Predictive value of interleukin-6 and neopterin in patients with multiple myeloma.
Concentrations of interleukin-6 and neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both neopterin (P = 0.0008) and interleukin-6 (P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and neopterin was weak but significant (Spearman's rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both neopterin (P = 0.0001) and interleukin-6 (P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and neopterin or neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, neopterin remained significant in all multivariate models.


The protective effects of resilience and hope on quality of life of the families coping with the criminal traumatisation of one of its members.
This paper investigated the possible predictive and mediating determinates of quality of life in this often forgotten population, focusing specifically on the role of sociodemographics, mental impairments, coping mechanisms, resilience and hope on subjective quality of life. The family members of survivors of man-made trauma are sometimes severely traumatised themselves and may suffer from post-traumatic stress disorder, depression and poor quality of life. Most studies focus on the victims and ignore the effect of the incidents on the victim's family members. Data were collected between October 2007-March 2008, a self-report questionnaire incorporating seven scales was administrated to 175 family members of victims of man-made trauma. One-way anova was performed to compare the variance in the reported quality of life. The structural equation models of path analysis was used to evaluate the main effects and interactions and interrelations among variables. Of the psychosocial factors, having a personal previous traumatic experience was found to significantly affect post-traumatic stress disorder, depression and physical health. Post-traumatic stress disorder and depression were found to directly and indirectly affect quality of life. Coping mechanism, resilience and a hope state mediated the effect of post-traumatic stress disorder and depression making the three significant predictors of subjective quality of life. Based on these findings and the scores of the different scales, clinicians may be able to design treatment plans that encourage the poorly adapting family members of victims of trauma, especially those with symptoms of post-traumatic stress disorder or depression, to accept changes as a part of life, nurture a positive view of the self, make connections for better social support and maintain or re-create a hopeful outlook towards life goals. Knowledge of the psychosocial factors associated with resistance to severe trauma can also help in the prevention and treatment of individuals at high risk for developing post-traumatic stress disorder or depression.


Stress hyperglycemia and the adrenergic regulation of pancreatic hormones in hypoxia.
Stress hyperglycemia occurs in normal and chronically hypoxemic dogs when PaO2's are acutely lowered below 30 torr. Several factors are thought to contribute to the rise in blood glucose. The initial fall in PaO2 activates the sympathetic nervous system, stimulating alpha and beta adrenergic receptors. Because of reduced beta receptor function, alpha receptor effects predominate, promoting glucagon and inhibiting insulin release. The changes in pancreatic hormones in conjunction with the direct effects of hypoxemia and alpha receptor stimulation increase hepatic glycogenolysis. Meanwhile, glucose clearance is decreased because of elevated circulating levels of catecholamines and low insulin concentrations. This combination of events plays a major role in the development of hyperglycemia. Since high blood glucose levels seems to protect the brain and other vital organs at low oxygen tensions, the development of hyperglycemia may represent an important protective mechanism in severely hypoxemic animals, including humans.


Until death do us part: an analysis of the economic well-being of widows in four countries.
Our objective was to show how a woman's economic well-being changes in the United States, Germany, Great Britain, and Canada after her husband's death and the importance of public and private income sources in offsetting the economic consequences of that death. With data from the Cross-National Equivalent File, we used event history analysis to track changes in the social security replacement rate and the more comprehensive total income replacement rate for women and to show how these changes vary across age and household income quintiles within and across countries. There were substantial differences across the countries in how income from specific sources changes, especially with respect to the mix of income from government and private sources, but the overall across-country pattern of total income replacement rates was remarkably similar both in size and in distribution across age and the woman's place in the income distribution prior to her husband's death. Studies that focus on a social security replacement rate will seriously understate the actual total income replacement rate of women following a husband's death. This will especially be the case in countries like the United States where private sources of income play a more important role in income replacement.


Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test.
Estrogen acts through two molecularly distinct receptors termed estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) which bind estradiol with similar affinities and mediate the effects of estrogen throughout the body. ERα plays a major role in reproductive physiology and behavior, and mediates classic estrogen signaling in such tissues as the uterus, mammary gland, and skeleton. ERβ, however, modulates estrogen signaling in the ovary, the immune system, prostate, gastrointestinal tract, and hypothalamus, and there is some evidence that ERβ can regulate ERα activity. Moreover, ERβ knockout studies and receptor distribution analyses in the CNS suggest that this receptor may play a role in the modulation of mood and cognition. In recent years several ERβ-specific compounds (selective estrogen receptor beta modulators; SERM-beta) have become available, and research suggests potential utility of these compounds in menopausal symptom relief, breast cancer prevention, diseases that have an inflammatory component, osteoporosis, cardiovascular disease, and inflammatory bowel disease, as well as modulation of mood, and anxiety. Here we demonstrate an antidepressant-like effect obtained using two SERM-beta compounds, SERM-beta1 and SERM-beta2. These compounds exhibit full agonist activity at ERβ in a cell based estrogen response element (ERE) transactivation assay. SERM-beta1 and 2 are non-proliferative with respect to breast as determined using the MCF-7 breast cancer cell-based assay and non-proliferative in the uterus as determined by assessing the effects of SERM-beta compounds on immature rat uterine weight and murine uterine weight. In vivo SERM-beta1 and 2 are brain penetrant and display dose dependent efficacy in the murine dorsal raphe assays for induction of tryptophan hydroxylase mRNA and progesterone receptor protein. These compounds show activity in the murine forced swim test and promote hippocampal neurogenesis acutely in rats. Taken together these data suggest that ERβ may play an important role in modulating mood and the ERβ specific compounds described herein will be useful tools for probing the utility of an ERβ agonist for treating neuroendocrine-related mood disturbance and menopausal symptoms.


In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature.
Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.


beta-thymosin is required for axonal tract formation in developing zebrafish brain.
beta-Thymosins are polypeptides that bind monomeric actin and thereby function as actin buffers in many cells. We show that during zebrafish development, &bgr;-thymosin expression is tightly correlated with neuronal growth and differentiation. It is transiently expressed in a subset of axon-extending neurons, essentially primary neurons that extend long axons, glia and muscle. Non-neuronal expression in the brain is restricted to a subset of glia surrounding newly forming axonal tracts. Skeletal muscle cells in somites, jaw and fin express beta-thymosin during differentiation, coinciding with the time of innervation. Injection of beta-thymosin antisense RNA into zebrafish embryos results in brain defects and impairment of the development of beta-thymosin-associated axon tracts. Furthermore, irregularities in somite formation can be seen in a subset of embryos. Compared to wild-type, antisense-injected embryos show slightly weaker and more diffuse engrailed staining at the midbrain-hindbrain boundary and a strong reduction of Isl-1 labeling in Rohon Beard and trigeminal neurons. The decreased expression is not based on a loss of neurons indicating that beta-thymosin may be involved in the maintenance of the expression of molecules necessary for neuronal differentiation. Taken together, our results strongly indicate that beta-thymosin is an important regulator of development.


Model for Emergence of Spacetime from Fluctuations.
We use a result of Hawking and Gilkey to define a Euclidean path integral of gravity and matter which has the special property of being independent of the choice of basis in the space of fields. This property allows the path integral to also describe physical regimes that do not admit position bases. These physical regimes are pregeometric in the sense that they do not admit a mathematical representation of the physical degrees of freedom in terms of fields that live on a spacetime. In regimes in which a spacetime representation does emerge, the geometric properties of the emergent spacetime, such as its dimension and volume, depend on the balance of fermionic pressure and bosonic and gravitational pull. That balance depends, at any given energy scale, on the number of bosonic and fermionic species that contribute, which in turn depends on their masses. This yields an explicit mechanism by which the effective spacetime dimension can depend on the energy scale.


Interdisciplinary, web-based, self-study, interactive programs in the dental undergraduate program: a pilot.
The goal of this project was to encourage interdisciplinary, integrative health teaching and research in dental education through the development of web-accessible programs, collectively called the "StudyWeb." The specific objective of the project was the construction and integration of a series of prototypes of self-study modules. Four pilot modules were developed using existing teaching materials in histology, pharmacology, prosthodontics, and oral radiology and utilizing a variety of widely available software programs, including FrontPage and Photoshop. Low-end technological choices were made in order to facilitate compatibility with a wide range of hardware, software, and types of Internet access. Modules were tested for functionality, usability, and ease of navigation. The scope of the initial project was limited to development and functionality testing of the original modules. The next phase of this project will involve testing of the effectiveness of these web-based self-instruction tools.


A novel approach to co-expression network analysis identifies modules and genes relevant for moulting and development in the Atlantic salmon louse (Lepeophtheirus salmonis).
The salmon louse (Lepeophtheirus salmonis) is an obligate ectoparasitic copepod living on Atlantic salmon and other salmonids in the marine environment. Salmon lice cause a number of environmental problems and lead to large economical losses in aquaculture every year. In order to develop novel parasite control strategies, a better understanding of the mechanisms of moulting and development of the salmon louse at the transcriptional level is required. Three weighted gene co-expression networks were constructed based on the pairwise correlations of salmon louse gene expression profiles at different life stages. Network-based approaches and gene annotation information were applied to identify genes that might be important for the moulting and development of the salmon louse. RNA interference was performed for validation. Regulatory impact factors were calculated for all the transcription factor genes by examining the changes in co-expression patterns between transcription factor genes and deferentially expressed genes in middle stages and moulting stages. Eight gene modules were predicted as important, and 10 genes from six of the eight modules have been found to show observable phenotypes in RNA interference experiments. We knocked down five hub genes from three modules and observed phenotypic consequences in all experiments. In the infection trial, no copepodids with a RAB1A-like gene knocked down were found on fish, while control samples developed to chalimus-1 larvae. Also, a FOXO-like transcription factor obtained highest scores in the regulatory impact factor calculation. We propose a gene co-expression network-based approach to identify genes playing an important role in the moulting and development of salmon louse. The RNA interference experiments confirm the effectiveness of our approach and demonstrated the indispensable role of a RAB1A-like gene in the development of the salmon louse. We propose that our approach could be generalized to identify important genes associated with a phenotype of interest in other organisms.


Method for Cryopreservation of Trigeminal Ganglion for Establishing Primary Cultures of Neurons and Glia.
Primary neuronal cultures are used to elucidate cellular and molecular mechanisms involved in disease pathology and modulation by pharmaceuticals and nutraceuticals, and to identify novel therapeutic targets. However, preparation of primary neuronal cultures from rodent embryos is labor-intensive, and it can be difficult to produce high-quality consistent cultures. To overcome these issues, cryopreservation can be used to obtain standardized, high-quality stocks of neuronal cultures. In this study, we present a simplified cryopreservation method for rodent primary trigeminal ganglion neurons and glia from Sprague-Dawley neonates, using a 90:10 (v/v) fetal bovine serum/dimethyl sulfoxide cell freezing medium. Cryopreserved trigeminal ganglion cells stored for up to one year in liquid nitrogen exhibited similar neuronal and glial cell morphology to fresh cultures and retained high cell viability. Proteins implicated in inflammation and pain signaling were expressed in agreement with the reported subcellular localization. Additionally, both neurons and glial cells exhibited an increase in intracellular calcium levels in response to a depolarizing stimulus. Cryopreserved cells were also transiently transfected with reporter genes. Our method is simple, does not require special reagents or equipment, will save time and money, increase flexibility in study design, and produce consistent cultures. This method for the preparation and cryopreservation of trigeminal ganglia results in primary cultures of neurons and glia similar in viability and morphology to fresh preparations that could be utilized for biochemical, cellular, and molecular studies, increase reproducibility, and save laboratory resources.


[Mother's hemoglobin in perinatal and mother health in the highlands: implications in the Andean Region].
This review analyzes the importance of hemoglobin levels in pregnant women and its implications in pregnancy. It discuss the use of biomass fuel for cooking and the impact on birthweight, maternal hemoglobin levels and the risk of late fetal death, pre-term delivery, and small for gestational age. Furthermore, the need to correct the cut-off points of hemoglobin level to define anemia at high altitudes is addressed. Current evidence suggests that corrections should not be made and iron supplements should be given to pregnant mothers with moderate or severe anemia. It is discussed whether iron supplementation should change its target population from pregnant women to infants aged 6 to 36 months.


Immunohistological localisation of rinderpest virus in formalin-fixed, paraffin-embedded tissues from experimentally infected cattle.
Six Freesian steers were subcutaneously inoculated with the virulent rinderpest virus strain Kabete "0" and sacrificed at the height of fever. Sections of formalin-fixed, paraffin-embedded tissues were stained according to the peroxidase anti-peroxidase (PAP) technique. Labelling of viral antigen, both in the cytoplasm and in the nuclei of infected cells, was observed in the epithelial cells of the upper and lower alimentary tract and in lymphoid organs, i.e. spleen, lymph nodes, pharyngeal tonsils, Peyer's patches and thymus. Electron microscopy studies confirmed the results.


The Cardiovascular Effects of Cocoa Polyphenols-An Overview.
Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%-38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%-65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health.


Lipid compositions modulate fluidity and stability of bilayers: characterization by surface pressure and sum frequency generation spectroscopy.
Cell membranes are crucial to many biological processes. Because of their complexity, however, lipid bilayers are often used as model systems. Lipid structures influence the physical properties of bilayers, but their interplay, especially in multiple-component lipid bilayers, has not been fully explored. Here, we used the Langmuir-Blodgett method to make mono- and bilayers of 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG), and 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine (POPS) as well as their 1:1 binary mixtures. We studied the fluidity, stability, and rigidity of these structures using sum frequency generation (SFG) spectroscopy combined with analyses of surface pressure-area isotherms, compression modulus, and stability. Our results show that single-component bilayers, both saturated and unsaturated, may not be ideal membrane mimics because of their low fluidity and/or stability. However, the binary saturated and unsaturated DPPG/POPG and DPPG/POPS systems show not only high stability and fluidity but also high resistance to changes in surface pressure, especially in the range of 25-35 mN/m, the range typical of cell membranes. Because the ratio of saturated to unsaturated lipids is highly regulated in cells, our results underline the possibility of modulating biological properties using lipid compositions. Also, our use of flat optical windows as solid substrates in SFG experiments should make the SFG method more compatible with other techniques, enabling more comprehensive future surface characterizations of bilayers.


The roles of canonical and non-canonical Wnt signaling in human de-differentiated articular chondrocytes.
Osteoarthritis is the most prevalent form of arthritis in the world and it is becoming a major public health problem. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to de-differentiation. The involvement of signaling pathways, such as the Wnt pathway, during cartilage pathology has been reported. Wnt signaling regulates critical biological processes. Wnt signals are transduced through at least three intracellular signaling pathways including the canonical Wnt/β-catenin pathway, the Wnt/Ca2 + pathway and the Wnt/planar cell polarity pathway. We investigated the involvement of the Wnt canonical and non-canonical pathways in human articular chondrocyte de-differentiation in vitro. Human articular chondrocytes were cultured through four passages with no treatment, or with sFRP3 treatment, an inhibitor of Wnt pathways, or with DKK1 treatment, an inhibitor of the canonical pathway. Chondrocyte-secreted markers and Wnt pathway components were analyzed using western blotting and qPCR. Inhibition of the Wnt pathway showed that the canonical Wnt signaling probably is responsible for inhibition of collagen II expression, activation of metalloproteinase 13 expression and regulation of Wnt7a and c-jun expression during chondrocyte de-differentiation in vitro. Our results also suggest that expressions of eNOS, Wnt5a and cyclinE1 are regulated by non-canonical Wnt signaling.


Impact of a hospital-based educational intervention on dietary salt-related knowledge and behaviour in a cardiac care unit population in Lebanon.
Cardiovascular disease is the most common cause of morbidity and mortality worldwide. Numerous strategies have been effective in reducing cardiovascular disease risk, from pharmacological approaches to lifestyle modification interventions. One of these strategies includes the reduction in dietary sodium which in turn reduces cardiovascular risk by reducing high blood pressure, perhaps the most important cardiovascular risk factor. We evaluated an educational dietary salt reduction intervention in a cardiac care unit population in Lebanon, assessing salt related knowledge and behaviours before and after administering an evidence-based educational leaflet to patients. Salt-related knowledge improved significantly immediately post-intervention and subsequently fell on 4-week follow-up, but remained above baseline. Three of the four salt-related behaviours measured improved on 4-week follow-up: trying to buy low-salt foods increased from 54% to 74% (P=0.007), adding salt at the table reduced from 44% to 34% (P=0.03) and trying to buy food with no added salt increased from 24% to 52% (P=0.02) of the cohort. Adding salt during cooking did not differ significantly. A trend towards improved behavioural risk category in the cohort overall was observed on follow-up (P=0.07), 32% of participants were categorised as high behavioural risk pre-intervention, reducing to 17% on follow-up. Multi-ordered regression modelling identified being in the high-risk behavioural category at baseline as a predictor of being in the high-risk or moderate-risk category on follow-up. This hospital-based educational intervention had a modestly positive impact on salt-related knowledge and behaviour, with participants in the highest behavioural risk category at baseline being most resistant to behavioural improvement.


Concurrent bariatric operations and association with perioperative outcomes: registry based cohort study.
Objective To determine whether perioperative outcomes differ between patients undergoing concurrent compared with non-concurrent bariatric operations in the USA.Design Retrospective, propensity score matched cohort study.Setting Hospitals in the US accredited by the American College of Surgeons' metabolic and bariatric surgery accreditation and quality improvement program.Participants 513 167 patients undergoing bariatric operations between 1 January 2014 and 31 December 2016.Main outcome measures The primary outcome measure was a composite of 30 day death, morbidity, readmission, reoperation, anastomotic or staple line leak, and bleeding events. Operative duration and lengths of stay were also assessed. Operations were defined as concurrent if they overlapped by 60 or more minutes or in their entirety.Results In this study of 513 167 operations, 739 (29.5%) surgeons at 483 (57.8%) hospitals performed 6087 (1.2%) concurrent operations. The most frequently performed concurrent bariatric operations were sleeve gastrectomy (n=3250, 53.4%) and Roux-en-Y gastric bypass (n=1601, 26.3%). Concurrent operations were more often performed at large academic medical centers with higher operative volumes and numbers of trainees and by higher volume surgeons. Compared with non-concurrent operations, concurrent operations lasted a median of 34 minutes longer (P<0.001) and resulted in 0.3 days longer average length of stay (P<0.001). Perioperative adverse events were not observed to more likely occur in concurrent compared with non-concurrent operations (7.5% v 7.4%; relative risk 1.02, 95% confidence interval 0.90 to 1.15; P=0.84).Conclusions Concurrent bariatric operations occurred infrequently, but when they did, there was no observable increased risk for adverse perioperative outcomes compared with non-concurrent operations. These results, however, do not argue against improved and more meaningful disclosure of concurrent surgery practices.


Bacteremia and skin/bone infections in two patients with X-linked agammaglobulinemia caused by an unusual organism related to Flexispira/Helicobacter species.
Two patients with Bruton's X-linked agammaglobulinemia are described with bacteremia and skin/bone infection due to an organism which by 16S rRNA gene sequence analysis was most closely related to "Flexispira" rappini (and thus designated a Flexispira-like organism, FLO) and more distantly related to the Helicobacter species. The organism required microaerobic conditions and, supplemental H(2) gas for growth and was reliably stained with acridine orange. In common with Helicobacter cinaedi infections, the focus of the FLO infection was in one case in the blood vessels or lymphatics of an extremity and in the other case in the skin and adjacent bone of an extremity. In both cases, prolonged IV antibiotic therapy was necessary to clear the infection. The susceptibility of XLA patients to FLO infection appears to be related to the fact that XLA is associated with severe B cell (humoral) immunodeficiency and thus these patients have difficulty with intravascular or intralymphatic infection. These findings elucidate the nature of FLO infections in humans and point the way to their detection and treatment.


False accusations of physical and sexual abuse.
Child sexual abuse is sometimes mistakenly over-reported. This discussion of seven cases focuses on one potential area which can generate a substantial segment of false positives: conflicted domestic relations litigation situation. Such situations generate striking, regressive affect and behavior especially when issues of child custody or visitation erupt. Parental regression has been discussed in the literature, but children regress too: behavioral symptoms erupt with vegetative and social disruption, and instinctual material regarding both sex and anger is more accessible to consciousness than is age-appropriate. Heightened instinctual forces in children and regressive loosening of pre-litigation character defenses in adults, both in the context of stressful family breakdown, combine to generate genuine perceptions of abuse but invalid reports.


Assembly and analysis of conical models for the HIV-1 core.
The genome of the human immunodeficiency virus (HIV) is packaged within an unusual conical core particle located at the center of the infectious virion. The core is composed of a complex of the NC (nucleocapsid) protein and genomic RNA, surrounded by a shell of the CA (capsid) protein. A method was developed for assembling cones in vitro using pure recombinant HIV-1 CA-NC fusion proteins and RNA templates. These synthetic cores are capped at both ends and appear similar in size and morphology to authentic viral cores. It is proposed that both viral and synthetic cores are organized on conical hexagonal lattices, which by Euler's theorem requires quantization of their cone angles. Electron microscopic analyses revealed that the cone angles of synthetic cores were indeed quantized into the five allowed angles. The viral core and most synthetic cones exhibited cone angles of approximately 19 degrees (the narrowest of the allowed angles). These observations suggest that the core of HIV is organized on the principles of a fullerene cone, in analogy to structures recently observed for elemental carbon.


Associate plant parasitic nematodes to weed species in some newly reclaimed lands.
Plant-parasitic nematodes (PPNs) are vital soil organisms well-known to damage and reduce crop yield worldwide. Surveys were attempts to determine the impact of weed species on the communities and composition of nematodes in barley, wheat, quinoa, eggplant, and tomato crops in Alexandria and Ismailia regions of Egypt. During the surveys, eight occurring genera of nematodes were found namely; Meloidogyne spp, Pratylenchus spp, Helicotylenchus spp, Rotylenchulus spp, Xiphinema spp, Criconemoides spp, Ditylenchus spp, and Longidorus spp associated with the soil's rhizosphere of 28 weed species belonging to 12 families. Among these weeds, Hordeum marinum and Sonchus oleraceus were good hosts to nematode species. Both wheat and barley had higher nematode diversity than quinoa in the winter season. Pratylenchus spp, Meloidogyne spp and Rotylenchulus spp can be considered vital potential PPNs with economic importance. Nematode abundances and structural indices varied greatly based on the host weed species, crop types and soil characteristics. A positive correlation was monitored among weeds, nematode frequencies and relative abundances as well as their crops. Finally, weed species are critical components in nematode communities that may increase the incidence and severity of nematode risks based on crop type and soil characteristics. Therefore weeds should be managed properly to diminish reservoir sites when developing nematode management options.


Metabolic products of microorganisms. 225. Elloramycin, a new anthracycline-like antibiotic from Streptomyces olivaceus. Isolation, characterization, structure and biological properties.
Elloramycin (1), a new antibiotic produced by Streptomyces olivaceus strain Tü 2353, was detected by chemical screening. The dark yellow compound, molecular formula C32H36O15, is weakly active against a variety of Gram-positive bacteria, especially streptomycetes and against stem cells of L-1210 leukemia. Acidic hydrolysis of the antibiotic liberated elloramycinone (3) as aglycone and 2,3,4-tri-O-methyl-L-rhamnose, which was identified as methyl glycoside 5b. The structure of elloramycin was established by comparison of the spectra (UV, 1H NMR, 13C NMR) with those of the known tetracenomycin C (2), 3 and the fact that 2 and 3 gave the same tetramethyl ether after permethylation. Elloramycin is an anthracycline-like antibiotic, the aglycone resembles tetracenomycin C, the sugar is connected in a phenolic alpha-glycosidic linkage.


Italian-Moldovan international nurse migration: rendering visible the loss of human capital.
To describe the process of the migration of Moldovan nurses to Italy. Formerly a part of the Soviet Union, the Republic of Moldova gained independence in 1991. Currently, there are 25 848 nurses (60.6 per 10,000 inhabitants) working mainly in the public health system. Each year, around 2000 nurses leave the country in search of better working conditions and a better quality of life. A longitudinal study design was adopted (2006-2007). In the first phase, we contacted all known nurses living in Moldova and their available colleagues following a snowball sampling strategy. Inclusion criteria were nurses who had decided to migrate to Italy and had already prepared the migration documents and/or were awaiting their departure. In the second phase, we interviewed the same sample of nurses on arrival in Italy. After one year, only 25 nurses out of the 110 initially interviewed (22.7%) had arrived in Italy; none were working as nurses. The cost of the migration process incurred by each nurse was around 3278 euros, and the waiting time from the decision to leave until arrival was around 24 months. All Moldovan nurses involved in this study, once they arrived in Italy, ceased to exist from an official perspective. Policy and recommendations need to be developed to ensure the integration of Moldovan-educated nurses into the health-care system and to monitor the amount of human capital (in terms of care drain, brain drain and youth drain) that this process risks wasting.


HER2 Amplification by Next-Generation Sequencing in Lung Carcinoma: A Comparison of NGS Amplified and Non-amplified Cases by Immunohistochemistry and In Situ Hybridization
Although the role of HER2 amplification and its evaluation methods are well known in breast carcinoma, methods for detection of HER2 amplification in non-small cell lung carcinoma are unclear. Next-generation sequencing is widely used in searching multiple therapeutic targets, and it is possible to evaluate copy number variation of genes by next-generation sequencing. To re-evaluate the HER2 status of non-small cell lung carcinoma cases detected as HER2 amplified and non-amplified by next-generation sequencing via the most commonly used HER2 investigation methods in routine pathology practice, namely immunohistochemistry and in situ hybridization. Retrospective cross-sectional study. Among the 256 patients whose mutation profiles were examined by next-generation sequencing, HER2 amplified (13 cases) and non-HER2-amplified (13 cases) were determined as study and control groups, respectively, by next-generation sequencing. HER2 next-generation sequencing amplified tumors were investigated for HER2 expression and amplification using immunohistochemistry and silver in situ hybridization. From a group of 256 non-small cell lung carcinoma, 33 tumors (12.8%) showed HER2 amplification with next-generation sequencing. Although we observed more frequent HER2 positivity by immunohistochemistry in next-generation sequencing-amplified cases, when compared to non-amplified cases (50% and 23% respectively), the difference was not significant (P = .221). Within the HER2 amplified group, inter-method-agreement was very good between next-generation sequencing results amplification and in situ hybridization status. Next-generation sequencing results showed a strong interclass correlation coefficient with HER2/cell (P = .009, r = 0.777) and HER2/CEP17 ratio (P = .001, r = 0.805). The median HER2/CEP17 ratio was higher in the next-generation sequencing amplified group (P = .013); however, three cases were found to be amplified by silver in situ hybridization among the next-generation sequencing non-amplified cases. EGFR and FGFR1 amplification were more frequent in HER2 next-generation sequencing amplified group than next-generation sequencing non-amplified group (P < .001). Until the effects of HER2 amplification on the HER2 protein are well understood and pulmonary carcinoma algorithms are defined, non-small cell lung carcinomas found to be amplified by next-generation sequencing should be verified by additional methods.


Lys Tag: an easy and robust chemical modification for improved de novo sequencing with a matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometer.
Mass spectrometry using a matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) instrument is a widespread technique for various types of proteomic analysis. Along with an expanding interest in proteomics, there is a strong requirement for the identification of proteins with high confidence from biological samples. Peptide modification by a wide variety of post-translational modifications (PTMs), the existence of different protein isoforms and the presence of uncharacterized genomes of many species, make protein identification through peptide mass fingerprinting (PMF) often unachievable. Peptide de novo sequencing has been proven to be a useful approach to overcome these variables, and efficient derivatization processes are important tools to achieve this goal. In the present work we describe the methodology and experimental applications of a fast, efficient and cheap lysine derivatization. This chemical modification improves the signals from lysine-terminated peptides and can be efficiently used as a lysine-blocking agent in combination with other derivatization techniques. Most importantly, upon peptide fragmentation it generates a neat series of predominantly y-ions, allowing the determination of unambiguous amino acid sequences. Moreover, this chemical compound was used with target-eluted samples, enabling a second, alternative analysis of the same sample in the MALDI mass spectrometer.


Study of factors responsible for recidivism in allergic fungal rhinosinusitis.
Patients with allergic fungal rhinosinusitis (AFRS) are typically atopic and immunocompetent. Despite combined modality treatment based on surgery and immunomodulation, the potential for recidivism is well recognized. A study was conducted in a military hospital in India to identify the factors responsible for recidivism in AFRS and to suggest measures to overcome it. Sixty patients with AFRS (42 new cases and 18 cases that required revision surgery) were managed between January 2009 and July 2013. Patients underwent endoscopic, radiologic, and laboratory evaluation for AFRS followed by functional endoscopic sinus surgery. Each patient received oral prednisolone, 1 mg/kg/day, for 1 week preoperatively and 0.5 mg/kg/day for 4 weeks postoperatively. A randomly selected group of 30 patients (group A) received oral prednisolone 0.4 mg/kg/day for the next 4 weeks, tapered to 0.2 mg/kg/day for the next 2 months and to 0.1 mg/kg/day for the last 2 months. The drug was stopped after 6 months. In the remaining 30 patients (group B), oral prednisolone was tapered within 2 months. Topical steroid sprays were advised in all patients. Recidivism was observed in 12 of 42 (28.6%) patients presenting for the first time with AFRS: 9 patients from group B (30%) and 3 patients from group A (10%). Besides inadequate postoperative oral steroid therapy, suboptimal functional endoscopic sinus surgery, noncompliance with intranasal sprays, nonadherence to Kupferberg staging, inadequate follow-up, failure of surgeons to impart health education to patients, and unavailability of ENT consultation in rural belts were found to be factors causing recidivism.


Demographic and preliminary employment data of the first two graduate cohorts from a rural veterinary school.
To report initial career experiences and graduate employment destinations 1 and 5 years following graduation of the 67 graduates from the first two graduating classes of the veterinary science program at Charles Sturt University. Online survey of graduates from the 2010 and 2011 cohorts undertaken 12 months following course completion and descriptive data on graduate practice locations 5 years post-graduation. Questions covered general demographic information, issues relating to work-life balance and factors influencing vocational choices. Descriptive statistics and qualitative responses are reported, with comparisons between continuous variables by two-sample t-test and between categories by Chi-square analyses. Significance was set at P < 0.05. Graduates' locations 5 years after graduation were obtained from veterinary registration details and staff contact with graduates. Complete survey responses were received from 39 graduates of whom 34 were employed in regional areas, 1 in a very remote area, 3 in major cities and 1 overseas. Hours worked and salary received were consistent with other survey data, with new graduates working in regional practices earning slightly more than those working in metropolitan practices. At 5 years following graduation, the majority (56/61, 92%) remained in rural or regional Australian veterinary practices, with a further five graduates overseas and one lost to follow-up. This study supported the selection criteria and educational approaches at CSU in establishing most of the new graduates in rural and regional mixed veterinary practice.


Dose-finding study of high-dose simvastatin combined with standard chemotherapy in patients with relapsed or refractory myeloma or lymphoma.
In vitro statins induce apoptosis in myeloma and lymphoma cells in a dose-and time-dependent way. In combination with dexamethasone and doxorubicin, statins have a chemo-sensitizing effect. Twenty-eight patients with relapsed myeloma or lymphoma were treated with a dose-escalating regimen of simvastatin for 7 days followed by VAD in myeloma patients and CHOP in lymphoma patients. The maximum tolerated dose was 15 mg/kg/day simvastatin. The most frequently reported side-effects were fatigue, gastrointestinal CTC grade 1-2 and neutropenic fever. The dose-limiting toxicity was neutropenic sepsis and grade 3 gastrointestinal side effects. High-dose simvastatin given immediately prior to chemotherapy is safe and tolerable up to a dose of 15 mg/kg/day.


Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.
Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety.


Characterization of cross-bridge elasticity and kinetics of cross-bridge cycling during force development in single smooth muscle cells.
Force development in smooth muscle, as in skeletal muscle, is believed to reflect recruitment of force-generating myosin cross-bridges. However, little is known about the events underlying cross-bridge recruitment as the muscle cell approaches peak isometric force and then enters a period of tension maintenance. In the present studies on single smooth muscle cells isolated from the toad (Bufo marinus) stomach muscularis, active muscle stiffness, calculated from the force response to small sinusoidal length changes (0.5% cell length, 250 Hz), was utilized to estimate the relative number of attached cross-bridges. By comparing stiffness during initial force development to stiffness during force redevelopment immediately after a quick release imposed at peak force, we propose that the instantaneous active stiffness of the cell reflects both a linearly elastic cross-bridge element having 1.5 times the compliance of the cross-bridge in frog skeletal muscle and a series elastic component having an exponential length-force relationship. At the onset of force development, the ratio of stiffness to force was 2.5 times greater than at peak isometric force. These data suggest that, upon activation, cross-bridges attach in at least two states (i.e., low-force-producing and high-force-producing) and redistribute to a steady state distribution at peak isometric force. The possibility that the cross-bridge cycling rate was modulated with time was also investigated by analyzing the time course of tension recovery to small, rapid step length changes (0.5% cell length in 2.5 ms) imposed during initial force development, at peak force, and after 15 s of tension maintenance. The rate of tension recovery slowed continuously throughout force development following activation and slowed further as force was maintained. Our results suggest that the kinetics of force production in smooth muscle may involve a redistribution of cross-bridge populations between two attached states and that the average cycling rate of these cross-bridges becomes slower with time during contraction.


The effect of the molluscicide N-tritylmorpholine on transmission of Fasciola hepatica.
Field trials were carried out in north Devon to investigate the relationship between molluscicide treatment of pastures and control of liver fluke infection in sheep. Seven tracer lambs per plot were used to estimate the infectivity of 17 pairs of 0.20 hectare plots. One plot in each pair was treated with the molluscicide Frescon (N-tritylmorpholine). There was a highly significant difference (P less than 0.001) between the numbers of Fasciola hepatica recovered from lambs grazed on treated and untreated plots in the period after molluscicide treatment. The overall degree of snail control achieved by one application of molluscicide to 17 plots was about 90 per cent and this was matched by a comparable degree of liver fluke control. There was considerable variation between the plots and there was no simple correlation between snail numbers and liver fluke numbers (r = -0.03). The use of molluscicides is discussed in relation to the biotic potential of Lymnaea truncatula and environmental factors which limit its population growth.


[Descriptive study of first visits in a multiple sclerosis specialised unit].
The need for optimal care has led to implementation of multiple sclerosis care units, specialised in diagnosis and follow-up of multiple sclerosis patients. Since information on multiple sclerosis prognosis is crucial, accurate diagnosis is one of their major roles. Prospective analysis of first visits during a year (origin and diagnosis) at the Unidad de Neuroinmunología Clínica of Hospital Vall d'Hebron. A total of 437 first visits were analysed; a moderate agreement (kappa = 0.468) between referral diagnoses and diagnosis at follow-up was obtained; agreement was very good (kappa = 0.844) between diagnosis at first visit and diagnosis at follow-up. In the subgroup of 200 patients with a demyelinating disease on follow-up after one year, 37.6% of referrals came from other non-specialised centers and 40.6% from our own center. Specialised care units enhance diagnostic precision; direct influence zone and non-specialised centers referrals are their more important sources of patients.


Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence.
Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study.


Evaluation of accuracy of multitest micromethod system for identification of Enterobacteriaceae.
The Analytab system of 20 biochemical tests for identification of Enterobacteriaceae was evaluated in parallel with conventional tests on 128 Enterobacteriaceae, 5 Aeromonas, and 1 Yersinia enterocolitica. The results of tests for H(2)S and indole production, citrate utilization, lysine and ornithine decarboxylase, arginine dihydrolase, nitrate reduction, beta-galactosidase, and fermentation of arabinose, rhamnose, mannitol, and glucose showed almost complete agreement between the two systems. Eighty-eight per cent of Enterobacteriaceae were correctly speciated with the Analytab system; on repeat testing with heavier inocula of organisms failing to ferment glucose initially, the proportion of Enterobacteriaceae correctly speciated became 93%.


Exploring the Pathways Between Transformative Group Experiences and Identity Fusion.
A growing body of evidence suggests that two distinct forms of group alignment are possible: identification and fusion (the former asserts that group and personal identity are distinct, while the latter asserts group and personal identities are functionally equivalent and mutually reinforcing). Among highly fused individuals, group identity taps directly into personal agency and so any attack on the group is perceived as a personal attack and motivates a willingness to fight and possibly even die as a defensive response. As such, identity fusion is relevant in explaining violent extremism, including suicidal terrorist attacks. Identity fusion is theorized to arise as a result from experiences which are (1) perceived as shared and (2) transformative, however evidence for this relationship remains limited. Here, we present a pre-registered study in which we examine the role of transformativeness and perceived sharedness of group-defining events in generating identity fusion. We find that both of these factors are predictive of identity fusion but that the relationship with transformativeness was more consistent than perceived sharedness across analyses in a sample of Indonesian Muslims.


Colostral proline-rich polypeptides--immunoregulatory properties and prospects of therapeutic use in Alzheimer's disease.
A proline-rich polypeptide complex (PRP), subsequently called Colostrinin(CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. PRP seems to restore balance in cellular immune functions and is not species specific. PRP is a complex of peptides of molecular masses ranging from 500 to 3000 Da. The polypeptide contains 25% proline and 40% hydrophobic amino acids. PRP shows a regulatory activity in cytokine (IFN, TNF-alpha, IL-6, IL-10) induction and possesses the ability to inhibit the overproduction of oxygen reactive species and nitric oxide. Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies. The results were confirmed in multicenter clinical trials. A very important property of PRP/Colostrinin is the prevention of Abeta aggregation and the disruption of already existing aggregates. The same properties were expressed by one of PRP's components, a nonapeptide (NP). Moreover, PRP modulates neurite outgrowth, suppresses uncontrolled activation of cells, reduces 4-HNE-mediated cellular damage, and modulates expression in cellular redox regulation, cell proliferation, and differentiation. Its biological response modifying activity can play an important role in its use in the treatment of Alzheimer's disease.


Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds.
Promoting angiogenesis is a key strategy for stimulating the repair of damaged tissues, including bone. Among other proangiogenic factors, ions have recently been considered a potent element that can be incorporated into biomaterials and then released at therapeutic doses. Silicate-based biomaterials have been reported to induce neovascularization through vascular endothelial growth factor signaling pathway, potentiating acceleration of bone regeneration. Here, we designed a silicate-shelled hydrogel fiber scaffold with a hard/soft layered structure to investigate the possibility of silicate coating on biopolymer for enhancing biological properties. An alginate hydrogel was injected to form a fiber scaffold with shape-tunability that was then coated with a thin silicate layer with various sol-gel compositions. The silicate/alginate scaffold could release calcium and silicate ions, and in particular, silicate ion release was highly sustainable for over one week at therapeutically relevant levels. The ionic release was highly effective in stimulating the mRNA expression of angiogenic markers (VEGF, KDR, eNOS, bFGF, and HIF1-α) in endothelial cells (HUVECs). Moreover, the in vitro tubular networking of cells was significantly enhanced (1.5 times). In vivo implantation in subcutaneous tissue revealed more pronounced blood vessel formation around the silicate-shelled scaffolds than around silicate-free scaffolds. The presence of a silicate shell was also shown to accelerate acellular mineral (hydroxyapatite) formation. The cellular osteogenesis potential of the silicate/alginate scaffold was further proven by the enhanced expression of osteogenic genes (Col1a1, ALP and OCN). When implanted in a rat calvarium defect, the silicate-shelled scaffold demonstrated significantly improved bone formation (2-3 times higher in bone volume and density) with a concurrent sign of proangiogenesis. This work highlights that the surface-layering of silicate composition is an effective approach for improving the bone regeneration capacity of polymeric hydrogel scaffolds by stimulating ion-induced angiogenesis and providing bone bioactivity to the surface.


Cardiovascular complications of inactivity.
Inactivity has a number of consequences for the cardiovascular system. In particular, inactivity can lead to obesity, which can aggravate arthritis. An examination of the effect of exercise on the cardiovascular system requires the review of epidemiologic or population-based studies, because there are no large randomized trials with an exercise control group. Small randomized trials looking at exercise and the individual risk factors are reviewed.


Association between renin-angiotensin-aldosterone system blockers and postoperative atrial fibrillation in patients with mild and moderate left ventricular dysfunction.
The aim of the study was to evaluate the association between renin - angiotensin - aldosterone system blockers and risk of postoperative atrial fibrillation (AF) development in patients with mild and moderate left ventricular systolic dysfunction. The population of this prospective and observational study consisted of 269 patients with an ejection fraction of < or = 50% undergoing coronary artery bypass and/or valve surgery. Use of renin -angiotensin-aldosterone system blockers (angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and spironolactone) and their association with postoperative AF (AF episode lasting < or = 5 min) were evaluated. In statistical analysis t test for independent samples, Chi-square test and Mann Whitney U test were used for comparison of variables between groups. Predictors of postoperative AF were determined by multiple logistic regression analysis. During follow-up, 50 patients (13%) developed postoperative AF. With multiple logistic regression analysis, risk factors for postoperative AF were determined: left atrial diameter (OR- 1.09; 95%CI 1.01-1.16, p=0.02), age (OR-1.04; 95%CI 1.002- 1.08, p=0.04), aortic cross-clamp duration (OR- 1.03, 95%CI -1.00-1.05, p=0.01), use of left internal mammarian artery (OR-0.33; 95%CI 0.13-0.88, p=0.03), ACEIs treatment (OR-0.27; 95%CI 0.12-0.62, p=0.002), and ARBs treatment (OR - 0.21, 95%CI 0.07-0.62, p=0.005). Our results indicate that although treatments with ACEIs and ARBs are associated with low incidence of postoperative AF in patients with mild and moderate left ventricular systolic dysfunction, treatment with spironolactone is not.


Rapid Inference of Direct Interactions in Large-Scale Ecological Networks from Heterogeneous Microbial Sequencing Data.
The availability of large-scale metagenomic sequencing data can facilitate the understanding of microbial ecosystems in unprecedented detail. However, current computational methods for predicting ecological interactions are hampered by insufficient statistical resolution and limited computational scalability. They also do not integrate metadata, which can reduce the interpretability of predicted ecological patterns. Here, we present FlashWeave, a computational approach based on a flexible Probabilistic Graphical Model framework that integrates metadata and predicts direct microbial interactions from heterogeneous microbial abundance data sets with hundreds of thousands of samples. FlashWeave outperforms state-of-the-art methods on diverse benchmarking challenges in terms of runtime and accuracy. We use FlashWeave to analyze a cross-study data set of 69,818 publicly available human gut samples and produce, to the best of our knowledge, the largest and most diverse network of predicted, direct gastrointestinal microbial interactions to date. FlashWeave is freely available for download here: https://github.com/meringlab/FlashWeave.jl.


[Radiation and chemoradiation therapy of malignant laryngopharyngeal tumors].
The paper is concerned with the results of open field gamma-beam therapy using grid filters. A group of patients with Stage III-IV tumors received chemoradiotherapy. A single focal radiotherapeutic dose varied from 1.6 to 2.5 Gy, a summary dose from 55 to 70 Gy depending on tumor stage and histological structure. A chemotherapeutic drug was prescribed within the limits of 1/2-2/3 of a standard dose. Intensive substitution and blood-stimulating therapy was provided. With the use of different radiotherapeutic and chemoradiotherapeutic methods the 3- and 5-year survival rates were 19.8% and 14.3%, respectively.


Issues in training and development.
In the last report in this series describing re-engineering at The Leicester Royal Infirmary NHS Trust, the implications of a re-engineered patient process on the training and development of staff are discussed.


Performance of x-ray imaging systems applied to intravenous angiography.
A review is made of the performance of X-ray systems applied to the imaging of dilute amounts of iodine using subtraction methods. Relevant performance criteria are defined and desired performance levels are derived. For a general purpose system these are iodine sensitivity of 1 mg/cm2, cancellation of 10 g/cm2 soft tissue and 2 g/cm2 bone to be equivalent to iodine sensitivity, capability of imaging through 25 cm soft tissue, spatial resolution exceeding 1 lp/mm and acceptable imaging time depending on the application. Conceptual aspects of several subtraction techniques are discussed including temporal, generalized temporal, dual-energy K-edge, dual-energy non-K-edge, three-energy K-edge, and hybrid subtraction. Experimental performance of several representative area and linear detector systems is tabulated according to subtraction algorithm. A table of references is provided.


The case for social evaluation in preverbal infants: gazing toward one's goal drives infants' preferences for Helpers over Hinderers in the hill paradigm.
In a 2007 empirical report, Hamlin, Wynn, and Bloom provided the first evidence that preverbal infants at 6 and at 10 months of age evaluate others on the basis of their helpful and unhelpful actions toward unknown third parties. In their "hill paradigm," a Climber puppet tried but failed to climb a steep hill, and was alternately bumped up the hill by the Helper and bumped down the hill by the Hinderer. After being habituated to these events, both 10- and 6-month-olds selectively reached for the Helper over the Hinderer. In response, Scarf et al. (2012b) provided evidence that rather than reflecting an early developing capacity for social evaluation, infants' choices in Hamlin et al. (2007) reflected low-level perceptual preferences whereby infants are drawn to any character who is associated with the Climber bouncing. The current studies represent an attempt to adjudicate between the social and perceptual accounts of infants' preferences for Helpers over Hinderers in the hill paradigm, by pitting a perceptual cue (e.g., bouncing) against a social cue (e.g., whether or not the Climber gazes toward his goal). Infants' patterns of preference across two experiments support the social account.


Dynamics of the melatonin MT1 receptor in the rat parotid gland upon melatonin administration.
Our recent ultrastructural study of human parotid glands revealed that the melatonin receptors, MT1 and MT2, are localised in the plasma cell membranes of acinar and ductal cells but also, and intriguingly, predominantly in acinar secretory granules, giving rise to the working hypothesis that secretory granules are a part of a transcytotic transport system for melatonin. To put this hypothesis to the test in rat parotid glands, anaesthetised animals were exposed to a high melatonin dose (3 mg/kg per hour), infused intravenously over two hours and aiming to stimulate a glandular melatonin-receptor-dependent intracellular transport system, if any. Thirty minutes later, the right parotids were removed. Pre-stimulation, left parotid gland tissue was removed to serve as (untreated) controls. Gland tissues were processed for the gold post-embedding technique and for western blot analysis. In untreated glands, on transmission electron microscope images, melatonin receptors displayed a distribution pattern similar to that in human parotids, i.e. here, too, the receptors were principally associated with the acinar secretory granules. In melatonin- treated glands, the number of granules associated with the MT1 receptor was twice that in untreated glands, despite the same total granule number in the two glands. Moreover, the density of gold particles showing MT1-receptor immunoreactivity associated with granules in melatonin-treated glands was 2.5 times that in untreated glands. The number of MT1 receptors associated with the granule membrane was about three times higher in melatonin-treated glands than in untreated glands, while the number of MT1 receptors inside the granules was about twice that in untreated glands. The immunoblotting of membrane-enriched samples showed that the MT1-receptor expression was about three times that of untreated glands. When it came to the MT2 receptor, no changes were observed. Melatonin itself thus exerts dynamic effects on its MT1 receptor, which may reflect an adaptive receptor-linked carrier system for melatonin, delivering - upon gland stimulation - melatonin to the saliva by exocytosis.


Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke.
Environmental tobacco smoke (ETS) is associated with lung cancer in nonsmokers. Most epidemiologic studies find a higher risk for lung cancer in nonsmoking women married to smokers than in those married to nonsmokers. We measured metabolites of a tobacco-specific lung carcinogen in urine from healthy, nonsmoking women exposed to ETS. We recruited women and their partners through advertisements. Couples completed questionnaires on smoking history and demographics, and both partners provided 100 mL of urine; 23 women had male partners who smoked in the home (i.e., exposed women), and 22 women had male partners who did not smoke (i.e., unexposed women). Urine samples were analyzed for nicotine, for cotinine, for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc), as well as for creatinine. NNAL and NNAL-Gluc are metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unpaired Student's t tests were conducted on log-transformed values. All statistical tests are two-sided. Urinary levels of nicotine, cotinine, NNAL, and NNAL-Gluc were statistically significantly higher in exposed women than in unexposed women. Geometric means for these compounds in exposed versus unexposed women, respectively, were as follows: nicotine, 0.050 nmol/mg of creatinine (95% confidence interval [CI] = 0.033 to 0.076) versus 0.008 nmol/mg of creatinine (95% CI = 0.004 to 0.014); cotinine, 0.037 nmol/mg of creatinine (95% CI = 0.022 to 0.061) versus 0.007 nmol/mg of creatinine (95% CI = 0.004 to 0.011); NNAL, 0.013 pmol/mg of creatinine (95% CI = 0.007 to 0.024) versus 0.004 pmol/mg of creatinine (95% CI = 0.002 to 0.007); and NNAL-Gluc, 0.027 pmol/mg of creatinine (95% CI = 0.016 to 0.045) versus 0.004 pmol/mg of creatinine (95% CI = 0.003 to 0.006). Nonsmoking women exposed to ETS take up and metabolize the tobacco-specific lung carcinogen NNK, which could increase their risk of lung cancer. Within couples, the NNAL plus NNAL-Gluc level in exposed women compared with that of their smoking partners averaged 5.6%. Notably, epidemiologic studies have estimated the excess risk for lung cancer in nonsmoking women exposed to ETS as 1%-2% of that in smokers.


Building a Bird: Musculoskeletal Modeling and Simulation of Wing-Assisted Incline Running During Avian Ontogeny.
Flapping flight is the most power-demanding mode of locomotion, associated with a suite of anatomical specializations in extant adult birds. In contrast, many developing birds use their forelimbs to negotiate environments long before acquiring "flight adaptations," recruiting their developing wings to continuously enhance leg performance and, in some cases, fly. How does anatomical development influence these locomotor behaviors? Isolating morphological contributions to wing performance is extremely challenging using purely empirical approaches. However, musculoskeletal modeling and simulation techniques can incorporate empirical data to explicitly examine the functional consequences of changing morphology by manipulating anatomical parameters individually and estimating their effects on locomotion. To assess how ontogenetic changes in anatomy affect locomotor capacity, we combined existing empirical data on muscle morphology, skeletal kinematics, and aerodynamic force production with advanced biomechanical modeling and simulation techniques to analyze the ontogeny of pectoral limb function in a precocial ground bird (Alectoris chukar). Simulations of wing-assisted incline running (WAIR) using these newly developed musculoskeletal models collectively suggest that immature birds have excess muscle capacity and are limited more by feather morphology, possibly because feathers grow more quickly and have a different style of growth than bones and muscles. These results provide critical information about the ontogeny and evolution of avian locomotion by (i) establishing how muscular and aerodynamic forces interface with the skeletal system to generate movement in morphing juvenile birds, and (ii) providing a benchmark to inform biomechanical modeling and simulation of other locomotor behaviors, both across extant species and among extinct theropod dinosaurs.


Infectious salmon anaemia virus.
Infectious salmon anaemia virus (ISAV) is a commercially important orthomyxovirus causing disease in farmed Atlantic salmon. The cumulative mortality in a net pen during an outbreak may vary from insignificant to more than 90%. The infection is spread by management activity such as well-boat traffic, but possibly also through contact with wild fish. In many of its aspects, including the structure of the virus particle and replication strategy, the ISAV is similar to the influenza viruses. Variations between ISAV and the influenza viruses can mostly be related to differences in the temperature at which replication occurs and the immune response of their respective host animals. ISAV shows both haemagglutinating and receptor-destroying activity. The variability of the ISAV haemagglutinin molecule is concentrated around a small domain close to the transmembrane region. The function of this variable region is unknown, but it may be related to a recent or ongoing crossing of a species barrier. Alignment studies based on genetic data indicate that the phylogenetic relationship to the influenza viruses is distant, and that ISAV therefore could possibly warrant a new genus within Orthomyxoviridae.


The supernatural characters and powers of sacred trees in the Holy Land.
This article surveys the beliefs concerning the supernatural characteristics and powers of sacred trees in Israel; it is based on a field study as well as a survey of the literature and includes 118 interviews with Muslims and Druze. Both the Muslims and Druze in this study attribute supernatural dimensions to sacred trees which are directly related to ancient, deep-rooted pagan traditions. The Muslims attribute similar divine powers to sacred trees as they do to the graves of their saints; the graves and the trees are both considered to be the abode of the soul of a saint which is the source of their miraculous powers. Any violation of a sacred tree would be strictly punished while leaving the opportunity for atonement and forgiveness. The Druze, who believe in the transmigration of souls, have similar traditions concerning sacred trees but with a different religious background. In polytheistic religions the sacred grove/forest is a centre of the community's official worship; any violation of the trees is regarded as a threat to the well being of the community. Punishments may thus be collective. In the monotheistic world (including Christianity, Islam and Druze) the pagan worship of trees was converted into the worship/adoration of saints/prophets; it is not a part of the official religion but rather a personal act and the punishments are exerted only on the violating individual.


Improved frequency/voltage converters for fast quartz crystal microbalance applications.
The monitoring of frequency changes in fast quartz crystal microbalance (QCM) applications is a real challenge in today's instrumentation. In these applications, such as ac electrogravimetry, small frequency shifts, in the order of tens of hertz, around the resonance of the sensor can occur up to a frequency modulation of 1 kHz. These frequency changes have to be monitored very accurately both in magnitude and phase. Phase-locked loop techniques can be used for obtaining a high performance frequency/voltage converter which can provide reliable measurements. Sensitivity higher than 10 mVHz, for a frequency shift resolution of 0.1 Hz, with very low distortion in tracking both the magnitude and phase of the frequency variations around the resonance frequency of the sensor are required specifications. Moreover, the resonance frequency can vary in a broad frequency range from 5 to 10 MHz in typical QCM sensors, which introduces an additional difficulty. A new frequency-voltage conversion system based on a double tuning analog-digital phase-locked loop is proposed. The reported electronic characterization and experimental results obtained with conducting polymers prove its reliability for ac-electrogravimetry measurements and, in general, for fast QCM applications.


Transforming growth factor-beta enhances and pro-inflammatory cytokines inhibit ob gene expression in 3T3-L1 adipocytes.
Leptin is a protein which is encoded by the obese (ob) gene. It is synthesized by adipocytes and binds to receptors in the hypothalamus, thereby suppressing appetite and increasing the metabolic rate. When mouse 3T3-L1 cells are induced to differentiate into adipocytes, they begin to constitutively express low levels of ob mRNA. Using reverse transcription and a semi-quantitative polymerase chain reaction, the experiments described herein demonstrate that the anti-inflammatory cytokine transforming growth factor-beta increases steady state ob mRNA. Conversely, treatment of 3T3-L1 adipocytes with the pro-inflammatory cytokines interleukin-1 beta, interleukin-6, interleukin-11, and tumor necrosis factor-alpha results in a decrease in ob transcripts. When considered in the context of animal studies showing that interleukin-1 and tumor necrosis factor-alpha induce leptin and ob mRNA, these results suggest that pro-inflammatory cytokines induce ob gene transcription in vivo via secondary mediators such as transforming growth factor-beta.


Naturally Inspired Molecules for Neuropathic Pain Inhibition-Effect of Mirogabalin and Cebranopadol on Mechanical and Thermal Nociceptive Threshold in Mice.
Neuropathic pain is drug-resistant to available analgesics and therefore novel treatment options for this debilitating clinical condition are urgently needed. Recently, two drug candidates, namely mirogabalin and cebranopadol have become a subject of interest because of their potential utility as analgesics for chronic pain treatment. However, they have not been investigated thoroughly in some types of neuropathic pain, both in humans and experimental animals. This study used the von Frey test, the hot plate test and the two-plate thermal place preference test supported by image analysis and machine learning to assess the effect of intraperitoneal mirogabalin and subcutaneous cebranopadol on mechanical and thermal nociceptive threshold in mouse models of neuropathic pain induced by streptozotocin, paclitaxel and oxaliplatin. Mirogabalin and cebranopadol effectively attenuated tactile allodynia in models of neuropathic pain induced by streptozotocin and paclitaxel. Cebranopadol was more effective than mirogabalin in this respect. Both drugs also elevated the heat nociceptive threshold in mice. In the oxaliplatin model, cebranopadol and mirogabalin reduced cold-exacerbated pain. Since mirogabalin and cebranopadol are effective in animal models of neuropathic pain, they seem to be promising novel therapies for various types of neuropathic pain in patients, in particular those who are resistant to available analgesics.


Nutritional status of cancer outpatients using scored patient generated subjective global assessment in two cancer treatment centers, Nairobi, Kenya.
Malnutrition is a universal problem in cancer patients renowned as an important factor for increased morbidity, decreased quality of life and high mortality. Early diagnosis of malnutrition risk through nutrition screening followed by comprehensive and timely interventions reduces mortality associated with malnutrition. The Scored Patient-Generated Subjective Global Assessment (PGSGA) method has been proved efficient in identifying cancer patients with nutrition challenges and guiding appropriate interventions. However this tool has not been adopted in management of cancer patients in Kenya. The aim of the study was to assess and describe nutrition status of cancer outpatients receiving treatment at Kenyatta National Hospital Hospital (KNH) and Texas Cancer Centre (TCC). The study adopted a hospital based descriptive cross sectional study. Cancer outpatients with confirmed stage 1-4 cancers, physically stable, aged 18 years and above and receiving cancer treatment were recruited and assessed using Scored PGSGA tool. Proportions, measures of central tendency and pearsons' chi-square test were used in statistical analysis. Among the 471 participants assessed, 71.8% were female and 28.2% male. Most participants had stage 2, 3 and 4 cancers at 27.2%, 27.2% and 24.3% respectively. Highest proportion of participants had breast (29.7%) and female genital cancers (22.9%). Sixty nine percent of participants were well nourished (SGA-A), 19.7% moderately malnourished (SGA-B) and 11.3% severely malnourished (SGA-C) and this difference was statistically significant. The mean PGSGA score was 6.76 (SD 5.17). Based on the score, 33.8% of participants required critical nutrition care, 34.8% symptoms management, 14.2% constant nutrition education and pharmacological intervention while 17.2% required routine assessments and reassurance. More (m;54.7%, f; 45.3%) males than females were severely malnourished(SGA-C) and this was statistically significant (P < 0.001).Prevalence of severe malnutrition was highest among participants with digestive organ cancers (49.1%) followed by those with lip cancer (17%) and the least prevalence reported in those with Karposi Sarcoma (0%). Most of stage 4 participants were moderately (37.5%) and severely (29.4%) malnourished. The Scored Patient-Generated Subjective Global Assessment is able to identify cancer patients both at risk of malnutrition and those severely malnourished. It also provides a guideline on the appropriate nutrition intervention hence an important tool in nutrition management of cancer patients.


The Pax protein Noi is required for commissural axon pathway formation in the rostral forebrain.
No-isthmus (Noi) is a member of the zebrafish Pax family of transcriptional regulators that is expressed in restricted domains of the developing CNS. In the developing eye and optic nerve, the Noi+ cells are primitive glial cells that line the choroid fissure and optic stalk/nerve to its junction with the optic tract. This pattern of Noi expression is retained in the adult, defining the optic nerve astroglia, which wrap the left and right nerves separately at the midline, thus forming the bodily crossed optic chiasm found in fish. In embryos carrying mutations in the noi gene, the choroid fissure fails to close, glial cells of the optic nerve fail to differentiate and optic axons exhibit abnormal trajectories exiting the eye and at the midline of the diencephalon. Optic axons select inappropriate pathways into the contralateral optic nerve, rostrally towards the anterior commissure and along the ipsilateral optic tract. Noi+ cells also border the pathway of axons in the postoptic commissure, which is located adjacent to the optic chiasm. These postoptic commissural axons are defasciculated and also exhibit pathfinding defects in noi- embryos. These results indicate that Noi is required in cells that line the pathways taken by optic and non-optic commissural axons for guidance across the midline of the diencephalon. We find that expression of two members of the Netrin family of axon guidance molecules and the signalling protein Sonic hedgehog is disturbed in noi- embryos, whereas several members of the Eph family of receptors and ligands show no obvious alterations in expression at the diencephalic midline.


Identification and function of the RNA chaperone Hfq in the Lyme disease spirochete Borrelia burgdorferi.
Hfq is a global regulatory RNA-binding protein. We have identified and characterized an atypical Hfq required for gene regulation and infectivity in the Lyme disease spirochete Borrelia burgdorferi. Sequence analyses of the putative B. burgdorferi Hfq protein revealed only a modest level of similarity with the Hfq from Escherichia coli, although a few key residues are retained and the predicted tertiary structure is similar. Several lines of evidence suggest that the B. burgdorferi bb0268 gene encodes a functional Hfq homologue. First, the hfq(Bb) gene (bb0268) restores the efficient translation of an rpoS::lacZ fusion in an E. coli hfq null mutant. Second, the Hfq from B. burgdorferi binds to the small RNA DsrA(Bb) and the rpoS mRNA. Third, a B. burgdorferi hfq null mutant was generated and has a pleiotropic phenotype that includes increased cell length and decreased growth rate, as found in hfq mutants in other bacteria. The hfq(Bb) mutant phenotype is complemented in trans with the hfq gene from either B. burgdorferi or, surprisingly, E. coli. This is the first example of a heterologous bacterial gene complementing a B. burgdorferi mutant. The alternative sigma factor RpoS and the outer membrane lipoprotein OspC, which are induced by increased temperature and required for mammalian infection, are not upregulated in the hfq mutant. Consequently, the hfq mutant is not infectious by needle inoculation in the murine model. These data suggest that Hfq plays a key role in the regulation of pathogenicity factors in B. burgdorferi and we hypothesize that the spirochete has a complex Hfq-dependent sRNA network.


Genetic evidence for interaction between eta- and beta-tubulins.
The thermosensitive allelic mutations sm19-1 and sm19-2 of Paramecium tetraurelia cause defective basal body duplication: growth at the nonpermissive temperature yields smaller and smaller cells with fewer and fewer basal bodies. Complementation cloning of the SM19 gene identified a new tubulin, eta-tubulin, showing low homology with each of the other five tubulins, alpha to epsilon, characterized in P. tetraurelia. In order to analyze eta-tubulin functions, we used a genetic approach to identify interacting molecules. Among a series of extragenic suppressors of the sm19-1 mutation, the su3-1 mutation was characterized as an E288K substitution in the beta-PT2 gene coding for a beta-tubulin, while the mutation nocr1 conferring nocodazole resistance and localized in another beta-tubulin gene, beta-PT3, was shown to enhance the mutant phenotype. The interaction between eta-tubulin and microtubules, revealed by genetic data, is supported by two further types of evidence: first, the mutant phenotype is rescued by taxol, which stabilizes microtubules; second, molecular modeling suggests that eta-tubulin, like gamma- and delta-tubulins, might be a microtubule minus-end capping molecule. The likely function of eta-tubulin as part of a complex specifically involved in basal body biogenesis is discussed.


Diseases attributable to asbestos exposure: years of potential life lost, United States, 1999-2010.
Although asbestos use has been restricted in recent decades, asbestos-associated deaths continue to occur in the United States. We evaluated premature mortality and loss of potentially productive years of life attributable to asbestos-associated diseases. Using 1999-2010 National Center for Health Statistics mortality data, we identified decedents aged ≥25 years whose death certificate listed asbestosis and malignant mesothelioma as the underlying cause of death. We computed years of potential life lost to life expectancy (YPLL) and to age 65 (YPLL65 ). During 1999-2010, a total of 427,005 YPLL and 55,184 YPLL65 were attributed to asbestosis (56,907 YPLL and 2,167 YPLL65 ), malignant mesothelioma (370,098 YPPL and 53,017 YPLL65 ). Overall and disease-specific asbestos-attributable total YPLL and YPLL65 and median YPLL and YPLL65 per decedent did not change significantly from 1999 to 2010. The continuing occurrence of asbestos-associated diseases and their substantial premature mortality burden underscore the need for maintaining prevention efforts and for ongoing surveillance to monitor temporal trends in these diseases.


Interdependence of "What" and "When" in the Brain.
From a brain's-eye-view, when a stimulus occurs and what it is are interrelated aspects of interpreting the perceptual world. Yet in practice, the putative perceptual inferences about sensory content and timing are often dichotomized and not investigated as an integrated process. We here argue that neural temporal dynamics can influence what is perceived, and in turn, stimulus content can influence the time at which perception is achieved. This computational principle results from the highly interdependent relationship of what and when in the environment. Both brain processes and perceptual events display strong temporal variability that is not always modeled; we argue that understanding-and, minimally, modeling-this temporal variability is key for theories of how the brain generates unified and consistent neural representations and that we ignore temporal variability in our analysis practice at the peril of both data interpretation and theory-building. Here, we review what and when interactions in the brain, demonstrate via simulations how temporal variability can result in misguided interpretations and conclusions, and outline how to integrate and synthesize what and when in theories and models of brain computation.


Biopolymers in Drug and Gene Delivery Systems 2.0.
In recent years, significant progress has been made in the design and development of biopolymer-based delivery systems for a wide range of applications, including cancer therapy, gene editing, regenerative medicine, and vaccine delivery [...].


[Impact of depressive symptoms on outcomes of a workplace smoking-cessation program].
Although smoking and depression have been related, little importance is given to the impact of depression on outcomes of smoking cessation interventions in the workplace. The aim of this study was to assess the influence of depressive symptoms and a history of depression on abstinence after a workplace smoking cessation intervention, and to explore the roles of gender, nicotine dependence and antidepressants. A retrospective study with employees of Barcelona City Council participating on a voluntary basis. The intervention consisted of a multicomponent approach combined with pharmacological treatment. Depressive symptoms were assessed with the Beck Depression Inventory (BDI), and history of depression was noted in the baseline assessment. Higher scores in BDI were associated with lower rates of abstinence at 3, 6 and 12 months. BDI scores >or= 13 were related to a 1.81x higher likelihood of relapse. This relationship was independent of the effect of dependence severity, of gender and of treatment with antidepressants. In contrast, a history of depression did not influence outcomes. New therapeutic strategies are needed to reduce the impact of employees depressive symptoms in workplace smoking cessation programmes.


Correlation between Vestibular Evoked Myogenic Potentials and Disease Progression in Ménière's Disease.
To assess the relationship between ocular (oVEMPs) and cervical (cVEMPs) vestibular evoked myogenic potentials and audiometrically determined clinical stage in Ménière's disease (MD). Thirty-four unilateral MD patients and 30 healthy volunteers were included in the study. Pure-tone hearing levels, oVEMPs, cVEMPs, and videonystagmography results were analyzed and compared between the groups. Both oVEMPs and cVEMPs were highly reproducible in the control group. At the early stages of MD, cVEMPs were particularly disturbed, while at the advanced stages both oVEMPs and cVEMPs were altered pathologically. In the study group, oVEMP and cVEMP amplitudes and interaural amplitude difference (IAD) statistically differed from those in the control sample. oVEMPs were absent in 7.7% of stage III and in 44.5% of stage IV MD patients, while cVEMPs were absent in 15.4% of stage III and in 54.5% of stage IV MD patients, respectively. In stage III and IV MD patients in whom oVEMPs and cVEMPs were obtained, IADs were increased. Caloric asymmetry was found in 64.7% of MD patients. Caloric weakness was more prominent in cases with advanced MD. VEMPs can be used for objective validation of the stage of MD.


Efficient single-mode photon-coupling device utilizing a nanofiber tip.
Single-photon sources are important elements in quantum optics and quantum information science. It is crucial that such sources be able to couple photons emitted from a single quantum emitter to a single propagating mode, preferably to the guided mode of a single-mode optical fiber, with high efficiency. Various photonic devices have been successfully demonstrated to efficiently couple photons from an emitter to a single mode of a cavity or a waveguide. However, efficient coupling of these devices to optical fibers is sometimes challenging. Here we show that up to 38% of photons from an emitter can be directly coupled to a single-mode optical fiber by utilizing the flat tip of a silica nanofiber. With the aid of a metallic mirror, the efficiency can be increased to 76%. The use of a silicon waveguide further increases the efficiency to 87%. This simple device can be applied to various quantum emitters.


Effects of postharvest application of 1-MCP and postcutting dip treatment on the quality and nutritional properties of fresh-cut kiwifruit.
Consumption of minimally processed fruit and vegetables has increased significantly in the past few years due to the consumers' life style. The aim of this study was to evaluate the effect of treatment with ascorbic acid or calcium chloride on the quality parameters of fresh-cut kiwifruit prepared from fruit previously stored for 3 months, either treated or not treated with 1-methylcyclopropene (1-MCP) before storage. Harvested fruit were treated with 1 microL L(-1) 1-MCP for 20 h at room temperature ( approximately 20 degrees C) (MCP) or had no treatment (C) and were then stored at 0 degrees C. After 3 months, fruit were removed from storage, peeled, and cut longitudinally in quarters, dipped in 2% ascorbic acid (Asc), 2% calcium chloride (Ca), or just water (cont), and kept at 2 degrees C for 8 days. Measurements of firmness, soluble solids content (SSC) ( degrees Brix), color (CIE L*, a*, b*), electrolyte leakage, sugars, organic acids, total phenolics, and antioxidant activity (DPPH and ABTS) were performed at 0, 4, and 8 days. A taste panel was performed on the seventh shelf life day. It was shown that whole MCP-treated kiwifruit kept better than the control through the 3 months storage, this effect being lost through the fresh-cut shelf life period. Furthermore, the postcut dip on 2% CaCl(2) was effective on delaying softening and browning of fresh-cut kiwifruit, which were also the fruit preferred by panelists. Both ascorbic acid and CaCl(2) were effective on preserving or improving nutritional properties (phenolics, ascorbic acid, DPPH, and ABTS) mainly in the first 4 days of shelf life. The CaCl(2) had a further beneficial effect until 8 shelf life days. It is suggested that CaCl(2) is better in keeping overall quality through 8 days of shelf life at 2 degrees C in fresh-cut kiwifruit followed by Asc, and 1-MCP has negligible effect in the conditions of this experiment.


Histone h3 modifications in rat hepatic stellate cells by ethanol.
Hepatic stellate cells (HSCs) play critical roles in the development of hepatic fibrosis caused by various agents including alcohol. Ethanol causes post-translational modification in histone. The goal of this study is to investigate whether ethanol affected acetylation and methylation of histone H3 in rat HSCs. We isolated and separated HSCs using collagenase perfusion of liver followed by Nycodenz density gradient centrifugation. HSCs were divided and treated with different concentrations of ethanol for various times. Histone was isolated using acid extraction method. Acetylation and methylation of histone H3 at Lys9 was analysed by both western blot and fluorescein isothiocyanate (FITC) immunochemical stain. Acetylation of histone H3 at Lys9 (Ac-H3-lys9), Lys14 (Ac-H3-Lys14), Lys18 (Ac-H3-lys18), or Lys23 (Ac-H3-lys23) was checked by western blotting. At lysine 9, ethanol caused dose-dependent increase of Ac-H3 up to 200 mM. Ac-H3-lys9 increased with a maximum of 86-fold at 72 h and 200 mM ethanol treatment, and decreased thereafter. This increase was confirmed by both western blotting and FITC stain. At high dose, ethanol increased acetylation of histone H3 at Lys23 (Ac-H3-lys23), but it had no effect on Ac-H3-lys14 or Ac-H3-lys18. The intensity of the FITC-labelled dimethyl-histone H3 at Lys9 (Me-H3-lys9) antibody appeared to decrease slightly with increasing dose of ethanol. But this did not appear to change when monitored by western blotting. Ethanol caused dose and time-dependent increase in acetylation of histone H3 at Lys9, but not at Lys14 or Lys18. Compared with hepatocytes the Ac-H3-lys9 in HSCs required longer ethanol exposure. Levels of Me-H3-lys9 seemed to remain unaltered. Thus increase in Ac-H3-lys9 represents a nuclear-chromatin modification event in HSCs exposed to ethanol.


NOX1 abet mesangial fibrogenesis via iNOS induction in diabetes.
Both NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS) are the main sources of reactive oxygen species in kidney. However, their interactions in oxidative stress and contributions to kidney fibrosis during diabetic nephropathy have not been studied. Human mesangial cells were treated with normal glucose (5.6 mmol/L), high glucose (30 mmol/L) in the presence or absence of AGE (200 mg/L). Protein expressions of NOX1, NOX2, NOX4, and iNOS were examined by immunoblotting. NOX was genetically silenced with specific RNAi to study the interactions between NOX and iNOS in diabetic milieu. Superoxide (O(·-)) and peroxynitrite (ONOO(·-)) productions were assessed by dihydroethidium and hydroxyphenyl fluorescein, respectively. Fibrotic factors were determined by biochemistry assay. Superoxide, peroxynitrite, TGF-β, and fibronectin productions as well as the protein expressions of NOX1, NOX2, NOX4, and iNOS were increased in the diabetic milieu (high glucose 30 mmol/L plus AGE 200 mg/L). However, abolishment of iNOS induction with 1400W or iNOS RNAi would restore peroxynitrite, TGF-β, and fibronectin productions completely to basal level and attenuate superoxide production. Moreover, NOX1 inhibition not only prevented iNOS induction but also abrogated changes consequent to iNOS induction such as mesangial fibrogenesis.


Curcumin affects β-catenin pathway in hepatic stellate cell in vitro and in vivo.
Emerging evidence indicates that Wnt/β-catenin pathway is linked to the fibrosis of different organs including liver fibrosis. β-Catenin promotes hepatic stellate cells (HSCs) activation, a key event in the development of liver fibrosis, and has emerged as a novel mediator of fibrosis. Curcumin, a natural active ingredient derived from turmeric, possesses an inhibitory effect on liver fibrosis. This study is aimed to examine whether curcumin affects β-catenin expression/activity in HSCs and explores the underlying mechanisms. The researchers used Western blot, real-time PCR, transfection assay and electrophoretic mobility shift assay and employed cultured HSCs and rat model of liver injury. Results showed that curcumin could reduce β-catenin protein level in HSCs in vitro and in vivo. Both β-catenin transactivation activity and DNA-binding activity were suppressed by curcumin. Moreover, nuclear β-catenin protein level was decreased by curcumin treatment. Further experiments suggested that delta-like homologue 1 contributed to curcumin inhibition of β-catenin transactivation activity in cultured HSCs. Curcumin affects β-catenin pathway in HSCs and might suggest a possible new explanation for the effects of curcumin on HSC activation and liver fibrosis.