bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological and medical applications of a brain-on-a-chip
Authors: Pamies David , Hartung Thomas , Hogberg Helena T
Published: June 2014

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology.
Physiology and metabolism of tissue-engineered skeletal muscle
Authors: Cheng Cindy S , Davis Brittany NJ , Madden Lauran , Bursac Nenad , Truskey George A
Published: June 2014

Skeletal muscle is a major target for tissue engineering, given its relative size in the body, fraction of cardiac output that passes through muscle beds, as well as its key role in energy metabolism and diabetes, and the need for therapies for muscle diseases such as muscular dystrophy and sarcopenia. To date, most studies with tissue-engineered skeletal muscle have utilized murine and rat cell sources. On the other hand, successful engineering of functional human muscle would enable different applications including improved methods for preclinical testing of drugs and therapies. Some of the requirements for engineering functional skeletal muscle include expression of adult forms of muscle proteins, comparable contractile forces to those produced by native muscle, and physiological force–length and force–frequency relations. This review discusses the various strategies and challenges associated with these requirements, specific applications with cultured human myoblasts, and future directions.
Female college students’ beliefs about cervical cancer screening
Authors: Ackerson Kelly , Zielinski Ruth , Patel Heena
Published: June 2014

Purpose

To explore female college students’ perceived benefits and barriers to cervical cancer screening and perceived vulnerability to cervical cancer.

Method

The study was exploratory and cross sectional. The Pap Smear Belief Questionnaire was distributed online to a sample of 267 female undergraduate baccalaureate nursing students.

Findings

Students who obtained routine Pap smears perceived greater benefits and fewer barriers to routine screening than the students who did not obtain routine Pap smears. Personal vulnerability to cervical cancer was not a significant finding. Students who were in a long-term relationship, non-smoking and initiated sexual intercourse at a younger age were more likely to obtain routine screening.

Conclusion

Stressing importance of preventive health care associated with routine cervical cancer screening is important to promote women’s health regardless of age or level of education. Further studies with a broader range of college students as participants are needed to better understand their beliefs about the benefits and barriers to obtaining routine screening, and their perceptions of vulnerability to cervical cancer.
Narrative approach to moral education: A case of Thailand
Authors: Singsuriya Pagorn , Aungsumalin Wipada , Worapong Seree
Published: June 2014

In Thailand, according to, for instance, the National Education Act 1999, the National Plan of Education, Religion, Arts and Culture (2002–2013), and the Core Curriculum of Basic Education 2008, moral education is given an important role not only in human development but also in citizenship building and solution of socio-political problems. Thailand has its unique Buddhist-laden definition of moral education whose approach is a mixture of religious education and character development partly spelt out in Kohlbergian terms of moral reasoning. In an effort to find an alternative, the influential narrative approach is studied and narrative methods reviewed. The method that can accommodate the Thai moral education, and solve some of its predicaments, is recommended. As a whole, this study portrays an interaction between Western theories and local practice.
Management of variceal and nonvariceal upper gastrointestinal bleeding in patients with cirrhosis
Authors: Cremers Isabelle , Ribeiro Suzane
Published: June 2014

Acute upper gastrointestinal haemorrhage remains the most common medical emergency managed by gastroenterologists. Causes of upper gastrointestinal bleeding (UGIB) in patients with liver cirrhosis can be grouped into two categories: the first includes lesions that arise by virtue of portal hypertension, namely gastroesophageal varices and portal hypertensive gastropathy; and the second includes lesions seen in the general population (peptic ulcer, erosive gastritis, reflux esophagitis, Mallory–Weiss syndrome, tumors, etc.).

Emergency upper gastrointestinal endoscopy is the standard procedure recommended for both diagnosis and treatment of UGIB. The endoscopic treatment of choice for esophageal variceal bleeding is band ligation of varices. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the same time as endoscopy. Bleeding from portal hypertensive gastropathy is less frequent, usually chronic and treatment options include β-blocker therapy, injection therapy and interventional radiology.

The standard of care of UGIB in patients with cirrhosis includes careful resuscitation, preferably in an intensive care setting, medical and endoscopic therapy, early consideration for placement of transjugular intrahepatic portosystemic shunt and, sometimes, surgical therapy or hepatic transplant.
The Effects of a Science-Focused STEM Intervention on Gifted Elementary Students’ Science Knowledge and Skills
Authors: Robinson Ann , Dailey Debbie , Hughes Gail , Cotabish Alicia
Published: June 2014

To develop Science, Technology, Engineering, and Mathematics (STEM) talents, both researchers and policy developers recommend that educators begin early. In this randomized study, we document the efficacy of teacher professional development and a rich problem-based inquiry curriculum to develop the science talent of elementary students. The intervention, STEM Starters, a federally funded Jacob K. Javits project, provided sustained and embedded professional development to classroom teachers and to pull-out gifted program teachers to support the implementation of a problem-based curriculum in their classrooms. During the intervention, randomly assigned teachers participated in 120 hr of professional development that focused on science content, inquiry-based instruction, technological applications, and differentiated instruction within problem-based curriculum units. Statistically significant gains in science process skills, science concepts, and science content knowledge were found among gifted students in the treatment group when compared with gifted students in the comparison group.
Short-Term Effects of Patellar Kinesio Taping on Pain and Hop Function in Patients With Patellofemoral Pain Syndrome
Authors: Freedman Scott R. , Brody Lori Thein , Rosenthal Michael , Wise Justin C.
Published: June 2014

Background:

Patellofemoral pain syndrome (PFPS) is the most prevalent orthopaedic condition among physically active individuals, contributing to an estimated 30% to 40% of all sports medicine visits. Techniques using Kinesio Tape (KT) have become increasingly popular; however, there has been scant research supporting its use on patients with PFPS.

Hypothesis:

The use of patellar KT to treat patients with PFPS will provide a statistically significant improvement in short-term pain and single-leg hop measures as compared with sham placement of KT.

Study Design:

Nonrandomized controlled clinical trial with repeated-measures design.

Level of Evidence:

Level 3.

Methods:

Forty-nine subjects (41 females, 8 males) between the ages of 12 and 24 years with PFPS participated in this study. Each subject underwent patellar kinesio taping with both experimental and sham applications while completing 4 functional tasks and the single-leg triple jump test (STJT). The treatment outcome was analyzed using separate paired t tests to measure improvement on a numeric pain rating scale. A 2-way, 2 × 2 analysis of variance was used to analyze the relationship between taping condition (experimental vs sham) and side (involved vs uninvolved) for STJT scores.

Results:

Separate paired t tests found step-up, step-down, and STJT pain improvement statistically significant between taping conditions. The 2-factor analysis of variance yielded a significant main effect for taping condition, but the main effect for side was not significant. The interaction between taping condition and side was significant. This showed there was little change in STJT distance between repeated measures performed on the untaped, noninvolved leg. However, subjects’ STJT distances were significantly greater for the experimental KT application than the sham application for the involved side.

Conclusion:

Patellar kinesio taping provided an immediate and statistically significant improvement in pain and single-leg hop function in patients with PFPS when compared with a sham application. However, improvement in STJT scores did not surpass the minimally detectable change value, and therefore, the clinical effectiveness of KT for improving single-leg hop function was not established in the current study.

Clinical Relevance:

Kinesio Tape provides a viable, short-term method to control pain.
Microparticles and sudden cardiac death due to coronary occlusion. The TIDE (Thrombus and Inflammation in sudden DEath) study
Authors: Empana Jean-Philippe , Boulanger Chantal M , Tafflet Muriel , Renard Jean M , Leroyer Aurelie S , Varenne Olivier , Prugger Christof , Silvain Johanne , Tedgui Alain , Cariou Alain , Montalescot Gilles , Jouven Xavier , Spaulding Christian
Published: June 2014

Aims:

The pattern of coronary occlusion might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD). We hypothesized that the concentrations of microparticles might differ between SCD and ST-elevation myocardial infarction (STEMI) patients without rhythmic disturbances.

Methods and results:

The study sample includes consecutive patients hospitalized in two French tertiary centres between 2006 and 2011 for SCD with angiographically-proven acute coronary occlusion ( n=23), for STEMI ( n=61) and for a planned percutaneous coronary angioplasty (PCI) ( n=35, controls). During PCI blood was collected in the arch of aorta (systemic blood) before and after the procedure and in the culprit coronary lesion with an aspiration catheter. Microparticles were analysed by flow cytometry in a blinded manner to quantify endothelial (CD144+), platelet (CD41+), leucocyte (CD11a+) and erythrocyte (CD235a+) derived microparticles. After multivariate analysis, intracoronary concentrations of endothelial-derived microparticles were significantly higher in SCD than in STEMI patients (129 (74–185) vs. 50 (21–118) nb/µl; p < 0.01). Intracoronary and systemic blood concentrations of platelet-derived microparticles were not different between SCD and controls, suggesting limited impact of cardiac massage and electric defibrillation in microparticle concentrations.

Conclusion:

The higher concentrations of endothelial-derived microparticles in SCD due to acute coronary occlusion compared with STEMI without rhythmic disturbances suggests different patterns of acute coronary occlusion.
Intraoperative ureteric injuries and litigation in the NHS
Authors: Nachiappan S , Currie A , Askari A , Faiz O
Published: June 2014

Objectives:

The objective of this article is to analyse medicolegal claims arising from intraoperative ureteric injuries across all surgical specialties and the consequent financial costs to the National Health Service (NHS) in the United Kingdom.

Materials and methods:

We conducted a retrospective review of medicolegal claims reported to the NHS Legal Authority between April 2007 and March 2013.

Results:

A total of 191 claims were reported with 122 claims being resolved at the time of data collation. Of these, 97 were successful with a total of £9.66 million paid by the NHS in indemnity, averaging £99,611 per successful claim. There was an increasing number of claims filed over the study years and a slight decrease in the average pay-out per successful claim. Gynaecology and obstetrics accounted for over two-thirds of successful claims, with the remainder being divided equally among urology and colorectal surgery. However, claims arising from colorectal surgery had higher indemnity pay-outs on average.

Conclusion:

This is the first study analysing medicolegal claims and cost burden pertaining to ureteric injuries across different specialties. The findings concur with clinical studies which indicate gynaecological procedures and other pelvic (e.g. colorectal) procedures are at increased risk of causing ureteric injury.
Timing of Hip Fracture Surgery in the Elderly
Authors: Lee Daniel J. , Elfar John C.
Published: June 2014

The effect of preoperative wait time for surgery is a long-standing subject of debate. Although there is disagreement among clinicians on whether early surgery confers a survival benefit per se, most reports agree that early surgery improves other outcomes such as length of stay, the incidence of pressure sores, and return to independent living. Therefore, it would seem prudent to surgically treat elderly patients with hip fractures within the first 48 hours of admission. However, the current body of evidence is observational in nature and carries the potential for bias inherent in such analyses. Evidence in the form of a large randomized controlled trial may ultimately be required to fully evaluate the impact of surgical timing on patients with fractures of the hip.
The Impact of Fatigue on the Kinematics of Collegiate Baseball Pitchers
Authors: Grantham W. Jeffrey , Byram Ian R. , Meadows Molly C. , Ahmad Christopher S.
Published: June 2014

Background:

Many factors are believed to contribute to throwing injuries in baseball pitchers, in particular overuse and poor throwing mechanics. The impact of fatigue on pitching biomechanics in live-game situations is not well understood.

Hypothesis:

Pitchers will demonstrate significant deviation in their pitching motions with increasing levels of fatigue.

Study Design:

Descriptive laboratory study.

Methods:

Eleven National Collegiate Athletic Association (NCAA) Division I collegiate baseball pitchers were filmed in multiple live-game situations throughout a single season using 2 orthogonal high-speed cameras at 120 Hz. The first fastball of each inning and, when available, the fastball subsequent to the 15th and 30th pitch of each inning were recorded and analyzed for 26 kinematic parameters. Pitch count and velocity were recorded. Kinematic differences were assessed for association with pitch count and subjective fatigue measures over the course of each inning and game through the season.

Results:

Twenty-six games were recorded. Pitchers had a mean of 97.2 ± 16.1 pitches per start and 1079 ± 251 pitches per collegiate season. Increased hip lean at hand separation, elbow height at foot contact, and hip flexion and shoulder tilt at maximum external rotation were seen in innings lasting longer than 15 pitches. Maximum external rotation of the shoulder and elbow height at foot contact decreased over the course of a game. Hip lean at hand separation and elbow height at foot contact increased over the course of the season. Season pitch count was weakly correlated with increased shoulder external rotation and shoulder alignment at maximum external rotation and with shoulder abduction at ball release. Elbow flexion decreased with greater season pitch counts.

Conclusion:

Hip lean, elbow height, and shoulder external rotation were the most sensitive kinematic parameters to inning, game, and season fatigue. Pitch count and fatigue have a significant impact on live-game pitching kinematics.

Clinical Relevance:

Fatigue likely alters pitching mechanics. Recognition of kinematic alterations may better demonstrate fatigue-related injury risk and may assist injury prevention in addition to standardized limitations of innings and pitches thrown.
Nurses’ Experiences of Managing and Management in a Critical Care Unit
Authors: Ogle K. Robyn , Glass Nel
Published: June 2014

In this article, we describe the major findings of an ethnographic study undertaken to investigate nurses’ experiences of managing nurses and being managed by nurses in an Australian critical care unit. Our purpose was to valorize and make space for nurses to speak of their experiences and investigate the cultural practices and knowledges that comprised nursing management discourses. Subjugated practices, knowledges, and discourses were identified, revealing how nurses were inscribed by, or resisted, the discourses, including their multiple mobile subject positions. Informed by critical, feminist, and postmodern perspectives, nine mobile subject positions were identified. Direct participant observation, participant interviews, and reflective field notes were analyzed for dominant and subjugated discourses. The major finding described is the subject position of “junior novice.” Nurses informed by dominant patriarchal and organizational discourses participated in constructing and reinscribing their own submissive identity reflected in interprofessional relations that lacked individual valuing and undermined their self-esteem.
Bond strength and oxidation resistance of YSZ/(Ni, Al) composite coatings
Authors: Li C. L. , Wang W. , Tan S. L. , Song S. G.
Published: June 2014

YSZ/(Ni, Al) composite coatings were deposited on superalloy Inconel 600 by the electrophoretic deposition (EPD) technique, followed by vacuum sintering method. In comparison with the bond strength of 3·5 N for YSZ coating, the bond strength for YSZ/(Ni, Al) composite coating increased to 4·4 N. YSZ/(Ni, Al) composite coatings exhibited a self crack healing ability by high temperature oxidation. Crack healing is promoted by the increase in the oxidation time exposure at 1100°C. YSZ/(Ni, Al) composite coatings show superior oxidation resistance than that of YSZ coating. Such composite coatings have potential in being used as thermal barrier coatings on superalloy substrates.
Rapamycin relieves lentiviral vector transduction resistance in human and mouse hematopoietic stem cells
Authors: Wang Cathy X. , Sather Blythe D. , Wang Xuefeng , Adair Jennifer , Khan Iram , Singh Swati , Lang Shanshan , Adams Amie , Curinga Gabrielle , Kiem Hans-Peter , Miao Carol H. , Rawlings David J. , Torbett Bruce E.
Published: June 2014

Key Points

Rapamycin significantly enhances lentiviral vector gene delivery to hematopoietic stem cells while preserving engraftment potential. Rapamycin-mediated transduction enhancement is not accompanied by alterations in lentiviral integration profile.
Acute graft-versus-host disease: a bench-to-bedside update
Authors: Holtan Shernan G. , Pasquini Marcelo , Weisdorf Daniel J.
Published: June 2014

Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.
The biology of graft-versus-host disease: experimental systems instructing clinical practice
Authors: Markey Kate A. , MacDonald Kelli P. A. , Hill Geoffrey R.
Published: June 2014

The last 6 decades have seen major advances in the understanding of immunologic diseases, driven by preclinical animal models. Indeed, bone marrow transplantation (BMT) has its genesis in rodent models dating back to the 1950s. Allogeneic BMT and its major complication, graft-versus-host disease (GVHD), represent a paradigm for the translation of preclinical concepts into clinical practice. The appreciation that GVHD can be thought of as a stepwise escalation in immune activation characterized by eventual massive target tissue apoptosis has allowed the design of rational approaches to better manage patients. Here, we describe the pathophysiology of GVHD as defined in preclinical models, focusing on the successes and failures of this research to instruct and translate clinical practice. We also provide a commentary on the limitations of these models so that they may be better appreciated and addressed in future studies. Notable preclinical successes include the definition of modern immune suppression, reductions in conditioning intensity, posttransplant cyclophosphamide, and the promotion of regulatory T-cell reconstitution. New strategies including naïve T-cell depletion, focused cytokine and chemokine inhibition, and the blockade of costimulation now also appear highly promising and very likely to translate into patients in the near future.
Fraud in a population-based study of headache: prevention, detection and correction
Authors: Ahmed Bilal , Ahmad Ali , Herekar Akbar A , Uqaili Umer L , Effendi Jahanzeb , Alvi S Zia , Herekar Arif D , Steiner Timothy J
Published: June 2014

Background

In medicine, research misconduct is historically associated with laboratory or pharmaceutical research, but the vulnerability of epidemiological surveys should be recognized. As these surveys underpin health policy and allocation of limited resources, misreporting can have far-reaching implications. We report how fraud in a nationwide headache survey occurred and how it was discovered and rectified before it could cause harm.

Methods

The context was a door-to-door survey to estimate the prevalence and burden of headache disorders in Pakistan. Data were collected from all four provinces of Pakistan by non-medical interviewers and collated centrally. Measures to ensure data integrity were preventative, detective and corrective. We carefully selected and trained the interviewers, set rules of conduct and gave specific warnings regarding the consequences of falsification. We employed two-fold fraud detection methods: comparative data analysis, and face-to-face re-contact with randomly selected participants. When fabrication was detected, data shown to be unreliable were replaced by repeating the survey in new samples according to the original protocol.

Results

Comparative analysis of datasets from the regions revealed unfeasible prevalences and gender ratios in one (Multan). Data fabrication was suspected. During a surprise-visit to Multan, of a random sample of addresses selected for verification, all but one had been falsely reported. The data (from 840 cases) were discarded, and the survey repeated with new interviewers. The new sample of 800 cases was demographically and diagnostically consistent with other regions.

Conclusion

Fraud in community-based surveys is seldom reported, but no less likely to occur than in other fields of medical research. Measures should be put in place to prevent, detect and, where necessary, correct it. In this instance, had the data from Multan been pooled with those from other regions before analysis, a damaging fraud might have escaped notice.
Structured RNAs and synteny regions in the pig genome
Authors: Anthon Christian , Tafer Hakim , Havgaard Jakob H , Thomsen Bo , Hedegaard Jakob , Seemann Stefan E , Pundhir Sachin , Kehr Stephanie , Bartschat Sebastian , Nielsen Mathilde , Nielsen Rasmus O , Fredholm Merete , Stadler Peter F , Gorodkin Jan
Published: June 2014

Background

Annotating mammalian genomes for noncoding RNAs (ncRNAs) is nontrivial since far from all ncRNAs are known and the computational models are resource demanding. Currently, the human genome holds the best mammalian ncRNA annotation, a result of numerous efforts by several groups. However, a more direct strategy is desired for the increasing number of sequenced mammalian genomes of which some, such as the pig, are relevant as disease models and production animals.

Results

We present a comprehensive annotation of structured RNAs in the pig genome. Combining sequence and structure similarity search as well as class specific methods, we obtained a conservative set with a total of 3,391 structured RNA loci of which 1,011 and 2,314, respectively, hold strong sequence and structure similarity to structured RNAs in existing databases. The RNA loci cover 139 cis-regulatory element loci, 58 lncRNA loci, 11 conflicts of annotation, and 3,183 ncRNA genes. The ncRNA genes comprise 359 miRNAs, 8 ribozymes, 185 rRNAs, 638 snoRNAs, 1,030 snRNAs, 810 tRNAs and 153 ncRNA genes not belonging to the here fore mentioned classes. When running the pipeline on a local shuffled version of the genome, we obtained no matches at the highest confidence level. Additional analysis of RNA-seq data from a pooled library from 10 different pig tissues added another 165 miRNA loci, yielding an overall annotation of 3,556 structured RNA loci. This annotation represents our best effort at making an automated annotation. To further enhance the reliability, 571 of the 3,556 structured RNAs were manually curated by methods depending on the RNA class while 1,581 were declared as pseudogenes. We further created a multiple alignment of pig against 20 representative vertebrates, from which predicted 83,859 de novo RNA loci with conserved RNA structures. 528 of the predictions overlapped with the homology based annotation or novel miRNAs. We further present a substantial synteny analysis which includes 1,004 lineage specific de novo RNA loci and 4 ncRNA loci in the known annotation specific for Laurasiatheria (pig, cow, dolphin, horse, cat, dog, hedgehog).

Conclusions

We have obtained one of the most comprehensive annotations for structured ncRNAs of a mammalian genome, which is likely to play central roles in both health modelling and production. The core annotation is available in Ensembl 70 and the complete annotation is available at http://rth.dk/resources/rnannotator/susscr102/version1.02.
Attributable fraction of alcohol consumption on cancer using population-based nationwide cancer incidence and mortality data in the Republic of Korea
Authors: Park Sohee , Shin Hai-Rim , Lee Boram , Shin Aesun , Jung Kyu-Won , Lee Duk-Hee , Jee Sun Ha , Cho Sung-Il , Park Sue Kyung , Boniol Mathieu , Boffetta Paolo , Weiderpass Elisabete
Published: June 2014

Background

In the Republic of Korea, cancer is the most common cause of death, and cancer incidence and mortality rates are the highest in East Asia. As alcoholic beverages are carcinogenic to humans, we estimated the burden of cancer related to alcohol consumption in the Korean population.

Methods

The cancer sites studied were those for which there is convincing evidence of a positive association with alcohol consumption: oral cavity, pharynx, esophagus, colon, rectum, liver, larynx and female breast. Sex- and cancer-specific population attributable fractions (PAF) were calculated based on: 1) the prevalence of alcohol drinkers among adults ≥20 years of age in 1989; 2) the average daily alcohol consumption (g/day) among drinkers in 1998; 3) relative risk (RR) estimates for the association between alcohol consumption and site-specific cancer incidence obtained either from a large Korean cohort study or, when more than one Korean study was available for a specific cancer site, meta-analyses were performed and the resulting meta-RRs were used; 4) national cancer incidence and mortality data from 2009.

Results

Among men, 3% (2,866 cases) of incident cancer cases and 2.8% (1,234 deaths) of cancer deaths were attributable to alcohol consumption. Among women, 0.5% (464 cancer cases) of incident cancers and 0.1% (32 deaths) of cancer deaths were attributable to alcohol consumption. In particular, the PAF for alcohol consumption in relation to oral cavity cancer incidence among Korean men was 29.3%, and the PAFs for pharyngeal and laryngeal cancer incidence were 43.3% and 25.8%, respectively. Among Korean women, the PAF for colorectal cancer incidence was the highest (4.2%) and that for breast cancer incidence was only 0.2%. Avoiding alcohol consumption, or reducing it from the median of the highest 4th quartile of consumption (56.0 g/day for men, 28.0 g/day for women) to the median of the lowest quartile (2.80 g/day for men, 0.80 g/day for women), would reduce the burden of alcohol-related cancers in Korea.

Conclusions

A reduction in alcohol consumption would decrease the cancer burden and a significant impact is anticipated specifically for the cancers oral cavity, pharynx, and larynx among men in the Republic of Korea.
Hyperglycemia, oxidative stress, and the diaphragm: a link between chronic co-morbidity and acute stress?
Authors: Hafner Sebastian , Radermacher Peter , Frick Manfred , Dietl Paul , Calzia Enrico
Published: June 2014

It is well established that prolonged, controlled mechanical ventilation is associated with contractile dysfunction of the diaphragm due to impaired function of the mitochondrial respiratory chain as a result of aggravated oxidative and nitrosative stress. Sepsis and circulatory failure induce a similar response pattern. Callahan and Supinski now show that streptozotocin-induced insulin-dependent diabetes causes a comparable response pattern, both with respect to function and physiology - that is, reduced fiber force and, consequently, muscle contractility - but also as far as the underlying mechanisms are concerned. In other words, the authors elegantly demonstrate that the consequences of a chronic metabolic disease and that of acute critical illness may lead to the same phenotype response. It remains to be elucidated whether the underlying co-morbidity (for example, diabetes) adds to or even synergistically enhances the effect of an acute stress situation (for example, sepsis, mechanical ventilation). In addition, extending their previous work during shock states, the authors also show that administration of a preparation of the enzymatic anti-oxidant superoxide dismutase can reverse the deleterious effects of diabetes. These data are discussed in the context of the fundamental role of hyperglycemia in relation to metabolism-dependent formation of reactive oxygen species.
Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study
Authors: Peyrani Paula , Wiemken Timothy L , Kelley Robert , Zervos Marcus J , Kett Daniel H , File Jr Thomas M , Stein Gary E , Ford Kimbal D , Scerpella Ernesto G , Welch Verna , Ramirez Julio A ,   the IMPACT-HAP Study Group
Published: June 2014

Introduction

Controversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP.

Methods

This was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success.

Results

A total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018).

Conclusions

This study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.
DOTS-Finder: a comprehensive tool for assessing driver genes in cancer genomes
Authors: Melloni Giorgio EM , Ogier Alessandro GE , de Pretis Stefano , Mazzarella Luca , Pelizzola Mattia , Pelicci Pier Giuseppe , Riva Laura
Published: June 2014

A key challenge in the analysis of cancer genomes is the identification of driver genes from the vast number of mutations present in a cohort of patients. DOTS-Finder is a new tool that allows the detection of driver genes through the sequential application of functional and frequentist approaches, and is specifically tailored to the analysis of few tumor samples. We have identified driver genes in the genomic data of 34 tumor types derived from existing exploratory projects such as The Cancer Genome Atlas and from studies investigating the usefulness of genomic information in the clinical settings. DOTS-Finder is available athttps://cgsb.genomics.iit.it/wiki/projects/DOTS-Finder/.
Gene response in rice plants treated with continuous fog influenced by pH, was similar to that treated with biotic stress
Authors: Satoh Kouji , Saji Shoko , Ito Shoko , Shimizu Hideyuki , Saji Hikaru , Kikuchi Shoshi
Published: June 2014

Background

Throughout Asia, including Japan, rice plants are cultivated in a wide range of areas from lowlands to highlands and are frequently exposed to fog, including acid fog. Some physiological studies have shown that acid fog can be a stress factor for plants. We analyzed the gene expression profiles of rice plants treated with artificially prepared simulated acid fog (SiAF) or simulated neutral fog (SiNF) for 1 or 7 days.

Results

Microarray analysis results suggested that both the SiAF and the SiNF treatments induced the expression of genes involved in the defense and stress responses in rice plants. Induction of such genes was detected in plants treated with SiAF for 1 day, and the number of induced genes increased in plants treated with SiAF for 7 days. The genes for defense and stress responses were also induced by SiNF for 7 days, although they were not induced by SiNF for 1 day. The gene expression profiles of the SiAF-treated and the SiNF-treated plants were compared to those of plants treated with other stress factors. The comparison revealed that both SiAF and SiNF treatments have similar effects to biotic stresses and ozone stress. The genes encoding NADPH oxidase and germin, which function in apoplasts, were also induced by SiAF, SiNF and biotic stresses.

Conclusions

These findings suggest that both the SiAF and the SiNF treatments may result in oxidative stress through the apoplastic production of reactive oxygen species.
Vasorelaxing and antihypertensive activities of synthesized peptides derived from computer-aided simulation of pepsin hydrolysis of yam dioscorin
Authors: Lin Yin-Shiou , Lu Yeh-Lin , Wang Guei-Jane , Liang Hong-Jen , Hou Wen-Chi
Published: June 2014

Background

We reported that yam dioscorin and its peptic hydrolysates exhibited ACE inhibition and antihypertensive effects on SHRs, however, the active peptides are not really isolated until now. Using ACE inhibitory screenings, two penta-peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments.

Results

KTCGY, KRIHF, and captopril were shown to have similar vasodilating effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent thoracic aortic rings, however, KTCGYKTCGY (two-repeated KTCGY) and TCGYTCGY (two-repeated TCGY) were showed endothelium-independent vasodilating effects against PE-induced tensions. KTCGY, KRIHF (10 or 20 mg/kg), and captopril (10 mg/kg) were used to evaluate antihypertensive activity during 24-h after a single oral administration to spontaneously hypertensive rats (SHRs). The KTCGY and KRIHF showed significantly different and reduced the systolic blood pressure of SHRs compared to the blank.

Conclusions

These results suggest that KTCGY and KRIHF may contribute important roles in yam dioscorin for regulating blood pressure in vivo.
Hyperbolic metamaterials: fundamentals and applications
Authors: Shekhar Prashant , Atkinson Jonathan , Jacob Zubin
Published: June 2014

Metamaterials are nano-engineered media with designed properties beyond those available in nature with applications in all aspects of materials science. In particular, metamaterials have shown promise for next generation optical materials with electromagnetic responses that cannot be obtained from conventional media. We review the fundamental properties of metamaterials with hyperbolic dispersion and present the various applications where such media offer potential for transformative impact. These artificial materials support unique bulk electromagnetic states which can tailor light-matter interaction at the nanoscale. We present a unified view of practical approaches to achieve hyperbolic dispersion using thin film and nanowire structures. We also review current research in the field of hyperbolic metamaterials such as sub-wavelength imaging and broadband photonic density of states engineering. The review introduces the concepts central to the theory of hyperbolic media as well as nanofabrication and characterization details essential to experimentalists. Finally, we outline the challenges in the area and offer a set of directions for future work.
Osteoarthritic cartilage explants affect extracellular matrix production and composition in cocultured bone marrow-derived mesenchymal stem cells and articular chondrocytes
Authors: Leyh Michaela , Seitz Andreas , Dürselen Lutz , Springorum Hans-Robert , Angele Peter , Ignatius Anita , Grifka Joachim , Grässel Susanne
Published: June 2014

Introduction

In the present study, we established a novel in vitro coculture model to evaluate the influence of osteoarthritis (OA) cartilage explants on the composition of newly produced matrix and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) and the phenotype of OA chondrocytes. In addition, we included a “tri-culture” model, whereby a mixture of BMSCs and chondrocytes was cultured on the surface of OA cartilage explants.

Methods

Gene expression analysis, protein and glycosaminoglycan (GAG) assays, dot-blot, immunofluorescence, and biomechanical tests were used to characterize the properties of newly generated extracellular matrix (ECM) from chondrocytes and chondrogenically differentiated BMSCs and a mix thereof. We compared articular cartilage explant cocultures with BMSCs, chondrocytes, and mixed cultures (chondrocytes and BMSCs 1:1) embedded in fibrin gels with fibrin gel-embedded cells cultured without cartilage explants (monocultures).

Results

In general, co- and tri-cultured cell regimens exhibited reduced mRNA and protein levels of collagens I, II, III, and X in comparison with monocultures, whereas no changes in GAG synthesis were observed. All co- and tri-culture regimens tended to exhibit lower Young’s and equilibrium modulus compared with monocultures. In contrast, aggregate modulus and hydraulic permeability seemed to be higher in co- and tri-cultures. Supernatants of cocultures contained significant higher levels of interleukin-1 beta (IL-1β), IL-6, and IL-8. Stimulation of monocultures with IL-1β and IL-6 reduced collagen gene expression in BMSCs and mixed cultures in general but was often upregulated in chondrocytes at late culture time points. IL-8 stimulation affected BMSCs only.

Conclusions

Our results suggest an inhibitory effect of OA cartilage on the production of collagens. This indicates a distinct modulatory influence that affects the collagen composition of the de novo-produced ECM from co- and tri-cultured cells and leads to impaired mechanical and biochemical properties of the matrix because of an altered fibrillar network. We suggest that soluble factors, including IL-1β and IL-6, released from OA cartilage partly mediate these effects. Thus, neighbored OA cartilage provides inhibitory signals with respect to BMSCs’ chondrogenic differentiation and matrix composition, which need to be accounted for in future cell-based OA treatment strategies.
Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01)
Authors: de Azambuja Evandro , Procter Marion J. , van Veldhuisen Dirk J. , Agbor-Tarh Dominique , Metzger-Filho Otto , Steinseifer Jutta , Untch Michael , Smith Ian E. , Gianni Luca , Baselga Jose , Jackisch Christian , Cameron David A. , Bell Richard , Leyland-Jones Brian , Dowsett Mitch , Gelber Richard D. , Piccart-Gebhart Martine J. , Suter Thomas M.
Published: June 2014

Purpose

To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy.

Patients and Methods

The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) –positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation.

Results

The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery.

Conclusion

Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.
A Change in Liver Metabolism but Not in Brown Adipose Tissue Thermogenesis Is an Early Event in Ovariectomy-Induced Obesity in Rats
Authors: Nigro Mariana , Santos Anderson T. , Barthem Clarissa S. , Louzada Ruy A. N. , Fortunato Rodrigo S. , Ketzer Luisa A. , Carvalho Denise P. , de Meis Leopoldo
Published: June 2014

Menopause is associated with increased visceral adiposity and disrupted glucose homeostasis, but the underlying molecular mechanisms related to these metabolic changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy expenditure that may be regulated by sexual steroids, and alterations in glucose homeostasis could precede increased weight gain after ovariectomy. Thus, the aim of this work was to evaluate the metabolic pathways in both the BAT and the liver that may be disrupted early after ovariectomy. Ovariectomized (OVX) rats had increased food efficiency as early as 12 days after ovariectomy, which could not be explained by differences in feces content. Analysis of isolated BAT mitochondria function revealed no differences in citrate synthase activity, uncoupling protein 1 expression, oxygen consumption, ATP synthesis, or heat production in OVX rats. The addition of GDP and BSA to inhibit uncoupling protein 1 decreased oxygen consumption in BAT mitochondria equally in both groups. Liver analysis revealed increased triglyceride content accompanied by decreased levels of phosphorylated AMP-activated protein kinase and phosphorylated acetyl-CoA carboxylase in OVX animals. The elevated expression of gluconeogenic enzymes in OVX and OVX + estradiol rats was not associated with alterations in glucose tolerance test or in serum insulin but was coincident with higher glucose disposal during the pyruvate tolerance test. Although estradiol treatment prevented the ovariectomy-induced increase in body weight and hepatic triglyceride and cholesterol accumulation, it was not able to prevent increased gluconeogenesis. In conclusion, the disrupted liver glucose homeostasis after ovariectomy is neither caused by estradiol deficiency nor is related to increased body mass.