bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the efficacy of elderly patients' hospital discharge through multi-professional safety briefings and behavioural change
Authors: Corrado Joanna , Topley Kathryn , Cracknell Alison
Published: September 2015

At Leeds Teaching Hospitals NHS Trust doctors type an electronic discharge advice note (eDAN) which includes a prescription for discharge medication, before a patient can be discharged from hospital. In 2014 staff on the Medical Admissions Unit for Older People identified significant delays in the completion of this document, with an average completion time of 138 minutes. This caused patient harm and exacerbated bed management problems as patients remained in hospital longer than necessary to obtain their discharge medication. Ward staff wanted to improve the efficacy of older peoples’ discharge by speeding up this process in as safe a manner as possible. A number of interventions were tested, led by junior doctors in a ‘bottom-up’ leadership strategy. Interventions included a daily discharge briefing to recap discharges and help junior doctors prioritise workload. After several months of sustained effort, the average time to complete eDANs fell by over an hour resulting in discharge medication dispensed earlier in the day and improved patient safety.
Respiratory and allergic health effects in a young population in proximity of a major industrial park in Oman
Authors: Alwahaibi Adil , Zeka Ariana
Published: September 2015

Background

Sohar industrial zone (SIZ), Oman, which started operating in 2006, contains many industries that potentially affect the health of the local population. This study's aim was to evaluate the health effects in a young population living near SIZ.

Methods

Patient visits to state health clinics for acute respiratory diseases (ARD), asthma, conjunctivitis and dermatitis were obtained for the period of 2006 to 2010, for children ages <20 years old, for two large provinces around SIZ. Three exposure zones were defined on the basis of the distance from SIZ determined as: ≤5, >5 to 10, ≥20 km to represent high, intermediate and control exposure zones, respectively. Age-specific and gender-specific monthly counts of visits were modelled using generalised additive models controlling for time trends. The high and intermediate exposure zones were later combined together due to the similarity of associations. Exposure effect modification by age, gender and socioeconomic status (SES) was also tested.

Results

Living within 10 km from SIZ showed a greater association with ARD (risk ratio (RR)=2.5; 95% CI=2.3 to 2.7), asthma (RR=3.7; 95% CI=3.1 to 4.5), conjunctivitis (RR=3.1; 95% CI=2.9 to 3.5) and dermatitis (RR=2.7; 95% CI=2.5 to 3.0) when compared with the control zone. No differences in associations were found for gender and SES groups; greater effects were noticed in the ≤14-year-old group for asthma.

Conclusions

This is the first study conducted in Oman to examine the health effects of a young population living near an industrial park. We hope that these findings will contribute in future developments of environmental health policies in Oman.
Effect of jumping interval training on neuromuscular and physiological parameters: a randomized controlled study
Authors: Ache-Dias Jonathan , Dellagrana Rodolfo A. , Teixeira Anderson S. , Dal Pupo Juliano , Moro Antônio R.P.
Published: September 2015

This study analyzed the effect of 4 weeks of jumping interval training (JIT), included in endurance training, on neuromuscular and physiological parameters. Eighteen recreational runners, randomized in control and experimental groups, performed 40 min of running at 70% of velocity at peak oxygen uptake, for 3 times per week. Additionally, the experimental group performed the JIT twice per week, which consisted of 4 to 6 bouts of continuous vertical jumps (30 s) with 5-min intervals. Three days before and after the training period, the countermovement (CMJ) and continuous jump (CJ30), isokinetic and isometric evaluation of knee extensors/flexors, progressive maximal exercise, and submaximal constant-load exercise were performed. The JIT provoked improvement in neuromuscular performance, indicated by (i) increased jump height (4.7%; effect size (ES) = 0.99) and power output (≈3.7%; ES ≈ 0.82) of CMJ and rate of torque development of knee extensors in isometric contraction (29.5%; ES = 1.02); (ii) anaerobic power and capacity, represented by the mean of jump height (7.4%; ES = 0.8), and peak power output (PPO) (5.6%; ES = 0.73) of the first jumps of CJ30 and the mean of jump height (10.2%, ES = 1.04) and PPO (9.5%, ES = 1.1), considering all jumps of CJ30; and (iii) aerobic power and capacity, represented by peak oxygen uptake (9.1%, ES = 1.28), velocity at peak oxygen uptake (2.7%, ES = 1.11), and velocity corresponding to the onset of blood lactate accumulation (9.7%, ES = 1.23). These results suggest that the JIT included in traditional endurance training induces moderate to large effects on neuromuscular and physiological parameters.
Multiple slips effects on MHD Casson fluid flow in porous media with radiation and chemical reaction
Authors: Mabood F. , Khan W.A. , Ismail A.I.M.
Published: September 2015

An investigation is carried out on magnetohydrodynamic (MHD) boundary layer flow as well as heat and mass transfer of a Casson fluid in a porous medium under the action of multiple slips, thermal radiation, and chemical reaction. An analytical solution has been obtained for the velocity, temperature, and concentration of the Casson fluid via the homotopy analysis method (HAM). Graphical and numerical demonstrations of the convergence of the HAM solutions are provided. The effect of certain parameters on the dimensionless velocity, temperature, concentration, as well as on the skin friction coefficient and heat and mass transfer rates are illustrated and examined in detail. A comparison with previously published data has been carried out and good agreement was found.
Metabolism and Epigenetics
Authors: Janke Ryan , Dodson Anne E. , Rine Jasper
Published: September 2015

Epigenetic mechanisms by which cells inherit information are, to a large extent, enabled by DNA methylation and posttranslational modifications of histone proteins. These modifications operate both to influence the structure of chromatin per se and to serve as recognition elements for proteins with motifs dedicated to binding particular modifications. Each of these modifications results from an enzyme that consumes one of several important metabolites during catalysis. Likewise, the removal of these marks often results in the consumption of a different metabolite. Therefore, these so-called epigenetic marks have the capacity to integrate the expression state of chromatin with the metabolic state of the cell. This review focuses on the central roles played by acetyl-CoA, S-adenosyl methionine, NAD+, and a growing list of other acyl-CoA derivatives in epigenetic processes. We also review how metabolites that accumulate as a result of oncogenic mutations are thought to subvert the epigenetic program.
AT1receptor blocker losartan protects against mechanical ventilation-induced diaphragmatic dysfunction
Authors: Kwon Oh Sung , Smuder Ashley J. , Wiggs Michael P. , Hall Stephanie E. , Sollanek Kurt J. , Morton Aaron B. , Talbert Erin E. , Toklu Hale Z. , Tumer Nihal , Powers Scott K.
Published: September 2015

Mechanical ventilation is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged ventilator support results in diaphragmatic atrophy and contractile dysfunction leading to diaphragm weakness, which is predicted to contribute to problems in weaning patients from the ventilator. While it is established that ventilator-induced oxidative stress is required for the development of ventilator-induced diaphragm weakness, the signaling pathway(s) that trigger oxidant production remain unknown. However, recent evidence reveals that increased plasma levels of angiotensin II (ANG II) result in oxidative stress and atrophy in limb skeletal muscles. Using a well-established animal model of mechanical ventilation, we tested the hypothesis that increased circulating levels of ANG II are required for both ventilator-induced diaphragmatic oxidative stress and diaphragm weakness. Cause and effect was determined by administering an angiotensin-converting enzyme inhibitor (enalapril) to prevent ventilator-induced increases in plasma ANG II levels, and the ANG II type 1 receptor antagonist (losartan) was provided to prevent the activation of ANG II type 1 receptors. Enalapril prevented the increase in plasma ANG II levels but did not protect against ventilator-induced diaphragmatic oxidative stress or diaphragm weakness. In contrast, losartan attenuated both ventilator-induced oxidative stress and diaphragm weakness. These findings indicate that circulating ANG II is not essential for the development of ventilator-induced diaphragm weakness but that activation of ANG II type 1 receptors appears to be a requirement for ventilator-induced diaphragm weakness. Importantly, these experiments provide the first evidence that the Food and Drug Administration-approved drug losartan may have clinical benefits to protect against ventilator-induced diaphragm weakness in humans.
Effects of ischemic preconditioning on maximal constant-load cycling performance
Authors: Cruz Rogério Santos de Oliveira , de Aguiar Rafael Alves , Turnes Tiago , Pereira Kayo Leonardo , Caputo Fabrizio
Published: September 2015

This study investigated the effects of ischemic preconditioning (IPC) on the ratings of perceived exertion (RPE), surface electromyography, and pulmonary oxygen uptake (V̇o2) onset kinetics during cycling until exhaustion at the peak power output attained during an incremental test. A group of 12 recreationally trained cyclists volunteered for this study. After determination of peak power output during an incremental test, they were randomly subjected on different days to a performance protocol preceded by intermittent bilateral cuff pressure inflation to 220 mmHg (IPC) or 20 mmHg (control). To increase data reliability, the performance visits were replicated, also in a random manner. There was an 8.0% improvement in performance after IPC (control: 303 s, IPC 327 s, factor SDs of ×/÷1.13, P = 0.01). This change was followed by a 2.9% increase in peak V̇o2 (control: 3.95 l/min, IPC: 4.06 l/min, factor SDs of ×/÷1.15, P = 0.04), owing to a higher amplitude of the slow component of the V̇o2 kinetics (control: 0.45 l/min, IPC: 0.63 l/min, factor SDs of ×/÷2.21, P = 0.05). There was also an attenuation in the rate of increase in RPE ( P = 0.01) and a progressive increase in the myoelectrical activity of the vastus lateralis muscle ( P = 0.04). Furthermore, the changes in peak V̇o2 ( r = 0.73, P = 0.007) and the amplitude of the slow component ( r = 0.79, P = 0.002) largely correlated with performance improvement. These findings provide a link between improved aerobic metabolism and enhanced severe-intensity cycling performance after IPC. Furthermore, the delayed exhaustion after IPC under lower RPE and higher skeletal muscle activation suggest they have a role on the ergogenic effects of IPC on endurance performance.
Intestinal epithelial barrier function and tight junction proteins with heat and exercise
Authors: Dokladny Karol , Zuhl Micah N. , Moseley Pope L.
Published: September 2015

A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise.
Altered Recruitment of the Attention Network Is Associated with Disability and Cognitive Impairment in Pediatric Patients with Acquired Brain Injury
Authors: Strazzer Sandra , Rocca Maria A. , Molteni Erika , De Meo Ermelinda , Recla Monica , Valsasina Paola , Arrigoni Filippo , Galbiati Susanna , Bardoni Alessandra , Filippi Massimo
Published: September 2015

We assessed abnormalities of brain functional magnetic resonance imaging (fMRI) activity during a sustained attention task (Conners’ Continuous Performance Test (CCPT)) in 20 right-handed pediatric acquired brain injury (ABI) patients versus 7 right-handed age-matched healthy controls, and we estimated the correlation of such abnormalities with clinical and cognitive deficits. Patients underwent the Wechsler Intelligence Scale for Children (WISC), Wisconsin Card Sorting Test, and Functional Independence Measure (FIM) evaluations. During fMRI, patients and controls activated regions of the attention network. Compared to controls, ABI patients experienced a decreased average fMRI recruitment of the left cerebellum and a decreased deactivation of the left anterior cingulate cortex. With increasing task demand, compared to controls, ABI patients had an impaired ability to increase the recruitment of several posterior regions of the attention network. They also experienced a greater activation of frontal regions, which was correlated with worse performance on FIM, WISC, and fMRI CCPT. Such abnormal brain recruitment was significantly influenced by the type of lesion (focal versus diffuse axonal injury) and time elapsed from the event. Pediatric ABI patients experienced an inability to optimize attention network recruitment, especially when task difficulty was increased, which likely contributes to their clinical and cognitive deficits.
Paclobutrazol Residue Determination in Potato and Soil Using Low Temperature Partition Extraction and Ultrahigh Performance Liquid Chromatography Tandem Mass Spectrometry
Authors: Liu Hongcheng , Lin Tao , Mao Jia , Lu Huan , Yang Dongshun , Wang Jiliang , Li Qiwan
Published: September 2015

A simple, accurate, and highly sensitive analytical method was developed for determining the paclobutrazol residue in potato and soil, the dynamics dissipation in soil. Extraction was carried out by low temperature partitioning and analyzed by ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). For a favor extraction yield, the parameters such as temperature and solvent were optimized. The result showed that sample would be easily frozen and separated using acetonitrile under −20°C for 10 min. The limit of detection (LOD) was 0.5 μg/kg, and the limit of quantification (LOQ) was 2 and 5 μg/kg for potato and soil, respectively. The influence of paclobutrazol residue in potato was evaluated. The possible contamination of paclobutrazol from surface can be rinsed by distilled water or peeled off, but the paclobutrazol in potato harvest comes mainly from absorption and transport, which could not be removed by peeling. The half-life of paclobutrazol in soil was 20.64 days, and the residue was below 0.22 mg/kg on 50th day after spraying. According to the risk assessment with Need Maximum Daily Intake (NEDI) and Acceptable Daily Intake (ADI), a Maximum Residue Limit (MRL) of paclobutrazol in potato was recommended as 1.0 mg/kg.
The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea
Authors: Drago Francesco , Ciccarese Giulia , Broccolo Francesco , Ghio Massimo , Contini Paola , Thanasi Hajdhica , Parodi Aurora
Published: September 2015

Introduction. Pityriasis rosea (PR) is an exanthematous disease related to human herpesvirus‐ (HHV‐) 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied. Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis. Materials and Methods. Interleukin‐ (IL‐) 1, IL‐6, IL‐17, interferon‐ (IFN‐) γ, tumor necrosis factor‐ (TNF‐) α, vascular endothelial growth factor (VEGF), granulocyte colony stimulating factor (G‐CSF), and chemokines, CXCL8 (IL‐8) and CXCL10 (IP‐10), were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days). Results and discussion. Serum levels of IL‐17, IFN‐γ, VEGF, and IP‐10 resulted to be upregulated in PR patients compared to controls. IL‐17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN‐γ has a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP‐10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis. Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.
Formation, Energetics, and Electronic Properties of Graphene Monolayer and Bilayer Doped with Heteroatoms
Authors: Fujimoto Yoshitaka
Published: September 2015

Doping with heteroatoms is one of the most effective methods to tailor the electronic properties of carbon nanomaterials such as graphene and carbon nanotubes, and such nanomaterials doped with heteroatom dopants might therefore provide not only new physical and chemical properties but also novel nanoelectronics/optoelectronics device applications. The boron and nitrogen are neighboring elements to carbon in the periodic table, and they are considered to be good dopants for carbon nanomaterials. We here review the recent work of boron and nitrogen doping effects into graphene monolayer as well as bilayer on the basis of the first-principles electronic structure calculations in the framework of the density-functional theory. We show the energetics and the electronic properties of boron and nitrogen defects in graphene monolayer and bilayer. As for the nitrogen doping, we further discuss the stabilities, the growth processes, and the electronic properties associated with the plausible nitrogen defect formation in graphene which is suggested by experimental observations.
Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways
Authors: Ruppert Shannon M. , Falk Ben A. , Long S. Alice , Bollyky Paul L.
Published: September 2015

Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA.
Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity
Authors: Jadoon Saima , Karim Sabiha , Asad Muhammad Hassham Hassan Bin , Akram Muhammad Rouf , Kalsoom Khan Abida , Malik Arif , Chen Chunye , Murtaza Ghulam
Published: September 2015

The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes variousin vivoantioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form includeAcacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomillaL.,Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erectaLinn.,Terminalia chebula, Trigonella foenum-graecum, andVitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed.
A Numerical Study on Impact of Taiwan Island Surface Heat Flux on Super Typhoon Haitang (2005)
Authors: Xu Hongxiong
Published: September 2015

Three to four tropical cyclones (TCs) by average usually impact Taiwan every year. This study, using the Developmental Tested Center (DTC) version of the Hurricane WRF (HWRF) model, examines the effects of Taiwan’s island surface heat fluxes on typhoon structure, intensity, track, and its rainfall over the island. The numerical simulation successfully reproduced the structure and intensity of super Typhoon Haitang. The model, especially, reproduced the looped path and landfall at nearly the right position. Sensitive experiments indicated that Taiwan’s surface heat fluxes have significant influence on the super Typhoon Haitang. Compared to sensible heat (SH) fluxes, latent heat (LH) is the dominant factor affecting the intensity and rainfall, but they showed opposite effects on intensity and rainfall. LH (SH) flux of Taiwan Island intensified (weakened) Typhoon Haitang’s intensity and structure by transferring more energy from (to) surface. However, only LH played a major role in the looped path before the landfall of the Typhoon Haitang.
The Rise and Fall of Hyaluronan in Respiratory Diseases
Authors: Lauer Mark E. , Dweik Raed A. , Garantziotis Stavros , Aronica Mark A.
Published: September 2015

In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.
Hyaluronan Synthase 3 Null Mice Exhibit Decreased Intestinal Inflammation and Tissue Damage in the DSS-Induced Colitis Model
Authors: Kessler Sean P. , Obery Dana R. , de la Motte Carol
Published: September 2015

Hyaluronan (HA) overproduction is a hallmark of multiple inflammatory diseases, including inflammatory bowel disease (IBD). Hyaluronan can act as a leukocyte recruitment molecule and in the most common mouse model of intestinal inflammation, the chemically induced dextran sodium sulfate (DSS) experimental colitis model, we previously determined that changes in colon distribution of HA occur before inflammation. Therefore, we hypothesized that, during a pathologic challenge, HA promotes inflammation. In this study, we tested the progression of inflammation in mice null for the hyaluronan synthase genes (HAS1, HAS3, or both HAS1 and HAS3) in the DSS-colitis model. Our data demonstrate that both the HAS1/HAS3 double and the HAS3 null mice are protected from colitis, compared to wild-type and HAS1 null mice, as determined by measurement of weight loss, disease activity, serum IL-6 levels, histologic scoring, and immunohistochemistry. Most notable is the dramatic increase in submucosal microvasculature, hyaluronan deposition, and leukocyte infiltration in the inflamed colon tissue of wild-type and HAS1 null mice. Our data suggest, HAS3 plays a crucial role in driving gut inflammation. Developing a temporary targeted therapeutic intervention of HAS3 expression or function in the microcirculation may emerge as a desirable strategy toward tempering colitis in patients undergoing flares of IBD.
Twin Studies of Atopic Dermatitis: Interpretations and Applications in the Filaggrin Era
Authors: Elmose Camilla , Thomsen Simon Francis
Published: September 2015

Aim. The aim of this study was to conduct a systematic review of population-based twin studies of (a) the concordance and heritability of AD and (b) the relationship between AD and asthma and, furthermore, to reinterpret findings from previous twin studies in the light of the emerging knowledge about filaggrin and its role in the atopic march and provide suggestions for future research in this area. Methods. We identified all twin studies (published after 1970) that have calculated the concordance rate and/or the heritability of AD, or the genetic and environmental correlations between AD and asthma. Results. Reported concordance rates for AD ranged, respectively. From 0.15 to 0.86 for MZ and from 0.05 to 0.41 for DZ twins, with an overall ratio of MZ : DZ twins of approximately three. The heritability of AD was estimated to be approximately 75%, and the association between AD and asthma was around 85% explained by genetic pleiotropy. Conclusions. Genetic factors account for most of the variability in AD susceptibility and for the association between AD and asthma. Controversy remains as to whether the atopic diseases are causally related or whether they are diverse clinical manifestations of a common, underlying (genetic) disease trait. Future twin studies may help solve this enigma.
Fas Ligand Deficiency Impairs Tumor Immunity by Promoting an Accumulation of Monocytic Myeloid-Derived Suppressor Cells
Authors: Peyvandi Sanam , Buart Stéphanie , Samah Boubekeur , Vétizou Marie , Zhang Yanyan , Durrieu Ludovic , Polrot Mélanie , Chouaib Salem , Benihoud Karim , Louache Fawzia , Karray Saoussen
Published: September 2015

The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor–positive cells. Here, we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naïve mice increased myeloid cell populations, but, in marked contrast, it reduced the levels of myeloid-derived suppressor cells (MDSC) in mice bearing Lewis lung carcinoma tumors. Analysis of the MDSC subset distribution revealed that FasL deficiency skewed cell populations toward the M-MDSC subset, which displays a highly immunosuppressive activity. Furthermore, tumor-bearing mice that were FasL-deficient displayed an enhanced proportion of tumor-associated macrophages and regulatory T cells. Overall, the immunosuppressive environment produced by FasL targeting correlated with reduced survival of tumor-bearing mice. These results disclose a new role for FasL in modulating immunosuppressive cells. Cancer Res; 75(20); 4292–301. ©2015 AACR.
NF2 Loss Promotes Oncogenic RAS-Induced Thyroid Cancers via YAP-Dependent Transactivation of RAS Proteins and Sensitizes Them to MEK Inhibition
Authors: Garcia-Rendueles Maria E.R. , Ricarte-Filho Julio C. , Untch Brian R. , Landa Iňigo , Knauf Jeffrey A. , Voza Francesca , Smith Vicki E. , Ganly Ian , Taylor Barry S. , Persaud Yogindra , Oler Gisele , Fang Yuqiang , Jhanwar Suresh C. , Viale Agnes , Heguy Adriana , Huberman Kety H. , Giancotti Filippo , Ghossein Ronald , Fagin James A.
Published: September 2015

Ch22q LOH is preferentially associated with RAS mutations in papillary and in poorly differentiated thyroid cancer (PDTC). The 22q tumor suppressor NF2, encoding merlin, is implicated in this interaction because of its frequent loss of function in human thyroid cancer cell lines. Nf2 deletion or Hras mutation is insufficient for transformation, whereas their combined disruption leads to murine PDTC with increased MAPK signaling. Merlin loss induces RAS signaling in part through inactivation of Hippo, which activates a YAP–TEAD transcriptional program. We find that the three RAS genes are themselves YAP–TEAD1 transcriptional targets, providing a novel mechanism of promotion of RAS-induced tumorigenesis. Moreover, pharmacologic disruption of YAP–TEAD with verteporfin blocks RAS transcription and signaling and inhibits cell growth. The increased MAPK output generated by NF2 loss in RAS-mutant cancers may inform therapeutic strategies, as it generates greater dependency on the MAPK pathway for viability.

Significance: Intensification of mutant RAS signaling through copy-number imbalances is commonly associated with transformation. We show that NF2/merlin inactivation augments mutant RAS signaling by promoting YAP/TEAD-driven transcription of oncogenic and wild-type RAS, resulting in greater MAPK output and increased sensitivity to MEK inhibitors. Cancer Discov; 5(11); 1178–93. ©2015 AACR.

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Depression and Quality of Life in Older Persons: A Review
Authors: Sivertsen Heidi , Bjørkløf Guro Hanevold , Engedal Knut , Selbæk Geir , Helvik Anne-Sofie
Published: September 2015

Background: Depression is a prevalent and disabling condition in older persons (≥60 years) that increases the risk of mortality and negatively influences quality of life (QOL). The relationship between depression, or depressive symptoms, and QOL has been increasingly addressed by research in recent years, but a review that can contribute to a better understanding of this relationship in older persons is lacking. Against this background, we undertook a literature review to assess the relationship between depression and QOL in older persons. Summary: Extensive electronic database searches revealed 953 studies. Of these, 74 studies fulfilled our criteria for inclusion, of which 52 were cross-sectional studies and 22 were longitudinal studies. Thirty-five studies were conducted in a clinical setting, while 39 were community-based epidemiological studies. A clear definition of the QOL concept was described in 25 studies, and 24 different assessment instruments were employed to assess QOL. Depressed older persons had poorer global and generic health-related QOL than nondepressed individuals. An increase in depression severity was associated with a poorer global and generic health-related QOL. The associations appeared to be stable over time and independent of how QOL was assessed. Key Messages: This review found a significant association between severity of depression and poorer QOL in older persons, and the association was found to be stable over time, regardless which assessment instruments for QOL were applied. The lack of a definition of the multidimensional and multilevel concept QOL was common, and the large variety of QOL instruments in various studies make a direct comparison between the studies difficult.
Versorgung Zwangserkrankter mit kognitiver Verhaltenstherapie als Behandlungsmethode erster Wahl
Authors: Voderholzer Ulrich , Schlegl Sandra , Diedrich Alice , Külz Anne Katrin , Thiel Nicola , Hertenstein Elisabeth , Schwartz Caroline , Rufer Michael , Herbst Nirmal , Nissen Christoph , Hillebrand Thomas , Osen Bernhard , Stengler Katarina , Jelinek Lena , Moritz Steffen
Published: September 2015

Hintergrund: Die kognitive Verhaltenstherapie (KVT) mit Exposition und Reaktionsverhinderung stellt die Behandlungsmethode erster Wahl für Patienten mit Zwangsstörung dar. Ziel der vorliegenden Studie war die Bestimmung des Anteils an Patienten mit einer Zwangsstörung, die in Deutschland eine KVT mit Exposition und Reaktionsverhinderung erhalten. Methode: Hierzu wurden die Daten aus einer Befragung zur Behandlungsvorgeschichte einer Stichprobe von 369 Patienten mit einer Zwangsstörung nach ICD-10 analysiert. Ergebnisse: Insgesamt berichteten 60% der Patienten, in ihrer Behandlungsvorgeschichte mindestens einmal eine KVT mit Expositionsübungen erhalten zu haben. Bei 37% war dies die erste Behandlung. 46% gaben an, mindestens einmal eine KVT mit therapeutenbegleiteten Expositionsübungen erhalten zu haben. Durchschnittlich vergingen 6 Jahre zwischen Beginn der Zwangsstörung und Beginn der ersten Behandlung. Schlussfolgerungen: Zwei Fünftel der Patienten unserer Stichprobe berichteten, dass sie noch nie eine KVT mit Exposition und Reaktionsverhinderung erhalten hatten, obwohl es sich dabei um die Methode erster Wahl bei Zwangsstörungen handelt. Wir diskutieren potenzielle Hürden aufseiten der Patienten, Ärzte und Therapeuten sowie Maßnahmen, die zur Verbesserung der Versorgungssituation beitragen könnten.
Effect of High-Dose Statin Therapy on Drug-Eluting Stent Strut Coverage
Authors: Kim Jung-Sun , Kim Jeong Hun , Shin Dong-Ho , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Hong Myeong-Ki
Published: September 2015

Objective—

The influence of high-dose statin therapy on the serial stent healing process has not been fully investigated. Using optical coherence tomography, the effect of high-dose statin therapy on stent strut coverage was evaluated in drug-eluting stent–treated patients.

Approach and Results—

Sixty patients were randomly assigned to 2 groups according to the statin dose (atorvastatin 40 mg as high-dose statin therapy [n=29] versus pravastatin 20 mg as low-dose statin therapy [n=31]). Serial optical coherence tomographic evaluation post procedure and at the 3-month and 12-month follow-ups was performed in 50 patients with 54 stents (23 atorvastatin-treated patients versus 27 pravastatin-treated patients). The percentage of uncovered struts was defined as the ratio of uncovered struts/total struts. The primary end point was the percentage of uncovered struts at the 12-month follow-up. The secondary end point was the percentage of uncovered struts at the 3-month follow-up and the comparative percentage change (Δ) of uncovered struts at the 3- and 12-month follow-ups between the different dose statin therapies. The percentage of uncovered struts was 7.4% (range, 4.3%–10.4%) in atorvastatin-treated patients versus 10.6% (range, 5.7%–22.6%) in pravastatin-treated patients at the 3-month follow-up (
P
=0.13) and 1.3% (0.3%–3.8%) versus 2.5% (0.9%–9.7%), respectively, at the 12-month follow-up (
P
=0.01). The percentage Δ of uncovered struts from 3 to 12 months of follow-up was −7.9±8.5% in atorvastatin-treated patients versus −9.3±12.5% in pravastatin-treated patients (
P
=0.67).

Conclusions—

This study suggested that high-dose statin therapy might provide a beneficial effect for the vascular healing process after drug-eluting stent implantation.
Characteristics and Outcomes of Patients With Severe Bioprosthetic Aortic Valve Stenosis Undergoing Redo Surgical Aortic Valve Replacement
Authors: Naji Peyman , Griffin Brian P. , Sabik Joseph F. , Kusunose Kenya , Asfahan Fadi , Popovic Zoran B. , Rodriguez L. Leonardo , Lytle Bruce W. , Grimm Richard A. , Svensson Lars G. , Desai Milind Y.
Published: September 2015

Background—

With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes.

Methods and Results—

We studied 276 patients with severe bioprosthetic PAS (64±16 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area <0.8 cm
2
, mean AV gradient ≥40 mm Hg, or dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8±8 and 53±17 mm Hg, whereas 28% had >II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2±3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all
P
<0.01).

Conclusions—

At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes.
Common Dorsal Stream Substrates for the Mapping of Surface Texture to Object Parts and Visual Spatial Processing
Authors: Zachariou Valentinos , Nikas Christine V. , Safiullah Zaid N. , Behrmann Marlene , Klatzky Roberta , Ungerleider Leslie G.
Published: September 2015

Everyday objects are often composed of multiple parts, each with a unique surface texture. The neural substrates mediating the integration of surface features on different object parts are not fully understood, and potential contributions by both the ventral and dorsal visual pathways are possible. To explore these substrates, we collected fMRI data while human participants performed a difference detection task on two objects with textured parts. The objects could either differ in the assignment of the same texture to different object parts (“texture-location”) or the types of texture (“texture-type”). In the ventral stream, comparable BOLD activation levels were observed in response to texture-location and texture-type differences. In contrast, in a priori localized spatial processing regions of the dorsal stream, activation was greater for texture-location than texture-type differences, and the magnitude of the activation correlated with behavioral performance. We confirmed the reliance of surface texture to object part mapping on spatial processing mechanisms in subsequent psychophysical experiments, in which participants detected a difference in the spatial distance of an object relative to a reference line. In this task, distracter objects occasionally appeared, which differed in either texture-location or texture-type. Distracter texture-location differences slowed detection of spatial distance differences, but texture-type differences did not. More importantly, the distracter effects were only observed when texture-location differences were presented within whole shapes and not between separated shape parts at distinct spatial locations. We conclude that both the mapping of texture features to object parts and the representation of object spatial position are mediated by common neural substrates within the dorsal visual pathway.
Gout, Beasts, and Other Metaphorical Punishments in ap 11.226-231
Authors: Mulligan Bret
Published: September 2015

The reference to retributive gout in 11.229 serves as a semiotic hinge between two sets of interdependent poems in what may be a coherent Ammianic sequence (ap 11.226-231). Ammianos’ approval of gout as a just punishment in 11.229 establishes themes of retribution and somatic torment that are elaborated in 11.230-231, riddling epigrams that express the hope that their target will endure repeated execution on the cross (11.230) and then in the arena (11.231). The torturous executions hoped for in 11.230-231 are further contextualized by analogous references to mythic and fabulistic punishments in an adjacent set of poems by the same author (11.226-228). When these epigrams are considered in light of the retributive nature and metaphorical implications of gout, their wit and substance can be better appreciated.
A Good Place to Be
Authors: van Tilburg Cornelis
Published: September 2015

The founding of a city requires certain hygienic and meteorological conditions. The climate must be moderate, neither too hot, nor too cold; neither too dry, nor too moist; fresh air and water are crucial. Ancient medical writers such as the authors of the Hippocratic Corpus, Celsus and Galen prescribe ideal conditions for the city. Wind-directions, local climate (heat, cold, humidity), quantity and quality of air and water and a clean environment were crucial factors to establish a healthy city. Did their opinions correspond with the opinions of non-medical ancient sources like Vitruvius, Varro, and Columella? And, finally, were these conditions really realised in practice, as proved by excavations? According to his book Res rusticae, the Roman author M. Terentius Varro improved the hygienic situation by cleaning polluted air, when he changed the position of doors and windows. If this story is true, there is evidence that there was some knowledge of improving health, bringing theory into practice.
What is Dramatic Recitation?
Authors: Bexley Erica
Published: September 2015

This article examines the literary evidence for recitations of drama in first- and early second-century c.e. Rome. It begins by contextualizing the practice of recitatio, and thereafter focuses on the central question of how a solo speaker could recite a play so as to render it intelligible for his audience. Two solutions suggested by extant sources are voice and gesture; it is possible that the individuals reciting plays either altered their intonation or inserted specific movements to signify a change of character. Although both of these solutions are tentative, they indicate nonetheless that dramatic recitation involved elements of performance.
A Swallow in Winter
Authors: Déniz Alcorac Alonso
Published: September 2015

The construction ἐν + accusative is a ghost in the dialect of Cyrene. The local inscriptions overwhelmingly attest to ἐς + accusative. A few alleged occurrences of this feature must be discarded. The only valid example, ἐν στάλ[αν] | λυγδίναν in the ‘Pact of the first settlers’ (seg 9.3, 16-7, 4th c. bce), remains an anomaly that calls for a justification. The paper tries to demonstrate that the co-occurrence of ἀναγράφω/καταγράφω ἐς + accusative and ἀναγράφω/καταγράφω ἐν + dative resulted in an unintentional blending of both constructions.
Visible Implant Elastomer tagging influences social preferences of zebrafish (Danio rerio)
Authors: Frommen Joachim G. , Hanak Sophie , Schmidl Christina A. , Thünken Timo
Published: September 2015

Identification of individuals is a prerequisite in many behavioural studies. Visible Implant Elastomer (VIE) colour tags are a well-established way to mark animals. VIE tagging does not seem to affect individual growth or survival. However, studies verifying their neutrality during social interactions are less common. Here, individual male and female zebrafish Danio rerio were simultaneously given the choice between two shoals, each consisting of six fish. Members of one shoal were uniformly marked with one VIE tag of a given colour, whereas the other shoal was sham-tagged. In total, 10 different colours were used. Test fish spent significantly more time near the tagged shoal (56%) than near the sham-tagged shoal (44%). Tag colour did not significantly influence the preferences. The results highlight the importance of confirming the neutrality of colour tags before using them in behavioural studies. Especially, our study advises caution when using marked and unmarked fish simultaneously.
Allonursing in white-faced capuchins (Cebus capucinus) provides evidence for cooperative care of infants
Authors: Sargeant Elizabeth J. , Wikberg Eva C. , Kawamura Shoji , Fedigan Linda M.
Published: September 2015

Allonursing is a highly cooperative behaviour that may have important fitness consequences for the infant while the benefits to the allomother are less clear. To investigate the function of this behaviour, we compared patterns of allonursing and nursing exhibited by white-faced capuchin monkeys (Cebus capucinus). We used a linear mixed model approach to analyse data collected on 21 infants from six social groups in Sector Santa Rosa, Costa Rica. Infants nursed at higher rates and for longer durations from their mothers than from allonurses. They also allonursed at higher rates from lactating and non-lactating parous females than from nulliparous females and at higher rates from maternally related female allonurses than other females. We found no observed effect of adult female rank or infant sex. We conclude that infant white-faced capuchins engage in allonursing as a means to acquire additional milk, and that participating allonurses may benefit from increased inclusive fitness.
Mononchoides macrospiculum n. sp. (Nematoda: Neodiplogastridae) and Teratorhabditis synpapillata Sudhaus, 1985 (Nematoda: Rhabditidae): nematode associates of Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae) in Italy
Authors: Troccoli Alberto , Oreste Monica , Tarasco Eustachio , Fanelli Elena , De Luca Francesca
Published: September 2015

Several juvenile and adult nematodes were isolated after dissection of pupae and adults of the red palm weevil,Rhynchophorus ferrugineus, recovered from an infestedPhoenix canariensisChabaud exemplar in Bari, Italy. Two species of nematodes were recovered,Teratorhabditis synpapillataandMononchoides macrospiculumn. sp. which is described herein. The mitochondrial cytochrome oxidase I (COI), the ITS-containing region, the 18S rRNA gene (SSU) and the D2-D3 expansion domains of the 28S rRNA gene (LSU) were amplified and sequenced. The new species,M. macrospiculumn. sp., is described at morphological and molecular level. Phylogenetic analyses using SSU and LSU sequences placedM. macrospiculumn. sp. together withM. composticolaandM. striatus. The sequences of the Italian population ofT. synpapillataare identical to those ofT. synpapillatafrom Japan. This is the first report on the association ofM. macrospiculumn. sp. andT. synpapillatawith the red palm weevil in Europe.