increased from 25% to 32% (p = 0.350). Survival after SBP among the two cohorts was comparable.ConclusionThis single‐center study in the Netherlands found a modest but nonsignificant increase in the proportion of patients with SBP caused by Gram‐positive bacteria and multidrug‐antibiotic–resistant bacteria over a 10‐year period. Our findings differ from reported data in other countries and suggest empiric antibiotic prophylaxis and treatment of SBP should be based on national and regional microbiological findings and resistance patterns.
History of Diabetes and Survival Outcome Among Participants 65 Years or Older in SWOG Clinical Trials
Authors: Hershman Dawn L. , Till Cathee , Wright Jason D. , Ramsey Scott , Barlow William E. , Unger Joseph M. 
Published: November 2017

Purpose Diabetes is common, increases with age, and may affect outcomes among people with cancer. Understanding the association between diabetes and cancer outcome is challenging, because patients with diabetes have increased all-cause mortality compared with patients without diabetes. Methods We systematically examined the phase III trial database of SWOG to identify patients enrolled in trials during the period from 1999 to 2011. We linked the SWOG clinical records to Medicare claims data according to Social Security number, sex, and date of birth. Medicare claims were used to identify diabetes with at least 6 months of continuous Medicare coverage immediately before registration. Multivariable Cox regression was used to compare survival outcomes between patients with and without diabetes for each of 10 tumor cohorts. The primary outcome was overall survival. We also examined progression-free survival and cancer-free survival. Results In total, 6,422 patients from 15 trials were ≥ 65.5 years of age, of whom 3,173 patients (49%) met the criteria for linkage to Medicare claims. Thirty percent (n = 952) had claims for diabetes before registration. Patients with diabetes were more likely to be black ( P < .001), but no other differences in demographic characteristics were observed. In multivariable Cox regression, no association was found between baseline diabetes and overall or progression-free survival; in one case, patients with diabetes had marginally worse cancer-free survival (advanced non–small-cell lung cancer; P = .05). A global test found that baseline diabetes was associated with worse overall survival ( P = .03) across the entire panel of analyses. Conclusion Diabetes is common among elderly patients enrolled in clinical trials. Unlike prior observational studies, among patients treated with uniform treatment regimens, and controlling for known prognostic factors, we did not observe an association between diabetes and progression-free or cancer-free survival.
Long-Term Outcomes of 107 Cases of Primary Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma at a Single Medical Institution in Japan
Authors: Watanabe Natsuko , Narimatsu Hiroto , Noh Jaeduk Yoshimura , Iwaku Kenji , Kunii Yo , Suzuki Nami , Ohye Hidemi , Suzuki Miho , Matsumoto Masako , Yoshihara Ai , Kameyama Kaori , Kobayashi Kazuhiko , Kami Masahiro , Sugino Kiminori , Ito Koichi 
Published: November 2017

Abstract

Context
Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis.

Objective
To provide information on long-term outcomes that would facilitate establishment of the optimal management strategy for thyroid lymphoma.

Design, Setting, and Participants
Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed.

Main Outcome Measure
Overall and event-free survival (EFS).

Results
Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% [95% confidence interval (CI), 87% to 97%] and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively.

Conclusions
Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities.
Ένα διδακτικό σενάριο για την “Οργανωσιακή Κουλτούρα” βασιζόμενο στη μέθοδο της Μετασχηματίζουσας Μάθησης μέσα από την αισθητική εμπειρία.
Authors: Αθανασιάδης Αναστάσιος 
Published: November 2017

Η χρήση της τέχνης ως εργαλείου κριτικής σκέψης στην ενήλικη μάθηση παρουσιάστηκε από τον Α. Κόκκο το 2009, στην 8η Διεθνή συνδιάσκεψη για τη μετασχηματίζουσα μάθηση. Η μέθοδος υποστηρίζει τη σημασία της συστηματικής παρατήρησης και της κριτικής ανάλυσης έργων τέχνης στο πλαίσιο της μετασχηματίζουσας μάθησης. Αποτελείται από 5 διακριτά στάδια, ενώ οι βασικές της παραδοχές στηρίζονται στις ιδέες του Freire, στη χρήση σημαντικών έργων τέχνης, στη χρήση της αισθητικής εμπειρίας και στις τεχνικές παρατήρησης Perkins και Visible thinking. Το διδακτικό σενάριο που ακολουθεί αποσκοπεί να αποτυπώσει τα βήματα της παραπάνω μεθόδου στην προσπάθεια μετασχηματισμού των στερεοτυπικών αντιλήψεων μιας ομάδας εκπαιδευομένων-δημοσίων υπαλλήλων- αναφορικά με το θέμα της Οργανωσιακής Κουλτούρας των δημόσιων υπηρεσιών. Η υλοποίησή του πραγματώθηκε στο πλαίσιο ενός 5νθήμερου επιμορφωτικού σεμιναρίου.