bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of visually estimated blood loss with direct hemoglobin measurement in multilevel spine surgery
Authors: Guinn Nicole R. , Broomer Bob W. , White William , Richardson William , Hill Steven E. 
Published: February 2013

BackgroundEstimates of blood loss in the operating room are typically performed as a visual assessment by providers, despite multiple studies showing this to be inaccurate. Use of a less subjective measurement of blood loss such as direct measurement of the hemoglobin (Hb) mass lost from the surgical field may better quantify surgical bleeding. The objective of this investigation was to compare anesthesiologist estimates of intraoperative blood loss with measured Hb loss.Study Design and MethodsSixty patients undergoing posterior spine surgery were enrolled in a prospective, randomized trial comparing intraoperative blood loss using unipolar cautery alone or with use of a bipolar tissue sealant device. Hb concentration and fluid volume were measured from all surgical sponges, suction canisters, and the cell salvage device. Using the volume and concentration of Hb from each solution allowed calculation of Hb mass, which was converted into volume of blood lost and compared with estimates of blood loss documented by the anesthesia team. A single‐sample t test of no difference was used to compare estimated with measured blood loss.ResultsMean estimated blood loss exceeded measured blood loss by 246 mL (860 mL vs. 614 mL, p < 0.0001).ConclusionEstimated blood loss exceeded measured blood loss by 40% on average. The likely etiology of this discrepancy relates to the inability to visually determine Hb concentration of sanguineous solutions in suction canisters and surgical sponges. Ramifications of excessive bleeding estimates include unnecessary transfusion and overadministration of intravenous fluids, both of which may have deleterious effects.
Aberrant wound healing in the horse: Naturally occurring conditions reminiscent of those observed in man
Authors: Theoret Christine L. , Wilmink Jacintha M. 
Published: February 2013

AbstractImpaired wound healing represents an enormous clinical and financial problem for companion animals and humans alike. Unfortunately, most models used to study healing rely on rodents, which have significant differences in the healing and scarring process and rarely develop complications. In order to better simulate impaired healing, the model should strive to reproduce the natural processes of healing and delayed healing. Wounds on the limbs of horses display similarities to wounds in humans in their epithelialization/contraction ratio, genetic influence as well as dysregulated cytokine profile and the spontaneous development of fibroproliferative disorders. Veterinarians have access to advanced wound therapies that are often identical to those provided to human patients. Wound research in large animals has resulted in new wound models as well as a better understanding of the physiology, immunology, and local environmental impact on both normal and aberrant wound healing. One such model reproduces the naturally occurring fibroproliferative disorder of horses known as exuberant granulation tissue. Comparisons between the normally healing and impaired wounds provide insight into the repair process and can facilitate product development. A better understanding of the wound healing physiopathology based on clinically accurate animal models should lead to the development of novel therapies thereby improving outcomes in both human and veterinary patients.
Dipeptidyl‐peptidase‐like‐proteins confer high sensitivity to the scorpion toxin AmmTX3 to Kv4‐mediated A‐type K+ channels
Authors: Maffie Jon K. , Dvoretskova Elena , Bougis Pierre Edouard , Martin‐Eauclaire Marie‐France , Rudy Bernardo 
Published: February 2013

Key points
AmmTX3, a member of the α‐KTX15 family of scorpion toxins, efficiently and specifically blocks the subthreshold‐operating A‐type K+ current in cerebellar granule neurons from wild‐type mice but not in neurons from mice lacking the Kv4 channel‐associated protein DPP6.
In heterologous cells high‐affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 requires the presence of the associated proteins DPP6 and DPP10.
These results validate AmmTX3 as a specific blocker of Kv4 channels in CNS neurons and explain the discrepancy between previous observations in neurons and heterologous cells.
They contribute a powerful tool to investigate the physiological role of A‐type K+ currents, believed to be important in dendritic integration and plasticity and to be involved in a number of diseases.
Our results demonstrate that, in addition to changing the kinetics and voltage dependence of Kv4 channel complexes, DDP‐like Kv4‐associated proteins also affect their pharmacological profile.
Abstract  K+ channels containing Kv4.2 and Kv4.3 pore‐forming subunits mediate most of the subthreshold‐operating somatodendritic A‐type K+ current in CNS neurons. These channels are believed to be important in regulating the frequency of repetitive firing, the backpropagation of action potential into dendrites, and dendritic integration and plasticity. Moreover, they have been implicated in several diseases from pain to epilepsy and autism spectrum disorders. The lack of toxins that specifically and efficiently block these channels has hampered studies aimed at confirming their functional role and their involvement in disease. AmmTX3 and other related members of the α‐KTX15 family of scorpion toxins have been shown to block the A‐type K+ current in cultured neurons, but their specificity has been questioned because the toxins do not efficiently block the currents mediated by Kv4.2 or Kv4.3 subunits expressed in heterologous cells. Here we show that the high‐affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 depends on the presence of the auxiliary subunits DPP6 and DPP10. These proteins are thought to be components of the Kv4 channel complex in neurons and to be important for channel expression in dendrites. These studies validate the use of AmmTX3 as a blocker of the Kv4‐mediated A‐type K+ current in neurons.
Inoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Model
Authors: Docobo-Pérez F. , López-Cerero L. , López-Rojas R. , Egea P. , Domínguez-Herrera J. , Rodríguez-Baño J. , Pascual A. , Pachón J. 
Published: February 2013

ABSTRACT

Escherichia coli
is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced
in vitro
activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing
E. coli
bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical
E. coli
strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {∼5.5 log
10
CFU/g [low inoculum concentration (LI)] or ∼7.5 log
10
CFU/g [high inoculum concentration (HI)]} using
E. coli
strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (−2.53 and −2.14 log
10
CFU/g [
P
< 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (−1.01 log
10
CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: −0.73, −1.89, and −1.62 log
10
CFU/g (
P
< 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to −1.67 log
10
CFU/g (
P
< 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing
E. coli
strains in patients with therapeutic failure with piperacillin-tazobactam.
Zafirlukast Inhibits Complexation of Lsr2 with DNA and Growth of Mycobacterium tuberculosis
Authors: Pinault Lucile , Han Jeong-Sun , Kang Choong-Min , Franco Jimmy , Ronning Donald R. 
Published: February 2013

ABSTRACT

The mycobacterial nucleoid-associated protein Lsr2 is a DNA-bridging protein that plays a role in condensation and structural organization of the genome and acts as a global repressor of gene transcription. Here we describe experiments demonstrating that zafirlukast inhibits the complexation between Lsr2 and DNA
in vitro
. Zafirlukast is shown to inhibit growth in two different species of mycobacteria tested but exhibits no growth inhibition of
Escherichia coli
. The Lsr2 inhibitory activity is reflected
in vivo
as determined by monitoring of transcription levels in
Mycobacterium tuberculosis
. These data suggest that zafirlukast inhibits Lsr2 function
in vivo
, promoting dysregulation of the expression of an array of genes typically bound by Lsr2 and hindering growth. Since zafirlukast likely operates by a mechanism distinct from current
M. tuberculosis
drugs and is currently used as a prophylactic treatment for asthma, it offers an intriguing lead for development of new treatments for tuberculosis.
The Actin-Polymerizing Activity of SipA Is Not Essential for Salmonella enterica Serovar Typhimurium-Induced Mucosal Inflammation
Authors: Li Dongju , Wang Xueqin , Wang Lu , Zhou Daoguo 
Published: February 2013

ABSTRACT

Salmonella enterica
serovar Typhimurium depends on type III secretion systems to inject effector proteins into host cells to promote bacterial invasion and to induce intestinal inflammation. SipA, a type III effector, is known to play important roles in both the invasion and the elicitation of intestinal inflammation. The actin-modulating activity of SipA has been shown to promote
Salmonella
entry into epithelial cells. To investigate whether the actin-modulating activity of SipA is required for its ability to induce an inflammatory response
in vivo
, we generated the SipA
K635A E637W
mutant, which is deficient in actin-modulating activity.
Salmonella
strains expressing the chromosomal SipA
K635A E637W
point mutation had reduced invasion abilities but still caused colitis similar to that caused by the wild-type strain in a mouse model of infection. Our data indicate that the SipA actin-polymerizing activity is not essential for the SipA-induced inflammatory response in the mouse model of infection.
H
2
-Independent Growth of the Hydrogenotrophic Methanogen Methanococcus maripaludis
Authors: Costa Kyle C. , Lie Thomas J. , Jacobs Michael A. , Leigh John A. 
Published: February 2013

ABSTRACT

Hydrogenotrophic methanogenic
Archaea
require reduced ferredoxin as an anaplerotic source of electrons for methanogenesis. H
2
oxidation by the hydrogenase Eha provides these electrons, consistent with an H
2
requirement for growth. Here we report the identification of alternative pathways of ferredoxin reduction in
Methanococcus maripaludis
that operate independently of Eha to stimulate methanogenesis. A suppressor mutation that increased expression of the glycolytic enzyme glyceraldehyde-3-phosphate:ferredoxin oxidoreductase resulted in a strain capable of H
2
-independent ferredoxin reduction and growth with formate as the sole electron donor. In this background, it was possible to eliminate all seven hydrogenases of
M. maripaludis
. Alternatively, carbon monoxide oxidation by carbon monoxide dehydrogenase could also generate reduced ferredoxin that feeds into methanogenesis. In either case, the reduced ferredoxin generated was inefficient at stimulating methanogenesis, resulting in a slow growth phenotype. As methanogenesis is limited by the availability of reduced ferredoxin under these conditions, other electron donors, such as reduced coenzyme F
420
, should be abundant. Indeed, when F
420
-reducing hydrogenase was reintroduced into the hydrogenase-free mutant, the equilibrium of H
2
production via an F
420
-dependent formate:H
2
lyase activity shifted markedly toward H
2
compared to the wild type.

IMPORTANCE
Hydrogenotrophic methanogens are thought to require H
2
as a substrate for growth and methanogenesis. Here we show alternative pathways in methanogenic metabolism that alleviate this H
2
requirement and demonstrate, for the first time, a hydrogenotrophic methanogen that is capable of growth in the complete absence of H
2
. The demonstration of alternative pathways in methanogenic metabolism suggests that this important group of organisms is metabolically more versatile than previously thought.
Unexpected Diversity during Community Succession in the Apple Flower Microbiome
Authors: Shade Ashley , McManus Patricia S. , Handelsman Jo 
Published: February 2013

ABSTRACT

Despite its importance to the host, the flower microbiome is poorly understood. We report a culture-independent, community-level assessment of apple flower microbial diversity and dynamics. We collected flowers from six apple trees at five time points, starting before flowers opened and ending at petal fall. We applied streptomycin to half of the trees when flowers opened. Assessment of microbial diversity using tag pyrosequencing of 16S rRNA genes revealed that the apple flower communities were rich and diverse and dominated by members of TM7 and
Deinococcus-Thermus
, phyla about which relatively little is known. From thousands of taxa, we identified six successional groups with coherent dynamics whose abundances peaked at different times before and after bud opening. We designated the groups Pioneer, Early, Mid, Late, Climax, and Generalist communities. The successional pattern was attributed to a set of prevalent taxa that were persistent and gradually changing in abundance. These taxa had significant associations with other community members, as demonstrated with a cooccurrence network based on local similarity analysis. We also detected a set of less-abundant, transient taxa that contributed to general tree-to-tree variability but not to the successional pattern. Communities on trees sprayed with streptomycin had slightly lower phylogenetic diversity than those on unsprayed trees but did not differ in structure or succession. Our results suggest that changes in apple flower microbial community structure are predictable over the life of the flower, providing a basis for ecological understanding and disease management.

IMPORTANCE
Flowering plants (angiosperms) represent a diverse group of an estimated 400,000 species, and their successful cultivation is essential to agriculture. Yet fundamental knowledge of flower-associated microbiotas remains largely unknown. Even less well understood are the changes that flower microbial communities experience through time. Flowers are particularly conducive to comprehensive temporal studies because they are, by nature, ephemeral organs. Here, we present the first culture-independent time series of bacterial and archaeal communities associated with the flowers of apple, an economically important crop. We found unexpected diversity on apple flowers, including a preponderance of taxa affiliated with
Deinococcus
-
Thermus
and TM7, phyla that are understudied but thought to be tolerant to an array of environmental stresses. Our results also suggest that changes in microbial community structure on the apple flower may be predictable over the life of the flower, providing the basis for ecological understanding and disease management.
The transition between work, sickness absence and pension in a cohort of Danish colorectal cancer survivors
Authors: Carlsen Kathrine , Harling Henrik , Pedersen Jacob , Christensen Karl Bang , Osler Merete 
Published: February 2013

ObjectivesThe aim of this study was to evaluate the impact of socioeconomic and clinical factors on the transitions between work, sickness absence and retirement in a cohort of Danish colorectal cancer survivors.DesignRegister-based cohort study with up to 10 years of follow-up.SettingPopulation-based study with use of administrative health-related and socioeconomic registers.ParticipantsAll persons (N=4343) diagnosed with colorectal cancer in Denmark during the years 2001–2009 while they were in their working age (18–63 years) and who were part of the labour force 1 year postdiagnosis.Primary and secondary outcome measuresBy the use of multistate models in Cox proportional hazards models, we analysed the HR for re-employment, sickness absence and retirement in models including clinical as well as health-related variables.Results1 year after diagnosis, 62% were working and 58% continued until the end of follow-up. Socioeconomic factors were found to be associated with retirement but not with sickness absence and return to work. The risk for transition from work to sickness absence increased if the disease was diagnosed at a later stage (stage III) 1.52 (95% CI 1.21 to 1.91), not operated curatively 1.35 (95% CI 1.11 to 1.63) and with occurrence of postoperative complications 1.25 (95% CI 1.11 to 1.41). The opposite was found for the transition from sickness absence back to work.ConclusionsThis nationwide study of colorectal cancer patients who have survived 1 year shows that the stage of disease, general health condition of the individual, postoperative complications and the history of sickness absence and unemployment have an impact on the transition between work, sickness absence and disability pension. This leads to an increased focus on the rehabilitation process for the more vulnerable persons who have a combination of severe disease and a history of work-related problems with episodes outside the working market.
Exploring the potential of expatriate social networks to reduce HIV and STI transmission: a protocol for a qualitative study
Authors: Crawford Gemma , Bowser Nicole Jasmine , Brown Graham Ernest , Maycock Bruce Richard 
Published: February 2013

IntroductionHIV diagnoses acquired among Australian men working or travelling overseas including Southeast Asia are increasing. This change within transmission dynamics means traditional approaches to prevention need to be considered in new contexts. The significance and role of social networks in mediating sexual risk behaviours may be influential. Greater understanding of expatriate and traveller behaviour is required to understand how local relationships are formed, how individuals enter and are socialised into networks, and how these networks may affect sexual intentions and behaviours. This paper describes the development of a qualitative protocol to investigate how social networks of Australian expatriates and long-term travellers might support interventions to reduce transmission of HIV and sexually transmitted infections.Methods and analysisTo explore the interactions of male expatriates and long-term travellers within and between their environments, symbolic interactionism will be the theoretical framework used. Grounded theory methods provide the ability to explain social processes through the development of explanatory theory. The primary data source will be interviews conducted in several rounds in both Australia and Southeast Asia. Purposive and theoretical sampling will be used to access participants whose data can provide depth and individual meaning.Ethics and disseminationThe role of expatriate and long-term traveller networks and their potential to impact health are uncertain. This study seeks to gain a deeper understanding of the Australian expatriate culture, behavioural contexts and experiences within social networks in Southeast Asia. This research will provide tangible recommendations for policy and practice as the findings will be disseminated to health professionals and other stakeholders, academics and the community via local research and evaluation networks, conference presentations and online forums. The Curtin University Human Research Ethics Committee has granted approval for this research.
Ex Vivo Activation of CD56+ Immune Cells That Eradicate Neuroblastoma
Authors: Rujkijyanont Piya , Chan Wing Keung , Eldridge Paul W. , Lockey Timothy , Holladay Martha , Rooney Barbara , Davidoff Andrew M. , Leung Wing , Vong Queenie 
Published: February 2013

Abstract
Despite the use of intensive contemporary multimodal therapy, the overall survival of patients with high-risk neuroblastoma is still less than 50%. Therefore, immunotherapy without cross-resistance and overlapping toxicity has been proposed. In this study, we report the development of a novel strategy to specifically activate and expand human CD56+ (NCAM1) natural killer (NK) immune cells from normal donors and patients with neuroblastoma. Enriched CD56+ cells from peripheral blood were mixed with CD56− fraction at 1:1 ratio and cultured in the presence of OKT3, interleukin (IL)-2, and -15 for five days and then without OKT3 for 16 more days. The final products contained more than 90% CD56+ cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B. Successful clinical scale-up in a good manufacturing practices (GMP)-compliant bioreactor yielded effector cells that in a neuroblastoma xenograft model slowed tumor growth and extended survival without GVHD. Investigation of CD56+ cells from patients with neuroblastoma revealed a similar postactivation phenotype and lytic activity. Our findings establish a novel and clinically expedient strategy to generate allogeneic or autologous CD56+ cells that are highly cytotoxic against neuroblastoma with minimal risk of GVHD. Cancer Res; 73(8); 2608–18. ©2013 AACR.
Regulation of Lung Cancer Metastasis by Klf4-Numb–like Signaling
Authors: Vaira Valentina , Faversani Alice , Martin Nina M. , Garlick David S. , Ferrero Stefano , Nosotti Mario , Kissil Joseph L. , Bosari Silvano , Altieri Dario C. 
Published: February 2013

Abstract
Metastatic traits seem to be acquired by transformed cells with progenitor-like cancer-initiating properties, but there remains little mechanistic insight into this linkage. In this report, we show that the polarity protein Numbl, which is expressed normally in neuronal progenitors, becomes overexpressed and mislocalized in cancer cells from a variety of human tumors. Numbl overexpression relies on loss of the tumor suppressor miRNA-296-5p (miR-296), which actively represses translation of Numbl in normal cells. In turn, deregulated expression of Numbl mediates random tumor cell migration and invasion, blocking anoikis and promoting metastatic dissemination. In clinical specimens of non–small cell lung cancer, we found that Numbl overexpression correlated with a reduction in overall patient survival. Mechanistically, Numbl-mediated tumorigenesis involved suppression of a “stemness” transcriptional program driven by the stem cell programming transcription factor Klf4, thereby preserving a pool of progenitor-like cells in lung cancer. Our results reveal that Numbl-Klf4 signaling is critical to maintain multiple nodes of metastatic progression, including persistence of cancer-initiating cells, rationalizing its therapeutic exploitation to improve the treatment of advanced lung cancer Cancer Res; 73(8); 2695–705. ©2013 AACR.