A direct brain interface based on event-related potentials.
Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERP's. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.


Brown adipose tissue-derived metabolites and their role in regulating metabolism.
The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as "batokines", which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.


Revision total knee arthroplasty complication rates in Northern Illinois.
A paucity of population-based data exist which describe the rapid growth of revision total knee arthroplasties, changes in patient characteristics, or the association of hospital volume with complication rates. We analyzed whether inpatient complications for 2986 revision knee arthroplasties done on patients admitted to 63 hospitals in northern Illinois from 1993-1999 were correlated with volume of revision total knee arthroplasties. Coded complication rates for hospitals with less than seven, seven to 14, or greater than 14 annual procedures were compared using logistic regression to control for clinical and demographic characteristics of patients, hospital teaching status, and the proportion of the hospitals' patients discharged to rehabilitation facilities. Revision total knee arthroplasties increased 59%, and the overall complication rate declined from 9.3% during 1993-1996 to 7.3% during 1997-1999 (p = .04). When compared with the lowest volume hospitals, medium-volume hospitals had higher complication rates, whereas the highest volume hospitals were not significantly different. The absence of volume-outcome effects may be related to the relatively high volume of primary knee arthroplasties done at almost all area hospitals, surgeon group coverage across multiple hospitals, and the small annual number of revision total knee arthroplasties done during these years.


Mechanochemical regulation of oscillatory follicle cell dynamics in the developing Drosophila egg chamber.
During tissue elongation from stage 9 to stage 10 in Drosophila oogenesis, the egg chamber increases in length by ∼1.7-fold while increasing in volume by eightfold. During these stages, spontaneous oscillations in the contraction of cell basal surfaces develop in a subset of follicle cells. This patterned activity is required for elongation of the egg chamber; however, the mechanisms generating the spatiotemporal pattern have been unclear. Here we use a combination of quantitative modeling and experimental perturbation to show that mechanochemical interactions are sufficient to generate oscillations of myosin contractile activity in the observed spatiotemporal pattern. We propose that follicle cells in the epithelial layer contract against pressure in the expanding egg chamber. As tension in the epithelial layer increases, Rho kinase signaling activates myosin assembly and contraction. The activation process is cooperative, leading to a limit cycle in the myosin dynamics. Our model produces asynchronous oscillations in follicle cell area and myosin content, consistent with experimental observations. In addition, we test the prediction that removal of the basal lamina will increase the average oscillation period. The model demonstrates that in principle, mechanochemical interactions are sufficient to drive patterning and morphogenesis, independent of patterned gene expression.


Elasticity, fracture and thermoreversible gelation of highly filled physical gels.
We describe a physically associating triblock copolymer-based gel that exhibits a reversible transition between solid and liquid states at a temperature of approximately 55 degrees C. The thermal transition of the gel enables us to compare the properties of liquid suspensions and elastic composites with identical particle loadings, with particle volume fractions as large as 0.55. The suspension viscosity and the composite elasticity scale in a similar manner with the overall particle volume fraction, a result that is rationalized in terms of an effective strain amplification factor that depends only on the particle loading. Measured values of the strain amplification factor are in good agreement with the expected form for well-dispersed spheres. We also find that the elastic composites are exceptionally strong, with fracture strengths that exceed the modulus of the base gel by a factor of 100 or more. Deviations from purely elastic behavior became important for high particle volume fractions, and were probed by stress relaxation experiments.


Studies on the site of termination of static and dynamic fusimotor fibres within muscle spindles of the tenuissimus muscle of the cat.
1. The site of termination of static and dynamic fusimotor fibres has been mapped by finding which intrafusal muscle fibres have been depleted of glycogen as a result of tetanic stimulation of single gamma fibres. Long periods of stimulation coupled with occlusion of the blood supply were necessary to cause glycogen depletion.2. In cat tenuissimus muscle, dynamic gamma motor fibres always activated bag intrafusal muscle fibres, and occasionally chain fibres. Static gamma fibres always activated chain fibres and frequently activated bag fibres as well.3. It is argued that these results can be fitted into the hypothesis of the mechanism of internal functioning of the spindle originally proposed by Jansen & Matthews (1962). It is also pointed out that the results raise problems concerning the mechanism of development of the spindle motor innervation.


Open air carbon monoxide poisoning in a child swimming behind a boat.
Carbon monoxide (CO) poisoning is the most common fatal poisoning in the United States. The circumstances often involve an unsuspected increase of CO in an enclosed environment. Victims often are unaware that their activity or environment placed them at risk for CO poisoning. The possibility of open air CO poisonings was first reported in 1987. We present a case of open air CO poisoning resulting in neurologic depression and a markedly elevated carboxyhemoglobin level in a child who had been swimming behind a house boat. Emergency physicians and pediatricians should be aware of the possibility of accidental open air CO poisoning in children and adults who swim around recreational boats.


The role of transcutaneous electrical nerve stimulation in management of labour in obstetric patients.
The study evaluated the effect of transcutaneous electrical nerve stimulation (TENS) in the management of labour. It comprised of 125 subjects with 93 primiparae and 32 multiparae. They were divided into 3 groups. The first group received electrical stimulation from the TENS unit (TENS); the second group (placebo group) had the TENS machine connected but with no current from the TENS unit (TPL); whereas the third group had no machine application (control group). Analgesic requirements, pain assessment, labour duration, Obstetric outcome, and the comments from mother and midwife were analysed. No negative effects on the mothers and babies were reported. Neither was there any objective clinical significant differences demonstrated among the 3 groups.


Modeling accident frequencies as zero-altered probability processes: an empirical inquiry.
This paper presents an empirical inquiry into the applicability of zero-altered counting processes to roadway section accident frequencies. The intent of such a counting process is to distinguish sections of roadway that are truly safe (near zero-accident likelihood) from those that are unsafe but happen to have zero accidents observed during the period of observation (e.g. one year). Traditional applications of Poisson and negative binomial accident frequency models do not account for this distinction and thus can produce biased coefficient estimates because of the preponderance of zero-accident observations. Zero-altered probability processes such as the zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) distributions are examined and proposed for accident frequencies by roadway functional class and geographic location. The findings show that the ZIP structure models are promising and have great flexibility in uncovering processes affecting accident frequencies on roadway sections observed with zero accidents and those with observed accident occurrences. This flexibility allows highway engineers to better isolate design factors that contribute to accident occurrence and also provides additional insight into variables that determine the relative accident likelihoods of safe versus unsafe roadways. The generic nature of the models and the relatively good power of the Vuong specification test used in the non-nested hypotheses of model specifications offers roadway designers the potential to develop a global family of models for accident frequency prediction that can be embedded in a larger safety management system.


Quantum key distribution over a 72 dB channel loss using ultralow dark count superconducting single-photon detectors.
We report the first quantum key distribution (QKD) experiment over a 72 dB channel loss using superconducting nanowire single-photon detectors (SSPD, SNSPD) with the dark count rate (DCR) of 0.01 cps. The DCR of the SSPD, which is dominated by the blackbody radiation at room temperature, is blocked by introducing cold optical bandpass filter. We employ the differential phase shift QKD (DPS-QKD) scheme with a 1 GHz system clock rate. The quantum bit error rate (QBER) below 3% is achieved when the length of the dispersion shifted fiber (DSF) is 336 km (72 dB loss), which is low enough to generate secure keys.


Role of Dopants on the Local Electronic Structure of Polymeric Carbon Nitride Photocatalysts.
Polymeric carbon nitride (PCN) is a promising class of materials for solar-to-chemical energy conversion. The increase of the photocatalytic activity of PCN is often achieved by the incorporation of heteroatoms, whose impact on the electronic structure of PCN remains poorly explored. This work reveals that the local electronic structure of PCN is strongly altered by doping with sulfur and iron using X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS). From XAS at the carbon and nitrogen K-edges, sulfur atoms are found to mostly affect carbon atoms, in contrast to iron doping mostly altering nitrogen sites. In RIXS at the nitrogen K-edge, a vibrational progression, affected by iron doping, is evidenced, which is attributed to a vibronic coupling between excited electrons in nitrogen atoms and C-N stretching modes in PCN heterocycling rings. This work opens new perspectives for the characterization of vibronic coupling in polymeric photocatalysts.


Resident microbial communities inhibit growth and antibiotic-resistance evolution of Escherichia coli in human gut microbiome samples.
Countering the rise of antibiotic-resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g., via resource competition) but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonisation by focal E. coli but also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found resistance genes, including a highly effective resistance plasmid, in resident microbial communities. We identified physical constraints on plasmid transfer that can explain why our focal strain failed to acquire some of these beneficial resistance genes, and we found some chromosomal resistance mutations were only beneficial in the absence of the resident microbiota. This suggests, depending on in situ gene transfer dynamics, interactions with resident microbiota can inhibit antibiotic-resistance evolution of individual species.


What Is in the Salad? Escherichia coli and Antibiotic Resistance in Lettuce Irrigated with Various Water Sources in Ghana.
Safety of the environment in which vegetables are grown, marketed and consumed is paramount as most are eaten raw. Irrigation sources include open drains and streams, which are often contaminated with human and animal waste due to poor sanitation infrastructure. In irrigated vegetable farms using such sources in Ghana, we assessed Escherichia coli counts, antibiotic resistance patterns and resistant genes on irrigated lettuce. A cross-sectional study was conducted between January-May 2022, involving five major vegetable farms in Ghana. Escherichia coli was found in all 25 composite lettuce samples analyzed. Counts expressed in CFU/g ranged from 186 to 3000, with the highest counts found in lettuce irrigated from open drains (1670) and tap water using hose pipes (3000). Among all bacterial isolates, resistance ranged between 49% and 70% for the Watch group of antibiotics, 59% for the Reserved group and 82% were multidrug-resistant. Of 125 isolates, 60 (48%) were extended-spectrum beta-lactamase-producing, of which five (8%) had the blaTEM-resistant gene. Lettuce was contaminated with Escherichia coli with high levels of antibiotic resistance. We call on the Ghana Ministry of Food and Agriculture, Food and Drugs Authority and other stakeholders to support farmers to implement measures for improving vegetable safety.


Protective effect and duration of action of formoterol aerosol on exercise-induced asthma.
The short-term protective effect on exercise-induced asthma (EIA) and the duration of action of formoterol, given by metered dose aerosol at a dose of 24 micrograms, were compared with salbutamol (200 micrograms) and placebo in twelve asthmatic EIA-positive patients in a double-blind, placebo-controlled, three period cross-over study. On each treatment day the patients were given one of the drugs or placebo and two exercise tests were performed at the second and at the eighth hour after dosing. Using a standard procedure, exercise was performed by treadmill in well-controlled environmental conditions. In the first test at 2 h a significant difference relative to placebo (p less than 0.001) at each incremental time after exercise (i.e. 5, 10, 15, 20, 30 min) was obtained with both formoterol and salbutamol, without any significant difference between formoterol and salbutamol. After the eighth hour test formoterol still protected against EIA in comparison to both salbutamol and placebo. The effect of salbutamol at this time was not different from placebo. No adverse effects were reported in any treatment group. Formoterol has a long duration of action in protecting against EIA that persisted for eight hours, removing the need to dose with beta 2-agonist before every exercise.


Life-long echoes--a critical analysis of the developmental origins of adult disease model.
The hypothesis that there is a developmental component to subsequent adult disease initially arose from epidemiological findings relating birth size to either indices of disease risk or actual disease prevalence in later life. While components of the epidemiological analyses have been challenged, there is strong evidence that developmental factors contribute to the later risk of metabolic disease--including insulin resistance, obesity, and heart disease--as well as have a broader impact on osteoporosis, depression and schizophrenia. We suggest that disease risk is greater when there is a mismatch between the early developmental environment (i.e., the phase of developmental plasticity) versus that experienced in mature life (i.e., adulthood), and that nutritional influences are particularly important. It is also critical to distinguish between those factors acting during the developmental phase that disrupt development from those influences that are less extreme and act through regulated processes of epigenetic change. A model of the relationship between the developmental and mature environment is proposed and suggests interventional strategies that will vary in different population settings.


Wound-related pain: features, assessment and treatment.
This article explores the problem of wound-related pain. It provides an overview of the different types of pain associated with wounds, discusses approaches to pain assessment and considers a range of strategies that may be used to minimise wound-related pain.


A synopsis of the WPA Educational Program on Personality Disorders.
This article describes the headlines of the Educational Program on Personality Disorders produced by the WPA Section on Personality Disorders and the International Society on the Study of Personality Disorders. Lifelong personality traits serve as a substrate and a context for understanding more florid and distinct forms of psychopathology. Personality disorders affect at least 10% of the population, and the direct and indirect social costs associated with crime, substance abuse, increased need for medical care, family disruption, delayed recovery from clinical syndromes and medical diseases is substantial. Numerous theories, models and methods have been proposed to describe and to understand personality and its disorders: descriptive, statistical, psychoanalytic, evolutionary, neurobiologic. Classification has either taken a prototypical or a polythetic approach, but in recent years dimensional formats for classifying personalities have gained more interest. Personality pathology has a complex and variable character of interwoven developmental bio-psycho-social influences. A number of reliable instruments for assessment of personality and its disorders have emerged during the last three decades and a wide range of tailored psychotherapeutic techniques are now available. Personality disorders are treatable and remission is more likely than treatment resistance. Education is needed for all health professionals in psychiatric services. The full WPA program is available to be downloaded for free from WPA's website www.wpanet.org.


The denticulate ligament: anatomy and functional significance.
The authors conducted a study to examine the detailed anatomy of the denticulate ligaments and to assess their classic role in spinal cord stability within the spinal canal. Detailed observation of the denticulate ligaments in 12 adult cadavers was performed. Stress was applied in all major planes to discern when the ligaments would become taut, and at the same time, gross motion of the cord was observed at sites distal to the stresses applied. Tension necessary for avulsion of the ligaments in various areas of the spinal cord was also measured. These results show that the denticulate ligaments do not inhibit cord motion to such discrete areas of the cord as was once thought. The authors have determined that the ligaments are stronger in the cervical region and that they decrease in strength as the spinal cord descends. These findings are demonstrative of the denticulate ligaments being more resistant to caudal compared with cephalad stresses in the cord. Anterior and posterior motion is constrained by these ligaments but to a limited degree, especially as one descends inferiorly along the cord. Further embryological and functional studies of these ligaments is needed in non-formalin fixed tissues.


Soaking RNAi in Bombyx mori BmN4-SID1 cells arrests cell cycle progression.
RNA interference (RNAi) is an evolutionarily conserved mechanism for sequence-specific gene silencing. Previously, the BmN4-SID1 cell expressing Caenorhabditis ele gans SID-1 was established, in which soaking RNAi could induce effective gene silencing. To establish its utility, 6 cell cycle progression related cDNAs, CDK1, MYC, MYB, RNRS, CDT1, and GEMININ, were isolated from the silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), and their expressions were further silenced by soaking RNAi in the BmN4-SID1 cells. The cell cycle progression analysis using flow cytometer demonstrated that the small amount of double stranded RNA was enough to arrest cell cycle progression at the specific cell phases. These data suggest that RNAi in the BmN4-SID1 cells can be used as a powerful tool for loss-of-function analysis of B. mori genes.


Global patterns in human consumption of net primary production.
The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our own use. Net primary production--the net amount of solar energy converted to plant organic matter through photosynthesis--can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, energy flows within food webs and the provision of important ecosystem services. Here we present a global map showing the amount of net primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial balance sheet of net primary production 'supply' and 'demand' for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production 'imports' and suggest policy options for slowing future growth of human appropriation of net primary production.


DAA-mediated HCV cure reduces HIV DNA levels in HCV/HIV coinfected people.
Antiretroviral therapy (ART) for human immunodeficiency virus (HIV) can control virus replication and prolong the life of people living with HIV (PLWH). However, the virus remains dormant within immune cells in what is called the HIV reservoir. Furthermore, 2.3 million PLWH are also coinfected with hepatitis C virus (HCV) and are at risk of developing chronic liver disease and cancer. HCV treatment with direct acting antivirals (DAA) can completely cure the infection in more than 95% of treated individuals and improve their long-term health outcomes. In this study, we investigated how HCV treatment and cure affect the HIV reservoir. We demonstrate the beneficial impact of DAA treatment as it reduces the HIV reservoirs in particular in people infected with HCV before HIV. These results support the need for early ART and DAA treatment in HIV/HCV coinfections.


Meiosis in an asymmetric dikaryotic genome of Tremella fuciformis Tr01 facilitates new chromosome formation.
The dikaryotic stage dominates most of the life cycle in basidiomycetes, and each cell carries two different haploid nuclei. Accurate phasing of these two nuclear genomes and their interactions have long been of interest. We combine PacBio HiFi reads, Nanopore ultra-long reads, and Hi-C data to generate a complete, high-quality asymmetric dikaryotic genome of Tremella fuciformis Tr01, including Haplotypes A and B genomes. We assemble a meiotic haploid DBZ04 genome and detect three recombination events in these two haplotypes. We identify several chromosomal rearrangements that lead to differences in chromosome number, length, content, and sequence arrangement between these two haplotypes. Each nucleus contains a two-speed genome, harboring three accessory chromosomes and two accessory compartments that affect horizontal chromatin transfer between nuclei. We find few basidiospores are ejected from fruiting bodies of Tr01. Most monospore isolates sequenced belong to Tr01-Haplotype A genome architecture. More than one-third of monospore isolates carry one or two extra chromosomes including Chr12B and two new chromosomes ChrN1 and ChrN2. We hypothesize that homologous regions of seven sister chromatids pair into a large complex during meiosis, followed by inter-chromosomal recombination at physical contact sites and formation of new chromosomes. We assemble two haplotype genomes of T. fuciformis Tr01 and provide the first overview of basidiomycetous genomes with discrete genomic architecture. Meiotic activities of asymmetric dikaryotic genomes result in formation of new chromosomes, aneuploidy of some daughter cells, and inviability of most other daughter cells. We propose a new approach for breeding of sporeless mushroom.


Early salt stress effects on the differential expression of vacuolar H(+)-ATPase genes in roots and leaves of Mesembryanthemum crystallinum.
In Mesembryanthemum crystallinum, the salt stress-induced metabolic switch from C3 photosynthesis to Crassulacean acid metabolism is accompanied by major changes in gene expression. However, early effects of salt exposure (i.e. prior to Crassulacean acid metabolism induction) on genes coding for vacuolar transport functions have not yet been studied. Therefore, the expression of vacuolar H(+)-ATPase genes was analyzed in different organs of 4-week-old plants stressed with 400 mM NaCl for 3, 8, or 24 h. Partial cDNAs for the subunits A, B, and c were cloned and used as homologous probes for northern blot analysis. In control plants, the mRNA levels for the different subunits showed organ-specific differences. In fully expanded leaves, subunit c mRNA was very low but increased transiently during the light period. Plant organs also differed in their salt-stress response. In roots and young leaves, mRNA levels for all three subunits increased about 2-fold compared to control plants, whereas in fully expanded leaves only subunit c mRNA responded to salt. The results indicate that the expression of vacuolar H(+)-ATPase genes does not always involve a fixed stoichiometry of mRNAs for the different subunits and that the mRNA level for subunit c is particularly sensitive to developmental and environmental changes.


Investigation of self-assembling proline- and glycine-rich recombinant proteins and peptides inspired by proteins from a symbiotic fungus using atomic force microscopy and circular dichroism spectroscopy.
Fiber-forming proteins and peptides are being scrutinized as a promising source of building blocks for new nanomaterials. Arabinogalactan-like (AGL) proteins expressed at the symbiotic interface between plant roots and arbuscular mycorrhizal fungi have novel sequences, hypothesized to form polyproline II (PPII) helix structures. The functional nature of these proteins is unknown but they may form structures for the establishment and maintenance of fungal hyphae. Here we show that recombinant AGL1 (rAGL1) and recombinant AGL3 (rAGL3) are extended proteins based upon secondary structural characteristics determined by electronic circular dichroism (CD) spectroscopy and can self-assemble into fibers and microtubes as observed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). CD spectroscopy results of synthetic peptides based on repeat regions in AGL1, AGL2 and AGL3 suggest that the synthetic peptides contain significant amounts of extended PPII helices and that these structures are influenced by ionic strength and, at least in one case, by concentration. Point mutations of a single residue of the repeat region of AGL3 resulted in altered secondary structures. Self-assembly of these repeats was observed by means of AFM and optical microscopy. Peptide (APADGK)(6) forms structures with similar morphology to rAGL1 suggesting that these repeats are crucial for the morphology of rAGL1 fibers. These novel self-assembling sequences may find applications as precursors for bioinspired nanomaterials.


[Inducing effects of ursolic acid on Jurkat cell apoptosis and its mechanisms].
The study was aimed to investigate the inducing effect of ursolic acid (UA) on the apoptosis of human T-cell leukemia/lymphoma (Jurkat), and whether the regulation of PTEN involved in the effect of UA on Jurkat cells. The Jurkat cells were treated with different concentrations of UA for different time. The cell proliferation was analyzed with cytotoxicity test (CCK8 method). Cell apoptosis was detected by fluorescence microscopy and flow cytometry. The expression of PTEN mRNA was detected by real-time quantitative PCR. The results indicated that UA could significantly inhibited the viability of Jurkat cells treated with 10-80 µmol/L and in dose- and time-dependent manner. UA could induce Jurkat cell apoptosis in a dose-dependent manner, which was statistical different from the control at the same time (P < 0.05). PTEN mRNA expression was up-regulated by UA, which was statistical different from the control (P < 0.05). It is concluded that UA may induce Jurkat cell apoptosis by up-regulating the PTEN mRNA expression.


The regulation of bone marrow-derived mononuclear phagocyte differentiation and mobilization in syngeneic and allogeneic YAC-lymphoma-bearing mice.
YAC-lymphoma inoculation (ip) into syngeneic A/J mice results in a massive in situ proliferation of the lymphoma cells, with non-significant increases in the peritoneal macrophage population, and also in a remarkable and progressive increase in the bone marrow precursor cells forming both macrophage and fibroblastoid colonies in vitro. In the allogeneic situation (BALB/c mice), YAC-lymphoma cells proliferate to a limited extent before tumour regression. These processes (i.e. proliferation and regression) were accompanied by a progressive increase in the peritoneal macrophage population, which declined to normal after tumour regression. Macrophages accumulating at the regression stage exhibited in vitro cytolytic activity towards YAC-lymphoma cells and cytostatic activity towards unrelated cells. No correlation was observed between the limited asynchronous increase in the bone marrow level of precursor cells for in vitro differentiating macrophage and fibroblastoid colonies, on one hand, and macrophage accumulation at the tumour site in BALB/c mice on the other. Conditioned media from in vitro proliferating YAC-lymphoma cells exhibited high colony-stimulating activity for macrophage colony formation in vitro. Bone marrow cells taken from YAC-lymphoma inoculated A/J mice expressed potent tumorogenic potential at early stages after tumour inoculation. At day 2 after tumour inoculation the bone marrow cells were already tumorogenic and concomitantly expressed augmented levels of macrophage and fibroblastoid colony-forming capacity. The results indicate an inter-relationship between tumour growth and mononuclear phagocyte differentiation and proliferation.


P2X7 Receptor-Dependent microRNA Expression Profile in the Brain Following Status Epilepticus in Mice.
The ionotropic ATP-gated P2X7 receptor is an important contributor to inflammatory signaling cascades via the release of Interleukin-1β, as well as having roles in cell death, neuronal plasticity and the release of neurotransmitters. Accordingly, there is interest in targeting the P2X7 receptor for the treatment of epilepsy. However, the signaling pathways downstream of P2X7 receptor activation remain incompletely understood. Notably, recent studies showed that P2X7 receptor expression is controlled, in part, by microRNAs (miRNAs). Here, we explored P2X7 receptor-dependent microRNA expression by comparing microRNA expression profiles of wild-type (wt) and P2X7 receptor knockout mice before and after status epilepticus. Genome-wide microRNA profiling was performed using hippocampi from wt and P2X7 receptor knockout mice following status epilepticus induced by intra-amygdala kainic acid. This revealed that the genetic deletion of the P2X7 receptor results in distinct patterns of microRNA expression. Specifically, we found that in vehicle-injected control mice, the lack of the P2X7 receptor resulted in the up-regulation of 50 microRNAs and down-regulation of 35 microRNAs. Post-status epilepticus, P2X7 receptor deficiency led to the up-regulation of 44 microRNAs while 13 microRNAs were down-regulated. Moreover, there was only limited overlap among identified P2X7 receptor-dependent microRNAs between control conditions and post-status epilepticus, suggesting that the P2X7 receptor regulates the expression of different microRNAs during normal physiology and pathology. Bioinformatic analysis revealed that genes targeted by P2X7 receptor-dependent microRNAs were particularly overrepresented in pathways involved in intracellular signaling, inflammation, and cell death; processes that have been repeatedly associated with P2X7 receptor activation. Moreover, whereas genes involved in signaling pathways and inflammation were common among up- and down-regulated P2X7 receptor-dependent microRNAs during physiological and pathological conditions, genes associated with cell death seemed to be restricted to up-regulated microRNAs during both physiological conditions and post-status epilepticus. Taken together, our results demonstrate that the P2X7 receptor impacts on the expression profile of microRNAs in the brain, thereby possibly contributing to both the maintenance of normal cellular homeostasis and pathological processes.


Pilot clinical investigation of risperidone in the treatment of psychotic patients.
Sixty-one adult psychotic patients were treated for four weeks in an open dose-finding study with the new combined serotonin-dopamine antagonist risperidone (R 64 766). Risperidone had a rapid onset of action; a highly significant decrease in the total score on the Brief Psychiatric Rating Scale (BPRS) was already noticed after the first week of treatment. There was also a significant decrease in score for individual BPRS items related to positive, negative, and affective symptoms. In spite of the withdrawal of antiparkinson medication at selection, a significant decrease in extra-pyramidal symptoms (EPS) was observed, as assessed on the Simpson and Angus Scale. The Clinical Global Impression of therapeutic effect was consistent with the BPRS scores, showing a constant improvement throughout the study. The mean daily dose of risperidone at the end of the study was 3.7 mg. Tolerance was excellent and only mild side-effects were reported. Vital signs, ECG-parameters, and laboratory values remained within normal limits. This study demonstrates that risperidone has great potential as an effective and well-tolerated alternative for the treatment of chronically psychotic patients. It has potent antipsychotic effects, a low EPS-inducing profile, and, at the same time, it improves the negative and affective symptoms of schizophrenia.


Cancer in East Azerbaijan, Iran: results of a population-based cancer registry.
Regardless of the fact that cancers of GI tract have been reported to be the most common fatal neoplasms in East Azerbaijan, there is a serious lack of population-based studies in this region. A comprehensive search was therefore undertaken to prospectively register all cases of cancer occurring in the province during March 2006-2007. Diagnosis of cancer was based on histopathology of primary lesions in 84.0% of cases, clinical investigation and ultrasound in 7.2%, only clinical investigation in 5.4%, and histology of metastasis in 2.9. Less than 1% were based on cytology and death certificates in one official year. A total of 4,922 cancers (mean age 60.2+18.13 years) were diagnosed during this population-based study. Of these, 56.8% (2114) were in males. ASRs for all cancers in males and females were 164.3 and 130.6 respectively. The top five sites for cancer in males (excluding skin cancer) according to the calculated ASR (world) were stomach (26.0), bladder (15.7), esophagus (12.4), colon and rectum (11.6) and blood (10.8); in females, they were breast (23.5), esophagus (11.7), stomach (11.6), colon and rectum (9.7) and nervous system (5.5). This first comprehensive report on cancer incidence in East Azerbaijan, documents particularly high incidence rates for esophageal and gastric cancer across the sexes.


Potassium uptake system Trk2 is crucial for yeast cell viability during anhydrobiosis.
Yeasts grow at very different potassium concentrations, adapting their intracellular cation levels to changes in the external environment. Potassium homeostasis is maintained with the help of several transporters mediating the uptake and efflux of potassium with various affinities and mechanisms. In the model yeast Saccharomyces cerevisiae, two uptake systems, Trk1 and Trk2, are responsible for the accumulation of a relatively high intracellular potassium content (200-300 mM) and the efflux of surplus potassium is mediated by the Tok1 channel and active exporters Ena ATPase and Nha1 cation/proton antiporter. Using a series of deletion mutants, we studied the role of individual potassium transporters in yeast cell resistance to dehydration. The Trk2 transporter (whose role in S. cerevisiae physiology was not clear) is important for cell viability in the stationary phase of growth and, moreover, it plays a crucial role in the yeast survival of dehydration/rehydration treatments. Mutants lacking the TRK2 gene accumulated significantly lower amounts of potassium ions in the stationary culture growth phase, and these lower amounts correlated with decreased resistance to dehydration/rehydration stress. Our results showed Trk2 to be the major potassium uptake system in stationary cells, and potassium content to be a crucial parameter for desiccation survival.


Experimental strategies in carrying out VCU for tobacco crop I: plot design and size.
We aimed to establish standards for tobacco Valor de Cultivo e Uso (VCU) in Brazil. We obtained information regarding the size and design of plots of two varietal groups of tobacco (Virginia and Burley). Ten inbred lines of each varietal group were evaluated in a randomized complete block design with four replications. The plot contained 42 plants with six rows of seven columns each. For each experiment plant, considering the position of the respective plant in the plot (row and column) as a reference, cured leaf weight (g/plant), total sugar content (%), and total alkaloid content (%) were determined. The maximum curvature of the variations in coefficients was estimated. Trials with the number of plants per plot ranging from 2 to 41 were simulated. The use of a border was not justified because the interactions between inbred lines x position in the plots were never significant, showing that the behavior of the inbred lines coincided with the different positions. The plant performance varied according to the column position in the plot. To lessen the effect of this factor, the use of plots with more than one row is recommended. Experimental precision, evaluated by the CV%, increased with an increase in plot size; nevertheless, the maximum curvature of the variation coefficient method showed no expressive increase in precision if the number of plants was greater than seven. The result in identification of the best inbred line, in terms of the size of each plot, coincided with the maximum curvature method.


Development of Useful Biomaterial for Bone Tissue Engineering by Incorporating Nano-Copper-Zinc Alloy (nCuZn) in Chitosan/Gelatin/Nano-Hydroxyapatite (Ch/G/nHAp) Scaffold.
Ceramic and metallic nanoparticles can improve the mechanical and biological properties of polymeric scaffolds for bone tissue engineering (BTE). In this work, nanohydroxyapatite (nHAp) and nano-copper-zinc alloy (nCuZn) were added to a chitosan/gelatin (Ch/G) scaffold in order to investigate the effects on morphological, physical, and biocompatibility properties. Scaffolds were fabricated by a freeze-drying technique using different pre-freezing temperatures. Microstructure and morphology were studied by scanning electron microscopy (SEM), glass transition (Tg) was studied using differential scanning calorimetry (DSC), cell growth was estimated by MTT assay, and biocompatibility was examined in vitro and in vivo by histochemistry analyses. Scaffolds and nanocomposite scaffolds presented interconnected pores, high porosity, and pore size appropriate for BTE. Tg of Ch/G scaffolds was diminished by nanoparticle inclusion. Mouse embryonic fibroblasts (MEFs) cells loaded in the Ch/G/nHAp/nCuZn nanocomposite scaffold showed suitable behavior, based on cell adhesion, cell growth, alkaline phosphatase (ALP) activity as a marker of osteogenic differentiation, and histological in vitro cross sections. In vivo subcutaneous implant showed granulation tissue formation and new tissue infiltration into the scaffold. The favorable microstructure, coupled with the ability to integrate nanoparticles into the scaffold by freeze-drying technique and the biocompatibility, indicates the potential of this new material for applications in BTE.


Role of thiosulfate in bisulfite reduction as catalyzed by Desulfovibrio vulgaris.
Studies with (35)S-labeled substrates were conducted to investigate the pathway involved in the reduction of sulfite to sulfide by cell-free extracts of the sulfate-reducing organism Desulfovibrio vulgaris. The results showed that accumulation of thiosulfate occurred when crude extracts were incubated under appropriate conditions with sulfite as substrate. With labeled sulfite as substrate, thiosulfate with equal distribution of radioactivity in both sulfur atoms was formed. When the rates of formation of (35)S(2-) from inner- and outer-labeled thiosulfate were compared, the rate of formation from outer-labeled thiosulfate was greater. Time studies with S-(35)SO(3) (2-) showed an increase of (35)S(2-) with time and an increasing ratio of doubly labeled to inner labeled thiosulfate remaining in the reaction mixture. From these studies it is concluded that thiosulfate is a stable intermediate formed from sulfite during the reduction of sulfate by D. vulgaris. Both sulfur atoms are derived from sulfite; during the utilization of thiosulfate, the outer sulfur is reduced to sulfide and the inner sulfur recycles through a sulfite pool.


Nav1.7 protein and mRNA expression in the dorsal root ganglia of rats with chronic neuropathic pain.
Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behavioral tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic pain rats 3-28 days following model induction. The results of immunohistochemistry, western blot assays and reverse transcription-PCR showed that Nav1.7 protein and mRNA expression was significantly increased in the injured dorsal root ganglia. These findings indicated that Nav1.7 might play an important role in the model of chronic neuropathic pain.


Increased structural covariance in brain regions for number processing and memory in children with developmental dyscalculia.
Developmental dyscalculia (DD) is a developmental learning disability associated with deficits in processing numerical and mathematical information. Several studies demonstrated functional network alterations in DD. Yet, there are no studies, which examined the structural network integrity in DD. We compared whole-brain maps of volume based structural covariance between 19 (4 males) children with DD and 18 (4 males) typically developing children. We found elevated structural covariance in the DD group between the anterior intraparietal sulcus to the middle temporal and frontal gyrus (p < 0.05, corrected). A hippocampus subfield analysis showed higher structural covariance in the DD group for area CA3 to the parahippocampal and calcarine sulcus, angular gyrus and anterior part of the intraparietal sulcus as well as to the lingual gyrus. Lower structural covariance in this group was seen for the subiculum to orbitofrontal gyrus, anterior insula and middle frontal gyrus. In contrast, the primary motor cortex (control region) revealed no difference in structural covariance between groups. Our results extend functional magnetic resonance studies by revealing abnormal gray matter integrity in children with DD. These findings thus indicate that the pathophysiology of DD is mediated by both structural and functional abnormalities in a network involved in number processing and memory function.


Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors.
Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation. Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles. A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004. We compared repeated measurements of interleukin 6 (IL-6), fibrinogen, and C-reactive protein (CRP) with concurrent levels of air pollution. We collected hourly data on particle number concentrations (PNC), mass concentrations of particulate matter (PM) < 10 microm (PM(10)) and < 2.5 microm (PM(2.5)), gaseous pollutants, and meteorologic data at central monitoring sites in each city. City-specific confounder models were built for each blood marker separately, adjusting for meteorology and time-varying and time-invariant covariates. Data were analyzed with mixed-effects models. Pooled results show an increase in IL-6 when concentrations of PNC were elevated 12-17 hr before blood withdrawal [percent change of geometric mean, 2.7; 95% confidence interval (CI), 1.0-4.6]. Five day cumulative exposure to PM(10) was associated with increased fibrinogen concentrations (percent change of arithmetic mean, 0.6; 95% CI, 0.1-1.1). Results remained stable for smokers, diabetics, and patients with heart failure. No consistent associations were found for CRP. Results indicate an immediate response to PNC on the IL-6 level, possibly leading to the production of acute-phase proteins, as seen in increased fibrinogen levels. This might provide a link between air pollution and adverse cardiac events.


[PKD3 contributes to up-regulation of prostate-specific antigen in prostate cancer cells].
To investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism. LNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy. PSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation. Elevated AR transcriptional activity and enhanced expression of PSA induced by PKD3 in response to DHT treatment suggest that PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells.


Nutrition Management in Acute Pancreatitis.
Acute pancreatitis (AP) is one of the most prevalent gastrointestinal conditions necessitating inpatient care. In the United States, over 275,000 patients are hospitalized for management of AP, with an estimate that over $2.5 billion is spent annually in treatment, with incidence continuing to rise. AP is a highly inflammatory and catabolic state, putting all patients with the condition at risk of malnutrition. Numerous approaches to nutrition support in pancreatitis have been evaluated and remain controversial. In this narrative review, we aim to give an overview of indications for nutrition and approach to management of nutrition in severe and predicted severe AP based on currently available data.


Occupational exposures to carcinogens in Italy: an update of CAREX database.
To update estimates of the prevalence of occupational exposures to carcinogens in Italy, the 85 CAREX agents were re-assessed. The original exposure estimates in the CAREX database were updated, taking into account changes in exposure patterns and in numbers of employees by industrial class. The 21.8 million employees in Italy, 19.4 in industry and services, 2.4 in agriculture, had 4.2 million exposures. Prevalences of exposures were highest for environmental (passive) tobacco smoke (800,000 exposures), solar radiation (700,000), diesel engine exhaust (500,000), wood dust (280,000), silica (250,000), lead and inorganic lead compounds (230,000), benzene (180 000), hexavalent chromium compounds (160,000), glass wool (140,000), and PAHs (120,000). Exposures to carcinogens at work are still an issue in Italy and do not appear to be controlled as strictly as they should be.


Simulation modeling of policies directed at youth sugar-sweetened beverage consumption.
Childhood obesity is a significant public health problem requiring innovative solutions. While recent reviews indicate that some policies show promise, there is a lack of information regarding which policies, and policy combinations, work best. Low-nutrition, energy-dense foods and beverages such as sugar-sweetened beverages (SSBs) have been identified as a major contributor to the problem. The purpose of this paper is to use simulation modeling to show how changes in three categories of SSB policies-school nutrition, school-based education, and taxes-impact SSB and other food consumption. The model shows that policies directed at SSBs, particularly tax hikes, could lead to substantial reductions in the number of calories consumed by youth. The estimates, however, are subject to a high degree of uncertainty. Estimates from school-based nutrition and school-based education policies, while also helping to reduce caloric intake, generally show smaller effects than tax policies and considerable variation around parameter estimates for individual and combined policies. We conclude with a discussion of the limits of the model, and suggest where additional information is needed. Limitations notwithstanding, simulation modeling is a promising methodology that can help advance our understanding of policy effects, thereby helping policymakers to better formulate effective policies to reduce obesity prevalence and the associated social harms.


Extensive sprouting of sensory afferents and hyperalgesia induced by conditional expression of nerve growth factor in the adult spinal cord.
Genetic transfer of growth-promoting molecules was proposed as a potential strategy to modify the nonpermissive nature of the adult CNS to induce axonal regeneration. To evaluate whether overexpression of neurotrophins or cellular adhesion molecules would effect axonal plasticity, adenoviruses encoding fibroblast growth factor-2 (FGF-2/Adts), nerve growth factor (NGF/Adts), neurotrophin-3, and the cell adhesion molecules N-cadherin and L1 were injected into the dorsal horn of the adult spinal cord. Transgene expression was primarily localized to astrocytes in the dorsal horn and motor neurons within the ventral horn. Overexpression of these factors, with the exception of NGF/Adts, failed to increase axonal sprouting. Eight days after NGF/Adts injections, axonal sprouting within the dorsal horn was apparent, and after 4 weeks, extensive spouting was observed throughout the entire dorsal horn, extending into the ventral horn and the white matter of the lateral funiculus. These axons were identified primarily as a subpopulation of nociceptive fibers expressing calcitonin gene-related peptide and substance-P. Behavioral analysis revealed thermal hyperalgesia and perturbation of accurate paw placement on grid-walking tasks for both FGF-2- and NGF-treated animals. These results indicate that the administration of growth-promoting molecules can induce robust axonal plasticity of normal adult primary sensory neurons into areas of transgene expression, causing significant alterations in behavioral responses. This observation also indicates that gene transfer protocols that aim to reconstruct diseased or injured pathways should also be designed to prevent the sprouting of the normal circuitry from adjacent unaffected neurons.


The Role of Mistrust in Sexual Revictimization: An Analysis of Serial Indirect Effects.
A sample of 819 female college students completed measures of childhood sexual abuse (CSA), adult sexual victimization (ASV), mistrust, trauma-related symptoms, and drinking problems. Using a serial indirect effects model, we hypothesized that CSA would be associated with ASV through the indirect effects of mistrust → trauma-related symptoms → drinking problems. The results indicated that this serial indirect effects model was significant. When the order of the first two indirect effects was reversed, the model was not significant. These results highlight the importance of examining potential factors involved in sexual revictimization in tandem rather than in isolation.


Aspergillus colonization in patients with bronchogenic carcinoma.
Aspergillus antigens such as galactomannan antigen, a cell wall polysaccharide, can be detected in patient's serum or bronchoalveolar lavage. To study the prevalence of Aspergillus infection in patients with bronchogenic carcinoma, we measured galactomannan antigen in serum and bronchoalveolar lavage samples of patients with bronchogenic carcinoma. The study was conducted on 45 bronchogenic carcinoma patients. The diagnosis of lung cancer was confirmed by bronchoscopy, histopathological and radiological examinations. Bronchoalveolar lavage fluid collected from each patient by fiberoptic bronchoscopy was subjected to direct microscopy and culture on Sabouraud's dextrose agar and Czapek-Dox agar, and Aspergillus galactomannan antigen was measured in serum and bronchoalveolar lavage samples. The majority of patients were male (93.3%) in the age group 51-60 years, 88.9% were addicted to gutka chewing, and 82.1% were addicted to smoking. Most patients complained of cough (73%) and shortness of breath (51.1%). Squamous cell carcinoma (64.4%) was the most common malignancy, followed by adenocarcinoma (13.3%). On culture of bronchoalveolar lavage samples, 35.5% showed growth of Aspergillus spp. (Aspergillus fumigatus in 17.8%, Aspergillus flavus in 13.3%, and Aspergillus niger in 4.4%). Galactomannan antigen was detected in 58.3% of bronchoalveolar lavage samples and 47.2% of serum samples. There is a high prevalence of aspergillosis in patients with lung carcinoma, especially among smokers and gutka chewers.


Ultra-forward surgical support for special operations forces. Conception, development and certification of the French Special Operations Surgical Team (SOST) airborne capability.
When special operations forces (SOF) are in action, a surgical team (SOST) is usually ground deployed as close as possible to the combat area, to try and provide surgical support within the golden hour. The French SOST is composed of 6 people: 2 surgeons, 1 scrub nurse, 1 anaesthetist, 1 anesthetic nurse and 1 SOF paramedic. It can be deployed in 45 min under a tent or in a building. However, some tactical situations prevent the ground deployment. A solution is to deploy the SOST in a tactical unprepared aircraft hold, to make it possible to offer DCS, to treat non-compressible exsanguinating trauma, without any ground logistical footprint. This article describes the stages of the design, development and certification process of the airborne SOST capability. The authors report the modifications and adaptations of the equipment and the surgical paradigms which make it possible to solve the constraints linked to the aeronautical and combat environment. Study type/level of evidence Care management Level of Evidence IV.


Experimental studies of vaccination, allergy, and immunity in tuberculosis: 3. Effect of killed BCG vaccine.
The antigenic effects of living and killed BCG vaccine have been investigated by comparing the degree of tuberculin allergy, the size of vaccinal lesions, and the survival time after challenge infection in large numbers of guinea-pigs vaccinated with BCG suspensions containing various concentrations of living and killed organisms.The allergizing as well as the immunizing potency of BCG was markedly reduced-though not entirely abolished-when the bacilli were killed, yet the size of the vaccinal lesion was only slightly reduced. Results were about the same regardless of whether heat, light, or phenol had been used to kill the organisms. It would thus appear that viability of the organisms in BCG vaccine is important for immunity as well as for allergy, whereas the size of the vaccinal lesion is determined largely by the total mass of bacterial cells injected.The results of this experiment in laboratory animals are in agreement with results of studies in human beings, so far as allergy and lesions are concerned. Persons vaccinated with heat-killed or irradiated BCG have been shown to have very low degrees of post-vaccination tuberculin allergy compared with persons given a corresponding dose of living BCG, yet the size of the vaccinal lesion differs only slightly. The combination of a large vaccinal lesion and a low degree of post-vaccination allergy should therefore invite suspicion that a vaccine contained mainly killed bacilli and, perhaps, the presumption that it has produced only a low degree of immunity.


The effect of maternal undernutrition on ovine fetal growth.
Modifications in maternal nutrition during pregnancy can significantly disrupt fetal growth and subsequent post-natal health and survival. This study investigated the effects of undernutrition on fetal growth and the potential mechanisms involved. Tissue from pregnant ewes (n=27) was investigated on days 45, 90 and 135 of gestation (term = approximately 150 days). The thoracic girth (P<0.05) was greater in fetuses from nutrient restricted ewes on day 45 and there was also a trend towards an increased gut weight (P<0.08). By day 90, the fetal brain and thymus weight were lighter in underfed than in well-fed animals whilst the weight of the fetal ovaries was heavier (P<0.05). On day 135 the fetal heart, pancreas, thymus, gut and kidney weights were lighter in undernourished ewes (P<0.05). When expressed as a percentage of fetal body weight, significance was retained in the heart, pancreas and thymus (P<0.05). Bone growth was also affected. At day 90 the fetal femur and metatarsal were longer in underfed mothers (P<0.05). In contrast, the fetal humerus and scapula were shorter in underfed than in well-fed animals on day 135 (P<0.05) when the weight of the semitendinosus muscle (P<0.05) was also reduced. The fall in fetal glucose (P<0.1), insulin (P<0.01) and IGF-I (P<0.01) levels in underfed ewes on day 135 may have compromised fetal growth. Fetal plasma IGF binding protein-2 also increased between days 90 and 135 in underfed ewes (P<0.03), whilst levels were unaltered in well-fed animals. Although maternal and fetal plasma IGF-I levels increased with gestation (P<0.01) and the placentome morphology altered in all ewes (P<0.05), the fall in placental mass (P<0.05), amniotic and allantoic glucose concentrations (P<0.05) and maternal plasma glucose and insulin levels (P<0.05) in underfed ewes in late gestation may have compromised fetal substrate delivery. These perturbations in fetal development may have significant implications on adult health and carcass conformation, raising important health and economic issues in medical and agricultural sectors.


Excess variants in AFF2 detected by massively parallel sequencing of males with autism spectrum disorder.
Autism spectrum disorder (ASD) is a heterogeneous disorder with substantial heritability, most of which is unexplained. ASD has a population prevalence of one percent and affects four times as many males as females. Patients with fragile X E (FRAXE) intellectual disability, which is caused by a silencing of the X-linked gene AFF2, display a number of ASD-like phenotypes. Duplications and deletions at the AFF2 locus have also been reported in cases with moderate intellectual disability and ASD. We hypothesized that other rare X-linked sequence variants at the AFF2 locus might contribute to ASD. We sequenced the AFF2 genomic region in 202 male ASD probands and found that 2.5% of males sequenced had missense mutations at highly conserved evolutionary sites. When compared with the frequency of missense mutations in 5545 X chromosomes from unaffected controls, we saw a statistically significant enrichment in patients with ASD (OR: 4.9; P < 0.014). In addition, we identified rare AFF2 3' UTR variants at conserved sites which alter gene expression in a luciferase assay. These data suggest that rare variation in AFF2 may be a previously unrecognized ASD susceptibility locus and may help explain some of the male excess of ASD.


Characteristics of COPD patients admitted to the ICU of a referral hospital for respiratory diseases in Brazil.
To report data regarding COPD patients admitted to the ICU of a referral hospital for respiratory diseases, including outcomes and treatment evaluation. Study of a series of patients with respiratory failure and COPD admitted to the ICU of Nereu Ramos Hospital, located in the city of Florianópolis, Brazil, between October of 2006 and October of 2007. Data related to demographics, causes of hospitalization, pharmacological treatment, ventilatory support, length of hospital stay, in-hospital complications, ICU mortality, and 28-day mortality were obtained from the medical charts of the patients. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated. Mortality at 18 months was assessed by subsequent telephone calls. During the study period, 192 patients were admitted to the ICU, 24 (12.5%) of whom were diagnosed with respiratory failure and COPD. The mean length of ICU stay was 12.0 ± 11.1 days. Noninvasive ventilation was used in 10 of the 24 patients (41.66%) and failed in 5 of those 10. Invasive mechanical ventilation (IMV) was used in a total of 15 patients (62.5%). Overall ICU mortality and 28-day mortality were 20.83% and 33.33%, respectively. However, 18-month mortality was 62.5%. Respiratory failure associated with COPD was responsible for 12.5% of the ICU admissions. Orotracheal intubation and IMV were necessary in 62.5% of the cases. The ICU mortality rate was in accordance with that predicted by the APACHE II scores. However, late mortality was high.


Dopamine D1 or D2 receptor-expressing neurons in the central nervous system.
Dopamine signals mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs); D1R-expressing or D2R-expressing neurons contribute to distinct reward and addictive behaviors. Traditionally, transgenic mice expressing green fluorescent protein (GFP) under D1R or D2R promoters are used for fluorescent verification in electrophysiology studies, whereas Cre mice are employed for behavioral research. However, it is unknown whether the same neuronal populations are targeted in GFP and Cre mice. Additionally, while D1Rs and D2Rs are known to be expressed in different striatal neurons, their expression patterns outside the striatum remain unclear. The present study addressed these two questions by using several transgenic mouse lines expressing fluorescent proteins (GFP or tdTomato) or Cre under the control of D1R or D2R promoters. We found a high degree of overlap between GFP-positive and Cre-positive neurons in the striatum and hippocampus. Additionally, we discovered that D1Rs and D2Rs were highly segregated in the orbitofrontal cortex, prefrontal cortex, dorsal and ventral hippocampus, and amygdala: ~4-34 percent of neurons co-expressed these receptors. Importantly, slice electrophysiological studies demonstrated that D1R-positive and D1R-negative hippocampal neurons were functionally distinct in a mouse line generated by crossing Drd1a-Cre mice with a Cre reporter Ai14 line. Lastly, we discovered that chronic alcohol intake differentially altered D1R-positive and D2R-positive neuron excitability in the ventral CA1. These data suggest that GFP and Cre mice target the same populations of striatal neurons, D1R-expressing or D2R-expressing neurons are highly segregated outside the striatum, and these neurons in the ventral hippocampal may exert distinct roles in alcohol addiction.


Internet advertising of artificial tanning in Australia.
Artificial tanning, defined as deliberate exposure to ultraviolet rays produced by artificial tanning devices, is a new and emerging public health issue in Australia and globally. Epidemiological research suggests that artificial tanning may contribute to the incidence of melanoma, nonmelanoma skin cancer as well as other health problems. Given that Australia has a high incidence of skin cancer, we have undertaken a study to explore how artificial tanning has been promoted to its users. The aim was to analyze the completeness and accuracy of information about artificial tanning. A content analysis of web sites of tanning salons and distributors of tanning equipment in Australia was conducted. A total of 22 web sites were analyzed. None of the solarium operators or distributors of equipment provided full information about the risks of artificial tanning. Fifty-nine percent of web advertisements had no information and 41% provided only partial information regarding the risks of artificial tanning. Pictures with the image of bronze-tanned bodies, predominantly women, were used by all web advertisers. In light of the success of sun-safety campaigns in Australia, the findings of future epidemiological research on the prevalence of artificial tanning and sociological and anthropological research on why people utilize artificial tanning should be a basis for developing effective targeted health promotion on the elimination of artificial tanning in the country.


A Chinese Herbal Formula Suppresses Colorectal Cancer Migration and Vasculogenic Mimicry Through ROS/HIF-1α/MMP2 Pathway in Hypoxic Microenvironment.
Various malignant tumors, including colorectal cancer, have the ability to form functional blood vessels for tumor growth and metastasis. Vasculogenic mimicry (VM) refers to the ability of highly invasive tumor cells to link each other to form vessels, which is associated with poor cancer prognosis. However, the antitumor VM agents are still lacking in the clinic. Astragalus Atractylodes mixture (AAM), a traditional Chinese medicine, has shown to inhibit VM formation; however the exact mechanism is not completely clarified. In this study, we found that HCT-116 and LoVo could form a VM network. Additionally, hypoxia increases the intracellular reactive oxygen species (ROS) level and accelerates migration, VM formation in colorectal cancer cells, while N-Acetylcysteine (NAC) could reverse these phenomena. Notably, further mechanical exploration confirmed that the matrix metalloprotease 2 (MMP2) induction is ROS dependent under hypoxic condition. On the basis, we found that AAM could effectively inhibit hypoxia-induced ROS generation, migration, VM formation as well as HIF-1α and MMP2 expression. In vivo, AAM significantly inhibits metastasis of colorectal cancer in murine lung-metastasis model. Taken together, these results verified that AAM effectively inhibits migration and VM formation by suppressing ROS/HIF-1α/MMP2 pathway in colorectal cancer under hypoxic condition, suggesting AAM could serve as a therapeutic agent to inhibit VM formation in human colorectal cancer.


A Hybrid Task Graph Scheduler for High Performance Image Processing Workflows.
Designing applications for scalability is key to improving their performance in hybrid and cluster computing. Scheduling code to utilize parallelism is difficult, particularly when dealing with data dependencies, memory management, data motion, and processor occupancy. The Hybrid Task Graph Scheduler (HTGS) improves programmer productivity when implementing hybrid workflows for multi-core and multi-GPU systems. The Hybrid Task Graph Scheduler (HTGS) is an abstract execution model, framework, and API that increases programmer productivity when implementing hybrid workflows for such systems. HTGS manages dependencies between tasks, represents CPU and GPU memories independently, overlaps computations with disk I/O and memory transfers, keeps multiple GPUs occupied, and uses all available compute resources. Through these abstractions, data motion and memory are explicit; this makes data locality decisions more accessible. To demonstrate the HTGS application program interface (API), we present implementations of two example algorithms: (1) a matrix multiplication that shows how easily task graphs can be used; and (2) a hybrid implementation of microscopy image stitching that reduces code size by ≈ 43% compared to a manually coded hybrid workflow implementation and showcases the minimal overhead of task graphs in HTGS. Both of the HTGS-based implementations show good performance. In image stitching the HTGS implementation achieves similar performance to the hybrid workflow implementation. Matrix multiplication with HTGS achieves 1.3× and 1.8× speedup over the multi-threaded OpenBLAS library for 16k × 16k and 32k × 32k size matrices, respectively.


Sick-listed workers' experiences with motivational interviewing in the return to work process: a qualitative interview study.
When returning to work after being on long-term sick leave, individuals may experience varying levels of motivation and self-efficacy. Motivational interviewing (MI) is a counseling style that aims to increase motivation towards change, and it may be useful in the return to work (RTW) process. The aim of this study was to explore sick-listed workers' experiences with MI in the RTW process. This qualitative study was part of a randomized controlled trial evaluating the effects of MI on the RTW process, and it was administered by caseworkers at the Norwegian Labor and Welfare Administration. Sixteen sick-listed individuals, aged 33-60, participated in semi-structured interviews. All had a sick leave status of 50-100% for at least 8 weeks when interviewed and all had completed 2 MI sessions. The data was analyzed with systematic text condensation. Participants' experiences of the MI sessions were categorized into three themes: (1) relationship with the MI caseworker, (2) normalizing sick leave, and (3) adjusting RTW strategies. The MI sessions were experienced as a positive encounter due to the supportive relationship that was built between the MI caseworker and the sick-listed worker. Being sick listed led to feelings of guilt and stigmatization, but acceptance and support from the MI caseworkers helped normalize the situation for the sick-listed workers. Furthermore, MI sessions allowed for personalized feedback and discussions on adjustments to their RTW strategies. Sick-listed workers experienced MI as positive due to the good relationship that developed with the MI caseworker, how this normalized sick leave, and the help they received with adjusting their RTW strategies. Professionals working with individuals attempting to RTW may benefit from using MI as a method for helping sick-listed workers to RTW. ClinicalTrials.gov: NCT03212118 (registered July 11, 2017).


Optoacoustic microscopy at multiple discrete frequencies.
Optoacoustic (photoacoustic) sensing employs illumination of transient energy and is typically implemented in the time domain using nanosecond photon pulses. However, the generation of high-energy short photon pulses requires complex laser technology that imposes a low pulse repetition frequency (PRF) and limits the number of wavelengths that are concurrently available for spectral imaging. To avoid the limitations of working in the time domain, we have developed frequency-domain optoacoustic microscopy (FDOM), in which light intensity is modulated at multiple discrete frequencies. We integrated FDOM into a hybrid system with multiphoton microscopy, and we examine the relationship between image formation and modulation frequency, showcase high-fidelity images with increasing numbers of modulation frequencies from phantoms and in vivo, and identify a redundancy in optoacoustic measurements performed at multiple frequencies. We demonstrate that due to high repetition rates, FDOM achieves signal-to-noise ratios similar to those obtained by time-domain methods, using commonly available laser diodes. Moreover, we experimentally confirm various advantages of the frequency-domain implementation at discrete modulation frequencies, including concurrent illumination at two wavelengths that are carried out at different modulation frequencies as well as flow measurements in microfluidic chips and in vivo based on the optoacoustic Doppler effect. Furthermore, we discuss how FDOM redefines possibilities for optoacoustic imaging by capitalizing on the advantages of working in the frequency domain.


Penis envy: from childhood wish to developmental metaphor.
Two phases of penis envy are considered. The first regularly occurs early in development and is registered as a narcissistic injury which can be resolved under optimal conditions and can contribute to female psychosexual development. If, however, it is not favorably resolved or, even more significantly, if the basic character disorder is of a narcissistic type, the awareness of the genital difference becomes one of many narcissistic traumas. A later phase of penis envy usually represents a regressive effort to resolve oedipal conflicts. In the past, these two phase-oriented forms of penis envy have not been adequately distinguished. Two clinical examples are presented in which the envy of men was only part of a tendency to envy in a narcissistic character disorder. In the analysis, the interpretation of the penis envy offered a metaphor around which all of the "free-floating" envy could coalesce. The cases illustrate the necessity to consider penis envy as the manifest content of a symptom that needs analysis, rather than as "bedrock" or ultimate conflict.


Expression of cytokeratin 19 during human liver organogenesis.
Immunohistochemistry with monoclonal anti-cytokeratin antibodies has revealed the presence of cytokeratin 19 in embryonic and early fetal hepatocytes. With the differentiation of bile ducts at about the 10th week, cytokeratin 19 disappears from liver cells but remains in bile duct cells. This marks an important step in the organogenesis of the liver.


Comparison of high ribavirin induction versus standard ribavirin dosing, plus peginterferon-α for the treatment of chronic hepatitis C in HIV-infected patients: the PERICO trial.
Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 μg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin β (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.


Single-dose pharmacokinetics of intravenous ampicillin plus sulbactam in healthy elderly and young adult subjects.
The pharmacokinetics of intravenous ampicillin and sulbactam, a beta-lactamase inhibitor, were evaluated in two different age groups. Twelve healthy elderly subjects (age 65-93 years) and 12 healthy young adult subjects (age 20-35 years) received both a dose of ampicillin 1 g plus sulbactam 0.5 g and a higher dose of ampicillin 2 g plus sulbactam 1 g after a one-week period between doses. A reverse-phase high-pressure liquid chromatography method was used for the quantitation of ampicillin and sulbactam in serum and urine. The pharmacokinetic parameters for both ampicillin and sulbactam were calculated by computer-based two-compartment nonlinear model. After a 30-min infusion, serum concentrations of both drugs declined in a biexponential manner for both doses. Elderly subjects demonstrated significantly lower total clearances (Clt) than young adult subjects of ampicillin 1 g (220.0 +/- 104.2 vs 360.0 +/- 95.8 ml/min/1.73 m2), ampicillin 2 g (72.6 +/- 36.6 vs 306.8 +/- 109.77 ml/min/1.73 m2), sulbactam 0.5 g (122.3 +/- 47.8 vs 263.9 +/- 93.7 ml/min/1.73 m2), and sulbactam 1 g (171.2 +/- 85.8 vs 391.7 +/- 70.8 ml/min/1.73 m2), respectively. Significance was defined as P less than 0.05. Renal clearance was also significantly reduced in the elderly subjects. Area under the curve was found to be significantly increased in the elderly subjects compared to the young subjects for both ampicillin and sulbactam as were the beta elimination half-lives. No significant difference in the apparent volume of distribution, when adjusted for body weight, was found for either sulbactam (P greater than 0.95) or ampicillin (P greater than 0.95) between the two groups. Linear regression analysis revealed that age was significantly correlated with the Clt of ampicillin 1 g (r = 0.85, P less than 0.001), ampicillin 2 g (r = 0.90, P less than 0.001), sulbactam 0.5 g (r = 0.80, P less than 0.001), and sulbactam 1 g (r = 0.93, P less than 0.001). A multivariate analysis showed a slight improvement in correlation when creatinine clearance was added to age and compared with Clt. Urinary recovery of both ampicillin and sulbactam was approximately 60% after 14 h.


hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.
Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.


Entitlement-Based Access Control for Smart Cities Using Blockchain.
Smart cities use the Internet of Things (IoT) devices such as connected sensors, lights, and meters to collect and analyze data to improve infrastructure, public utilities, and services. However, the true potential of smart cities cannot be leveraged without addressing many security concerns. In particular, there is a significant challenge for provisioning a reliable access control solution to share IoT data among various users across organizations. We present a novel entitlement-based blockchain-enabled access control architecture that can be used for smart cities (and for any ap-plication domains that require large-scale IoT deployments). Our proposed entitlement-based access control model is flexible as it facilitates a resource owner to safely delegate access rights to any entities beyond the trust boundary of an organization. The detailed design and implementation on Ethereum blockchain along with a qualitative evaluation of the security and access control aspects of the proposed scheme are presented in the paper. The experimental results from private Ethereum test networks demonstrate that our proposal can be easily implemented with low latency. This validates that our proposal is applicable to use in the real world IoT environments.


Effects of infant feeding practices and maternal characteristics on early childhood obesity.
Early childhood obesity is a serious health problem not only because it causes serious health problems in children, but also because it poses a risk of obesity in the later stages of life. The aim of our study was to determine the effect of feeding (breastfeeding times, exclusive breastfeeding times, instances of night-time bottle feeding) and maternal characteristics (weight gain during pregnancy, BMI, socioeconomic status) on childhood overweight and obesity in children up to 36 months old. Babies born in the province of Rize (Turkey) between the dates of November 1, 2013 and September 30, 2014 whom birth weights between 2500gr and 4500gr participated in our prospective cohort study. The present study lasted for 3 years and 11 interviews were conducted with each mother of the infants during this period. Relationship between obesity or overweight and feeding practices evaluated into two groups according to their feeding practices. 294 healthy children were included. Mean weight of the babies at 36 months were 14.6 kilograms, 6 babies (2 %) were overweight, 20 babies (7 %) were obese, and 268 babies (91 %) were at an normal weight. 82 babies (21 %) exclusive breastfed less than six months and 212 babies (55 %) exclusive breastfed six months or more. Overweight and obesity is less frequent among children who were exclusively breastfed for at least six months (p<0.05). We concluded.that exclusive breastfeeding time and maternal obesity have a significant effect on childhood overweight and obesity.


Effect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors.
Antioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species (ROS). The present study evaluated the effects of prolonged antioxidant treatment on arterial elasticity, inflammatory and metabolic measures in patients with multiple cardiovascular risk factors. Study participants were randomly assigned to two groups. Group 1 received oral supplementation with 2 capsules per day of Mid Life Guard, SupHerb, Israel. In each capsule vitamin C (500 mg) vitamin E (200 iu), co-enzyme Q10 (60 mg) and selenium (100 mcg), Group 2 received matching placebo(SupHerb) for 6 months. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, hs-CRP, endothelin, aldosterone, plasma renin activity and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). Antioxidant-treated patients exhibited significant increases in large arterial elasticity index (LAEI) as well as small arterial elasticity index (SAEI). A significant decline HbA1C and a significant increase in HDL-cholesterol were also observed. In the placebo group, significant changes in LAEI, SAEI or metabolic measures were not observed. Antioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors. This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure.


Au/Ag-cocatalyzed aldoximes to amides rearrangement under solvent- and acid-free conditions.
The gold/silver-cocatalyzed conversion of aldoximes into primary amides is reported. The reaction, which proceeds under neat and acid-free conditions, allows for the conversion of a range of aldoximes, and is a rare example of cooperative catalysis involving well-defined gold species.


Antimicrobial Resistance in Enterococcus Spp. Isolated from a Beef Processing Plant and Retail Ground Beef.
Antimicrobial use in food-producing animals has come under increasing scrutiny due to its potential association with antimicrobial resistance (AMR). Monitoring of AMR in indicator microorganisms such as Enterococcus spp. in meat production facilities and retail meat products can provide important information on the dynamics and prevalence of AMR in these environments. In this study, swabs or samples were obtained from various locations in a commercial beef packing operation (n = 600) and from retail ground beef (n = 60) over a 19-month period. All samples/swabs were enriched for Enterococcus spp., and suspected enterococci isolates were identified using species-specific PCR primers. Enterococcus faecalis was the most frequently isolated species, followed by Enterococcus hirae, which was found mostly on post-hide removal carcasses and in ground beef. Enterococcus faecium (n = 9) and E. faecalis (n = 120) isolates were further characterized for AMR. Twenty-one unique AMR profiles were identified, with 90% of isolates resistant to at least two antimicrobials and two that were resistant to nine antimicrobials. Tetracycline resistance was observed most often in E. faecalis (28.8%) and was likely mediated by tet(M). Genomic analysis of selected E. faecalis and E. faecium isolates revealed that many of the isolates in this study clustered with other publicly available genomes from ground beef, suggesting that these strains are well adapted to the beef processing environment. IMPORTANCE Antimicrobial resistance (AMR) is a serious challenge facing the agricultural industry. Understanding the flow of antimicrobial-resistant bacteria through the beef fabrication process and into ground beef is an important step in identifying intervention points for reducing AMR. In this study, we used enterococci as indicator bacteria for monitoring AMR in a commercial beef packaging facility and in retail ground beef over a 19-month period. Although washing of carcasses post-hide removal reduced the isolation frequency of Enterococcus spp., a number of antimicrobial-resistant Enterococcus faecalis isolates were recovered from ground beef produced in the packaging plant. Genome analysis showed that several E. faecalis isolates were genetically similar to publicly available isolates recovered from retail ground beef in the United States.


Testing the role of solvent surface tension in protein ionization by electrospray.
This work was aimed at probing the influence of solvent surface tension on protein ionization by electrospray. In particular, we were interested in testing the previously suggested hypothesis that the charge-state distributions (CSDs) of proteins in electrospray ionization mass spectrometry (ESI-MS) are controlled by the surface tension of the least volatile solvent component. In the attempt to minimize uncontrolled conformational effects, we used acid-sensitive proteins (cytochrome c and myoglobin) at low pH or highly stable proteins (ubiquitin and lysozyme) in the presence of low concentrations of organic solvents. A first set of experiments compared the effect of 1- and 2-propanol. These two alcohols have similar chemico-physical properties but values of vapor pressure below and above that of water, respectively. Both compounds have much lower surface tension than water. The solvents employed allowed testing of the influence of surface tension on protein spectra obtained from similarly denaturing solutions. The compared solvent conditions gave rise to very similar spectra for each tested protein. We then investigated the effect of the addition of dimethyl sulfoxide to acid-unfolded proteins. We observed enhanced ionization in the presence of acetic or formic acid, consistent with the previously described supercharging effect, but almost no shift of the CSD in the presence of HCl. Finally, we analyzed thermally denatured cytochrome c, to obtain reference spectra of the unfolded protein in high-surface-tension solutions. Also in this case, the CSD of the unfolded protein was shifted towards lower m/z values relative to low-surface-tension systems. In contrast to the other results reported here, this effect is consistent with an influence of solvent surface tension on CSD. The magnitude of the effect, however, is much smaller than predicted by the Rayleigh equation. The results presented here are not easy to reconcile with the hypothesis that the maximum charge state exhibited by proteins in ESI-MS reflects the Rayleigh-limit charge of the precursor droplet. The data are discussed with reference to models for the mechanism of electrospray ionization.


Temperature stability of thin film refractory plasmonic materials.
Materials such as W, TiN, and SrRuO3 (SRO) have been suggested as promising alternatives to Au and Ag in plasmonic applications owing to their stability at high operational temperatures. However, investigation of the reproducibility of the optical properties after thermal cycling between room and elevated temperatures is so far lacking. Here, thin films of W, Mo, Ti, TiN, TiON, Ag, Au, SrRuO3 and SrNbO3 are investigated to assess their viability for robust refractory plasmonic applications. These results are further compared to the performance of SrMoO3 reported in literature. Films ranging in thickness from 50 to 105 nm are deposited on MgO, SrTiO3 and Si substrates by e-beam evaporation, RF magnetron sputtering and pulsed laser deposition, prior to characterisation by means of AFM, XRD, spectroscopic ellipsometry, and DC resistivity. Measurements are conducted before and after annealing in air at temperatures ranging from 300 to 1000° C for one hour, to establish the maximum cycling temperature and potential longevity at elevated temperatures for each material. It is found that SrRuO3 retains metallic behaviour after annealing at 800° C, while SrNbO3 undergoes a phase transition resulting in a loss of metallic behaviour after annealing at 400° C. Importantly, the optical properties of TiN and TiON are degraded as a result of oxidation and show a loss of metallic behaviour after annealing at 500° C, while the same is not observed in Au until annealing at 600° C. Nevertheless, both TiN and TiON may be better suited than Au or SRO for high temperature applications operating under vacuum conditions.


Evaluation of a combined rotavirus and enterotoxigenic Escherichia coli vaccine in cattle.
A vaccine of rotavirus and K99 antigen from enterotoxigenic Escherichia coli was emulsified in oil adjuvant and administered intramuscularly to pregnant cows. Calves born to and reared on vaccinated dams were protected against experimental rotavirus infection at five days old when compared with calves from unvaccinated control cows. Field trials of the vaccine were carried out in 40 commercial herds, in which half the cows in each herd were selected at random for vaccination and half were left unvaccinated. In 31 herds (2641 cows) there was no significant diarrhoea problem (less than 10 per cent morbidity); these herds were excluded from further analysis. The nine remaining herds did experience a calf diarrhoea problem of greater than 10 per cent morbidity, but on four farms the disease was associated with cryptosporidiosis and on a fifth no enteropathogens were detected; these five farms (461 cows) were also excluded from further analysis. Of the remaining four herds, two beef suckler herds (105 cows) had concurrent rotavirus and cryptosporidial infections, and vaccination was associated with a decreased excretion of rotavirus but not with a decreased incidence of diarrhoea. In the other two dairy herds (68 cows) with prevaccination rotavirus problems, there was a significantly decreased incidence of diarrhoea in calves born to vaccinated cows. No natural field challenge of enterotoxigenic E coli was encountered on any of the trial farms.


Multidiscipline Care for Type 2 Diabetes Patients: from General to Asian Population.
Multidiscipline care is defined as a care consisting of at least a physician, a nurse, and other healthcare worker (eg. dietician). Multidiscipline care has generated benefits, both in medical aspects (eg. increasing patients' compliance) and nonmedical aspects (eg. more cost-effective than conventional treatment). There are several models of multidiscpline care; however, which model is more suitable for type 2 diabetes care is not clear yet. In this review, we aimed to identify and compare multidiscipline care method for reducing glycated hemoglobin ( HbA1C) levels in type 2 diabetes patients, particularly Asian patients because they have greater tendency to develop type 2 diabetes at lower degrees of obesity and at younger ages than Caucasian ethnic group. There were limited number of studies examining multidiscipline care for type 2 diabetes patients, moreover for Asian patients. They showed mixed results on the efficacy of multidiscipline care in achieving HbA1C target. Healthcare personnel visit, either personal or group session, appeared effective both for general and Asian T2DM patients. It needs further studies to clarify which models are most effective for practices of varying cultures, socio-economic condition, and healthcare settings.


Control of force through feedback in small driven systems.
Controlling a time-dependent force applied to single molecules or colloidal particles is crucial for many types of experiments. Since in optical tweezers the primary controlled variable is the position of the trap, imposing a target force requires an active feedback process. We analyze this feedback process for the paradigmatic case of a nonequilibrium steady state generated by a dichotomous force protocol, first theoretically for a colloidal particle in a harmonic trap and then with both simulations and experiments for a long DNA hairpin. For the first setup, we find there is an optimal feedback gain separating monotonic from oscillatory response, whereas a too strong feedback leads to an instability. For the DNA molecule, reaching the target force requires substantial feedback gain since weak feedback cannot overcome the tendency to relax towards the equilibrium force.