bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of the Antimicrobial Peptide Pardaxin (GE33) To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice with Skin Injuries
Authors: Huang Han-Ning , Pan Chieh-Yu , Chan Yi-Lin , Chen Jyh-Yih , Wu Chang-Jer 
Published: December 2013

ABSTRACT

Antimicrobial peptides (AMPs) have recently been determined to be potential candidates for treating drug-resistant bacterial infections. Pardaxin (GE33), a marine antimicrobial peptide, has been reported to possess antimicrobial function. In this study, we investigated whether pardaxin promoted healing of contaminated wounds in mice. One square centimeter of outer skin was excised from the ventral region of mice, and a lethal dose of methicillin-resistant
Staphylococcus aureus
(MRSA) was applied in the presence or absence of methicillin, vancomycin, or pardaxin. While untreated mice and mice treated with methicillin died within 3 days, mice treated with pardaxin survived infection. Pardaxin decreased MRSA bacterial counts in the wounded region and also enhanced wound closure. Reepithelialization and dermal maturation were also faster in mice treated with pardaxin than in mice treated with vancomycin. In addition, pardaxin treatment controlled excess recruitment of monocytes and macrophages and increased the expression of vascular endothelial growth factor (VEGF). In conclusion, these results suggest that pardaxin is capable of enhancing wound healing. Furthermore, this study provides an excellent platform for comparing the antimicrobial activities of peptide and nonpeptide antibiotics.
Not all suffering is pain: sources of patients’ suffering in the emergency department call for improvements in communication from practitioners
Authors: Body Richard , Kaide Ergul , Kendal Sarah , Foex Bernard 
Published: December 2013

BackgroundProvision of prompt, effective analgesia is rightly considered as a standard of care in the emergency department (ED). However, much suffering is not ‘painful’ and may be under-recognised. We sought to describe the burden of suffering in the ED and explore how this may be best addressed from a patient centred perspective.MethodsIn a prospective cohort study, we included undifferentiated patients presenting to the ED. We undertook two face to face questionnaires with the first immediately following triage. We asked patients: (a) if they were ‘suffering’; (b) how they were suffering; and (c) what they hoped would be done to ease this. Prior to leaving the ED, we asked patients what had been done to ease their suffering. Data were analysed thematically.ResultsOf 125 patients included, 77 (61.6%) reported suffering on direct questioning and 92 (73.6%) listed at least one way in which they were suffering. 90 (72.0%) patients had a pain score >0/10 but only 37 (29.6%) reported that pain was causing suffering. Patients reported suffering from both physical symptoms (especially pain, nausea, vomiting and dizziness) and emotional distress (notably anxiety). Treatment (to ease physical and emotional symptoms), information (particularly diagnosis, reassurance and explanation), care (notably friendly staff) and closure (being seen, resolving the problem and going home) were the key themes identified as important for relief of suffering.ConclusionsIn seeking to ease suffering in the ED, clinicians must focus not only on providing analgesia but on treatingEmotional distress,Physical symptoms, providingInformation,Care andClosure (EPICC).
Targeting a Glioblastoma Cancer Stem-Cell Population Defined by EGF Receptor Variant III
Authors: Emlet David R. , Gupta Puja , Holgado-Madruga Marina , Del Vecchio Catherine A. , Mitra Siddhartha S. , Han Shuang-Yin , Li Gordon , Jensen Kristin C. , Vogel Hannes , Xu Linda Wei , Skirboll Stephen S. , Wong Albert J. 
Published: December 2013

Abstract
The relationship between mutated proteins and the cancer stem-cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGF receptor (EGFR) variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here, we show that EGFRvIII is highly coexpressed with CD133 and that EGFRvIII+/CD133+ defines the population of cancer stem cells (CSC) with the highest degree of self-renewal and tumor-initiating ability. EGFRvIII+ cells are associated with other stem/progenitor markers, whereas markers of differentiation are found in EGFRvIII− cells. EGFRvIII expression is lost in standard cell culture, but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII+/CD133+ coexpression, self-renewal, and tumor initiating abilities. Elimination of the EGFRvIII+/CD133+ population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC-specific expression and be used to specifically target this population. Cancer Res; 74(4); 1238–49. ©2013 AACR.
Tumor-Derived GM-CSF Promotes Inflammatory Colon Carcinogenesis via Stimulating Epithelial Release of VEGF
Authors: Wang Yi , Han Gencheng , Wang Ke , Liu Guijun , Wang Renxi , Xiao He , Li Xinying , Hou Chunmei , Shen Beifen , Guo Renfeng , Li Yan , Chen Guojiang 
Published: December 2013

Abstract
Chronic inflammation is a major driving force for the development of colitis-associated cancer (CAC). Elevated production of granulocyte macrophage colony-stimulating factor (GM-CSF) has been observed in mucosa of patients with inflammatory bowel disease. Its actions in the progression from colitis to cancer, however, remain poorly understood. Herein, we demonstrated that colonic epithelial cells (CEC) were a major cellular source of GM-CSF and its production was significantly augmented when CAC model was established by administration of azoxymethane and dextran sulfate sodium. Furthermore, we showed that GM-CSF was a driver for VEGF release by CEC in autocrine and/or paracrine manners through the extracellular signal-regulated kinase (ERK)-dependent pathway. Blocking GM-CSF activity in vivo significantly decreased epithelial release of VEGF, thereby abrogating CAC formation. In vitro treatment of transformed CEC with recombinant GM-CSF dramatically augmented its invasive potentials, largely in VEGF-dependent fashion. Furthermore, commensal microbiota-derived lipopolysaccharides were identified as a trigger for GM-CSF expression in CEC, as antibiotics treatment or Toll-like receptor 4 ablation considerably impaired its epithelial expression. Overall, these findings may have important implications for the understanding of mechanisms underlying CAC pathogenesis and the therapeutic potentials of regimens targeting GM-CSF or VEGF in clinic. Cancer Res; 74(3); 716–26. ©2013 AACR.
CRR9/CLPTM1L Regulates Cell Survival Signaling and Is Required for Ras Transformation and Lung Tumorigenesis
Authors: James Michael A. , Vikis Haris G. , Tate Everett , Rymaszewski Amy L. , You Ming 
Published: December 2013

Abstract
The transmembrane protein CLPTM1L is overexpressed in non–small cell lung cancer, where it protects tumor cells from genotoxic apoptosis. Here, we show that RNA interference-mediated blockade of CLPTM1L inhibits K-Ras–induced lung tumorigenesis. CLPTM1L expression was required in vitro for morphologic transformation by H-RasV12 or K-RasV12, anchorage-independent growth, and survival of anoikis of lung tumor cells. Mechanistic investigations indicated that CLPTM1L interacts with phosphoinositide 3-kinase and is essential for Ras-induced AKT phosphorylation. Furthermore that the anti-apoptotic protein Bcl-xL is regulated by CLPTM1L independently of AKT activation. Constitutive activation of AKT or Bcl-xL rescued the transformed phenotype in CLPTM1L-depleted cells. The CLPTM1L gene lies within a cancer susceptibility locus at chromosome 5p15.33 defined by genome-wide association studies. The risk genotype at the CLPTM1L locus was associated with high expression of CLPTM1L in normal lung tissue, suggesting that cis-regulation of CLPTM1L may contribute to lung cancer risk. Taken together, our results establish a protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization. Cancer Res; 74(4); 1116–27. ©2013 AACR.
Cyclin E1 Deregulation Occurs Early in Secretory Cell Transformation to Promote Formation of Fallopian Tube–Derived High-Grade Serous Ovarian Cancers
Authors: Karst Alison M. , Jones Paul M. , Vena Natalie , Ligon Azra H. , Liu Joyce F. , Hirsch Michelle S. , Etemadmoghadam Dariush , Bowtell David D.L. , Drapkin Ronny 
Published: December 2013

AbstractThe fallopian tube is now generally considered the dominant site of origin for high-grade serous ovarian carcinoma. However, the molecular pathogenesis of fallopian tube-derived serous carcinomas is poorly understood and there are few experimental studies examining the transformation of human fallopian tube cells. Prompted by recent genomic analyses that identified cyclin E1 (CCNE1) gene amplification as a candidate oncogenic driver in high-grade serous ovarian carcinoma, we evaluated the functional role of cyclin E1 in serous carcinogenesis. Cyclin E1 was expressed in early- and late-stage human tumor samples. In primary human fallopian tube secretory epithelial cells, cyclin E1 expression imparted malignant characteristics to untransformed cells if p53 was compromised, promoting an accumulation of DNA damage and altered transcription of DNA damage response genes related to DNA replication stress. Together, our findings corroborate the hypothesis that cyclin E1 dysregulation acts to drive malignant transformation in fallopian tube secretory cells that are the site of origin of high-grade serous ovarian carcinomas. Cancer Res; 74(4); 1141–52. ©2013 AACR.
Myocardial Expression Level of Neural Cell Adhesion Molecule Correlates With Reduced Left Ventricular Function in Human Cardiomyopathy
Authors: Nagao Kazuya , Sowa Naoya , Inoue Katsumi , Tokunaga Motoko , Fukuchi Kohei , Uchiyama Koji , Ito Haruyasu , Hayashi Fujio , Makita Toshinori , Inada Tsukasa , Tanaka Masaru , Kimura Takeshi , Ono Koh 
Published: December 2013

Background—
Recently, we screened for cardiac genes induced by metabolic stress and identified neural cell adhesion molecule (NCAM) as a candidate. This study aimed to clarify the expression pattern of NCAM in human cardiomyopathy.

Methods and Results—

A total of 64 cardiac tissue samples of patients with dilated cardiomyopathy were dichotomized according to the immunohistochemically determined signal intensity of NCAM staining (NCAM-high and NCAM-low groups). Clinical and hemodynamic data of the patients were compared between the 2 groups. Fibrosis area, left ventricular end-diastolic volume index, and left ventricular diastolic pressure were greater in the NCAM-high group (22.8% versus 11.6%,
P
<0.05; 130.3±57.6 versus 104.8±31.7 mL/m
2
,
P
<0.05; 14.3±8.0 versus 8.8±4.7 mm Hg,
P
<0.005; respectively). Incidence of cardiac death and admission for worsening heart failure was higher in the NCAM-high group during a follow-up of 6.3 years (log-rank
P
<0.05). Another 18 tissue samples were analyzed to determine the relationships between expression level of NCAM and major metabolic genes as well as hemodynamic parameters. The mRNA level of NCAM correlated with the serum (
r
=0.58;
P
=0.01) and mRNA levels (
r
=0.61;
P
=0.008) of brain-derived natriuretic peptides. It was also correlated with the mRNA levels of proliferator-activated receptor-γ coactivator-1 α (
r
=0.69;
P
=0.002) and the nuclear respiratory factor 1 (
r
=0.74;
P
<0.001).

Conclusions—
Expression of NCAM was associated with worsening hemodynamic parameters and major metabolic genes. Together with our previous findings, these data support the involvement of NCAM in left ventricular remodeling, revealing new insights into the pathophysiology of heart failure.
Factors Associated With the Prevalence of Hypertension in the Southeastern United States
Authors: Sampson Uchechukwu K.A. , Edwards Todd L. , Jahangir Eiman , Munro Heather , Wariboko Minaba , Wassef Mariam G. , Fazio Sergio , Mensah George A. , Kabagambe Edmond K. , Blot William J. , Lipworth Loren 
Published: December 2013

Background—
Lifestyle and socioeconomic status have been implicated in the prevalence of hypertension; thus, we evaluated factors associated with hypertension in a cohort of blacks and whites with similar socioeconomic status characteristics.

Methods and Results—

We evaluated the prevalence and factors associated with self-reported hypertension (SR-HTN) and ascertained hypertension (A-HTN) among 69 211 participants in the Southern Community Cohort Study. Multivariable logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with hypertension. The prevalence of SR-HTN was 57% overall. Body mass index was associated with SR-HTN in all race-sex groups, with the OR rising to 4.03 (95% CI, 3.74–4.33) for morbidly obese participants (body mass index, >40 kg/m
2
). Blacks were more likely to have SR-HTN than whites (OR, 1.84; 95% CI, 1.75–1.93), and the association with black race was more pronounced among women (OR, 2.08; 95% CI, 1.95–2.21) than men (OR, 1.47; 95% CI, 1.36–1.60). Similar findings were noted in the analysis of A-HTN. Among those with SR-HTN and A-HTN who reported use of an antihypertensive agent, 94% were on at least one of the major classes of antihypertensive agents, but only 44% were on ≥2 classes and only 29% were on a diuretic. The odds of both uncontrolled hypertension (SR-HTN and A-HTN) and unreported hypertension (no SR-HTN and A-HTN) were twice as high among blacks as whites (OR, 2.13; 95% CI, 1.68–2.69; and OR, 1.99; 95% CI, 1.59–2.48, respectively).

Conclusions—
Despite socioeconomic status similarities, we observed suboptimal use of antihypertensives in this cohort and racial differences in the prevalence of uncontrolled and unreported hypertension, which merit further investigation.
Aggregate Risk of Cardiovascular Disease Among Adolescents Perinatally Infected With the Human Immunodeficiency Virus
Authors: Patel Kunjal , Wang Jiajia , Jacobson Denise L. , Lipshultz Steven E. , Landy David C. , Geffner Mitchell E. , DiMeglio Linda A. , Seage George R. , Williams Paige L. , Van Dyke Russell B. , Siberry George K. , Shearer William T. , Young Luciana , Scott Gwendolyn B. , Wilkinson James D. , Fisher Stacy D. , Starc Thomas J. , Miller Tracie L. 
Published: December 2013

Background—
Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy.

Methods and Results—
Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period.

Conclusions—
A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.
Redescription of Paragaleus tengi (Chen, 1963) (Carcharhiniformes: Hemigaleidae) and first record of Paragaleus randalli Compagno, Krupp &amp; Carpenter, 1996 from the western North Pacific
Authors: WHITE WILLIAM T. , HARRIS MARK 
Published: December 2013

Paragaleus tengi was previously considered to be the only member of this genus occurring in the Western Pacific, with Paragaleus randalli occurring in the Indian Ocean and allopatric in distribution. Recent molecular and morphological studies showed that P. randalli also occurs in the Western Pacific with records from Thailand, Malaysia and Indonesia previously mostly incorrectly attributed to P. tengi. This paper provides a redescription of P. tengi and confirms the presence of P. randalli from off Taiwan in the western North Pacific. These two species are morphologically very similar in appearance but differ in meristics, dentition, some coloration attributes and minor morphological characters. The conservation status of these two species needs to be reassessed based on this new information.
Redescription of Hexanchus nakamurai Teng 1962, (Chondrichthyes: Hexanchiformes: Hexanchidae), with designation of a neotype
Authors: Ebert David A. , White William T. , HO HSUAN-CHING 
Published: December 2013

Hexanchus nakamurai Teng, 1962 is one of two valid nominal species in the genus Hexanchus; the other being H. griseus. The taxonomic history of H. nakamurai is somewhat convoluted due to questions about the validity of whether it constituted a publication or an unpublished dissertation. The issue appeared to have been resolved once it was determined that the Teng’s original description met the criteria under the International Commission on Zoological Nomenclature code (Article 8a) of a publication. However, recent molecular studies have indicated that the western North Atlantic H. nakamurai (=?H. vitulus) may be distinct from western Indian Ocean H. nakamurai. Compounding the issue is the loss of the holotype of H. nakamurai from Taiwan. A neotype is herein designated and the species redescribed based on the neotype and eight additional Taiwanese specimens.
Economic impact of hospitalisations among patients in the last year of life: An observational study
Authors: Gardiner Clare , Ward Sue , Gott Merryn , Ingleton Christine 
Published: December 2013

Background: Hospital admissions among patients at the end of life have a significant economic impact. Avoiding unnecessary hospitalisations has the potential for significant cost savings and is often in line with patient preference. Objective: To determine the extent of potentially avoidable hospital admissions among patients admitted to hospital in the last year of life and to cost these accordingly. Design: An observational retrospective case note review with economic impact assessment. Setting: Two large acute hospitals in the North of England, serving contrasting socio-demographic populations. Patients: A total of 483 patients who died within 1 year of admission to hospital. Measurements: Data were collected across a range of clinical, demographic, economic and service use variables and were collected from hospital case notes and routinely collected sources. Palliative medicine consultants identified admissions that were potentially avoidable. Results: Of 483 admissions, 35 were classified as potentially avoidable. Avoiding these admissions and caring for the patients in alternative locations would save the two hospitals £5.9 million per year. Reducing length of stay in all 483 patients by 14% has the potential to save the two hospitals £47.5 million per year; however, this cost would have to be offset against increased community care costs. Limitations: A lack of accurate cost data on alternative care provision in the community limits the accuracy of economic estimates. Conclusions: Reducing length of hospital stay in palliative care patients may offer the potential to achieve higher hospital cost savings than preventing avoidable admissions. Further research is required to determine both the feasibility of reducing length of hospital stay for patients with palliative care needs and the economic impact of doing so.
Calcium and fat metabolic balance, and gastrointestinal tolerance in term infants fed milk-based formulas with and without palm olein and palm kernel oils: a randomized blinded crossover study
Authors: Leite Maria Efigênia de Queiroz , Lasekan John , Baggs Geraldine , Ribeiro Tereza , Menezes-Filho Jose , Pontes Mariana , Druzian Janice , Barreto Danile Leal , de Souza Carolina Oliveira , Mattos Ângela , Costa-Ribeiro Hugo 
Published: December 2013

Abstract

Background
Effects of palm olein (POL) on calcium and fat metabolic balance and gastrointestinal (GI) tolerance have been clinically evaluated but its use in combination with palm kernel oil (PKO), and canola oil has not been similarly assessed in infants.

Methods
Calcium and fat balance and GI tolerance were evaluated in 33 healthy term infants (age = 68-159d) in a randomized, double-blinded, 14d crossover trial at a day care center in Salvador, Brazil; followed by a 4d hospital ward metabolic balance study in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; one containing POL (44% of total fat), PKO (21.7%) and canola oil (18.5%) as predominant fats (PALM), and the other containing none (NoPALM). Occasional human milk (HM) supplementation was allowed at home.

Results
Formula and HM intakes, and growth were not different (p > 0.05). Calcium absorption (%) for infants fed NoPALM (58.8 ± 16.7%; means ± SD) was higher (p = 0.023) than those fed PALM (42.1 ± 19.2%), but was not significant (p = 0.104) when calcium intake was used as a covariate. Calcium intake was higher (p < 0.001) in NoPALM versus PALM fed infants. However, calcium retention (%) was higher in infants fed NoPALM compared to PALM with (p = 0.024) or without (p = 0.015) calcium intake as a covariate. Fat absorption (%) for NoPALM was greater than PALM fed infants (NoPALM = 96.9 ± 1.2 > PALM = 95.1 ± 1.5; p = 0.020 in Study Period I). Mean rank stool consistency was softer in infants fed NoPALM versus PALM (p < 0.001; metabolic period). Adverse events, spit-up/vomit, fussiness and gassiness were not different (p > 0.05). Formula acceptability was high and comparable for both formula feedings, regardless of HM supplementation.

Conclusions
Term infants fed PALM based formula (containing palm olein, palm kernel and canola oils) demonstrated lower calcium retention and fat absorption, and less softer stool consistency versus infants fed NoPALM based formula. Study suggested formula fat differences may affect GI function in infants.

Clinical trial registration
Clinical Trial.Gov # (http://www.clinicaltrials.gov): NCT00941564.