bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute myocardial infarction elevates serine protease activity in saliva of patients with periodontitis
Authors: Mäntylä P. , Buduneli E. , Emingil G. , Tervahartiala T. , Pussinen P. J. , Barış N. , Akıllı A. , Atilla G. , Sorsa T.
Published: December 2011

Mäntylä P, Buduneli E, Emingil G, Tervahartiala T, Pussinen PJ, Barış N, Akıllı A, Atilla G, Sorsa T. Acute myocardial infarction elevates serine protease activity in saliva of patients with periodontitis. J Periodont Res 2012; 47: 345–353. © 2011 John Wiley & Sons A/S

Background and Objective:  There are indications that acute myocardial infarction (AMI) may have an effect on the oral environment, which is reflected in the expression of salivary and gingival proteinases. According to our knowledge, no studies have been carried out to investigate the effect of AMI on the activities of two major tissue‐destructive serine protease and microbial effectors, elastase and cathepsin G, produced by oral fluid polymorphonuclear granulocytes (PMN). Therefore, we compared the activities of elastase and cathepsin G in saliva from patients with AMI and from systemically healthy subjects (non‐AMI) with similar periodontal conditions.

Material and Methods:  A total of 92 patients (47 AMI and 28 non‐AMI patients with gingivitis or periodontitis, and 17 systemically and periodontally healthy subjects as a control group) were recruited. Clinical periodontal measurements were recorded, and stimulated whole‐saliva samples were collected. The patients with AMI were clinically examined within 3–4 d after admission to the coronary care unit. The activities of saliva neutrophil elastase and cathepsin G were measured after collection, at specific time‐points during incubation (from baseline to 23 h) by specific synthetic peptide substrate assays.

Results:  The saliva of patients with AMI and periodontitis had a significant trend for the highest elastase activities among the study groups. Elastase and cathepsin G activities correlated significantly with each other in the AMI periodontitis group (r = 0.8, p < 0.01). In a logistic regression analysis, the level of salivary elastase activity associated significantly with periodontitis.

Conclusion:  AMI may be reflected in PMN serine protease elastase activity in saliva, despite its strong association with periodontitis.
National prevalence of oral HPV infection and related risk factors in the U.S. adult population
Authors: Sanders AE , Slade GD , Patton LL
Published: December 2011

Oral Diseases (2012) 18, 430–441

This article reviews the rapidly growing evidence that oral human papilloma viruses (HPV) infection contributes to the risk of oral squamous cell carcinoma. It also reports the first nationally representative estimates of oral HPV prevalence in the United States adult population. An estimated 7.3% (95% CI: 6.0, 8.9) of the U.S. population had one or more oral HPV types detected in oral rinse; 3.1% (95%CI: 2.4, 3.9) of the U.S. population had one or more oncogenic HPV types. A substantial excess risk of HPV infection in men is not explained by education, smoking, age of sexual debut, or number of lifetime sex partners. Based on the published finding from a case–control study, where there was an odds ratio of 2.6 (95% CI: 1.5, 4.2) for the association of head and neck cancer oncogenic oral HPV infection, the estimated population attributable risk for head and neck cancer in the U.S. population was 4.7%. In other words, there would be a 4.7% reduction in incidence rate of head and neck cancer in the United States if oncogenic HPV infection could be prevented. The results also provide population data that help evaluate the likely public health benefits of prophylactic vaccination against oral HPV acquisition.
Growth of the Kalahari Desert’s bushman ‐ the Ju/’hoansi San
Authors: Eideh Hasan , Jonsson Bjorn , Hochberg Ze’ev
Published: December 2011

Aim:  The Ju/’hoansi San (JHS) of the Kalahari Desert are the archetype of a hunter‐gatherer society that practices natural fertility, living on a rich diet in a harsh environs.

Methods:  To explore the evolutionary adaptation of child growth under such conditions, the present study takes a life history approach and compares the growth data of 140 JHS females and 126 JHS males age 1–25 to those in 3rd percentile American and Swedish references. The data are based on observations of the JHS that were made in 1967–1969.

Results:  During infancy, the JHS boys lose 1.5 SDS and girls – 0.3 SDS in terms of Swedish reference. The height SDS of the JHS did not change significantly during their childhood, but growth deceleration during the juvenile period (middle childhood) was substantially greater and longer, amounting to a loss of 1.6 SDS for both girls and boys. Adolescent spurt was substantially later and smaller than that of the short‐statured Americans.

Conclusions:  The results suggest that the short stature of the JHS is mostly established during juvenility, in adaptation to their unique living conditions.
IMAGING DIAGNOSIS: CT FINDINGS IN A DOG WITH INTRACRANIAL HEMORRHAGE SECONDARY TO ANGIOSTRONGYLOSIS
Authors: Zarelli Micaela , Shiel Robert , Gallagher Barbara , Skelly Cliona , Cahalan Stephen , McAllister Hester
Published: December 2011

A seven‐month‐old Cocker Spaniel had a cough, acute lethargy, decreased responsiveness, and episodes of hyperexcitability. There were bilateral generalized increased lung sounds, bilateral episcleral hemorrhage, and systemic hypertension. Prolonged buccal mucosal bleeding time and elevated D‐dimer concentrations were detected. Radiographically, there was a generalized moderate unstructured interstitial pattern. In thoracic CT images, there was a diffuse moderate hyperattenuating appearance of the bronchial walls and interstitium and diffuse areas of moderate bronchiectasis. The brain CT images were characterized by marked hyperattenuating well‐defined masses. In addition, there were smaller hyperattenuating and hypoattenuating masses scattered throughout the cerebral and cerebellar parenchyma. A zinc sulphate flotation test confirmed large numbers of Angiostrongylus vasorum L1 larvae. Despite therapy the dog continued to deteriorate and underwent euthanasia. Postmortem examination confirmed the presence of multiple intracranial and extracranial hemorrhages. Angiostrongylosis should be considered as one of the differential diagnoses in dogs presenting with neurologic signs consistent with acute intracranial haemorrhage.
RESPONSE RATE AND DURATION ASSOCIATED WITH A 4GY 5 FRACTION PALLIATIVE RADIATION PROTOCOL
Authors: McDonald Catie , Looper Jayme , Greene Shawna
Published: December 2011

The purpose of this retrospective study was to determine if 4Gy fractions over 5 consecutive days is an effective and safe palliative radiation protocol for dogs and cats. Eighty patients (22 cats, 58 dogs) with complete follow‐up information were evaluated. Overall response rate (ORR) for all patients was 67%. Median progression free survival (MPFS) was 3.3 months and median survival (MST) was 4.2 months. Primary bone tumors were the most common tumors treated. TheORRfor primary bone tumors was 66.6%, theMPFSwas 3.5 months, andMSTwas 3 months. The most common tumor treated in cats was oral squamous cell carcinoma andORRwas 54.5 %, theMPFSwas 1.8 months, andMSTwas 3 months. Soft tissue sarcomas were the second most common tumor treated in dogs (10).ORRwas 80% and the two other patients had stable disease.MPFSwas 5.7 months andMSTwas 7.9 months. Overall rate of toxicity was 18.4% in 65 sites that were evaluated for toxicity. Acute toxicities were all grade I or II and occurred in 16.9 % of patients evaluated. All late toxicity was grade I alopecia and leukotrichia. There appears to be a comparable response rate for this palliative protocol as compared to others historically. This response was seen over a wide range of tumors. We also documented a low toxicity profile in a shorter overall treatment time, making this protocol more attractive for some clients.
Availability of, access to and consumption of fruits and vegetables in a peri‐urban area in KwaZulu‐Natal, South Africa
Authors: Faber Mieke , Laubscher Ria , Laurie Sunette
Published: December 2011

Availability and consumption of fruits and vegetables were assessed in peri‐urban households in KwaZulu‐Natal Province, South Africa. Caregivers of 400 randomly selected grade 6 and 7 learners were interviewed using a questionnaire that included unquantified food frequency questions. Using a repeated 24‐h dietary recall, dietary intake was quantified for learners, caregivers and 2‐ to 5‐year‐old children in the household. Usual household fruit and vegetable consumption was expressed over three Living Standard Measure (LSM) categories. Average per capita intake of fruit and/or vegetables was 99 g for 2‐ to 5‐year‐old children and 124 g for caregivers. For consumers, fruits and/or vegetables contributed towards total dietary intake of fibre (16–21%), calcium (13–21%), vitamin A (27–31%) and vitamin C (47–62%). For households not consuming fruits (n = 297) and vegetables (n = 178) daily, cost was the major constraint (≥75%). Of all households, 52% had fruit trees and 25% had a vegetable garden. Animals destroying vegetables was the major constraint to 59% of vegetable growers. Household consumption of fruits and vegetables increased over the LSM categories. Caregivers in the higher LSM group more likely used printed material for information on healthy eating, had fruit trees, were confident about vegetable gardening and sold some of their produce. To enable peri‐urban populations of low socio‐economic status to consume more frequently a bigger variety of fruits and vegetables, the cost of purchasing these food items needs to be addressed by government and business sector. Households should further receive support to overcome constraints which hamper the success of home gardens.
Trade‐offs underlying maternal breastfeeding decisions: a conceptual model
Authors: Tully Kristin P. , Ball Helen L.
Published: December 2011

This paper presents a new conceptual model that generates predictions about breastfeeding decisions and identifies interactions that affect outcomes. We offer a contextual approach to infant feeding that models multi‐directional influences by expanding on the evolutionary parent–offspring conflict and situation‐specific breastfeeding theories. The main hypothesis generated from our framework suggests that simultaneously addressing breastfeeding costs and benefits, in relation to how they are interpreted by mothers, will be most effective. Our approach focuses on contributors to the attitudes and commitment underlying breastfeeding outcomes, beginning in the prenatal period. We conclude that some maternal–offspring conflict is inherent with the dynamic infant feeding relationship. Guidance that anticipates and addresses family trade‐offs over time can be incorporated into breastfeeding support for families.
Airway Effects of Inhaled Quaternary Ammonium Compounds in Mice
Authors: Larsen Søren T. , Verder Henrik , Nielsen Gunnar D.
Published: December 2011

Quaternary ammonium compounds (QAC) constitute a family of widely used chemical substances. The QAC benzalkonium chloride (BAC) has caused bronchoconstriction in human beings by poorly understood mechanisms and lung damage at high concentration as shown in a single rat study. This study evaluates acute airway effects in mice after inhalation of aerosols of the QACs, BAC, hexadecyl trimethyl ammonium bromide (HTA), cetyl pyridinium chloride (CPC) and dimethyl dioctadecyl ammonium bromide (DDA). The QACs gave rise to concentration‐dependent decreases in the tidal volume (VT) and a concomitant increase in respiratory rate indicating pulmonary irritation. The potencies of the QAC to induce these effects were in the order: BAC > HTA = CPC > DDA. Furthermore, inhalation of BAC and CPC aerosols gave rise to pulmonary inflammation as apparent from bronchoalveolar lavage. Stimulation of nasal trigeminal nerve endings by QAC, which may serve as a warning signal, was absent.
Fabrication of Innovative Compliant Current Collector‐Supported Microtubular Solid Oxide Fuel Cells
Authors: De la Torre Ricardo , Sglavo Vincenzo M.
Published: December 2011

In this work, an innovative compliant current collector‐supported microtubular solid oxide fuel cell has been designed and produced. A nickel wire is coiled around carbon‐composite rods to fabricate the cells support, and dip coating technique is used to deposit the anode and the electrolyte from ceramic slurries containing NiO/yttria‐stabilized zirconia (YSZ) and YSZ, respectively. Pyrolizable materials are eliminated by heat treatment in air at 800°C; the half‐cell is then sintered in Ar at 1380°C to avoid the oxidation of the Ni wire whose compliance allows to minimize stresses generated during heat treatments. The cathode consists of two layers made by lanthanum strontium manganate–YSZ mixture and pure lanthanum strontium manganate co‐sintered at 1150°C. Electrochemical I–V characterization of single microtubular solid oxide fuel cells points out great potentiality of the innovative architecture demonstrated by the maximum power output of ~200 mW/cm2 at 800°C under a wet H2 fuel flow.
Resolving high Reynolds numbers in smoothed particle hydrodynamics simulations of subsonic turbulence
Authors: Price Daniel J.
Published: December 2011

Accounting for the Reynolds number is critical in numerical simulations of turbulence, particularly for subsonic flow. For smoothed particle hydrodynamics (SPH) with constant artificial viscosity coefficient α, it is shown that the effective Reynolds number in the absence of explicit physical viscosity terms scales linearly with the Mach number — compared to mesh schemes, where the effective Reynolds number is largely independent of the flow velocity. As a result, SPH simulations with α= 1 will have low Reynolds numbers in the subsonic regime compared to mesh codes, which may be insufficient to resolve turbulent flow. This explains the failure of Bauer & Springel to find agreement between the moving-mesh code arepo and the gadget SPH code on simulations of driven, subsonic (v∼ 0.3cs) turbulence appropriate to the intergalactic/intracluster medium, where it was alleged that SPH is somehow fundamentally incapable of producing a Kolmogorov-like turbulent cascade. We show that turbulent flow with a Kolmogorov spectrum can be easily recovered by employing standard methods for reducing α away from shocks.
Dissipation efficiency of reconfinement shocks in relativistic jets
Authors: Nalewajko Krzysztof
Published: December 2011

We calculate the dissipation efficiency of relativistic reconfinement shocks. Building on previous work, we consider different distributions of the external pressure. The average dissipation efficiency εdiss is a function of the product of two parameters — the jet Lorentz factor Γj and the reconfinement angle Θr, which is related to the opening angle Θj and the external pressure index η. The spatial distribution of the dissipation rate strongly depends on η. We discuss the significance of these results for the properties of relativistic jets in gamma-ray bursts and active galactic nuclei and propose that reconfinement shocks may explain a very high dissipation efficiency of the former and a moderate dissipation efficiency of the latter. Finally, we estimate the dissipation efficiency of the reconfinement shock associated with the quasi-stationary knot HST-1 in the jet of radio galaxy M87 and show that it is roughly consistent with the observational constraints.
Observing turbulent fragmentation in simulations: predictions for CARMA and ALMA
Authors: Offner Stella S. R. , Capodilupo John , Schnee Scott , Goodman Alyssa A.
Published: December 2011

Determining the initial stellar multiplicity is a challenging problem since protostars are faint and deeply embedded at early times; once formed, multiple protostellar systems may significantly dynamically evolve before they are optically revealed. Interferometers such as Combined Array for Research in Millimeter-wave Astronomy (CARMA) and Atacama Large Millimeter/submillimeter Array (ALMA) make it possible to probe the scales at which turbulent fragmentation occurs in dust continuum emission, potentially constraining early stellar multiplicity. In this Letter, we present synthetic observations of starless and protostellar cores undergoing fragmentation on scales of a few thousand astronomical units to produce wide binary systems. We show that interferometric observations of starless cores by CARMA should be predominantly featureless at early stages, although wide protostellar companions should be apparent. The enhanced capabilities of ALMA improve the detection of core morphology so that it may be possible to detect substructure at earlier times. In either case, spatial filtering from interferometry reduces the observed core substructure and often eradicates traces of existing filamentary morphology on scales down to 0.025 pc. However, some missing structure may be recaptured by combining data from the ALMA full science and Atacama compact arrays.
Teaching inhaler use in chronic obstructive pulmonary disease patients
Authors: Lareau Suzanne C. , Hodder Richard
Published: December 2011

Purpose: To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use.

Data sources: Review of the national and international scientific literature.

Conclusions: Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy.

Implications for practice: Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up‐to‐date inhaler education for other healthcare team members, who may then act as patient educators.
Patient‐centered outcomes research and nurse practitioners’ role in shared decision making
Authors: Clancy Carolyn M.
Published: December 2011

This article provides a brief overview of a new program from the Agency for Healthcare Research and Quality (AHRQ) called the Effective Healthcare Program. This program has supported more than 70 research projects since its inception and published more than 50 products, including guides for clinicians and patients that provide a comprehensive analysis of treatment options for common, chronic illnesses. Research summaries are also available for mobile devices.
Morphological features, development and reproduction of Melittobia acasta on Bombus terrestris
Authors: KWON Yong Jung , AMIN Md Ruhul , INN Nang Soi Lao
Published: December 2011

Morphological features, development and reproduction behavior of the parasite Melittobia acasta (Walker) were studied when reared on the pupae of the bumblebee Bombus terrestris L. in the laboratory under 23°C, 50% relative humidity and 12 h light : 12 h dark conditions. The parasites laid transparent white and elongated eggs. Newly hatched larval size and shape were very similar to eggs but they were identified by their body segments. Larvae increased their body size through moulting and transformed into a vermiform shape. Male pupae were shiny brown with dots. The female pupae were distinguished by their black shiny color, shorter size and the presence of compound eyes. Adult male pupae were dark brown and dwarf‐winged, whereas female pupae were macropterous and brachypterous. Reproduction took place by fertilization and also parthenogenetically. Mean fecundity within 5 days by mated (47.9 ± 30.5 female−1) and virgin (7.4 ± 6.8 female−1) females were statistically different. Mated females laid fertilized eggs that produced adult males or females, whereas virgin females laid unfertilized eggs that produced males. Development durations of the virgin female originated eggs, larvae, pupae and adults were statistically identical with those of mated females. The parasites were female‐biased and foundress number did not affect offspring sex ratio. This study shows that both mated and virgin females of M. acasta can produce many offspring on B. terrestris pupae within a short period, indicating that they are dangerous parasites of the bumblebee in a mass rearing system.
Preliminary investigation on rodent–ectoparasite associations in the highlands of Tigray, Northern Ethiopia: implications for potential zoonoses
Authors: YONAS Meheretu , WELEGERIMA Kiros , LAUDISOIT Anne , BAUER Hans , GEBREHIWOT Kindeya , DECKERS Seppe , KATAKWEBA Abdul , MAKUNDI Rhodes , LEIRS Herwig
Published: December 2011

We studied associations between rodents and their arthropod ectoparasites in crop fields and household compounds in the highlands of Tigray, Northern Ethiopia. Ectoparasite infestation indices, such as percent infestation, mean abundance, prevalence and host preferences, were calculated for each taxon. In total, 172 rodents from crop fields and 97 from household compounds were trapped. Rodent species and numbers trapped from the crop fields and household compounds were Mastomys awashensis (Lavrenchenko, Likhnova & Baskevich, 1998) (88 and 44), Arvicanthis dembeensis (Ruppel, 1842) (63 and 37) and Acomys sp. (21 and 16), respectively. A total of 558 insects and acarids (belonging to 11 taxa) were recovered from the rodents trapped in the crop fields, and 296 insects and acarid (belonging to 6 taxa) from the rodents trapped in the household compounds. Approximately 66% of the rodents trapped from the crop fields and 47% of those trapped from the household compounds were infested with ectoparasites. Laelaps sp. (64.9%) and Xenopsylla sp. (20.6%) comprised the highest proportion of the ectoparasites recovered in the crop fields, and the same ectoparasites, but in reverse order, comprised the highest proportions in the household compounds (Xenopsylla [50.3%] and Laelaps sp. [29%]). Our study revealed that crop fields and household compounds in the highlands share similar rodents and several ectoparasites. Furthermore, at least 1 of the rodent species and some of the ectoparasites identified in this study were reported to have posed medical and veterinary threats in other parts of Ethiopia and neighboring countries.
Temporal niche overlap among insectivorous small mammals
Authors: VIEIRA Emerson M. , PAISE Gabriela
Published: December 2011

Being active in the same environment at different times exposes animals to the effects of very different environmental factors, both biotic and abiotic. In the present study, we used live traps equipped with timing devices to evaluate the potential role of biotic factors (competition and food abundance) on overall overlap in the temporal niche axis of 4 insectivorous small mammals in high‐elevation grassland fields (‘campos de altitude’) of southern Brazil. Based on resources availability (invertebrates), data on animal captures were pooled in 2 seasons: ‘scarcity’ (June 2001–September 2001) and ‘abundance’ (November 2001–May 2002) seasons. We tested for non‐random structure in temporal niche overlap among the species in each season. These species were the rodents Oxymycterus nasutus (Waterhouse, 1837), Deltamys sp., Akodon azarae (Fischer, 1829), and the marsupial Monodelphis brevicaudis Olfers, 1818. The studied community was mainly diurnal with crepuscular peaks. Simulations using the Pianka index of niche overlap indicated that the empirical assemblage‐wide overlap was not significantly different from randomly generated patterns in the abundance season but significantly greater than expected by chance alone in the scarcity season. All the species showed an increase in temporal niche breadth during the abundance season, which appears to be related to longer daylength and high nocturnal temperatures. Patterns on both temporal niche overlap and temporal niche breadth were the opposite to those that we were expecting in the case of diel activity patterns determined by competition for dietary resources. Therefore, we conclude that competition did not seem to be preponderant for determining patterns of temporal niche overlap by the studied community.
Pomegranate Fruit Extract Inhibits UVB‐induced Inflammation and Proliferation by Modulating NF‐κB and MAPK Signaling Pathways in Mouse Skin†
Authors: Khan Naghma , Syed Deeba N. , Pal Harish Chandra , Mukhtar Hasan , Afaq Farrukh
Published: December 2011

There is considerable interest in the identification of natural agents capable of affording protection to skin from the adverse effects of solar ultraviolet B (UVB) radiation. Pomegranate (Punica granatum L.) fruit possesses as strong antioxidant, anti‐inflammatory and antiproliferative properties. Recently, we have shown that oral feeding of pomegranate fruit extract (PFE) to mice afforded substantial protection from the adverse effects of single UVB radiation via modulation in early biomarkers of photocarcinogenesis. This study was designed to investigate the photochemopreventive effects of PFE (0.2%, wt/vol) after multiple UVB irradiations (180 mJ cm−2, on alternative day, for a total of seven treatments) to the skin of SKH‐1 hairless mice. Oral feeding of PFE to SKH‐1 mice inhibited UVB‐induced epidermal hyperplasia, infiltration of leukocytes, protein oxidation and lipid peroxidation. Immunoblot analysis demonstrated that oral feeding of PFE to mice inhibited UVB‐induced (1) nuclear translocation and phosphorylation of nuclear factor kappa B/p65, (2) phosphorylation and degradation of IκBα, (3) activation of IKKα/ΙΚΚβ and (4) phosphorylation of mitogen‐activated protein kinase proteins and c‐Jun. PFE consumption also inhibited UVB‐induced protein expression of (1) COX‐2 and iNOS, (2) PCNA and cyclin D1 and (3) matrix metalloproteinases‐2,‐3 and ‐9 in mouse skin. Taken together, these data show that PFE consumption afforded protection to mouse skin against the adverse effects of UVB radiation by modulating UVB‐induced signaling pathways.
A randomized trial of family focused treatment for adolescents and young adults at risk for psychosis: study rationale, design and methods
Authors: Schlosser Danielle A. , Miklowitz David J. , O'Brien Mary P. , De Silva Sandra D. , Zinberg Jamie L. , Cannon Tyrone D.
Published: December 2011

Aim: This article outlines the rationale for a family‐focused psychoeducational intervention for individuals at risk for psychosis and explains the design of a randomized multisite trial to test its efficacy.

Methods: Adolescents and young adults that meet criteria for a psychosis risk syndrome at eight participating North American Prodromal Longitudinal Study sites are randomly assigned to a 6‐month, 18‐session family‐focused treatment for prodromal youth or a 3‐session psychoeducational enhanced care control intervention and followed over 1 year.

Results: The results will determine whether the use of a family intervention is able to significantly improve functional outcomes, decrease the severity of positive symptoms and possibly prevent the onset of full psychosis, compared with enhanced care alone. Levels of familial criticism at baseline are hypothesized to moderate responses to family intervention. Improvements in knowledge about symptoms, family communication and problem solving will be tested as mediators in the pathways between treatment assignment and clinical or psychosocial outcomes in high‐risk youth.

Conclusions: The ongoing trial evaluates whether a non‐invasive psychosocial approach can significantly enhance functional outcomes and prevent the ultra high risk patients from developing psychosis. The results will provide an important stepping stone in the movement of the field from refining early detection strategies to developing efficacious preventative treatments.
Prediction and prevention of intrahepatic recurrence of hepatocellular carcinoma
Authors: Izumi Namiki
Published: December 2011

Hepatocellular carcinoma (HCC) has characteristic features of the coexistence of two life‐threatening conditions, cancer and cirrhosis, which makes prognostic assessment difficult. In addition, the high rate of intrahepatic recurrence is a key feature that correlates with poor prognosis and its prevention is an issue for urgent investigation. Gene expression in the tumor and adjacent liver tissue for the prediction of intrahepatic recurrence of HCC has been extensively investigated. Among them, the expression of progenitor cell feature markers in the cancer cells such as epidermal cell adhesion molecule (EpCAM), cytokeratin 19 (CK19) and CD 133 have been shown to be associated with intrahepatic recurrence of HCC. Gene expression patterns from adjacent tissues were shown to predict early and overall recurrence in patients with HCC. Insulin resistance should be included in the analysis for the prevention of recurrence. To suppress or eradicate the replication of hepatitis B and C virus must be the most important issue for prevention. Supplementation by branched chain amino acid‐enrichment and administration of vitamin K, acyclic retinoid and chemotherapeutic agents have been examined. There is an urgent need to develop a predictive tool and an effective treatment for prevention. It would be extremely valuable to find a useful biomarker for prediction and to develop new molecular targeting agents for the prevention of HCC recurrence in the near future.
Umami taste in mice uses multiple receptors and transduction pathways
Authors: Yasumatsu Keiko , Ogiwara Yoko , Takai Shingo , Yoshida Ryusuke , Iwatsuki Ken , Torii Kunio , Margolskee Robert F. , Ninomiya Yuzo
Published: December 2011

Non‐technical summary  The distinctive umami taste elicited by l‐glutamate and some other amino acids is thought to be initiated by G‐protein‐coupled receptors, such as heteromers of taste receptor type 1, members 1 and 3, and metabotropic glutamate receptors 1 and 4. We demonstrate the existence of multiple types of glutamate‐sensitive gustatory nerve fibres and the contribution of multiple receptors and transduction pathways to umami taste. Such multiple systems for umami taste may differentially contribute to the behavioural preference for glutamate and discriminability of glutamate taste.
AM1‐receptor‐dependent protection by intermedin of human vascular and cardiac non‐vascular cells from ischaemia–reperfusion injury
Authors: Bell David , Campbell Malcolm , Ferguson Matthew , Sayers Leah , Donaghy Liz , O’Regan Anna , Jewhurst Victoria , Harbinson Mark
Published: December 2011

Key points 

Coronary artery disease occurs when fatty deposits cause obstruction to blood flow in the coronary arteries, reducing the supply of blood to the heart. This can damage the heart muscle (heart attack).

In this study, a small protein named intermedin is shown to be present in cells from the human heart and blood vessels.

Intermedin, acting on a specific type of receptor protein shown to be present on the surface of these cells, is found to protect against damage occurring during experiments conducted in human cardiac and vascular cells in culture under conditions designed to simulate initial obstruction and subsequent restoration of blood flow, respectively.

These results suggest that administration of intermedin might provide a novel therapeutic strategy to minimise damage to heart muscle following a heart attack.
Numerical Analysis of JNES Seismic Tests on Degraded Combined Piping System
Authors: Zhang Tao , Brust Frederick W. , Wilkowski Gery , Shim Do-Jun , Nie Jinsuo , Hofmayer Charles H. , Ali Syed A.
Published: December 2011

Nuclear power plant safety under seismic conditions is an important consideration. The piping systems may have some defects caused by fatigue, stress corrosion cracking, etc., in aged plants. These cracks may not only affect the seismic response but also grow and break through causing loss of coolant. Therefore, an evaluation method needs to be developed to predict crack growth behavior under seismic excitation. This paper describes efforts conducted to analyze and better understand a series of degraded pipe tests under seismic loading that was conducted by Japan Nuclear Energy Safety Organization (JNES). A special “cracked-pipe element” (CPE) concept, where the element represented the global moment-rotation response due to the crack, was developed. This approach was developed to significantly simplify the dynamic finite element analysis in fracture mechanics fields. In this paper, model validation was conducted by comparisons with a series of pipe tests with circumferential through-wall and surface cracks under different excitation conditions. These analyses showed that reasonably accurate predictions could be made using the abaqus connector element to model the complete transition of a circumferential surface crack to a through-wall crack under cyclic dynamic loading. The JNES primary loop recirculation piping test was analyzed in detail. This combined-component test had three crack locations and multiple applied simulated seismic block loadings. Comparisons were also made between the ABAQUS finite element (FE) analyses results to the measured displacements in the experiment. Good agreement was obtained, and it was confirmed that the simplified modeling is applicable to a seismic analysis for a cracked pipe on the basis of fracture mechanics. Pipe system leakage did occur in the JNES tests. The analytical predictions using the CPE approach did not predict leakage, suggesting that cyclic ductile tearing with large-scale plasticity was not the crack growth mode for the acceleration excitations considered here. Hence, the leakage was caused by low-cycle fatigue with small-scale yielding. The procedure used to make predictions of low-cycle fatigue crack growth with small-scale yielding was based on the Dowling ΔJ procedure, which is an extension of linear-elastic fatigue crack growth methodology into the nonlinear plasticity region. The predicted moments from the CPE approach were used using a cycle-by-cycle crack growth procedure. The predictions compare quite well with the experimental measurements.
Study of Pressure Wave Propagation in a Two-Phase Bubbly Mixture
Authors: Raju Reni , Singh Sowmitra , Hsiao Chao-Tsung , Chahine Georges
Published: December 2011

(1) Background. Bubbly flows are used in a wide variety of applications and require accurate modeling. In this paper, three modeling approaches are investigated using the geometrically simple configuration of a gas bubble strongly oscillating in a bubbly medium. (2) Method of approach. A coupled Eulerian-Lagrangian, a multicomponent compressible, and an analytical approach are compared for different void fractions. (3) Results. While the homogeneous mixture models (analytical and multicomponent) compare well with each other, the Eulerian-Lagrangian model captures additional features and inhomogeneities. The discrete bubbles appear to introduce localized perturbations in the void fraction and the pressure distributions not captured by homogeneous mixture models. (4) Conclusions. The bubbly mixture impedes the growth and collapse of the primary bubble while wavy patterns in the velocity, pressure, and void fraction fields propagate in space and time.
Micro-Channels: Reality and Myth
Authors: Hetsroni G. , Mosyak A. , Pogrebnyak E. , Yarin L. P.
Published: December 2011

Many important problems connected to flows in micro-heat exchangers were not studied in sufficient detail. In particular, the governing physical mechanisms are still not well understood for flows in pipes and channels with hydraulic diameter ranging from 5 to 103 μm, which are often defined as micro-tubes or micro-channels. Experimental and numerical results of pressure driven laminar, continuous, incompressible, flow in different scale and shape channels are analyzed to highlight variations between various studies and these discrepancies are considered. The main objective is to determine whether the classical fluid flow theory based on the Navier- Stokes equations is valid to predict velocity distribution, pressure drop and transition from laminar to turbulent flow in micro-channels. No differences were found between results in micro-channels, unaffected by fluid ionic composition and the nature of the wall, and conventional size channels. The distinctions between different experimental studies must be attributed to different initial conditions, difference between actual conditions of a given experiment and conditions corresponding to the theoretical model, and measurement accuracy.
Pyrrolamide DNA Gyrase Inhibitors: Fragment-Based Nuclear Magnetic Resonance Screening To Identify Antibacterial Agents
Authors: Eakin Ann E. , Green Oluyinka , Hales Neil , Walkup Grant K. , Bist Shanta , Singh Alok , Mullen George , Bryant Joanna , Embrey Kevin , Gao Ning , Breeze Alex , Timms Dave , Andrews Beth , Uria-Nickelsen Maria , Demeritt Julie , Loch James T. , Hull Ken , Blodgett April , Illingworth Ruth N. , Prince Bryan , Boriack-Sjodin P. Ann , Hauck Sheila , MacPherson Lawrence J. , Ni Haihong , Sherer Brian
Published: December 2011

DNA gyrase is an essential enzyme in bacteria, and its inhibition results in the disruption of DNA synthesis and, subsequently, cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase. These compounds were identified by a fragment-based lead generation (FBLG) approach using nuclear magnetic resonance (NMR) screening to identify low-molecular-weight compounds that bind to the ATP pocket of DNA gyrase. A pyrrole hit with a binding constant of 1 mM formed the basis of the design and synthesis of a focused library of compounds that resulted in the rapid identification of a lead compound that inhibited DNA gyrase with a 50% inhibitory concentration (IC
50
) of 3 μM. The potency of the lead compound was further optimized by utilizing iterative X-ray crystallography to yield DNA gyrase inhibitors that also displayed antibacterial activity. Spontaneous mutants were isolated in
Staphylococcus aureus
by plating on agar plates containing pyrrolamide 4 at the MIC. The resistant variants displayed 4- to 8-fold-increased MIC values relative to the parent strain. DNA sequencing revealed two independent point mutations in the pyrrolamide binding region of the
gyrB
genes from these variants, supporting the hypothesis that the mode of action of these compounds was inhibition of DNA gyrase. Efficacy of a representative pyrrolamide was demonstrated against
Streptococcus pneumoniae
in a mouse lung infection model. These data demonstrate that the pyrrolamides are a novel class of DNA gyrase inhibitors with the potential to deliver future antibacterial agents targeting multiple clinical indications.
Effect of Food on the Pharmacokinetics of the Integrase Inhibitor Dolutegravir
Authors: Song Ivy , Borland Julie , Chen Shuguang , Patel Parul , Wajima Toshihiro , Peppercorn Amanda , Piscitelli Stephen C.
Published: December 2011

Healthy subjects received dolutegravir at 50 mg in a single-dose crossover study while they were in the fasted state or with low-, moderate-, or high-fat meals. Food increased dolutegravir exposure and reduced the rate of absorption. The area under the concentration-time curve from 0 h to infinity (AUC
0–∞
) increased by 33%, 41%, and 66% when administered with low-, moderate-, or high-fat meals, respectively, compared with fasting. This increase in dolutegravir exposure is not anticipated to impact clinical safety, and therefore dolutegravir can be taken with or without food and without regard to fat content.
Enhanced Wound Healing by Recombinant Escherichia coli Nissle 1917 via Human Epidermal Growth Factor Receptor in Human Intestinal Epithelial Cells: Therapeutic Implication Using Recombinant Probiotics
Authors: Choi Hye Jin , Ahn Jung Hoon , Park Seong-Hwan , Do Kee Hun , Kim Juil , Moon Yuseok
Published: December 2011

The gastrointestinal mucosa has a remarkable ability to repair damage with the support of epidermal growth factor (EGF), which stimulates epithelial migration and proliferative reepithelialization. For the treatment of mucosal injuries, it is important to develop efficient methods for the localized delivery of mucoactive biotherapeutics. The basic idea in the present study came from the assumption that an intestinal probiotic vehicle can carry and deliver key recombinant medicinal proteins to the injured epithelial target in patients with intestinal ulcerative diseases, including inflammatory bowel disease. The study was focused on the use of the safe probiotic
E. coli
Nissle 1917, which was constructed to secrete human EGF in conjunction with the lipase ABC transporter recognition domain (LARD). Using the
in vitro
physically wounded monolayer model, ABC transporter-mediated EGF secretion by probiotic
E. coli
Nissle 1917 was demonstrated to enhance the wound-healing migration of human enterocytes. Moreover, the epithelial wound closure was dependent on EGF receptor-linked activation, which exclusively involved the subsequent signaling pathway of the mitogen-activated protein kinase kinase (MEK) extracellular-related kinases 1 and 2 (ERK1/2). In particular, the migrating frontier of the wounded edge displayed the strongest EGF receptor-linked signaling activation in the presence of the recombinant probiotic. The present study provides a basis for the clinical application of human recombinant biotherapeutics via an efficient, safe probiotic vehicle.
Use of the Chinchilla Model for Nasopharyngeal Colonization To Study Gene Expression by Moraxella catarrhalis
Authors: Hoopman Todd C. , Liu Wei , Joslin Stephanie N. , Pybus Christine , Sedillo Jennifer L. , Labandeira-Rey Maria , Laurence Cassie A. , Wang Wei , Richardson James A. , Bakaletz Lauren O. , Hansen Eric J.
Published: December 2011

Young adult chinchillas were atraumatically inoculated with
Moraxella catarrhalis
via the nasal route. Detailed histopathologic examination of nasopharyngeal tissues isolated from these
M. catarrhalis
-infected animals revealed the presence of significant inflammation within the epithelium. Absence of similar histopathologic findings in sham-inoculated animals confirmed that
M. catarrhalis
was exposed to significant host-derived factors in this environment. Twenty-four hours after inoculation, viable
M. catarrhalis
organisms were recovered from the nasal cavity and nasopharynx of the animals in numbers sufficient for DNA microarray analysis. More than 100
M. catarrhalis
genes were upregulated
in vivo
, including open reading frames (ORFs) encoding proteins that are involved in a truncated denitrification pathway or in the oxidative stress response, as well as several putative transcriptional regulators. Additionally, 200
M. catarrhalis
genes were found to be downregulated when this bacterium was introduced into the nasopharynx. These downregulated genes included ORFs encoding several well-characterized
M. catarrhalis
surface proteins including Hag, McaP, and MchA1. Real-time reverse transcriptase PCR (RT-PCR) was utilized as a stringent control to validate the results of
in vivo
gene expression patterns as measured by DNA microarray analysis. Inactivation of one of the genes (MC ORF 1550) that was upregulated
in vivo
resulted in a decrease in the ability of
M. catarrhalis
to survive in the chinchilla nasopharynx over a 3-day period. This is the first evaluation of global transcriptome expression by
M. catarrhalis
cells
in vivo
.
Hcp Family Proteins Secreted via the Type VI Secretion System Coordinately Regulate Escherichia coli K1 Interaction with Human Brain Microvascular Endothelial Cells
Authors: Zhou Yan , Tao Jing , Yu Hao , Ni Jinjing , Zeng Lingbing , Teng Qihui , Kim Kwang Sik , Zhao Guo-Ping , Guo Xiaokui , Yao Yufeng
Published: December 2011

Type VI secretion systems (T6SSs) are involved in the pathogenicity of several Gram-negative bacteria. Based on sequence analysis, we found that a cluster of

E

scherichia coli
v
irulence
f
actors (EVF) encoding a putative T6SS exists in the genome of the meningitis-causing
E. coli
K1 strain RS218. The T6SS-associated deletion mutants exhibited significant defects in binding to and invasion of human brain microvascular endothelial cells (HBMEC) compared with the parent strain. Hcp family proteins (the hallmark of T6SS), including Hcp1 and Hcp2, were localized in the bacterial outer membrane, but the involvements of Hcp1 and Hcp2 have been shown to differ in
E. coli
-HBMEC interaction. The deletion mutant of
hcp2
showed defects in the bacterial binding to and invasion of HBMEC, while Hcp1 was secreted in a T6SS-dependent manner and induced actin cytoskeleton rearrangement, apoptosis, and the release of interleukin-6 (IL-6) and IL-8 in HBMEC. These findings demonstrate that the T6SS is functional in
E. coli
K1, and two Hcp family proteins participate in different steps of
E. coli
interaction with HBMEC in a coordinate manner, e.g., binding to and invasion of HBMEC, the cytokine and chemokine release followed by cytoskeleton rearrangement, and apoptosis in HBMEC. This is the first demonstration of the role of T6SS in meningitis-causing
E. coli
K1, and T6SS-associated Hcp family proteins are likely to contribute to the pathogenesis of
E. coli
meningitis.
Reforming Science: Structural Reforms
Authors: Fang Ferric C. , Casadevall Arturo
Published: December 2011

Science has a critical role to play in addressing humanity's most important challenges in the twenty-first century. However, the contemporary scientific enterprise has developed in ways that prevent it from reaching maximum effectiveness and detract from the appeal of a research career. To be effective, the methodological and culture reforms discussed in the accompanying essay must be accompanied by fundamental structural reforms that include a renewed vigorous societal investment in science and scientists.
The Acid Phosphatase AcpA Is SecretedIn Vitroand in Macrophages by Francisella spp
Authors: Dai Shipan , Mohapatra Nrusingh P. , Schlesinger Larry S. , Gunn John S.
Published: December 2011

Francisella tularensisis a remarkably infectious facultative intracellular pathogen that causes the zoonotic disease tularemia. Essential to the pathogenesis ofF. tularensisis its ability to escape the destructive phagosomal environment and inhibit the host cell respiratory burst.F. tularensissubspecies encode a series of acid phosphatases, which have been reported to play important roles inFrancisellaphagosomal escape, inhibition of the respiratory burst, and intracellular survival. However, rigorous demonstration of acid phosphatase secretion by intracellularFrancisellahas not been shown. Here, we demonstrate that AcpA, which contributes most of theF. tularensisacid phosphatase activity, is secreted into the culture supernatantin vitrobyF. novicidaandF. tularensissubsp.holarcticaLVS. In addition, bothF. novicidaand the highly virulentF. tularensissubsp.tularensisSchu S4 strain are able to secrete and also translocate AcpA into the host macrophage cytosol. This is the first evidence of acid phosphatase translocation during macrophage infection, and this knowledge will greatly enhance our understanding of the functions of these enzymes inFrancisellapathogenesis.