bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of process for reduction of antinutritional factors in edible cereal brans
Authors: Kaur Satinder , Sharma Savita , Dar BN , Singh Baljit
Published: October 2012

Reduction of various antinutritional factors in cereal brans by different treatments (microwave heating, dry heating and wet heating) were studied. There was significant difference ( p ≤ 0.05) in reduction of antinutritional factors of treated cereal brans except for dry heating at low temperature. Microwave heating at 2450 MHz for 2.5 min resulted in 53.85%, 57.21%, 65.00% and 100% reduction in phytic acid, polyphenols, oxalates and saponins, respectively. Wet heating resulted in maximum reduction in trypsin inhibitor activity (83.07%) at 110 °C for 25 min. Processing treatment resulted in increase in bulk density and slight darkening of the brans. The most effective method of detoxifying most of the toxicants was microwave heating for 2.5 min, and therefore it could be exploited for making treated brans an ideal source for potential food application.
Bioactive compounds in cereal grains – occurrence, structure, technological significance and nutritional benefits – a review
Authors: Bartłomiej Siurek , Justyna Rosicka-Kaczmarek , Ewa Nebesny
Published: October 2012

This review presents current information about principal, biologically active compounds contained in grains of cereals that are most popular in Europe (wheat, rye, barley and oat). The tendency to provide consumers with safe foods, which promote their health and are based on cereal grains and/or their components with the high nutritive value, has been recently observed. The intake of protective substances contained in whole grains and their fractions contributes to a decreased risk of food-dependent diseases like the coronary heart disease and insulin-dependent diabetes. This study describes the structure, occurrence in cereal grains, technological importance and beneficial influence on human health of bioactive substances such as arabinoxylans, β-glucans, alkylresorcinols, tocols and phytosterols.
Askēsis and organizational culture
Authors: Halsall Robert , Brown Mary
Published: October 2012

This article makes the case for the contribution of the cultural theory of Sloterdijk and the tradition of philosophical anthropology on which it is based to an understanding of the processes of culture formation in organizations. Rather than see culture formation as the model of an autonomous self which sacrifices or gives up this autonomy as a result of identification with the organizational culture, or retains it by resisting or distancing from the culture, the article argues that we should see organizational selves as engaged in processes of askēsis, understood as ‘systems of spiritual exercises, … practised in collectives of personalised regimes’ (Sloterdijk, 2009: 12), the aim of which is the fulfilment of the imperative ‘you must change your life!’ (Sloterdijk, 2009). The article illustrates the application of the theory to the formation of ‘secessionist’ cultures, cultures devoted to the pursuit of radical ascetic aims, by outlining the mechanisms of askēsis in contemporary organizations: the splitting of the self into ‘willing’ and ‘unwilling’ elements which are in constant ‘endo-rhetorical’ dialogue; the imitation of exemplars of ascetic behaviour, or the ‘perfectionist vita’; ‘conversion’ to the organizational culture, whether as a sudden experience or as a gradual process, and organizational cultures understood as ‘cultures of observance’, the aim of which are to encourage the employee to scrutinize habitual behaviour and change this behaviour in line with the ideals of the secessionist culture. The end point of askēsis is reached when the employee conceives organizational life itself as a continual ‘test’ of commitment and will.
Attribution of words versus attribution of responsibilities: Academic plagiarism and university practice
Authors: Luke Belinda , Kearins Kate
Published: October 2012

This article examines a case of academic plagiarism and the subsequent treatment of the issues across several academic institutions. It calls for academic leaders in universities to act on what constitutes a serious breach of standards, engendered in part by broader institutional norms and values promoting the need for publications in a ‘publish or perish’ environment. While universities often promote high-sounding ideals and would generally wish to be seen to uphold high academic standards, it is argued that silence and complicity surround the way in which instances of plagiarism in academic publications are often dealt with. Actions (and inaction) by academic leaders in universities in dealing with cases of academic plagiarism speak volumes in terms of the values academic institutions profess, and those they actually uphold. The article prompts readers to consider the need for a more consistent and proactive stance on the part of their own institutions to exercise ethical leadership in identifying and addressing academic plagiarism when it occurs.
Neo-colonialism in the academy? Anglo-American domination in management journals
Authors: Murphy Jonathan , Zhu Jingqi
Published: October 2012

Leading business and management journals claim to be ‘world-leading’ but are dominated by Anglo-American scholars. The extent of this domination is demonstrated graphically in this article through cartograms based on 2010/2011 authorship and editorship data in top management journals. The dramatically skewed production of management scholarship is both ethically problematic in terms of Anglo-American domination of leading journals and the exclusion of many developing regions, and anachronistic given the shift of global production away from the North Atlantic in recent years. This continuing neo-colonial domination of intellectual production underpins the inequitable organization of the global economy and specifically the disproportionate realisation of wealth in the global North at the expense of the global South. The article proposes a series of measures to begin redressing the imbalance.
Foucault, subjectivity and ethics: towards a self-forming subject
Authors: Skinner Diane
Published: October 2012

In this article, I examine self-formation through the activity of organic farming in a self-managing community. How do producing and consuming subjects organize their selves around the ‘false natural object’ (Veyne, 1997) that is organic? To inform this ethnographic account of self-formation, I draw on the work of Michel Foucault. A study is made of technologies of the self in the contemporary setting of a self-managing organic farming community without compromising the self-forming, self-regulating activity of the ethical subject presented by Foucault in his studies of Antiquity. I contend that the self is formed by the subject as a thinking and acting being through the modes of subjectivation and objectivation (Foucault, 2000a). The article contributes empirical support to theoretical studies that consider how Foucault’s texts account for the intervention of human subjects alongside sociological factors when exploring organizational issues (Bardon and Josserand, 2011; McKinlay and Pezet, 2010). It is recommended that a wider range of responses could be opened up in Foucault-inspired studies at other organizational sites, including the workplace, by exploring the self-formation of the subject as a starting point for understanding the importance of the individual alongside sociological factors.
Beyond macro- and micro- emancipation: Rethinking emancipation in organization studies
Authors: Huault Isabelle , Perret Véronique , Spicer André
Published: October 2012

Organizational life is replete with claims for emancipation. Existing approaches understand these claims either through theories of macro-emancipation (which focus on larger social structural challenges) or micro-emancipation (which focus on everyday challenges). However, these theories fundamentally misrecognize many emancipatory challenges in organizations. Drawing on the work of Jacques Rancière, we argue that this philosophy is fertile for shifting or unframing traditional approaches of emancipation in organization studies. Emancipation is triggered by the assertion of equality in the face of institutionalized patterns of inequality, it works through a process of articulating dissensus, and it creates a redistribution of what is considered to be sensible. By focusing on these three aspects, we argue that a whole range of emancipatory struggles which had previously been disregarded by studies of macro-emancipation and micro-emancipation come back into view. This significantly extends how we conceptualize emancipation in organizations and allows us to address some of the shortcomings of existing theories.
Assessment of the effect of temperature, shear rate and thickener content on the thixotropy of lithium lubricating greases
Authors: Paszkowski Maciej
Published: October 2012

As part of this research the thixotropy of lubricating greases based on mineral oil ORLEN OIL SN-400, thickened with lithium 12-hydroxystearate has been investigated. The investigations consisted in shearing grease samples in the rotational rheometer head for 1 h, followed by 24- h relaxation and again 1-h shearing, at a constant shear rate gradient. The increase in the structural viscosity of the grease, caused by the partial reconstruction of the lithium thickener microstructure between the two shearing stages, after 24- h relaxation, was studied. The studies have shown that there is a non-unique dependence between grease temperature T, shear rate gradient [Formula: see text], thickener percentage Sc and the intensity of grease microstructure reconstruction. In the adopted ranges of the input quantities: T (from −20 °C to  + 80 °C), [Formula: see text] (from 8.1 to 48.6 s−1) and Sc (from 4% to 9%), the largest increment in structural viscosity was observed for the grease with thickener percentage Sc = 7.5%, sheared at shear rate gradient [Formula: see text] = 8.1 s−1 at temperature T = 28 °C. On the basis of the experimental studies, a mathematical relation for predicting the increment in the structural viscosity of lithium greases in different shearing conditions has been developed. The relation can find wide application in engineering practice in the design of machine lubrication systems and in the selection of lubricating media thickened with lithium soap.
Building Partnerships to Build the Best Bones Forever!
Authors: Abercrombie Ann , Sawatzki Darcy , Lotenberg Lynne Doner
Published: October 2012

Government, nonprofit, and corporate partners can be critical to achieving national, state, or local social marketing goals. Yet, partners are often underutilized by social marketing programs. Managers of a national bone health campaign targeting girls ages 9–14 in the United States avoid this problem using marketing principles and the marketing mix to involve partners in developing and delivering campaign components and to manage mutually beneficial partnership efforts. The approach has resulted in a campaign that attracts an ever-increasing number of partners and activities that provide girls with opportunities, motivation, and ability to engage in bone healthy behaviors.
Segmenting Audiences and Tailoring Messages
Authors: Campo Shelly , Askelson Natoshia M. , Carter Knute D. , Losch Mary
Published: October 2012

Half of all pregnancies in young adult women are unintended, but few interventions have been successful in encouraging contraceptive use. The group heterogeneity likely contributes to the lack of success. Segmenting based on theories that provide meaningful information may improve tailoring and targeting of behavioral interventions. Previous research has indicated that threat, efficacy, and fear were important factors in influencing intentions to use contraceptives; therefore, the extended parallel process model (EPPM) was used for this cluster analysis. A telephone survey of randomly selected 18- to 30-year-old women in Iowa was conducted ( N = 401). The constructs of EPPM and age were used for conducting a K means cluster analysis with four clusters. The cluster analysis pointed to the importance of fear, perceived susceptibility, and age. All of the clusters had varying degrees of ambivalence about the severity of a pregnancy. Cluster 1 (27.8%) had high susceptibility, with little fear. Cluster 2 (23.8%) had high efficacy and higher fear. The third cluster (34.7%) was not fearful and had low susceptibility. The final cluster (13.8%) was younger than the other groups and had the lowest efficacy. Additional analyses were conducted to explore how the clusters varied on other variables. The clusters help campaign developers prioritize audiences and tailor messages.
Bostin Value
Authors: Woodhouse Leila , Bussell Patricia , Jones Stacey , Lloyd Helen , Macdowall Wendy , Merritt Rowena
Published: October 2012

“Bostin Value” was a pilot scheme aiming to improve fruit and vegetable consumption in a deprived neighborhood in the borough of Dudley, England. Research identified the need to address both supply and demand to encourage the target audience (parents/carers of young children) to consume more fruit and vegetables along with their children. Bostin Value improved supply through commissioning a local greengrocer to sell fresh fruit and vegetables twice a week at a local primary school. Promotions were used to encourage sales, including a loyalty card system, money off vouchers, and recipe cards. To increase demand, educational sessions were run at the school to improve parent’s skills in cooking seasonal produce. Children at the school received tasting workshops to encourage them to try a variety of fruit and vegetables. Results saw the mean portions of fruit consumed weekly by parents significantly increase from 2.4 portions in April 2009 to 3.1 in July 2010. This was mirrored in children whose weekly portions increased from 2.6 to 3.7. The mean number of different fruits and vegetables tasted by children also increased significantly.
Changing Channels
Authors: Ledford Christy J. W.
Published: October 2012

Many health promotion campaigns are designed to communicate complex, potentially ambiguous messages. The strategic communication stages of formative research, strategy, tactics, and evaluation provide campaign guidance for communicating messages, but less direction is available for the specific tactics of channel selection and message delivery. The research question explored here is what channel characteristics should campaign designers consider and assess when selecting the most effective channels for disseminating their messages. A review of extant literature of channel selection theory informed the application of media richness theory and the concept of medium control. Synthesizing this theory and concept provides a typology of channels from which to select channels for communicators as they negotiate the media landscape. Often with limited resources and budgets, health communicators must make critical choices about what channels to use in disseminating their messages. While new and social media offer exciting opportunities, communicators must consider the media’s ability to transmit potentially ambiguous messages.
Tobacco Consumption and Illegal Drug Use Among Bangladeshi Males
Authors: Kabir M. A. , Goh Kim-Leng , Khan M. M. H.
Published: October 2012

This article aimed to identify the determinants of tobacco consumption and illegal drug use (IDU) as well as to examine the association between these two variables using a representative sample of 3,771 Bangladeshi males aged 15 to 54 years. Data were collected through Bangladesh Demographic and Health Survey 2007. To identify the determinants, the patterns of tobacco consumption and IDU were analyzed by age, education and occupation, residence, mass media, premarital sex, wealth, and sexually transmitted infections (STIs). Prevalence of smoking cigarette and bidi was roughly 60%. However, the prevalence of IDU was 3.4%, and this proportion is statistically significant ( Z = 11.32, p = .000). After bivariate analysis, almost all variables except STIs were significantly associated with tobacco consumption. Similarly, all variables except residence and mass media were associated with IDU. Based on multivariable adjusted logistic regression analysis, the likelihood of using IDU was approximately twofold (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.23-2.53) among bidi smokers and fourfold (OR = 3.8, 95% CI = 2.62-5.56) among cigarette smokers as compared with nonsmokers.
Men on Fathering in the Context of Children’s Unintentional Injury Prevention
Authors: Brussoni Mariana , Creighton Genevieve , Olsen Lise L. , Oliffe John L.
Published: October 2012

Injuries are a leading cause of death for children, and parental safety behaviors are fundamental to child injury prevention. Fathers’ perspectives are largely absent. Our novel research connects masculinities, fathering, and childhood injury. Sixteen fathers of children aged 2 to 7 years in two Canadian urban settings participated in photo-elicitation interviews detailing activities they enjoyed with their children and concerns regarding child safety. Participants described how elements of risk, protection, and emotional connection influenced their approach to fathering as it related to injury prevention. Most men considered engaging children in risk as key to facilitating development and described strategies for protecting their children while engaging in risk. Many men identified how the presence of an emotional connection to their children allowed them to gauge optimal levels of risk and protection. There exists a tremendous opportunity to work with fathers to assist in their efforts to keep their children safe.
Potential Benefits of Cinnamon in Type 2 Diabetes
Authors: Howard Molly E. , White Nicole D.
Published: October 2012

Long known as a spice, cinnamon’s potential efficacy in the treatment of type 2 diabetes has been gaining interest. Evidence from animal models shows efficacy as an insulin mimetic and insulin sensitizing agent, in addition to other potential mechanisms of action. Human clinical data regarding its efficacy have shown inconsistent results but may be related to differentials in baseline glucose control, type of cinnamon used, and duration of study. Overall, a significant number of trials have shown cinnamon to be an effective option for lowering blood sugar in uncontrolled type 2 diabetics. Cinnamon’s reasonable cost, over-the-counter availability, and safety profile make it a relatively low-risk option for this population.
Food, Technology and Hunger
Authors: Bratspies Rebecca M.
Published: October 2012

This article uses genetically modified crops as a springboard for examining the role ascribed to technology by the international institutional framework for responding to food insecurity. It argues that food insecurity is a problem rooted in political will formation rather than in the mechanics of food production. From this starting point, the article examines the failure of various global initiatives to end hunger, highlighting how these initiatives emphasized new technologies for increasing food production while giving short shrift to the thorny structural problems associated with hunger.
Retrospective Analysis of Mini-Open Repair Versus Open Repair for Acute Achilles Tendon Ruptures
Authors: Klein Erin E. , Weil Lowell , Baker Jeffrey R. , Weil Lowell Scott , Sung Wenjay , Knight Jessica
Published: October 2012

Purpose: Debate exists over optimal treatment for acute Achilles tendon ruptures. Recent literature suggests the mini-open technique may provide the reliability of the open repair with the decreased complication rate of non-operative treatment. This retrospective review compares acute tendon ruptures treated with one of two techniques: open repair (TO) or mini-open repair (MOA). Methods & Results: Records were reviewed and 34 patients were found to meet the inclusion criteria for open or mini-open repair of an acute Achilles tendon rupture with follow up of at least 12 months. TO (n=16) and MOA (n=18) had no statistically significant differences in age at time of injury [TO: 41 + 2.5 years (range 20 – 68); MOA: 46 + 2.5 years (range 33 – 73)] or time between injury and surgical repair [TO: 15 + 2 days (range 2 – 30); MOA: 15 + 2 days (range 2 – 30)]. Post-operative VISA-A scores were 82 + 10 (range 42 – 98) and 92 + 5 (range 66 – 100) for TO and MOA, respectively. Significant differences were found in the time between surgical intervention and beginning of rehabilitation [TO: Post op day 37 + 5 (range 21 – 46); MOA: Post op day 19 + 2 (range 7 – 32)] and the time between surgical intervention and full return to activity [TO: Post op month 7 + 1 (range 4 – 11); MOA: Post op month 5 + 0.6 (range 4 – 11)]. Conclusion: These results suggest that the mini-open repair provides acceptable surgical outcomes while optimizing patient function after Achilles tendon repair.

Level of Evidence: Therapeutic, Level III: Retrospective Comparative
Criterion-Related Validity of the Foot Health Status Questionnaire Regarding Strength and Plantar Pressure Measurements in Elderly People
Authors: Cuesta-Vargas Antonio I. , Galan-Mercant Alejandro , Martín-Borras Maria Carmen , González-Sánchez Manuel
Published: October 2012

Background. Criterion-related validity of a self-administered questionnaire listed as gold standard requires objective testing. The aim of this study was to analyze the Foot Health Status Questionnaire (FHSQ) using functional variable measures (dynamic plantar pressure and foot strength). Materials and methods. A total of 22 elderly healthy participants (13 women and 9 men) were screened by interview and physical examination for foot or gait abnormalities. Foot strength, footprint pressure, and foot health status were measured. Results. All the items of the FHSQ show significant correlation with functional variables, but general foot health shows the highest correlation with the 4 physical variables related to plantar pressure (R2 = 0.741), followed by foot pain (R2 = 0.652). Conclusion. A set of different, directly measured physical variables related to foot strength and plantar pressure significantly correlate with the FHSQ dimensions.

Level of Evidence: Cross-sectional trial
The Relationship between Perceived Health, Health Attitude, and Healthy Offerings for Seniors at Family Restaurants
Authors: Lee Sangtak (Tak) , McCleary Ken
Published: October 2012

Customer behavior—particularly regarding restaurant patronage—is heavily influenced by health concerns, and this influence appears to be particularly strong among older consumers (often called the “senior market segment”). Because the restaurant industry is strongly affected by customers’ health priorities, the purpose of this study was to investigate how senior customers’ health status and attitudes influence their family restaurant patronage and menu choices. Using the Health Perceptions Questionnaire and the Perceived Health Competence Scale, 321 respondents indicated their health status and attitudes. The overall results of this study revealed that health status and health attitude for seniors were positively correlated with health-related family-restaurant-selection criteria. The results also showed that senior customers who have a positive health attitude are willing to pay more money for their healthy menu items.
Return to Play in Athletes Following Ankle Injuries
Authors: Clanton Thomas O. , Matheny Lauren M. , Jarvis Hannah C. , Jeronimus Anastasia B.
Published: October 2012

Background:

The decision to return to play following an ankle injury is a multifactorial process involving both physical and psychological parameters. The current body of literature lacks evidence-based guidelines to assist in the decision.

Objective:

This article reviews the evidence to support such testing: the dorsiflexion lunge test, star excursion balance test, agility T-test, and sargent/vertical jump test. The importance of psychological factors is also highlighted.

Evidence Acquisition:

The primary literature search was conducted using PubMed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) with the search terms “ankle AND injury” and the following limits activated: English language. A secondary search was then conducted with the search terms “return to play” and “sport injuries and return to play.”

Results:

Various functional tests have been used to determine whether a patient is able to return to play following an ankle injury. This study documented four tests that have been used to assess range of motion, balance and proprioception, agility and strength and the reasoning as to why these tests are used.

Conclusions:

Functional testing provides objective measures for gauging an athlete’s progression through the rehabilitation process. Testing balance and proprioception, strength, range of motion, and agility coupled with psychological assessment evaluates readiness for return to play.
Water vapor permeability and tensile properties of poly(l-lactic acid)/synthetic mica nanocomposites prepared by melt blending
Authors: Borges Soraia V , Dias Marcos L , Pita Victor JRR , Azuma Chiaki , Dias Marali V
Published: October 2012

Poly(L-lactic acid)/synthetic mica (Somasif) nanocomposites were obtained by melt blending in a mixing chamber according to a factorial experimental design and considering the following variables: temperature, rotor speed, nanofiller concentration and residence time. Relatively high degree of dispersion was attained by the melt processing which generates poly(L-lactic acid)/synthetic mica nanocomposites with particle size even in the order of 40 nm. The tensile properties and the water vapor permeability of these nanocomposites were evaluated. The introduction of synthetic mica into neat poly(L-lactic acid) decreased the water vapor permeability by about 50%. The variables which most affected the tensile properties were the mixing time and clay concentration, but the levels studied or the degree of intercalation/exfoliation were insufficient to significantly improve the tensile properties of poly(L-lactic acid)/somasif mica nanocomposites.
Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph-borne viral particles
Authors: Garcia Zacarias , Lemaître Fabrice , van Rooijen Nico , Albert Matthew L. , Levy Yves , Schwartz Olivier , Bousso Philippe
Published: October 2012

Natural killer (NK) cells become activated during viral infection in response to cytokines or to engagement of NK cell activating receptors. However, the identity of cells sensing viral particles and mediating NK cell activation has not been defined. Here, we show that local administration of a modified vaccinia virus Ankara vaccine in mice results in the accumulation of NK cells in the subcapsular area of the draining lymph node and their activation, a process that is strictly dependent on type I IFN signaling. NK cells located in the subcapsular area exhibited reduced motility and were found associated with CD169+-positive subcapsular sinus (SCS) macrophages and collagen fibers. Moreover, depletion of SCS macrophages using clodronate liposomes abolished NK cell accumulation and activation. Our results identify SCS macrophages as primary mediators of NK cell activation in response to lymph-borne viral particles suggesting that they act as early sensors of local infection or delivery of viral-based vaccines.
Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice
Authors: Hur Eun Mi , Patel Sonal N. , Shimizu Saki , Rao Dinesh S. , Gnanapragasam Priyanthi N. P. , An Dong Sung , Yang Lili , Baltimore David
Published: October 2012

HIV-1 infections are generally initiated at mucosal sites. Thus, IgA antibody, which plays pivotal roles in mucosal immunity, might efficiently prevent HIV infection. However, mounting a highly effective HIV-specific mucosal IgA response by conventional immunization has been challenging and the potency of HIV-specific IgA against infection needs to be addressed in vivo. Here we show that the polymeric IgA form of anti-HIV antibody inhibits HIV mucosal transmission more effectively than the monomeric IgA or IgG1 form in a comparable range of concentrations in humanized mice. To deliver anti-HIV IgA in a continual manner, we devised a hematopoietic stem/progenitor cell (HSPC)–based genetic approach using an IgA gene. We transplanted human HSPCs transduced with a lentiviral construct encoding a class-switched anti-HIV IgA (b12-IgA) into the humanized bone marrow-liver-thymus (BLT) mice. The transgene was expressed specifically in B cells and plasma cells in lymphoid organs and mucosal sites. After vaginal HIV-1 challenge, mucosal CD4+ T cells in the b12-IgA–producing mice were protected from virus-mediated depletion. Similar results were also obtained in a second humanized model, “human immune system mice.” Our study demonstrates the potential of anti-HIV IgA in immunoprophylaxis in vivo, emphasizing the importance of the mucosal IgA response in defense against HIV/AIDS.
The vitamin K–dependent anticoagulant factor, protein S, inhibits multiple VEGF-A–induced angiogenesis events in a Mer- and SHP2-dependent manner
Authors: Fraineau Sylvain , Monvoisin Arnaud , Clarhaut Jonathan , Talbot Julie , Simonneau Claire , Kanthou Chryso , Kanse Sandip M. , Philippe Michel , Benzakour Omar
Published: October 2012

Protein S is a vitamin K–dependent glycoprotein, which, besides its anticoagulant function, acts as an agonist for the tyrosine kinase receptors Tyro3, Axl, and Mer. The endothelium expresses Tyro3, Axl, and Mer and produces protein S. The interaction of protein S with endothelial cells and particularly its effects on angiogenesis have not yet been analyzed. Here we show that human protein S, at circulating concentrations, inhibited vascular endothelial growth factor (VEGF) receptor 2–dependent vascularization of Matrigel plugs in vivo and the capacity of endothelial cells to form capillary-like networks in vitro as well as VEGF-A–induced endothelial migration and proliferation. Furthermore, protein S inhibited VEGF-A–induced endothelial VEGFR2 phosphorylation and activation of mitogen-activated kinase-Erk1/2 and Akt. Protein S activated the tyrosine phosphatase SHP2, and the SHP2 inhibitor NSC 87877 reversed the observed inhibition of VEGF-A–induced endothelial proliferation. Using siRNA directed against Tyro3, Axl, and Mer, we demonstrate that protein S-mediated SHP2 activation and inhibition of VEGF-A–stimulated proliferation were mediated by Mer. Our report provides the first evidence for the existence of a protein S/Mer/SHP2 axis, which inhibits VEGFR2 signaling, regulates endothelial function, and points to a role for protein S as an endogenous angiogenesis inhibitor.
Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome
Authors: Funderburg Nicholas T. , Zidar David A. , Shive Carey , Lioi Anthony , Mudd Joseph , Musselwhite Laura W. , Simon Daniel I. , Costa Marco A. , Rodriguez Benigno , Sieg Scott F. , Lederman Michael M.
Published: October 2012

The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14+CD16++) and intermediate (CD14++CD16+) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.
Characteristics and outcome of patients with second primary lung cancer
Authors: Reinmuth Niels , Stumpf Andreas , Stumpf Patrick , Muley Thomas , Kobinger Sonja , Hoffmann Hans , Herth Felix J.F. , Schnabel Philipp A. , Warth Arne , Bischoff Helge , Thomas Michael
Published: October 2012

Patients with lung cancer are at risk of developing a second primary lung cancer (SPLC). However, the characteristics of patients at risk remain largely speculative.

We reviewed 2816 lung cancer patients from our institution for the occurrence of SPLC. Any SPLC was categorised as synchronous when diagnosed within 2 years of the first primary lung cancer (FPLC) and after direct histological comparison of both tumours. All other SPLCs were considered as metachronous.

139 patients developed a second malignancy including 69 nonsmall cell lung cancer (NSCLC) and 9 small cell lung cancer. The median interval for diagnosis of metachronous SPLC (n=59) after FPLC occurrence was 72 months. SPLC detected within 5 years of FPLC diagnosis had a more favourable stage distribution (p=0.02). After diagnosis of SPLC, patients had a superior median overall survival compared to controls (57.7versus18.1 months; p<0.0001). Interestingly, comparing only stage IV NSCLC patients, a history of FPLC was also associated with a favourable survival (median 27.4versus8.97 months; p=0.007).

In summary, previous lung cancer treatment does not lead to impaired prognosis after diagnosis of SPLC. Improved surveillance programmes beyond 5 years after FPLC treatment may result in more favourable disease stages for detected SPLC.
Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses
Authors: Kager Liesbeth M. , de Boer J. Daan , Bresser Paul , van der Zee Jaring S. , Zeerleder Sacha , Meijers Joost C.M. , van 't Veer Cornelis , van der Poll Tom
Published: October 2012

Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals. Investigations in rodents demonstrated that direct intrapulmonary delivery of APC also exerts anticoagulant and anti-inflammatory effects. The effect of intrabronchial administration of recombinant human (rh)APC on lipopolysaccharide (LPS)-induced haemostatic and inflammatory alterations in the bronchoalveolar space of humans was studied.

Eight subjects received rhAPCviaintrabronchial instillation by bronchoscope, while in a contralateral subsegment subjects received saline; all subjects were challenged bilaterally with LPS in the same lung subsegments. Four additional subjects received rhAPC (75 μg), with saline as a control in the contralateral subsegment, while they were bilaterally “challenged” with saline. After 6 h a bronchoalveolar lavage was performed and coagulation and inflammatory parameters were measured.

rhAPC enhanced LPS-induced coagulation activation in the bronchoalveolar space, when compared with the control side. In addition, rhAPC amplified LPS-induced pro-inflammatory responses, as indicated by higher concentrations of cytokines and chemokines. rhAPC alone did not have procoagulant or pro-inflammatory effects.

Locally administered rhAPC has unexpected procoagulant and pro-inflammatory effects in LPS-challenged lung subsegments. These data argue against a role for intrapulmonary delivery of rhAPC as a treatment strategy for lung inflammatory disorders in humans.
The use of inhaled corticosteroids and the risk of adrenal insufficiency
Authors: Lapi Francesco , Kezouh Abbas , Suissa Samy , Ernst Pierre
Published: October 2012

Adrenal insufficiency is a potential complication of therapy with an inhaled corticosteroid (ICS). Although prior studies found the highest risk of adrenal insufficiency with fluticasone, a more potent ICS, these results might be explained by a channelling bias and concomitant exposure to oral corticosteroids.

We re-examined the relationship between the use of ICSs and adrenal insufficiency by using a cohort of patients treated for respiratory conditions during 1990–2005, identified in the healthcare databases from the province of Quebec, Canada, with follow-up until 2007. A nested case–control analysis was performed within this cohort. Cases of adrenal insufficiency were matched with up to 10 controls.

392 cases were identified (incidence rate 1.1 per 10 000 person-years). Although the rate of adrenal insufficiency was not significantly higher among all current users of ICSs, patients receiving the highest dosages showed a greater risk (OR 1.84, 95% CI 1.16–2.90). Consistently, an increased risk was estimated for the highest tertile of ICS dose (OR 1.90, 95% CI 1.07–3.37) cumulated in the year before the event.

ICS at high doses appear to be a significant independent risk factor for adrenal insufficiency. Physicians prescribing ICS at such dosages should be sensitive to the signs and symptoms of adrenal insufficiency in their patients.
Intermittent hypoxia-activated cyclooxygenase pathway: role in atherosclerosis
Authors: Gautier-Veyret Elodie , Arnaud Claire , Bäck Magnus , Pépin Jean-Louis , Petri Marcelo H. , Baguet Jean-Philippe , Tamisier Renaud , Lévy Patrick , Stanke-Labesque Françoise
Published: October 2012

Intermittent hypoxia, the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to intermittent hypoxia-induced atherosclerosis remains to be determined.

We studied the effects of 8-weeks of intermittent hypoxia exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of apolipoprotein E-/-mice. Urinary 11-dehydrothromboxane B2(11-dTXB2) was assessed in 50 OSA subjects free of cardiovascular risk factor matched for age and body mass index with 25 controls, and 56 OSA with cardiovascular risk factor.

Intermittent hypoxia significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r = 0.654, p = 0.0003) and TXBS (r = 0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in intermittent hypoxia mice only (p = 0.04). Urinary 11-dTXB2was similar in OSA subjects free of cardiovascular risk factor and controls, but was increased by 13% (p = 0.007) in OSA subjects with cardiovascular risk factor compared with those without.

Although OSA itself was not associated with increased urinary 11-dTXB2concentration, the COX-1 pathway was activated in intermittent hypoxia-exposed mice and in OSA subjects presenting with cardiovascular risk factor, and may contribute to intermittent hypoxia-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA.
Identification of asthma clusters in two independent Korean adult asthma cohorts
Authors: Kim Tae-Bum , Jang An-Soo , Kwon Hyouk-Soo , Park Jong-Sook , Chang Yoon-Seok , Cho Sang-Heon , Choi Byoung Whui , Park Jung-Won , Nam Dong-Ho , Yoon Ho-Joo , Cho Young-Joo , Moon Hee-Bom , Cho You Sook , Park Choon-Sik
Published: October 2012

Asthma is a heterogeneous airway disease with various clinical phenotypes. It is crucial to clearly identify clinical phenotypes to achieve better asthma management.

We used cluster analysis to classify the clinical groups of 724 asthmatic patients from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), and in 1843 subjects from another independent Korean asthma cohort of Soonchunhyang University Asthma Genome Research Centre (SCH) (Bucheon, Republic of Korea). Hierarchical cluster analysis was performed by Ward's method, followed by κ-means cluster analysis.

Cluster analysis of the COREA cohort indicated four asthma subtypes: 1) smoking asthma; 2) severe obstructive asthma; 3) early-onset atopic asthma; and 4) late-onset mild asthma. An independent cluster analysis of the SCH cohort also indicated four clusters that were similar to the COREA clusters.

Our results indicate that adult Korean asthma patients can be classified into four distinct clusters.
Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis
Authors: Migliori Giovanni Battista , Sotgiu Giovanni , Gandhi Neel R. , Falzon Dennis , DeRiemer Kathryn , Centis Rosella , Hollm-Delgado Maria-Graciela , Palmero Domingo , Pérez-Guzmán Carlos , Vargas Mario H. , D'Ambrosio Lia , Spanevello Antonio , Bauer Melissa , Chan Edward D. , Schaaf H. Simon , Keshavjee Salmaan , Holtz Timothy H. , Menzies Dick ,   The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB
Published: October 2012

The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition.

Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug,i.e.ethionamide/protionamide, cycloserine/terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ).

Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2–0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6–2.8).

Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.
Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs
Authors: Gaffey Kate , Reynolds Sophie , Plumb Jonathan , Kaur Manminder , Singh Dave
Published: October 2012

The p38 mitogen-activated protein kinase (MAPK) pathway is upregulated in chronic obstructive pulmonary disease (COPD). To date, dual labelling to identify cell-type-specific presence of phosphorylated (phospho-)p38 MAPK has not been carried out.

Phospho-p38 MAPK was quantified in a variety of cell types in the lung tissue of 20 COPD patients, 12 smokers and 12 nonsmokers using immunohistochemistry. Paired blood and sputum neutrophils (from seven subjects with COPD), and CD8 and epithelial cells (from three subjects with COPD) were cultured with a p38 MAPK inhibitor. Supernatant tumour necrosis factor-α and CXCL8 levels were analysed by ELISA. Sputum and blood neutrophil cytospins were analysed for phospho-p38 MAPK.

Phospho-p38 MAPK was increased in bronchial epithelial cells, macrophages and CD20+ and CD8+ lymphocytes in COPD lungs. Sputum and lung tissue neutrophils were devoid of phospho-p38 in all patient groups. The p38 MAPK inhibitor SB100 attenuated pro-inflammatory mediator release in COPD lung CD8 cells and airway epithelia, but there was no effect on COPD sputum neutrophils.

Our data indicate cell-specific anti-inflammatory effects of p38 MAPK inhibition in the lung.
Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays
Authors: Patenge Nadja , Billion André , Raasch Peter , Normann Jana , Wisniewska-Kucper Aleksandra , Retey Julia , Boisguérin Valesca , Hartsch Thomas , Hain Torsten , Kreikemeyer Bernd
Published: October 2012

Background

Small non-coding RNAs (sRNAs) have attracted attention as a new class of gene regulators in both eukaryotes and bacteria. Genome-wide screening methods have been successfully applied in Gram-negative bacteria to identify sRNA regulators. Many sRNAs are well characterized, including their target mRNAs and mode of action. In comparison, little is known about sRNAs in Gram-positive pathogens. In this study, we identified novel sRNAs in the exclusively human pathogenStreptococcus pyogenesM49 (Group AStreptococcus, GAS M49), employing a whole genome intergenic tiling array approach. GAS is an important pathogen that causes diseases ranging from mild superficial infections of the skin and mucous membranes of the naso-pharynx, to severe toxic and invasive diseases.

Results

We identified 55 putative sRNAs in GAS M49 that were expressed during growth. Of these, 42 were novel. Some of the newly-identified sRNAs belonged to one of the common non-coding RNA families described in the Rfam database. Comparison of the results of our screen with the outcome of two recently published bioinformatics tools showed a low level of overlap between putative sRNA genes. Previously, 40 potential sRNAs have been reported to be expressed in a GAS M1T1 serotype, as detected by a whole genome intergenic tiling array approach. Our screen detected 12 putative sRNA genes that were expressed in both strains. Twenty sRNA candidates appeared to be regulated in a medium-dependent fashion, while eight sRNA genes were regulated throughout growth in chemically defined medium. Expression of candidate genes was verified by reverse transcriptase-qPCR. For a subset of sRNAs, the transcriptional start was determined by 5′rapid amplification of cDNA ends-PCR (RACE-PCR) analysis.

Conclusions

In accord with the results of previous studies, we found little overlap between different screening methods, which underlines the fact that a comprehensive analysis of sRNAs expressed by a given organism requires the complementary use of different methods and the investigation of several environmental conditions. Despite a high conservation of sRNA genes within streptococci, the expression of sRNAs appears to be strain specific.