Poly(ester-urethane) scaffolds: effect of structure on properties and osteogenic activity of stem cells.
The present study aimed to investigate the effect of structure (design and porosity) on the matrix stiffness and osteogenic activity of stem cells cultured on poly(ester-urethane) (PEU) scaffolds. Different three-dimensional (3D) forms of scaffold were prepared from lysine-based PEU using traditional salt-leaching and advanced bioplotting techniques. The resulting scaffolds were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), mercury porosimetry and mechanical testing. The scaffolds had various pore sizes with different designs, and all were thermally stable up to 300 °C. In vitro tests, carried out using rat bone marrow stem cells (BMSCs) for bone tissue engineering, demonstrated better viability and higher cell proliferation on bioplotted scaffolds compared to salt-leached ones, most probably due to their larger and interconnected pores and stiffer nature, as shown by higher compressive moduli, which were measured by compression testing. Similarly, SEM, von Kossa staining and EDX analyses indicated higher amounts of calcium deposition on bioplotted scaffolds during cell culture. It was concluded that the design with larger interconnected porosity and stiffness has an effect on the osteogenic activity of the stem cells.


New insights into necrotizing enterocolitis: From laboratory observation to personalized prevention and treatment.
Necrotizing enterocolitis (NEC) is a devastating disease of prematurity that develops after feeding, often without warning, and results in diffuse intestinal necrosis leading to sepsis and death in many cases. The lack of improvement in overall survival is influenced by nonspecific diagnostic modalities as well as inexact and nonpersonalized treatment strategies. Recently, we and others have shown that NEC develops in response to exaggerated bacterial signaling in the premature intestine, as a consequence of elevated expression and activity of the bacterial receptor toll-like receptor 4 (TLR4), which is important for normal gut development. Breast milk is a powerful TLR4 inhibitor, while mutations in TLR4 genes lead to increased NEC risk in humans, providing proof-of-concept for its role in NEC. Recently, a drug discovery approach has revealed a novel class of TLR4 inhibitors which are being developed for personalized approaches to NEC treatment. This review will highlight the current understanding of the role of bacterial signaling in NEC pathogenesis, and will describe advances in diagnosis, prevention and treatment of NEC that may hopefully improve survival for these most fragile patients. Level of Evidence: Level II.


Barriers and facilitators of effective self-management in asthma: systematic review and thematic synthesis of patient and healthcare professional views.
Self-management is an established, effective approach to controlling asthma, recommended in guidelines. However, promotion, uptake and use among patients and health-care professionals remain low. Many barriers and facilitators to effective self-management have been reported, and views and beliefs of patients and health care professionals have been explored in qualitative studies. We conducted a systematic review and thematic synthesis of qualitative research into self-management in patients, carers and health care professionals regarding self-management of asthma, to identify perceived barriers and facilitators associated with reduced effectiveness of asthma self-management interventions. Electronic databases and guidelines were searched systematically for qualitative literature that explored factors relevant to facilitators and barriers to uptake, adherence, or outcomes of self-management in patients with asthma. Thematic synthesis of the 56 included studies identified 11 themes: (1) partnership between patient and health care professional; (2) issues around medication; (3) education about asthma and its management; (4) health beliefs; (5) self-management interventions; (6) co-morbidities (7) mood disorders and anxiety; (8) social support; (9) non-pharmacological methods; (10) access to healthcare; (11) professional factors. From this, perceived barriers and facilitators were identified at the level of individuals with asthma (and carers), and health-care professionals. Future work addressing the concerns and beliefs of adults, adolescents and children (and carers) with asthma, effective communication and partnership, tailored support and education (including for ethnic minorities and at risk groups), and telehealthcare may improve how self-management is recommended by professionals and used by patients. Ultimately, this may achieve better outcomes for people with asthma.


WUSCHEL-RELATED HOMEOBOX4 (WOX4)-like genes regulate cambial cell division activity and secondary growth in Populus trees.
Plant secondary growth derives from the meristematic activity of the vascular cambium. In Arabidopsis thaliana, cell divisions in the cambium are regulated by the transcription factor WOX4, a key target of the CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (ESR)-RELATED 41 (CLE41) signaling pathway. However, function of the WOX4-like genes in plants that are dependent on a much more prolific secondary growth, such as trees, remains unclear. Here, we investigate the role of WOX4 and CLE41 homologs for stem secondary growth in Populus trees. In Populus, PttWOX4 genes are specifically expressed in the cambial region during vegetative growth, but not after growth cessation and during dormancy, possibly involving a regulation by auxin. In PttWOX4a/b RNAi trees, primary growth was not affected whereas the width of the vascular cambium was severely reduced and secondary growth was greatly diminished. Our data show that in Populus trees, PttWOX4 genes control cell division activity in the vascular cambium, and hence growth in stem girth. This activity involves the positive regulation of PttWOX4a/b through PttCLE41-related genes. Finally, expression profiling suggests that the CLE41 signaling pathway is an evolutionarily conserved program for the regulation of vascular cambium activity between angiosperm and gymnosperm tree species.


Conceptual Alignment: How Brains Achieve Mutual Understanding.
We share our thoughts with other minds, but we do not understand how. Having a common language certainly helps, but infants' and tourists' communicative success clearly illustrates that sharing thoughts does not require signals with a pre-assigned meaning. In fact, human communicators jointly build a fleeting conceptual space in which signals are a means to seek and provide evidence for mutual understanding. Recent work has started to capture the neural mechanisms supporting those fleeting conceptual alignments. The evidence suggests that communicators and addressees achieve mutual understanding by using the same computational procedures, implemented in the same neuronal substrate, and operating over temporal scales independent from the signals' occurrences.


Activation of premotor vocal areas during musical discrimination.
Two same/different discrimination tasks were performed by amateur-musician subjects in this functional magnetic resonance imaging study: Melody Discrimination and Harmony Discrimination. Both tasks led to activations not only in classic working memory areas--such as the cingulate gyrus and dorsolateral prefrontal cortex--but in a series of premotor areas involved in vocal-motor planning and production, namely the somatotopic mouth region of the primary and lateral premotor cortices, Broca's area, the supplementary motor area, and the anterior insula. A perceptual control task involving passive listening alone to monophonic melodies led to activations exclusively in temporal-lobe auditory areas. These results show that, compared to passive listening tasks, discrimination tasks elicit activation in vocal-motor planning areas.


Developing new treatments: on the interplay between theories, experimental science and clinical innovation.
It is often argued that behaviour therapy and cognitive-behaviour therapy have a sound theoretical and experimental basis. In the early days of behaviour therapy, the learning theory accounts that were the basis of treatment made clear suggestions about the procedures that were likely to be effective in treatment. In contrast, more recent cognitive-behavioural models tend to specify targets for therapy, but not the procedures that might be optimal for changing the targets. As a consequence, a considerable amount of work has to be done in order to create an effective cognitive-behavioural treatment from a promising cognitive-behavioural model. The process by which cognitive-behavioural treatments are developed is rarely discussed in the literature. For this reason, the way in which one group has used a mixture of phenomenological, experimental and treatment development studies to create effective cognitive therapy programmes for anxiety disorders is described.


NGS barcoding reveals high resistance of a hyperdiverse chironomid (Diptera) swamp fauna against invasion from adjacent freshwater reservoirs.
Macroinvertebrates such as non-biting midges (Chironomidae: Diptera) are important components of freshwater ecosystems. However, they are often neglected in biodiversity and conservation research because invertebrate species richness is difficult and expensive to quantify with traditional methods. We here demonstrate that Next Generation Sequencing barcodes ("NGS barcodes") can provide relief because they allow for fast and large-scale species-level sorting of large samples at low cost. We used NGS barcoding to investigate the midge fauna of Singapore's swamp forest remnant (Nee Soon Swamp Forest). Based on > 14.000 barcoded specimens, we find that the swamp forest maintains an exceptionally rich fauna composed of an observed number of 289 species (estimated 336 species) in a very small area (90 ha). We furthermore barcoded the chironomids from three surrounding reservoirs that are located in close proximity. Although the swamp forest remnant is much smaller than the combined size of the freshwater reservoirs in the study (90 ha vs. > 450 ha), the latter only contains 33 (estimated 61) species. We show that the resistance of the swamp forest species assemblage is high because only 8 of the 314 species are shared despite the close proximity. Moreover, shared species are not very abundant (3% of all specimens). A redundancy analysis revealed that ~ 21% of the compositional variance of midge communities within the swamp forest was explained by a range of variables with conductivity, stream order, stream width, temperature, latitude (flow direction), and year being significant factors influencing community structure. An LME analysis demonstrates that the total species richness decreased with increasing conductivity. Our study demonstrates that midge diversity of a swamp forest can be so high that it questions global species diversity estimates for Chironomidae, which are an important component of many freshwater ecosystems. We furthermore demonstrate that small and natural habitat remnants can have high species turnover and can be very resistant to the invasion of species from neighboring reservoirs. Lastly, the study shows how NGS barcodes can be used to integrate specimen- and species-rich invertebrate taxa in biodiversity and conservation research.


Enhanced multiposition method to suppress the north finding error caused by bias drift with fiber optic gyroscopes.
We present an enhanced multiposition method (EMM) to suppress the north finding error caused by bias drift with fiber optic gyroscopes (FOGs). The new proposal is a static method to find the true north, and it employs a differential strategy and a rotation scheme of increasing step angle. Using the noise model of Allan variance, we analyze the north finding errors caused by angle random walk (ARW), rate random walk (RRW), and rate ramp (RR) theoretically, where RRW and RR are two main noise sources of bias drift, and ARW is the rate white noise. Theoretical analysis indicates that, in the traditional multiposition method (TMM), as the position number increases, the error caused by ARW decreases while that by bias drift increases. Therefore, the suppressions of ARW and bias drift are conflicted with each other. The north finding accuracy is limited by bias drift. In contrast, in EMM, both errors caused by ARW and bias drift will decrease as the position number increases. Experimental results with two specific FOGs verify our theoretical analysis. In our experiments, we study the effect of position number and step angle on the north finding accuracy. Utilizing the proposed EMM, for FOG-1, the north finding error has been reduced by 76.60%, and for FOG-2, a 36.33% reduction has been achieved. Our proposal provides a more effective and stable way to find true north, and it can also be applied to other rate gyroscopes.


Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci.
To ascertain recommendations for the treatment of gonorrhoea in the WHO Western Pacific Region (WPR) following the emergence of "cephalosporin-resistant" Neisseria gonorrhoeae and to relate these to clinical and laboratory measures directed towards disease and antibiotic resistance control. WHO WPR Gonococcal Antimicrobial Resistance Programme members provided data on the type, dose and source of third-generation cephalosporins recommended for the treatment of gonorrhoea. Ceftriaxone was recommended more widely (11/15 respondents) than cefixime (five centres). No cephalosporins were recommended in three jurisdictions. One other oral (ceftibuten) and injectable (cefodizime) agent was recommended. Uniform (400 mg) doses of cefixime were recommended but ceftriaxone regimens ranged between 125 mg and 1 g, with nine of 11 respondents using a 250 mg dose. Both generic and proprietary preparations were widely used. Third-generation cephalosporins are widely recommended for the treatment of gonorrhoea in the WPR, with injectable ceftriaxone more extensively so than oral cefixime and in an expanded dose range. Few other cephalosporins were recommended. Current knowledge suggests that the trend towards ceftriaxone treatment in higher doses may decrease the impact of the circulation of "cephalosporin-resistant" gonococci in the WPR. These recommendations represent public sector practice only and of themselves are unlikely to contain the further spread of "cephalosporin-resistant" gonococci because of the general clinical use of cephalosporins. Optimisation of strategies for laboratory detection of third-generation cephalosporin resistance can be simplified in the WPR because of the restricted spectrum of cephalosporins recommended. Additional efforts are urgently required for both disease and antibiotic resistance control in gonorrhoea.


Myelin oligodendrocyte glycoprotein antibodies in neurological disease.
Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) were first detected by immunoblot and enzyme-linked immunosorbent assay nearly 30 years ago, but their association with multiple sclerosis (MS) was not specific. Use of cell-based assays with native MOG as the substrate enabled identification of a group of MOG-Ab-positive patients with demyelinating phenotypes. Initially, MOG-Abs were reported in children with acute disseminated encephalomyelitis (ADEM). Further studies identified MOG-Abs in adults and children with ADEM, seizures, encephalitis, anti-aquaporin-4-antibody (AQP4-Ab)-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes (optic neuritis, myelitis and brainstem encephalitis), but rarely in MS. This shift in our understanding of the diagnostic assays has re-invigorated the examination of MOG-Abs and their role in autoimmune and demyelinating disorders of the CNS. The clinical phenotypes, disease courses and responses to treatment that are associated with MOG-Abs are currently being defined. MOG-Ab-associated disease is different to AQP4-Ab-positive NMOSD and MS. This Review provides an overview of the current knowledge of MOG, the metrics of MOG-Ab assays and the clinical associations identified. We collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. We also highlight differences between MOG-Ab-associated disease, NMOSD and MS, and describe our current understanding on how best to treat MOG-Ab-associated disease.


Hepatic biomarkers of xenobiotic metabolism in eighteen marine fish from NW Mediterranean shelf and slope waters in relation to some of their biological and ecological variables.
A suite of hepatic biomarkers currently used in pollution monitoring were measured in eighteen common fish species, comprising five orders, eleven families of teleosts and two elasmobranchs. The sampling was carried out seasonally in front of the Barcelona coast (NW Mediterranean) during 2007. The hepatic enzymes considered were the activities of catalase, glutathione reductase, ethoxyresorufin O-deethylase, carboxylesterase and glutathione S-transferase. As markers at higher levels of biological organization, feeding preferences (on benthic, suprabenthic or zooplanktonic species), swimming capability, stomach fullness and trophic level were considered. Significant species differences were found among all the biochemical parameters analysed, although no relationships among the biomarkers themselves were evidenced. In general enzymatic activities were much higher in teleosts than in elasmobranchs, and in perciforms than in gadiforms. Seasonality was observed in some species with higher activities usually corresponding to the winter period. No site related differences were observed in the two selected sites, which differ over a small pollution gradient. A multivariate canonical Correspondence analysis (CCA) was performed on shelf and slope species separately to relate biochemical markers with ecological variables. CCA revealed that for shelf species, EROD was positively related to benthos feeding as well as trophic level, while on the slope the clearest association was between suprabenthos feeders and trophic level. Our present results, including seasonality, slightly differ from former observations (Solé et al., 2009a) and reveal a more significant role of the ecological variables in controlling biomarkers expression in fish from the shelf.


Modernising epidemic science: enabling patient-centred research during epidemics.
Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers. The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence. It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence.


The mechanism of RNA capping by SARS-CoV-2.
The RNA genome of SARS-CoV-2 contains a 5' cap that facilitates the translation of viral proteins, protection from exonucleases and evasion of the host immune response1-4. How this cap is made in SARS-CoV-2 is not completely understood. Here we reconstitute the N7- and 2'-O-methylated SARS-CoV-2 RNA cap (7MeGpppA2'-O-Me) using virally encoded non-structural proteins (nsps). We show that the kinase-like nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain5 of nsp12 transfers the RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers the RNA to GDP, forming the core cap structure GpppA-RNA. The nsp146 and nsp167 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system8 that the N terminus of nsp9 and the kinase-like active-site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.


Optic disc edema in an astronaut after repeat long-duration space flight.
A number of ophthalmic findings including optic disc edema, globe flattening, and choroidal folds have been observed in several astronauts after long-duration space flights. The authors report the first astronaut with previously documented postflight ophthalmic abnormalities who developed new pathological changes after a repeat long-duration mission. A case study of an astronaut with 2 long-duration (6 months) exposures to microgravity. Before and after his first long-duration space flight, he underwent complete eye examination, including fundus photography. Before and after his second flight, 9 years later, he underwent fundus photography, optical coherence tomography, ocular ultrasonography, and brain magnetic resonance imaging, as well as in-flight fundus photography and ultrasound. After his first long-duration mission, the astronaut was documented to have eye findings limited to unilateral choroidal folds and a single cotton wool spot. During a subsequent 6-month mission, he developed more widespread choroidal folds and new onset of optic disc edema in the same eye. Microgravity-induced anatomical changes that occurred during the first mission may have set the stage for recurrent or additional changes when the astronaut was subjected to physiological stress of repeat space flight.


Peripheral blood mononuclear cells produce normal amounts of defective Vif- human immunodeficiency virus type 1 particles which are restricted for the preretrotranscription steps.
Previous studies have demonstrated the absence of viral replication of Vif- mutants in stimulated primary blood mononuclear cells (PBMC). Human immunodeficiency virus type 1 strain NDK Vif- mutants were propagated on the semipermissive CEM cell line, and the viral stock obtained was compared with the wild-type virus during a single cycle in PBMC. The Vif- virus was able to enter PBMC with the same efficiency as the wild type, as demonstrated by quantification of the strong-stop cDNA, and retrotranscription was observed for both viruses within 4 h postinfection. Using a PCR assay with an Alu-long terminal repeat pair of primers, we detected integration for both the wild-type and Vif- viruses. We then used qualitative and quantitative reverse transcription-mediated PCR techniques to study the steady-state level of intracellular and extracellular viral RNAs. All mRNA species were detected in PBMC infected with the wild-type virus or with the Vif- virus 36 h postinfection. Furthermore, quantification of viral RNA released from infected cells demonstrated similar levels of virus produced after a unique cycle of replication. However, the Vif- virus obtained after one replication cycle in PBMC was unable to initiate retrotranscription in permissive target cells. These data strongly suggest that the failure to infect target cells is due to a defect in the formation of the viral particle in PBMC.


Fish wariness is a more sensitive indicator to changes in fishing pressure than abundance, length or biomass.
Identifying the most sensitive indicators to changes in fishing pressure is important for accurately detecting impacts. Biomass is thought to be more sensitive than abundance and length, while the wariness of fishes is emerging as a new metric. Periodically harvested closures (PHCs) that involve the opening and closing of an area to fishing are the most common form of fisheries management in the western Pacific. The opening of PHCs to fishing provides a unique opportunity to compare the sensitivity of metrics, such as abundance, length, biomass and wariness, to changes in fishing pressure. Diver-operated stereo video (stereo-DOV) provides data on fish behavior (using a proxy for wariness, minimum approach distance) simultaneous to abundance and length estimates. We assessed the impact of PHC protection and harvesting on the abundance, length, biomass, and wariness of target species using stereo-DOVs. This allowed a comparison of the sensitivity of these metrics to changes in fishing pressure across four PHCs in Fiji, where spearfishing and fish drives are common. Before PHCs were opened to fishing they consistently decreased the wariness of targeted species but were less likely to increase abundance, length, or biomass. Pulse harvesting of PHCs resulted in a rapid increase in the wariness of fishes but inconsistent impacts across the other metrics. Our results suggest that fish wariness is the most sensitive indicator of fishing pressure, followed by biomass, length, and abundance. The collection of behavioral data simultaneously with abundance, length, and biomass estimates using stereo-DOVs offers a cost-effective indicator of protection or rapid increases in fishing pressure. Stereo-DOVs can rapidly provide large amounts of behavioral data from monitoring programs historically focused on estimating abundance and length of fishes, which is not feasible with visual methods.


Plasticity of hypothalamic dopamine neurons during lactation results in dissociation of electrical activity and release.
Tuberoinfundibular dopamine (TIDA) neurons are the central regulators of prolactin (PRL) secretion. Their extensive functional plasticity allows a change from low PRL secretion in the non-pregnant state to the condition of hyperprolactinemia that characterizes lactation. To allow this rise in PRL, TIDA neurons are thought to become unresponsive to PRL at lactation and functionally silenced. Here we show that, contrary to expectations, the electrical properties of the system were not modified during lactation and that the neurons remained electrically responsive to a PRL stimulus, with PRL inducing an acute increase in their firing rate during lactation that was identical to that seen in non-pregnant mice. Furthermore, we show a long-term organization of TIDA neuron electrical activity with an harmonization of their firing rates, which remains intact during lactation. However, PRL-induced secretion of dopamine (DA) at the median eminence was strongly blunted during lactation, at least in part attributable to lack of phosphorylation of tyrosine hydroxylase, the key enzyme involved in DA synthesis. We therefore conclude that lactation, rather than involving electrical silencing of TIDA neurons, represents a condition of decoupling between electrical activity at the cell body and DA secretion at the median eminence.


Perspective: Spectroscopy and kinetics of small gaseous Criegee intermediates.
The Criegee intermediates, carbonyl oxides proposed by Criegee in 1949 as key intermediates in the ozonolysis of alkenes, play important roles in many aspects of atmospheric chemistry. Because direct detection of these gaseous intermediates was unavailable until recently, previous understanding of their reactions, derived from indirect experimental evidence, had great uncertainties. Recent laboratory detection of the simplest Criegee intermediate CH2OO and some larger members, produced from ultraviolet irradiation of corresponding diiodoalkanes in O2, with various methods such as photoionization, ultraviolet absorption, infrared absorption, and microwave spectroscopy opens a new door to improved understanding of the roles of these Criegee intermediates. Their structures and spectral parameters have been characterized; their significant zwitterionic nature is hence confirmed. CH2OO, along with other products, has also been detected directly with microwave spectroscopy in gaseous ozonolysis reactions of ethene. The detailed kinetics of the source reaction, CH2I + O2, which is critical to laboratory studies of CH2OO, are now understood satisfactorily. The kinetic investigations using direct detection identified some important atmospheric reactions, including reactions with NO2, SO2, water dimer, carboxylic acids, and carbonyl compounds. Efforts toward the characterization of larger Criegee intermediates and the investigation of related reactions are in progress. Some reactions of CH3CHOO are found to depend on conformation. This perspective examines progress toward the direct spectral characterization of Criegee intermediates and investigations of the associated reaction kinetics, and indicates some unresolved problems and prospective challenges for this exciting field of research.


Tractable multivariate binary density estimation and the restricted Boltzmann forest.
We investigate the problem of estimating the density function of multivariate binary data. In particular, we focus on models for which computing the estimated probability of any data point is tractable. In such a setting, previous work has mostly concentrated on mixture modeling approaches. We argue that for the problem of tractable density estimation, the restricted Boltzmann machine (RBM) provides a competitive framework for multivariate binary density modeling. With this in mind, we also generalize the RBM framework and present the restricted Boltzmann forest (RBForest), which replaces the binary variables in the hidden layer of RBMs with groups of tree-structured binary variables. This extension allows us to obtain models that have more modeling capacity but remain tractable. In experiments on several data sets, we demonstrate the competitiveness of this approach and study some of its properties.


Case of Paradoxical Cultural Sensitivity: Mixed Method Study of Web-Based Health Informational Materials About the Human Papillomavirus Vaccine in Israel.
Designing web-based informational materials regarding the human papillomavirus (HPV) vaccine has become a challenge for designers and decision makers in the health authorities because of the scientific and public controversy regarding the vaccine's safety and effectiveness and the sexual and moral concerns related to its use. The study aimed to investigate how cultural sensitivity (CS) is articulated in the explanatory informational materials on the HPV vaccine that are posted on the websites of the Israeli health authorities. In addition, the study examined the effect of transparency on the expression of CS in the informational materials. The study employed a quantitative and qualitative content analysis of the texts of explanatory informational materials published on the Arabic and Hebrew websites of the Israel Ministry of Health and the Clalit health maintenance organization (HMO). The findings revealed the differences in the dimensions of CS (based on the CS model by Resnicow) between the informational materials targeting the majority Jewish population and those targeting the minority Arab population. Indeed, the research findings point to a paradox. On the one hand, the materials appealing to the conservative Arab population exhibited CS, in that the sexual context of the vaccine was missing. On the other hand, analysis of Resnicow's deep dimensions showed that disregarding the sexual context does not allow the relevant target audience to reflect on the barriers and concerns. In addition, the way the information was provided exhibited a lack of transparency regarding the CS dimensions (surface and deep). The public health authorities have 2 main objectives in the context of vaccinations. One is to raise the vaccination rates and the other is to provide full and culturally sensitive information to give the public the tools to make intelligent decisions. The findings of this study indicated that despite the high uptake rate for HPV vaccination in the Arab population, the health authorities did not exercise full transparency and CS in transmitting the association between engaging in sexual relations and the necessity of the vaccination. Thus, the major challenge for the health authorities is to find ways to implement the objective of communicating information about the vaccination in a way that is transparent and culturally sensitive, even if this raises questions and fears among the public deriving from their culture.


Progressive immune dysfunction in cats experimentally infected with feline immunodeficiency virus.
Within 6 months of infection with the Petaluma isolate of feline immunodeficiency virus, specific-pathogen-free domestic cats exhibited a decrease in the percentage and number of circulating CD4+ lymphocytes and in the CD4+/CD8+ T-cell ratio, along with a marginally significant depression of pokeweed mitogen-induced lymphocyte proliferation in vitro. There was no loss of responsiveness to concanavalin A during this stage, and the cats were capable of mounting a satisfactory antibody response to a T-dependent, synthetic polypeptide immunogen. The pokeweed mitogen response deficit became clearly demonstrable by 11 to 12 months postinfection. A decline in the lymphocyte proliferative response to concanavalin A and a diminished ability to mount an in vivo antibody response to the T-dependent immunogen evolved by 25 to 44 months postinfection. Virus infection did not affect the ability of cats to mount an antibody response to a T-independent synthetic polypeptide immunogen. These data indicate that feline immunodeficiency virus produces a slowly progressive deterioration of T-cell function but does not affect the ability of B cells to recognize and respond to a T-independent antigenic stimulus.


Intussusception in children: experience with 105 patients in a department of paediatric surgery, Turkey.
The aim of this study was to present our experience in patients with intussusception (IN). One hundred and five cases of IN treated between 1991 and 2007 were analysed. Age, gender, symptoms, signs, diagnostic and treatment methods, types of IN including leading point, and postoperative complications were evaluated. The mean age of the patients was 2.5 years (range 1 month - 15 years). Fifty-nine per cent (62/105) were under 1 year of age, and of these 28% were receiving therapy for upper respiratory tract infection. The most common symptom was colicky abdominal pain. Rectal bleeding was present in all patients under 2 years of age. In 23 children (21.9%) leading points were detected. Thirty per cent of the patients were older than 4 years, and 76.6% of these had leading points. Ultrasonography demonstrated the invaginated segment in 93 patients. Hydrostatic reduction was attempted in 71.4% (75) of the patients and was successful in 48% (36), 70% of whom were under 1 year of age. Of the patients with unsuccessful hydrostatic reduction, 11 required intestinal resection and primary anastomosis and 35 manual reduction. Twenty-four patients were diagnosed by means of ultrasonography and were operated on immediately. Ten of these patients had signs of peritonitis on admission and were treated by resection-primary anastomosis. In patients with IN under 2 years of age, hydrostatic or pneumatic reduction may be successful. Considering the high incidence of leading points in older children, one should not persist with reduction but should rather design a treatment plan accordingly, i.e. laparotomy with manual reduction or resection.


'Double jeopardy' measure suggests blacks and hispanics face more severe disparities than previously indicated.
Eliminating disparities in health and health care is a long-standing objective of the US government. Racial and ethnic differences in insurance coverage pose a major obstacle to achieving this objective. With important coverage provisions of the Affordable Care Act beginning to take effect, we propose a new way of conceptualizing and quantifying the racial and ethnic disadvantages of uninsurance over the course of a lifetime. Using a life expectancy approach, we estimate the number of years whites, blacks, and Hispanics can expect to live in insurance "double jeopardy": being uninsured while also in lesser health and, therefore, at higher risk of needing medical care. Our measures indicate that compared to whites, Hispanics and blacks are more likely not only to be uninsured at any point throughout most of their lives, but also to spend more years uninsured and spend more of these uninsured years at high risk of needing medical care. These life expectancy measures--designed for ease of use by policy makers, researchers, and the general public--have the potential to reframe the discussion of disparities and monitor progress toward their elimination.


Space-bandwidth extension in parallel phase-shifting digital holography using a four-channel polarization-imaging camera.
We propose a method for extending the space bandwidth (SBW) available for recording an object wave in parallel phase-shifting digital holography using a four-channel polarization-imaging camera. A linear spatial carrier of the reference wave is introduced to an optical setup of parallel four-step phase-shifting interferometry using a commercially available polarization-imaging camera that has four polarization-detection channels. Then a hologram required for parallel two-step phase shifting, which is a technique capable of recording the widest SBW in parallel phase shifting, can be obtained. The effectiveness of the proposed method was numerically and experimentally verified.


Immobilization of different biomolecules by atomic force microscopy.
Micrometer resolution placement and immobilization of probe molecules is an important step in the preparation of biochips and a wide range of lab-on-chip systems. Most known methods for such a deposition of several different substances are costly and only suitable for a limited number of probes. In this article we present a flexible procedure for simultaneous spatially controlled immobilization of functional biomolecules by molecular ink lithography. For the bottom-up fabrication of surface bound nanostructures a universal method is presented that allows the immobilization of different types of biomolecules with micrometer resolution. A supporting surface is biotinylated and streptavidin molecules are deposited with an AFM (atomic force microscope) tip at distinct positions. Subsequent incubation with a biotinylated molecule species leads to binding only at these positions. After washing streptavidin is deposited a second time with the same AFM tip and then a second biotinylated molecule species is coupled by incubation. This procedure can be repeated several times. Here we show how to immobilize different types of biomolecules in an arbitrary arrangement whereas most common methods can deposit only one type of molecules. The presented method works on transparent as well as on opaque substrates. The spatial resolution is better than 400 nm and is limited only by the AFM's positional accuracy after repeated z-cycles since all steps are performed in situ without moving the supporting surface. The principle is demonstrated by hybridization to different immobilized DNA oligomers and was validated by fluorescence microscopy. The immobilization of different types of biomolecules in high-density microarrays is a challenging task for biotechnology. The method presented here not only allows for the deposition of DNA at submicrometer resolution but also for proteins and other molecules of biological relevance that can be coupled to biotin.


Interprofessional education increases knowledge, promotes team building, and changes practice in the care of Parkinson's disease.
Examine outcomes for the National Parkinson Foundation (NPF) Allied Team Training for Parkinson (ATTP), an interprofessional education (IPE) program in Parkinson's disease (PD) and team-based care for medicine, nursing, occupational, physical and music therapies, physician assistant, social work and speech-language pathology disciplines. Healthcare professionals need education in evidence-based PD practices and working effectively in teams. Few evidence-based models of IPE in PD exist. Knowledge about PD, team-based care, the role of other disciplines and attitudes towards healthcare teams were measured before and after a protocol-driven training program. Knowledge, attitudes and practice changes were again measured at 6-month post-training. Trainee results were compared to results of controls. Twenty-six NPF-ATTP trainings were held across the U.S. (2003-2013). Compared to control participants (n = 100), trainees (n = 1468) showed statistically significant posttest improvement in all major outcomes, including self-perceived (p < 0.001) and objective knowledge (p < 0.001), Understanding Role of Other Disciplines (p < 0.001), Attitudes Toward Health Care Teams Scale (p < 0.001), and the Attitudes Toward Value of Teams (p < 0.001) subscale. Despite some decline, significant improvements were largely sustained at six-month post-training. Qualitative analyses confirmed post-training practice changes. The NPF-ATTP model IPE program showed sustained positive gains in knowledge of PD, team strategies and role of other disciplines, team attitudes, and important practice improvements. Further research should examine longer-term outcomes, objectively measure practice changes and mediators, and determine impact on patient outcomes.


Evidence for a rapid rate of molecular evolution at the hypervariable and immunogenic Mycobacterium tuberculosis PPE38 gene region.
PPE38 (Rv2352c) is a member of the large PPE gene family of Mycobacterium tuberculosis and related mycobacteria. The function of PPE proteins is unknown but evidence suggests that many are cell-surface associated and recognised by the host immune system. Previous studies targeting other PPE gene members suggest that some display high levels of polymorphism and it is thought that this might represent a means of providing antigenic variation. We have analysed the genetic variability of the PPE38 genomic region on a cohort of M. tuberculosis clinical isolates representing all of the major phylogenetic lineages, along with the ancestral M. tuberculosis complex (MTBC) member M. canettii, and supplemented this with analysis of publicly available whole genome sequences representing additional M. tuberculosis clinical isolates, other MTBC members and non tuberculous mycobacteria (NTM). Where possible we have extended this analysis to include the adjacent plcABC and PPE39/40 genomic regions. We show that the ancestral MTBC PPE38 region comprises 2 homologous PPE genes (PPE38 and PPE71), separated by 2 esat-6 (esx)-like genes and that this structure derives from an esx/esx/PPE duplication in the common ancestor of M. tuberculosis and M. marinum. We also demonstrate that this region of the genome is hypervariable due to frequent IS6110 integration, IS6110-associated recombination, and homologous recombination and gene conversion events between PPE38 and PPE71. These mutations result in combinations of gene deletion, gene truncation and gene disruption in the majority of clinical isolates. These mutations were generally found to be IS6110 strain lineage-specific, although examples of additional within-lineage and even within-cluster mutations were observed. Furthermore, we provide evidence that the published M. tuberculosis H37Rv whole genome sequence is inaccurate regarding this region. Our results show that this antigen-encoding region of the M. tuberculosis genome is hypervariable. The observation that numerous different mutations have become fixed within specific lineages demonstrates that this genomic region is undergoing rapid molecular evolution and that further lineage-specific evolutionary expansion and diversification has occurred subsequent to the lineage-defining mutational events. We predict that functional loss of these genes could aid immune evasion. Finally, we also show that the PPE38 region of the published M. tuberculosis H37Rv whole genome sequence is not representative of the ATCC H37Rv reference strain.


Policies on Conflicts of Interest in Health Care Guideline Development: A Cross-Sectional Analysis.
To assess whether organisations that develop health care guidelines have conflict of interest (COI) policies and to review the content of the available COI policies. Survey and content analysis of COI policies available in English, French, Spanish, and Italian conducted between September 2014 and June 2015. A 24-item data abstraction instrument was created on the basis of guideline development standards. The survey identified 29 organisations from 19 countries that met the inclusion criteria. From these organisations, 19 policies were eligible for inclusion in the content analysis. Over one-third of the policies (7/19, 37%) did not report or did not clearly report whether disclosure was a prerequisite for membership of the guideline panel. Strategies for the prevention of COI such as divestment were mentioned by only two organisations. Only 21% of policies (4/19) used criteria to determine whether an interest constitutes a COI and to assess the severity of the risk imposed. The finding that some organisations, in contradiction of widely available standards, still do not have COI policies publicly available is concerning. Also troubling were the findings that some policies did not clearly report critical steps in obtaining, managing and communicating disclosure of relationships of interest. This in addition to the variability encountered in content and accessibility of COI policies may cause confusion and distrust among guideline users. It is in the interest of guideline users and developers to design an agreed-upon, comprehensive, clear, and accessible COI policy.


Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium.
Magnesium deficiency and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. The link between these two factors is unclear in humans although, in experimental animals, severe Mg deficiency has been shown to lead to increased oxidative stress. The relationship between Mg body stores, dietary intakes and supplements on the one hand and parameters of the oxidant-antioxidant balance on the other was investigated in human subjects. The study population consisted of 93 patients with unexplained chronic fatigue (median age 38 years, 25% male, 16% smokers and 54% with Chronic Fatigue Syndrome (CFS). Mg deficient patients (47%) had lower total antioxidant capacity in plasma (p=0.007) which was related to serum albumin. Mg deficient patients whose Mg body stores did not improve after oral supplementation with Mg (10 mg/kg/day) had persistently lower blood glutathione levels (p=0.003). In vitro production of thiobarbituric acid reactive substances (TBARS) by non-HDL lipoproteins incubated with copper was related to serum cholesterol (p<0.001) but not to Mg or antioxidants and did not improve after Mg supplementation. In contrast, velocity of formation of fluorescent products of peroxidation (slope) correlated with serum vitamin E (p<0.001), which was, in turn, related to Mg dietary intakes. Both slope and serum vitamin E improved after Mg supplementation (p<0.001). These results show that the lower antioxidant capacity found in moderate Mg deficiency was not due to a deficit in Mg dietary intakes and was not accompanied by increased lipid susceptibility to in vitro peroxidation. Nevertheless, Mg supplementation was followed by an improvement in Mg body stores, in serum vitamin E and its interrelated stage of lipid peroxidation.


[Reflex responses of human perioral muscles to mechanical stimulation of the vestibular oris mucosa].
To investigate the effects on perioral muscles with mechanical stimulation to the mucosa electromyograms were recorded in nine subjects. Results were as follows: 1. Tonic excitatory reflex of m. orbicularis oris and m. mentalis was evoked by the non-painful pressure stimulation to lower lip mucosa. These responses were increased, as the stimulus strength was increased. 2. Reflex responses to stimulation of the corner of the mouth and lower lip mucosa were greater than that of buccal mucosa. The response in m. orbicularis oris superior (O.O.S.) to stimulation of upper lip mucosa was greater than in m. orbicularis oris inferior (O.O.I.). And the response in O.O.I. to stimulation of lower lip mucosa was greater than the response in O.O.S. 3. Tonic excitatory reflex was abolished after local anesthesia of the stimulation area. 4. Excitatory reflex was reversed to inhibitory reflex, when background activity of three muscles was changed by voluntary lip closure. When background activity was weak, excitatory reflex was induced by pressure stimulation. On the contrary, when background activity was strong, inhibitory reflex was induced by the same stimulation. When background activity was moderate, excitatory reflex in O.O.I. and inhibitory one in O.O.S. was easily induced by lower lip stimulation. On the other hand, by upper stimulation, excitatory reflex in O.O.S. and inhibitory one in O.O.I. was easily induced. These results suggest that the orthodontic appliance placed on the vestibular oris gives mechanical stimulation to oral mucosa, which induce reflex contraction in perioral muscles.


NUAK2 Amplification Coupled with PTEN Deficiency Promotes Melanoma Development via CDK Activation.
The AMPK-related kinase NUAK2 has been implicated in melanoma growth and survival outcomes, but its therapeutic utility has yet to be confirmed. In this study, we show how its genetic amplification in PTEN-deficient melanomas may rationalize the use of CDK2 inhibitors as a therapeutic strategy. Analysis of array-CGH data revealed that PTEN deficiency is coupled tightly with genomic amplification encompassing the NUAK2 locus, a finding strengthened by immunohistochemical evidence that phospho-Akt overexpression was correlated with NUAK2 expression in clinical specimens of acral melanoma. Functional studies in melanoma cells showed that inactivation of the PI3K pathway upregulated p21 expression and reduced the number of cells in S phase. NUAK2 silencing and inactivation of the PI3K pathway efficiently controlled CDK2 expression, whereas CDK2 inactivation specifically abrogated the growth of NUAK2-amplified and PTEN-deficient melanoma cells. Immunohistochemical analyses confirmed an association of CDK2 expression with NUAK2 amplification and p-Akt expression in melanomas. Finally, pharmacologic inhibition of CDK2 was sufficient to suppress the growth of NUAK2-amplified and PTEN-deficient melanoma cells in vitro and in vivo. Overall, our results show how CDK2 blockade may offer a promising therapy for genetically defined melanomas, where NUAK2 is amplified and PTEN is deleted.


Nudicauline and elatine as potent norditerpenoid ligands at rat neuronal alpha-bungarotoxin binding sites: importance of the 2-(methylsuccinimido)benzoyl moiety for neuronal nicotinic acetylcholine receptor binding.
Methyllycaconitine (MLA, 1) is a novel, potent probe for mammalian and insect nicotinic acetylcholine receptors (nAChR) and displays remarkable selectivity toward neuronal [125I]-alpha-bungarotoxin (alpha BgTX) binding sites that correspond to alpha 7-type nAChR in mammalian brain. We have shown that, among a number of selected norditerpenoid alkaloids, elatine (2) and nudicauline (3) are equipotent with, or better than, MLA (1) in binding to brain [125I]-alpha BgTX binding sites, with IC50 values of 6.1, 1.7, and 7.6 nM, respectively. The 2-((S)-methylsuccinimido)benzoyl moiety of these ligands is crucial for high-affinity binding, whereas structural modifications to the norditerpenoid core of the ligand can be tolerated without loss of activity or selectivity. In addition to MLA (1), elatine (2), and nudicauline (3), we have examined lycoctonine (4), inuline (6), lappaconitine (7), N-desacetyllappaconitine (8), delsoline (10), delcorine (11), deltaline (12), condelphine (13), and karacoline (14). This study therefore extends the range of norditerpenoids, other than MLA, which can be used to probe this important class of nAChR. All 12 alkaloids were assessed for activity at [3H]nicotine binding sites which are considered to represent alpha 4 beta 2 nAChR. Furthermore, the 1H and 13C NMR spectroscopic data of MLA and elatine have been critically compared.


Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins.
To determine the involvement of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in cytoprotection, we subjected N2-A cells to oxygen-glucose deprivation followed by reoxygenation (H-R). Following H-R insults, H(2)O(2) production was increased while cell viability declined, which was accompanied by loss of mitochondrial membrane potential (MMP), cytochrome c release, caspases 9 and 3 activation, poly(ADP-ribose)polymerase (PARP) cleavage and apoptosis. Rosiglitazone up to 5 microM protected cell viability, normalized MMP, and prevented apoptotic signals. The protective effect of rosiglitazone was abrogated by GW9662, a PPAR-gamma antagonist, or a specific PPAR-gamma small interference RNA (siRNA) but not a control scRNA. PPAR-gamma overexpression alone was effective in maintaining MMP and preventing apoptosis and its protective effect was also abrogated by PPAR-gamma siRNA or GW9662. To elucidate the mechanism by which PPAR-gamma protects MMP and prevents apoptosis, we analyzed Bcl-2, Bcl-xl, and phosphorylated Bad (p-Bad). H-R suppressed them. Rosiglitazone or PPAR-gamma overexpression restored them via PPAR-gamma. Rosiglitazone or PPAR-gamma overexpression preserved phosphorylated Akt and 3-phosphoinositide-dependent kinase-1 (PDK-1) in a PPAR-gamma dependent manner. These results indicate that ligand-activated PPAR-gamma protects N2-A cells against H-R damage by enhancing Bcl-2/Bcl-xl and maintaining p-Bad via preservation of p-Akt.


Prospective, randomized, multicenter study of cervical arthroplasty: 269 patients from the Kineflex|C artificial disc investigational device exemption study with a minimum 2-year follow-up: clinical article.
Cervical total disc replacement (CTDR) represents a relatively novel procedure intended to address some of the shortcomings associated with anterior cervical discectomy and fusion (ACDF) by preserving motion at the treated level. This prospective, randomized, multicenter study evaluates the safety and efficacy of a new metal-on-metal CTDR implant (Kineflex|C) by comparing it with ACDF in the treatment of single-level spondylosis with radiculopathy. The study was a prospective, randomized US FDA Investigational Device Exemption (IDE) pivotal trial conducted at 21 centers across the US. The primary clinical outcome measures included the Neck Disability Index (NDI), visual analog scale (VAS) scores, and a composite measure of clinical success. Patients were randomized to CTDR using the Kineflex|C (SpinalMotion, Inc.) cervical artificial disc or ACDF using structural allograft and an anterior plate. A total of 269 patients were enrolled and randomly assigned to either CTDR (136 patients) or to ACDF (133 patients). There were no significant differences between the CTDR and ACDF groups when comparing operative time, blood loss, length of hospital stay, or the reoperation rate at the index level. The overall success rate was significantly greater in the CTDR group (85%) compared with the ACDF group (71%) (p = 0.05). In both groups, the mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the 24-month follow-up (p < 0.0001). Similarly, the VAS pain scores improved significantly by 6 weeks and remained significantly improved through the 24-month follow-up (p < 0.0001). The range of motion (ROM) in the CTDR group decreased at 3 months but was significantly greater than the preoperative mean at 12- and 24-month follow-up. The ROM in the ACDF group was significantly reduced by 3 months and remained so throughout the follow-up. Adjacent-level degeneration was also evaluated in both groups from preoperatively to 2-year follow-up and was classified as none, mild, moderate, or severe. Preoperatively, there were no significant differences between groups when evaluating the different levels of adjacent-level degeneration. At the 2-year follow-up, there were significantly more patients in the ACDF group with severe adjacent-level radiographic changes (p < 0.0001). However, there were no significant differences between groups in adjacent-level reoperation rate (7.6% for the Kineflex|C group and 6.1% for the ACDF group). Cervical total disc replacement allows for neural decompression and clinical results comparable to ACDF. Kineflex|C was associated with a significantly greater overall success rate than fusion while maintaining motion at the index level. Furthermore, there were significantly fewer Kineflex|C patients showing severe adjacent-level radiographic changes at the 2-year follow-up. These results from a prospective, randomized study support that Kineflex|C CTDR is a viable alternative to ACDF in select patients with cervical radiculopathy.


Predictors of mental health problems in formal and informal caregivers of patients with Alzheimer's disease.
Caring for a person with Alzheimer's disease (AD) is associated with significant mental burden e.g., depression and anxiety, and difficulties with social, familial, and professional functioning. To date, few studies have examined variables which would allow for a comprehensive and detailed study of the relationship between personal resources and caregiver health status, with a majority of studies focusing on factors that contribute to increased caregiver's burden. Moreover, the available evidence fails to address differences in the functioning of formal and informal carers. Paying proper attention to the problems of nursing home staff can help identify important risk factors. Therefore, this study compared mental health problems in informal and formal caregivers and examined the relationship between mental resources and mental health problems in both groups of caregivers. This cross-sectional study examined 100 formal (n = 50) and informal (n = 50) caregivers of AD patients. Personal resources were measured with the Social Support Questionnaire (SSQ), the Generalized Self-Efficacy Scale (GSES), and the Sense of Coherence Questionnaire (SCQ), while mental health was assessed with the Depression Assessment Questionnaire (DAQ) and the General Health Questionnaire (GHQ). Multivariate stepwise regression was performed separately for both investigated groups. There were no significant differences between informal and formal caregivers in terms of psychological variables, i.e., sense of coherence, social support, self-efficacy, or mental health problems. In contrast, there were different significant predictors of mental health problems in both groups. Comprehensibility (SCQ) was a significant predictor of mental health problems measured by DAQ and self-efficacy (GSES) was a significant predictor of mental health problems measured by GHQ in informal caregivers. For formal caregivers, emotional support (SSQ) and comprehensibility (SCQ) were significant predictors of mental health problems measured by DAQ, while tangible support (SSQ) and meaningfulness (SCQ) were significant predictors of mental health problems measured by GHQ. Personal resources are significant predictors of mental health outcomes in caregivers of AD patients. Preventive actions should therefore include assessment of factors affecting caregivers' mental health in order to provide them with necessary care and create appropriate support groups.


Improvement of photon correlation spectroscopy method for measuring nanoparticle size by using attenuated total reflectance.
Photon correlation spectroscopy is an effective method for measuring nanoparticle sizes and has several advantages over alternative methods. However, this method suffers from a disadvantage in that its measuring accuracy reduces in the presence of convective flows of fluid containing nanoparticles. In this paper, we propose a scheme based on attenuated total reflectance in order to reduce the influence of convection currents. The autocorrelation function for the light-scattering intensity was found for this case, and it was shown that this method afforded a significant decrease in the time required to measure the particle sizes and an increase in the measuring accuracy.


Adequacy of nutrient intakes in elite junior basketball players.
The aim of this study was to assess the nutrient intakes of elite junior basketball players in comparison with nonathletes. A previously designed food frequency questionnaire was undertaken by 57 male elite junior basketball players 15 to 16 years of age and 53 nonathlete peers. Mean estimated energy intake was more than 700 kcal higher in basketball players than in the nonathletes (p = .002). In both groups estimated energy intake was ~14% from protein, 38% from fat, and ~48% from carbohydrates. For the basketball players, estimated protein intake was below 1.4 g/kg in 32% of the group and above 1.7 g/ kg in 51%, while carbohydrate intake was below 6 g/kg in 56%. Percentages of participants who apparently failed to meet the estimated average requirement for micronutrients were higher in the nonathlete group. The nutrients most likely to fail to meet the recommendations for nutrient density were vitamin A (~70%), zinc (49% in basketball players and 30% in nonathletes), niacin and calcium (~30% for both micronutrients in both groups). Within the limitations of the survey methodology, elite junior basketball players appear to consume higher absolute energy, macronutrient and micronutrient intakes than nonathletes, but the contribution of macronutrients to daily energy intake and the nutrient density of food choices was similar for both groups. Elite junior basketball players might benefit from nutrition education targeting carbohydrate and protein intake. Dietary modifications that increase intakes of vitamin A, zinc, calcium and niacin in the diets of both groups might also be of value.


Attenuation of some alcohol-induced mood changes and the desire to drink by 5-HT3 receptor blockade: a preliminary study in healthy male volunteers.
We studied the effect of the 5-HT3 receptor antagonist ondansetron (4 mg orally) on some of the psychological effects of a small dose of alcohol (580 ml of 3.6% alcohol content by volume of lager) in 16 healthy male volunteers using a double-blind placebo controlled, Latin Square cross-over design. Pretreatment with ondansetron significantly attenuated several of the subjective pleasurable effects of alcohol, and also decreased the subjective desire to drink. These findings are consistent with preclinical studies suggesting that the reinforcing properties of alcohol may be attenuated by 5-HT3 receptor blockade.


Complete genome of a metabolically-diverse marine bacterium Shewanella japonica KCTC 22435T.
Shewanella japonica KCTC 22435T is a facultatively anaerobic, Gram-negative, mesophilic, rod-shaped bacterium isolated from sea water at the Pacific Institute of Bio-organic Chemistry of the Marine Experimental Station, Troitza Bay, Gulf of Peter the Great, Russia. Here, we report the complete genome of S. japonica KCTC 22435T, which consists of 4,975,677bp (G+C content of 40.80%) with a single chromosome, 4036 protein-coding genes, 97 tRNAs and 8 rRNA operons. Genes detected in the genome reveal that the strain possesses a type II secretion system, cytochrome c family proteins with various numbers of heme-binding motifs, and metabolic pathways for utilizing diverse carbon sources, supporting the potential of KCTC 22435T to generate electricity in salinity culture conditions.


A meta-analysis of robotic vs. conventional mitral valve surgery.
The present study is the first meta-analysis to compare the surgical outcomes of robotic vs. conventional mitral valve surgery in patients with degenerative mitral valve disease. A systematic review of the literature was conducted to identify all relevant studies with comparative data on robotic vs. conventional mitral valve surgery. Predefined primary endpoints included mortality, stroke and reoperation for bleeding. Secondary endpoints included cross-clamp time, cardiopulmonary bypass time, length of hospitalization and duration of intensive care unit (ICU) stay. Echocardiographic outcomes were assessed when possible. Six relevant retrospective studies with comparative data for robotic vs. conventional mitral valve surgery were identified from the existing literature. Meta-analysis demonstrated a superior perioperative survival outcome for patients who underwent robotic surgery. Incidences of stroke and reoperation were not statistically different between the two treatment arms. Patients who underwent robotic surgery required a significantly longer period of cardiopulmonary bypass time and cross-clamp time. However, the lengths of hospitalization and ICU stay were not significantly different. Both surgical techniques appeared to achieve satisfactory echocardiographic outcomes in the majority of patients. Current evidence on comparative outcomes of robotic vs. conventional mitral surgery is limited, and results of the present meta-analysis should be interpreted with caution due to differing patient characteristics. However, it has been demonstrated that robotic mitral valve surgery can be safely performed by expert surgeons for selected patients. A successful robotic program is dependent on a specially trained team and a sufficient volume of referrals to attain and maintain safety.


In vivo imaging in cancer.
Imaging has become an indispensable tool in the study of cancer biology and in clinical prognosis and treatment. The rapid advances in high resolution fluorescent imaging at single cell level and MR/PET/CT image registration, combined with new molecular probes of cell types and metabolic states, will allow the physical scales imaged by each to be bridged. This holds the promise of translation of basic science insights at the single cell level to clinical application. In this article, we describe the recent advances in imaging at the macro- and micro-scale and how these advances are synergistic with new imaging agents, reporters, and labeling schemes. Examples of new insights derived from the different scales of imaging and relevant probes are discussed in the context of cancer progression and metastasis.


Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta-analysis.
Novel endoscopic technologies could allow optical diagnosis and resection of colonic polyps without histopathological testing. Our aim was to establish the sensitivity, specificity, and real-time negative predictive value of three types of narrowed spectrum endoscopy (narrow-band imaging [NBI], image-enhanced endoscopy [i-scan], and Fujinon intelligent chromoendoscopy [FICE]), confocal laser endomicroscopy (CLE), and autofluorescence imaging for differentiation between neoplastic and non-neoplastic colonic lesions. We identified relevant studies through a search of Medline, Embase, PubMed, and the Cochrane Library. Clinical trials and observational studies were eligible for inclusion when the diagnostic performance of NBI, i-scan, FICE, autofluorescence imaging, or CLE had been assessed for differentiation, with histopathology as the reference standard, and for which a 2 × 2 contingency table of lesion diagnosis could be constructed. We did a random-effects bivariate meta-analysis using a non-linear mixed model approach to calculate summary estimates of sensitivity and specificity, and plotted estimates in a summary receiver-operating characteristic curve. We included 91 studies in our analysis: 56 were of NBI, ten of i-scan, 14 of FICE, 11 of CLE, and 11 of autofluorescence imaging (more than one of the investigated modalities assessed in eight studies). For NBI, overall sensitivity was 91·0% (95% CI 88·6-93·0), specificity 85·6% (81·3-89·0), and real-time negative predictive value 82·5% (75·4-87·9). For i-scan, overall sensitivity was 89·3% (83·3-93·3), specificity 88·2% (80·3-93·2), and real-time negative predictive value 86·5% (78·0-92·1). For FICE, overall sensitivity was 91·8% (87·1-94·9), specificity 83·5% (77·2-88·3), and real-time negative predictive value 83·7% (77·5-88·4). For autofluorescence imaging, overall sensitivity was 86·7% (79·5-91·6), specificity 65·9% (50·9-78·2), and real-time negative predictive value 81·5% (54·0-94·3). For CLE, overall sensitivity was 93·3% (88·4-96·2), specificity 89·9% (81·8-94·6), and real-time negative predictive value 94·8% (86·6-98·1). All endoscopic imaging techniques other than autofluorescence imaging could be used by appropriately trained endoscopists to make a reliable optical diagnosis for colonic lesions in daily practice. Further research should be focused on whether training could help to improve negative predictive values. None.


Impact of electron-beam lithography irregularities across millimeter-scale resonant grating filter performances.
We investigated the impact of electron-beam lithography writing imperfections on the performance of two-dimensional resonant grating notch filters. This large area photonic device provides an interesting benchmark to assess the acceptable limits of unavoidable fabrication errors. We found that field stitching errors up to 100 nm have no detrimental effect on the filter linewidth, whereas a 2.5 nm electron-beam writing resolution, responsible for digitization disorder, is tolerable only for high-index contrast filter designs. Such an electron-beam writing strategy could also be beneficial for photonic crystal guiding structures or any periodic nanopatterned device with which the optical mode interacts with a large number of periodic elementary units.


Controlling interfacial film formation in mixed polymer-surfactant systems by changing the vapor phase.
Here we show that transport-generated phase separation at the air-liquid interface in systems containing self-assembling amphiphilic molecules and polymers can be controlled by the relative humidity (RH) of the air. We also show that our observations can be described quantitatively with a theoretical model describing interfacial phase separation in a water gradient that we published previously. These phenomena arises from the fact that the water chemical potential corresponding to the ambient RH will, in general, not match the water chemical potential in the open aqueous solution. This implies nonequilibrium conditions at the air-water interface, which in turn can have consequences on the molecular organization in this layer. The experimental setup is such that we can control the boundary conditions in RH and thereby verify the predictions from the theoretical model. The polymer-surfactant systems studied here are composed of polyethylenimine (PEI) and hexadecyltrimethylammonium bromide (CTAB) or didecyldimethylammonium bromide (DDAB). Grazing-incidence small-angle X-ray scattering results show that interfacial phases with hexagonal or lamellar structure form at the interface of dilute polymer-surfactant micellar solutions. From spectroscopic ellipsometry data we conclude that variations in RH can be used to control the growth of micrometer-thick interfacial films and that reducing RH leads to thicker films. For the CTAB-PEI system, we compare the phase behavior of the interfacial phase to the equilibrium bulk phase behavior. The interfacial film resembles the bulk phases formed at high surfactant to polymer ratio and reduced water contents, and this can be used to predict the composition of interfacial phase. We also show that convection in the vapor phase strongly reduces film formation, likely due to reduction of the unstirred layer, where diffusive transport is dominating.


Cardio-metabolic and immunological impacts of extra virgin olive oil consumption in overweight and obese older adults: a randomized controlled trial.
Both aging and obesity are related to dysregulated immune function, which may be responsible for increased risk of infection and also chronic non-infectious diseases. Dietary lipids have been shown to impact immune and inflammatory responses and cardio-metabolic risk factors. No information on the impact of olive oil on immune responses of overweight and obese older adults is available. We aimed to determine the effect of replacing oils used in a typical American diet with extra virgin olive oil for 3 months on immune responses and cardio-metabolic risk factors in overweight and obese older adults. This was a randomized, single-blinded and placebo-controlled trial in 41 overweight or obese participants (aged ≥ 65) who consumed a typical American diet. Participants in the control (CON, n = 21) group were provided with a mixture of corn, soybean oil and butter, and those in the olive oil (OO, n = 20) group, with extra virgin olive oil, to replace substitutable oils in their diet. At baseline and 3 months, we measured blood pressure, biochemical and immunological parameters using fasting blood, and delayed-type hypersensitivity (DTH) skin response. Compared to the CON group, the OO group showed decreased systolic blood pressure (P < 0.05), a strong trend toward increased plasma HDL-C concentrations (P = 0.06), and increased anti-CD3/anti-CD28 -stimulated T cell proliferation (P < 0.05). No differences were found in T cell phenotype, cytokine production, and DTH response between the two groups. Our results indicate that substitution of oils used in a typical American diet with extra virgin olive oil in overweight and obese older adults may have cardio-metabolic and immunological health benefits. This trial was registered at clinicaltrials.gov as NCT01903304.


A simple method for in-field sex determination of the multicolored Asian lady beetle Harmonia axyridis.
The multicolored Asian lady beetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), has become a popular study organism due to its promise as a biological control agent and its potential adverse, non-target impacts. Behavioral and ecological research on H. axyridis, including examinations of its impacts, could benefit from non-destructive or non-disruptive sexing techniques for this coccinellid. External morphological characters were evaluated for H. axyridis (succinea color form) sex determination in laboratory and field studies. The shape of the distal margin of the fifth visible abdominal sternite accurately predicted H. axyridis sex for all beetles examined. Males consistently had a concave distal margin, while females had a convex distal margin. In addition, pigmentation of the labrum and prosternum were both significantly associated with H. axyridis sex; males had light pigmentation and females had dark pigmentation. Labrum and prosternum pigmentation increased from light to dark with decreasing rearing temperature and increasing time after adult eclosion for females. Male pigmentation was only affected by a decrease in rearing temperature. Validation through in-field collections indicated that these predictors were accurate. However, labrum pigmentation is a more desirable character to use to determine sex, because it is more accurate and easily accessible. Therefore, we recommend using labrum pigmentation for in-field sex determination of H. axyridis. Implications of this diagnostic technique for applied and basic research on this natural enemy are discussed.


Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer.
Protein hydroxylation affects protein stability, activity, and interactome, therefore contributing to various diseases including cancers. However, the transiency of the hydroxylation reaction hinders the identification of hydroxylase substrates. By developing an enzyme-substrate trapping strategy coupled with TAP-TAG or orthogonal GST- purification followed by mass spectrometry, we identify adenylosuccinate lyase (ADSL) as an EglN2 hydroxylase substrate in triple negative breast cancer (TNBC). ADSL expression is higher in TNBC than other breast cancer subtypes or normal breast tissues. ADSL knockout impairs TNBC cell proliferation and invasiveness in vitro and in vivo. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. Hydroxylation-proficient ADSL, by affecting adenosine levels, represses the expression of the long non-coding RNA MIR22HG, thus upregulating cMYC protein level. Our findings highlight the role of ADSL hydroxylation in controlling cMYC and TNBC tumorigenesis.


Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger.
The mechanism of the enhanced vascular permeability and retention (EPR) effect seen in solid tumors was investigated with sarcoma 180 (S-180) in mice by using the bradykinin receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin] (HOE 140), the nitric oxide (NO) scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), and the cyclooxygenase (prostaglandin synthase) inhibitor indomethacin. In the S-180 solid tumor model, administration of HOE 140 (0.65 or 1.3 microg/kg/8 h, s.c.), PTIO (167 mg/kg/2 h, four times/8 h, i.p.), or indomethacin (5 or 10 mg/kg/day, three times, i.p.) significantly suppressed the EPR effect in the tumor, and the combined administration of these agents achieved a stronger inhibition of the EPR effect than did each compound alone. Indomethacin (10 mg/kg/day, three times) plus PTIO (167 mg/kg/2 h, four times) given i.p. had the greatest inhibition (70%) on the EPR effect. When HOE 140 was administered s.c. at a dose of 13 microg/kg/12 h for 2 weeks after tumor inoculation, growth of the solid tumor was also suppressed by 32%, by tumor weight. In the ascitic form of S-180, i.p. administration of HOE 140 at 13 microg/kg/12 h initiated immediately after tumor inoculation significantly suppressed formation of S-180 tumor ascites; the life span of ascitic S-180 tumor-bearing mice was prolonged at the same dose of HOE 140. The expression of inducible NO synthase mRNA and of cyclooxygenase 2 mRNA in S-180 tumor tissue was highly elevated, as evidenced by Northern blotting and reverse transcription-PCR and by Southern blot analyses. These results indicate that bradykinin, NO, and prostaglandins play an important role in enhanced vascular permeability in tumor tissue and sustain tumor growth. More importantly, bradykinin antagonists such as HOE 140 may be beneficial for the inhibition of tumor growth.


Computed Tomography Assessment of Anatomic Graft Placement After ACL Reconstruction: A Comparative Study of Grid and Angle Measurements.
The anatomic placement of anterior cruciate ligament (ACL) grafts is often assessed with postoperative imaging. In clinical practice, graft angles are measured to indicate anatomic placement on magnetic resonance imaging, whereas grid measurements are performed on computed tomography (CT). Recently, a study indicated that graft angle measurements could also be assessed on CT. No consensus has yet been reached on which measurement method is best suited to assess anatomic graft placement. To compare the ability of grid measurements and angle measurements to identify anatomic versus nonanatomic tunnel placement on CT performed in patients undergoing ACL reconstruction. Case series; Level of evidence, 4. A total of 100 knees undergoing primary reconstruction with a hamstring graft (HAM group), 91 undergoing reconstruction with a bone-patellar tendon-bone graft (BPTB group), and 117 undergoing revision ACL reconstruction (REV group) were assessed with CT. Grid measurements of the femoral and tibial tunnels and angle measurements of grafts were performed. Graft placement, rated as anatomic or nonanatomic, was assessed with both methods. Pearson chi-square, analysis of variance, Kruskal-Wallis, and weighted kappa tests were performed as appropriate. The grid assessment classified 10% of the HAM group, 4% of the BPTB group, and 17% of the REV group as nonanatomic (P < .001). The angle assessment classified 37% of the HAM group, 54% of the BPTB group, and 47% of the REV group as nonanatomic. The weighted kappa between angle measurements and grid measurements was low in all groups (HAM: 0.009; BPTB: 0.065; REV: 0.041). The agreement between grid measurements and angle measurements was very low. The angle measurements seemed to overestimate nonanatomic tunnel placement. Grid measurements were better in identifying malpositioned grafts.


A conserved RNA structural motif for organizing topology within picornaviral internal ribosome entry sites.
Picornaviral IRES elements are essential for initiating the cap-independent viral translation. However, three-dimensional structures of these elements remain elusive. Here, we report a 2.84-Å resolution crystal structure of hepatitis A virus IRES domain V (dV) in complex with a synthetic antibody fragment-a crystallization chaperone. The RNA adopts a three-way junction structure, topologically organized by an adenine-rich stem-loop motif. Despite no obvious sequence homology, the dV architecture shows a striking similarity to a circularly permuted form of encephalomyocarditis virus J-K domain, suggesting a conserved strategy for organizing the domain architecture. Recurrence of the motif led us to use homology modeling tools to compute a 3-dimensional structure of the corresponding domain of foot-and-mouth disease virus, revealing an analogous domain organizing motif. The topological conservation observed among these IRESs and other viral domains implicates a structured three-way junction as an architectural scaffold to pre-organize helical domains for recruiting the translation initiation machinery.


CB1 receptor blockade counters age-induced insulin resistance and metabolic dysfunction.
The endocannabinoid system can modulate energy homeostasis by regulating feeding behaviour as well as peripheral energy storage and utilization. Importantly, many of its metabolic actions are mediated through the cannabinoid type 1 receptor (CB1R), whose hyperactivation is associated with obesity and impaired metabolic function. Herein, we explored the effects of administering rimonabant, a selective CB1R inverse agonist, upon key metabolic parameters in young (4 month old) and aged (17 month old) adult male C57BL/6 mice. Daily treatment with rimonabant for 14 days transiently reduced food intake in young and aged mice; however, the anorectic response was more profound in aged animals, coinciding with a substantive loss in body fat mass. Notably, reduced insulin sensitivity in aged skeletal muscle and liver concurred with increased CB1R mRNA abundance. Strikingly, rimonabant was shown to improve glucose tolerance and enhance skeletal muscle and liver insulin sensitivity in aged, but not young, adult mice. Moreover, rimonabant-mediated insulin sensitization in aged adipose tissue coincided with amelioration of low-grade inflammation and repressed lipogenic gene expression. Collectively, our findings indicate a key role for CB1R in aging-related insulin resistance and metabolic dysfunction and highlight CB1R blockade as a potential strategy for combating metabolic disorders associated with aging.


Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins.
The mitochondrial genome is a significant target of exogenous and endogenous genotoxic agents; however, the determinants that govern this susceptibility and the pathways available to resist mitochondrial DNA (mtDNA) damage are not well characterized. Here we report that oxidative mtDNA damage is elevated in strains lacking Ntg1p, providing the first direct functional evidence that this mitochondrion-localized, base excision repair enzyme functions to protect mtDNA. However, ntg1 null strains did not exhibit a mitochondrial respiration-deficient (petite) phenotype, suggesting that mtDNA damage is negotiated by the cooperative actions of multiple damage resistance pathways. Null mutations in ABF2 or PIF1, two genes implicated in mtDNA maintenance and recombination, exhibit a synthetic-petite phenotype in combination with ntg1 null mutations that is accompanied by enhanced mtDNA point mutagenesis in the corresponding double-mutant strains. This phenotype was partially rescued by malonic acid, indicating that reactive oxygen species generated by the electron transport chain contribute to mitochondrial dysfunction in abf2 Delta strains. In contrast, when two other genes involved in mtDNA recombination, CCE1 and NUC1, were inactivated a strong synthetic-petite phenotype was not observed, suggesting that the effects mediated by Abf2p and Pif1p are due to novel activities of these proteins other than recombination. These results document the existence of recombination-independent mechanisms in addition to base excision repair to cope with oxidative mtDNA damage in Saccharomyces cerevisiae. Such systems are likely relevant to those operating in human cells where mtDNA recombination is less prevalent, validating yeast as a model system in which to study these important issues.


Internet-based survey of nonmedical prescription opioid use in the United States.
Prescription opioid misuse is a growing problem in the United States. There are limited data to illuminate the nature of this issue. The Internet seems to be a novel approach in surveying populations of opioid users. An Internet-based survey of nonmedical opioid users visiting informational drug websites was used to measure rates of nonmedical use and characterize users. The prescription opioid module of the Addiction Severity Index Multimedia Version Connect was adapted to include variables such as favorite opioid. Links to the survey were posted on an informational drug website. Nonmedical use rates for KADIAN (morphine sulfate extended-release tablets), OxyContin (oxycodone HCl controlled-release tablets), Vicodin (hydrocodone bitartrate and acetaminophen tablets), and product-classes (morphine ER, oxycodone ER, and hydrocodone) were calculated. Descriptive statistics were calculated for remaining questions. During a 1-month recruitment period, 896 valid individuals completed the survey. Majority were white (78.3%) and male (72.4%). Participants were less likely to have used KADIAN in the past 30 days compared with OxyContin (P<0.0001) and Vicodin (P=0.0021). Additionally, participants were less likely to have used morphine ER in the previous 30 days than either oxycodone ER (P<0.0001) or hydrocodone (P<0.0001). Among OxyContin, Vicodin, and KADIAN users, OxyContin (43.8%), Dilaudid (15.6%), and fentanyl (9.4%) were the top 3 favorite opioids. This project demonstrates the feasibility of conducting product-specific, online surveys with rapid recruitment of participants from websites. This approach differentiates rates of nonmedical use of specific prescription opioids and provides other insights into individuals who nonmedically use opioids.


Coexistence of minicircular and a highly rearranged mtDNA molecule suggests that recombination shapes mitochondrial genome organization.
Recombination has been proposed as a possible mechanism to explain mitochondrial (mt) gene rearrangements, although the issue of whether mtDNA recombination occurs in animals has been controversial. In this study, we sequenced the entire mt genome of the megaspilid wasp Conostigmus sp., which possessed a highly rearranged mt genome. The sequence of the A+T-rich region contained a number of different types of repeats, similar to those reported previously in the nematode Meloidogyne javanica, in which recombination was discovered. In Conostigmus, we detected the end products of recombination: a range of minicircles. However, using isolated (cloned) fragments of the A+T-rich region, we established that some of these minicircles were found to be polymerase chain reaction (PCR) artifacts. It appears that regions with repeats are prone to PCR template switching or PCR jumping. Nevertheless, there is strong evidence that one minicircle is real, as amplification primers that straddle the putative breakpoint junction produce a single strong amplicon from genomic DNA but not from the cloned A+T-rich region. The results provide support for the direct link between recombination and mt gene rearrangement. Furthermore, we developed a model of recombination which is important for our understanding of mtDNA evolution.


Burkholderia sordidicola sp. nov., isolated from the white-rot fungus Phanerochaete sordida.
Two bacterial strains associated with the white-rot fungus Phanerochaete sordida were subjected to taxonomic investigation. The isolates, designated KCTC 12081(T) and KCTC 12082, were Gram-negative, non-motile, non-spore-forming and ovoid to rod-shaped. The strains contained major amounts of hexadecanoic acid, cyclo-heptadecanoic acid and omega-7-cis-octadecenoic acid in their cell envelopes. Strain KCTC 12081(T) contained ubiquinone-8 as the major isoprenoid quinone and the G+C content of its genomic DNA was 61.3 mol%. Morphological and chemotaxonomic properties of the strains were consistent with classification in the genus BURKHOLDERIA: In a comparison of 16S rDNA sequence, KCTC 12081(T) shared 100 % similarity with KCTC 12082 and both strains formed a distinct phylogenetic lineage within the genus BURKHOLDERIA: The two strains were also differentiated from other species of this genus by fatty acid composition and phenotypic properties. DNA-DNA relatedness data further supported the separation of the new isolates from closely related species. It is therefore proposed that strains KCTC 12081(T) (=JCM 11778(T)) and KCTC 12082 be recognized as a novel species, for which the name Burkholderia sordidicola sp. nov. is proposed.


Aerobic And Anaerobic Changes In Collegiate Male Runners Across A Cross-County Season.
The purpose of this study was to assess the physiological characteristics of trained NCAA Division III male runners across a competitive season of cross-country. Eight male distance runners (age 20.6±1.4 y) were administered a battery of aerobic and anaerobic laboratory tests at the beginning and end of an 8-10 week racing season. Aerobic testing included maximal oxygen uptake (VO2max), running economy (RE), ventilatory threshold (VT) and the onset of blood lactate accumulation (OBLA). Anaerobic testing consisted of the vertical jump (VJ) and the Wingate test. Final testing revealed anaerobic Wingate peak power significantly declined (11.8±1.1 to 10.7±1.0 W·kg-1) (P = 0.006), while no significant changes were seen in VJ or any aerobic parameters (P > 0.05). These results indicate that a competitive cross-country season of training and racing diminished anaerobic peak power and failed to elicit quantifiable aerobic adaptations in previously trained collegiate distance runners.


Celecoxib effectively inhibits the formation of joint adhesions.
The present study investigated the effectiveness of celecoxib in preventing the formation of joint adhesions. Rabbit models of joint adhesion were created and the rabbits in two treatment groups were orally administered celecoxib or ibuprofen (as a positive control) for 30 days. Rabbits in the control group did not receive any treatment. Following the 30-day experimental period, the inhibitory effects of celecoxib and ibuprofen on the formation of joint adhesion were assessed using a number of methods, including the study of macroscopic appearance, histology and contracture angle. Thick fibrous adhesions developed in the knees of the rabbits in the control group. By contrast, few adhesions were observed in the two treatment groups, and those observed were soft, weak and easily stretched. Fewer adhesions were observed in the rabbits treated with celecoxib than in the rabbits in the other groups. The adhesion scores and contracture angles in the celecoxib (P<0.001) and ibuprofen (0.001<P<0.0025) groups were significantly lower than those of the control group. Moreover, the adhesion scores and contracture angles were significantly lower in the celecoxib group than in the ibuprofen group (0.025<P<0.05). Histologically, the adhesion tissues in the two treatment groups, particularly in the celecoxib group, were loose and thin with sparse fiber formation. The cell densities in the two treatment groups, of which the ibuprofen group had higher cell densities (0.025<P<0.05), were significantly lower than those in the control group (celecoxib group, P<0.001; ibuprofen group, 0.001<P<0.0025). These results indicated that celecoxib effectively inhibited the formation of joint adhesions and therefore may provide a novel and potent approach for their prevention.


Fabrication and sensing behavior of one-dimensional ZnO-Zn2GeO4 heterostructures.
Well-crystalline one-dimensional ZnO-Zn2GeO4 (ZGO) heterostructures were successfully synthesized using a high-temperature solid-state reaction between the ZnO and Ge layers of ZnO-Ge core-shell nanostructures. The polycrystalline ZGO crystallites had a thickness in the range of 17 to 26 nm. The high-temperature solid-state reaction induced grooves and crystal defects on the surfaces of the ZGO crystallites. The sensors made from the ZnO-ZGO heterostructures exhibited a marked photocurrent response to UV light at room temperature and a gas sensing response to acetone gas at 325°C. The observed sensing properties are attributed to the rugged surface of the ZGO heterointerfaces between ZnO and ZGO, surface crystal defects of ZGO, and cross-linked contact regions of ZnO-ZGO.


Base sequence effects in bending induced by bulky carcinogen-DNA adducts: experimental and computational analysis.
The covalent binding of bulky mutagenic or carcinogenic compounds to DNA can lead to bending, which could significantly alter the interactions of DNA with critical replication and transcription proteins. The impact of adducts derived from the highly reactive bay region enantiomeric (+)- and (-)-anti-7,8-diol-9,10-epoxide derivatives of benzo[a]pyrene (BPDE) are of interest because the (+)-7R,8S,9S,10R-anti-BPDE enantiomer is highly tumorigenic in rodents, while the (-)-7S,8R,9R,10S-anti-BPDE enantiomer is not. Both (+)- and (-)-anti-BPDE bind covalently with DNA predominantly by trans addition at the exocyclic amino group of guanine to yield 10S (+)- and 10R (-)-trans-anti-[BP]-N(2)-dG adducts. We have synthesized a number of different oligonucleotides with single (+)- and (-)-trans-anti-[BP]-N(2)-dG adducts (G) in the base sequence context XG*Y, where X and Y are different DNA bases. The G* residues were positioned at or close to the center of 11 base pair ( approximately 1 helical turn) or 16 base pair ( approximately 1.5 turns) duplexes. All bases, except for X and Y and their partners, were identical. These sequences were self-ligated with T4 ligase to form multimers that yield a ladder of bands upon electrophoresis in native polyacrylamide gels. The extent of bending in each oligonucleotide was assessed by monitoring the decrease in gel mobilities of these linear, self-ligated oligomers, relative to unmodified oligonucleotides of the same base sequence. The extent of global bending was then estimated using a sequence-specific three-dimensional model from which the values of the base-pair step parameter roll adjacent to the lesion site could be extracted. We find that (+)-trans-anti-[BP]-N(2)-dG adducts are considerably more bent than the (-) isomers regardless of sequence and that A-T base pairs flanking the [BP]-N(2)-dG lesion site allow for local flexibility consistent with adduct conformational heterogeneity. Interestingly, the fit of computed versus observed gel mobilities using classical reptation treatments requires enhancement of unmodified DNA flexibility in gels, compared to aqueous salt solution. The differences in bending between the two stereoisomeric adduct duplexes and the observed base sequence context effects may play a significant role in the differential processing of these lesions by cellular replication, transcription, and repair enzymes.


Ultrasound imaging in psoriatic arthritis and ankylosing spondylitis.
Musculoskeletal ultrasound (US) is a reliable imaging technique which has a key role in the assessment of patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). US can help in the diagnosis of the disorder, in the evaluation of the extent of the joint and enthesis involvement and in therapy monitoring because it can reflect both morphostructural changes and inflammatory activity. Several studies have reported that US revealed pathological findings at joints and enthesis in a large number of PsA patients who do not complain of active pain and/or swelling at the time of the clinical examination and in psoriasis patients with no signs of musculoskeletal disease. The application of US in the evaluation of nail and skin involvement in patients affected by psoriasis, with or without arthritis, and the imaging of sacroiliac joints is an interesting approach. US has already become commonplace in both clinical and research fields, and improvements in US technology will offer further possibilities for future research.