Obscurin regulates the organization of myosin into A bands.
Obscurin is a giant sarcomeric protein composed of adhesion modules and signaling domains. It surrounds myofibrils at the level of the Z disk and the M line. To study the role of obscurin during myofibrillogenesis, we used adenovirus-mediated gene delivery to overexpress part of its COOH terminus in primary cultures of postnatal day 1 (P1) skeletal myotubes. Examination of the subcellular distribution of a number of sarcomeric proteins revealed that the organization of myosin into A bands was dramatically reduced. Myosin assembled into A bands normally in mock- or control-infected P1 myotubes. Overexpression of the COOH terminus of obscurin did not affect the organization of other sarcomeric markers, including actin, alpha-actinin, titin, and myomesin. Assembly of myomesin into nascent M lines in treated myotubes suggests that these structures can form independently of A bands. Immunoblot analysis indicated that there was a small ( approximately 20%) but consistent decrease in the amount of myosin expressed in cells infected with the COOH terminus of obscurin. Coimmunoprecipitation experiments in which we used adult skeletal muscle homogenates demonstrated that obscurin exists in a complex with myosin. Thus our findings suggest that the COOH-terminal region of obscurin interacts with sarcomeric myosin and may play a critical role in its ability to assemble into A bands in striated muscle.


Microsatellite mapping of quantitative trait loci affecting meat quality, stress hormones and production traits in Duroc × Large White F2 pigs.
An F2 cross between Duroc and Large White pigs was carried out in order to detect quantitative trait loci (QTL) for 11 meat quality traits (L*, a* and b* Minolta coordinates and water-holding capacity (WHC) of two ham muscles, ultimate pH of two ham and one loin muscles), 13 production traits (birth weight, average daily gain during post-weaning and fattening periods, carcass fat depths at three locations, estimated lean meat content, carcass length and weights of five carcass cuts) and three stress hormone-level traits (cortisol, adrenaline and noradrenaline). Animals from the three generations of the experimental design (including 456 F2 pigs) were genotyped for 91 microsatellite markers covering all the autosomes. A total of 56 QTL were detected: 49 reached the chromosome-wide level (suggestive QTL with a maximal probability of 0.05) and seven were significant at the genome-wide level (with a probability varying from 6 × 10(-4) to 3 × 10(-3)). Twenty suggestive QTL were identified for ultimate pH, colour measurements and WHC on chromosome (SSC) 5, 6, 7, 8, 9, 11, 13, 14, 15 and 17. For production traits, 33 QTL were detected on all autosomes except SSC6, 8 and 9. Seven of these QTL, located on SSC2, 3, 10, 13, 16 and 17, exceeded the genome-wide significance threshold. Finally, three QTL were identified for levels of stress hormones: a QTL for cortisol level on SSC7 in the cortisol-binding globulin gene region, a QTL for adrenaline level on SSC10 and a QTL for noradrenaline level on SSC13. Among all the detected QTL, seven are described for the first time: a QTL for ultimate pH measurement on SSC5, two QTL affecting birth weight on SSC2 and 10, two QTL for growth rate on SSC15 (during fattening) and 17 (during post-weaning) and two QTL affecting the adrenaline and noradrenaline levels. For each QTL, only one to five of the six F1 sires were found to be heterozygous. It means that all QTL are segregating in at least one of the founder populations used in this study. These results suggest that both meat quality and production traits can be improved in purebred Duroc and Large White pigs through marker-assisted selection. It is of particular interest for meat quality traits, which are difficult to include in classical selection programmes.


The SARS-CoV-2 Cytopathic Effect Is Blocked by Lysosome Alkalizing Small Molecules.
Understanding the SARS-CoV-2 virus' pathways of infection, virus-host-protein interactions, and mechanisms of virus-induced cytopathic effects will greatly aid in the discovery and design of new therapeutics to treat COVID-19. Chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including alkalizing lysosomes and blocking autophagy as well as exhibiting dose-limiting toxicities in patients. Therefore, we evaluated additional lysosomotropic compounds to identify an alternative lysosome-based drug repurposing opportunity. We found that six of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero E6 cells with half-maximal effective concentration (EC50) values ranging from 2.0 to 13 μM and selectivity indices (SIs; SI = CC50/EC50) ranging from 1.5- to >10-fold. The compounds (1) blocked lysosome functioning and autophagy, (2) prevented pseudotyped particle entry, (3) increased lysosomal pH, and (4) reduced (ROC-325) viral titers in the EpiAirway 3D tissue model. Consistent with these findings, the siRNA knockdown of ATP6V0D1 blocked the HCoV-NL63 cytopathic effect in LLC-MK2 cells. Moreover, an analysis of SARS-CoV-2 infected Vero E6 cell lysate revealed significant dysregulation of autophagy and lysosomal function, suggesting a contribution of the lysosome to the life cycle of SARS-CoV-2. Our findings suggest the lysosome as a potential host cell target to combat SARS-CoV-2 infections and inhibitors of lysosomal function could become an important component of drug combination therapies aimed at improving treatment and outcomes for COVID-19.


Complex surgery and perioperative systemic therapy for genitourinary cancer of the retroperitoneum.
The purpose of the present guideline is to recommend surgical or systemic treatment for metastatic testicular cancer; T3b or T4, or node-positive, and metastatic renal cell cancer (rcc); and T3, T4, or node-positive upper tract urothelial (utuc) cancer. Draft recommendations were formulated based on evidence obtained through a systematic review of randomized controlled trials, comparative retrospective studies, and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners. The primary literature search yielded eight guidelines, five systematic reviews, and twenty-seven primary studies that met the eligibility criteria. Cytoreductive nephrectomy should no longer be considered the standard of care in patients with T3b or T4, or node-positive, and metastatic rcc. Eligible patients should be treated with systemic therapy and have their primary tumour removed only after review at a multidisciplinary case conference (mcc). Adjuvant sunitinib after surgery is not recommended. Patients with venous tumour thrombus should be considered for surgical intervention. Patients with T3, T4, or node-positive utuc should have their tumour removed without delay. Decisions concerning lymph node dissection should be done at a mcc and be based on stage, expertise, and imaging. Adjuvant systemic treatment is recommended for resected high-risk utuc. Patients with metastasis-positive testicular cancer with residual tumour after systemic treatment should be treated at specialized centres. For all complex retroperitoneal surgeries, the evidence shows that higher-volume centres are associated with lower rates of procedure-related mortality, and patients should be referred to higher-volume centres for surgical resection.


Inherited metabolic diseases of the nervous system.
This overview was designed primarily to provide examples of hereditary metabolic disorders that result in nervous system dysfunction. Some of the more frequently encountered pathological conditions were selected in order to illustrate the mechanisms and the consequences of the metabolic derangements. Therapeutic approaches for the correction of such disorders are discussed where it appears appropriate. In time the precise etiology for those eponymous genetic conditions with stereotyped pathologic and clinical manifestations such as Huntington's chorea (79) and Friedreich's ataxia (80) will be disclosed. It is possible that some forms of epilepsy (81) and perhaps certain psychiatric disturbances (82) will be shown to be inherited metabolic disorders. As our knowledge and skill increase, this logic may eventually be extended to biochemical explanations of variation in individual skills and talents. Certainly innovative extrapolation and novel research directions will be necessary to provide an understanding of these differences. However, it is axiomatic in research that each useful contribution serves largely as a point of departure for further accomplishments.


Dye-doped silica nanoparticles as luminescent organized systems for nanomedicine.
The ability to find synergic solutions is the core of scientific research and scientific advancement. This is particularly true for medicine, where multimodal imaging and theranostic tools represent the frontier research. Nanotechnology, which by its very nature is multidisciplinary, has opened up the way to the engineering of new organized materials endowed with improved performances. In particular, merging nanoparticles and luminescent signalling can lead to the creation of unique tools for the design of inexpensive, hand-held diagnostic and theranostic kits. In this wide scenario, dye-doped silica nanoparticles constitute very effective nanoplatforms to obtain efficient luminescent, stable, biocompatible and targeted agents for biomedical applications. In this review we discuss the state of the art in the field of luminescent silica-based nanoparticles for medical imaging, starting with an overview of the most common synthetic approaches to these materials. Trying to rationalize the presentation of this extremely multifaceted and complex subject, we have gathered significant examples of systems applied in cancer research, also discussing those that take a multifunctional approach, including theranostic structures. Nanoprobes designed for applications that do not include cancer are a minor part, but interesting achievements have been published and we present a selection of these in the subsequent section. To conclude, we propose a debate on the advantages of creating chemosensors based on luminescent silica nanoparticles. This is far from easy but is a particularly valuable goal in the medical field and therefore subject to extensive research worldwide.


Addiction and the kynurenine pathway: A new dancing couple?
Drug use poses a serious threat to health systems throughout the world and the number of consumers rises relentlessly every year. The kynurenine pathway, main pathway of tryptophan degradation, has drawn interest in this field due to its relationship with addictive behaviour. Recently it has been confirmed that modulation of kynurenine metabolism at certain stages of the pathway can reduce, prevent or abolish drug seeking-like behaviours in studies with several different drugs. In this review, we present an up-to-date summary of the evidences of a relationship between drug use and the kynurenine pathway, both the alterations of the pathway due to drug use as well as modulation of the pathway as a potential approach to treat drug addiction. The review discusses ethanol, nicotine, cannabis, amphetamines, cocaine and opioids and new prospects in the drug research field are proposed.


Thermal response to running across the Sahara desert: data for three men.
There are limited data concerning the physiological responses to long-duration exercise collected under field conditions, and less data under harsh environmental conditions. This paper describes select environmental conditions and physiological responses of three runners attempting to run across the entire Sahara desert over a 111-d period. The runners started in Saint-Louis, Senegal, and we collected data on 2 d at the start of the expedition. Core temperature was measured via telemetry pill (Tpill), heart rate via Polar monitor, and metabolic rate (M) was estimated from two equations. The Pandolf equation uses movement speed and grade while Berglund's equation predicts M from heart rate and dry-bulb temperature. Data are presented as mean +/- SD (range). The runners intermittently ran 8.0 km x h(-1) over 6 h during Night (warm-humid) conditions and 6.9 km x h(-1) over 7 h 40 min during Day (hot-dry) desert conditions. Mean Tpill was similar for both days (37.8 +/- 10.34 vs. 37.82 +/- 0.50 degrees C) while range was greater during the day (Day: 36.69-38.91 vs. Night: 37.11-38.48 degrees C). Heart rate was 128 +/- 16 (72-156) and 119 +/- 17 (75-147) bpm for Night and Day, respectively. Mmean was 299 +/- 66 (65-418) W x m(-2) and 364 +/- 117 (58-542) W x m(-2) during Night and 239 +/- 60 (67-356) and 244 +/- 139 (54-464) W x m(-2) during Day, estimated by Berglund and Pandolf, respectively. During Day, the athletes ran slower than during Night, though Tpill was similar, indicative of the greater environmental strain. Mean predicted M was similar between equations, though maximum and minimal values were more extreme and rate-of-change dynamics faster according to Pandolf's equation.


Reproductive Life Planning: A Cross-Sectional Study of What College Students Know and Believe.
Objectives The Centers for Disease Control and Prevention recommends a reproductive life plan (RLP) to promote individual responsibility for preconception health. The objectives of this study were to determine existing awareness of RLPs in a cohort of reproductive-age adults and to evaluate their knowledge level and beliefs about reproductive life planning. Methods We performed a cross-sectional survey study of adults ages 18-40 years old seeking care at the student health center of a large public university. Participation was voluntary. Survey responses were analyzed by age and gender. Results A total of 559 surveys were collected and analyzed. Only 24 % of participants had heard of an RLP although a majority (62.9 %) agreed that it is important to develop an RLP. Most respondents (85.4 %) preferred to receive information about reproductive life planning from a primary care provider or obstetrician-gynecologist, while only 4.2 % of patients surveyed reported ever being actually asked about an RLP by their healthcare provider. Among those who agreed that an RLP was important, knowledge of specific aspects of an RLP was lacking. Conclusions In our cohort of reproductive-age adults, general health literacy regarding RLPs was poor. Most of the young adults who responded to our survey did not know what an RLP was and even fewer had ever discussed one with their health provider.


Molecular and lipid biomarker analysis of a gypsum-hosted endoevaporitic microbial community.
Modern evaporitic microbial ecosystems are important analogs for understanding the record of earliest life on Earth. Although mineral-depositing shallow-marine environments were prevalent during the Precambrian, few such environments are now available today for study. We investigated the molecular and lipid biomarker composition of an endoevaporitic gypsarenite microbial mat community in Guerrero Negro, Mexico. The 16S ribosomal RNA gene-based phylogenetic analyses of this mat corroborate prior observations indicating that characteristic layered microbial communities colonize gypsum deposits world-wide despite considerable textural and morphological variability. Membrane fatty acid analysis of the surface tan/orange and lower green mat crust layers indicated cell densities of 1.6 × 10(9) and 4.2 × 10(9) cells cm(-3) , respectively. Several biomarker fatty acids, ∆7,10-hexadecadienoic, iso-heptadecenoic, 10-methylhexadecanoic, and a ∆12-methyloctadecenoic, correlated well with distributions of Euhalothece, Stenotrophomonas, Desulfohalobium, and Rhodobacterales, respectively, revealed by the phylogenetic analyses. Chlorophyll (Chl) a and cyanobacterial phylotypes were present at all depths in the mat. Bacteriochlorophyl (Bchl) a and Bchl c were first detected in the oxic-anoxic transition zone and increased with depth. A series of monomethylalkanes (MMA), 8-methylhexadecane, 8-methylheptadecane, and 9-methyloctadecane were present in the surface crust but increased in abundance in the lower anoxic layers. The MMA structures are similar to those identified previously in cultures of the marine Chloroflexus-like organism 'Candidatus Chlorothrix halophila' gen. nov., sp. nov., and may represent the Bchl c community. Novel 3-methylhopanoids were identified in cultures of marine purple non-sulfur bacteria and serve as a probable biomarker for this group in the lower anoxic purple and olive-black layers. Together microbial culture and environmental analyses support novel sources for lipid biomarkers in gypsum crust mats.


Identification of Top-ranked Proteins within a Directional Protein Interaction Network using the PageRank Algorithm: Applications in Humans and Plants.
Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.


Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium.
Transmyocardial laser revascularization (TMR) has been demonstrated effective for relieving angina, although prior studies have yielded inconsistent results regarding postoperative myocardial perfusion and function. This study evaluated long-term changes in myocardial perfusion and contractile reserve after TMR in a model of hibernating myocardium. Miniswine had subtotal left circumflex coronary artery occlusion to reduce resting blood flow to 10% of baseline. After 2 weeks in the low-flow state, positron emission tomography and dobutamine stress echocardiography were performed to document ischemic, viable (hibernating) myocardium in the left circumflex distribution. Animals then had sham redo thoracotomy (n = 4) or TMR (n = 6). Six months later the positron emission tomography and dobutamine stress echocardiography studies were repeated. Myocardial blood flow in the left circumflex distribution as measured by positron emission tomography was significantly reduced in all animals after 2 weeks in the low-flow state. In animals that had TMR, there was significant improvement in myocardial blood flow to the lased regions 6 months postoperatively. No significant change in myocardial blood flow was seen in sham animals at 6 months. Dobutamine stress echocardiography after 2 weeks of low-flow demonstrated severe hypocontractility at rest in the left circumflex region of all animals, with a biphasic response to dobutamine consistent with hibernating myocardium. In animals that had TMR, there was a trend toward improved resting function and significantly improved regional stress function in the lased segments 6 months postoperatively, consistent with a reduction in ischemia. Global left ventricular wall motion at peak stress improved significantly as well. There was no change in wall motion 6 months postoperatively in sham-operated animals. This study found improvements in myocardial perfusion and regional and global contractile reserve 6 months after TMR in a porcine model of hibernating myocardium. This improved perfusion and function likely accounts for the clinical benefits of the procedure.


Measles.
Measles is an infectious disease in humans caused by the measles virus (MeV). Before the introduction of an effective measles vaccine, virtually everyone experienced measles during childhood. Symptoms of measles include fever and maculopapular skin rash accompanied by cough, coryza and/or conjunctivitis. MeV causes immunosuppression, and severe sequelae of measles include pneumonia, gastroenteritis, blindness, measles inclusion body encephalitis and subacute sclerosing panencephalitis. Case confirmation depends on clinical presentation and results of laboratory tests, including the detection of anti-MeV IgM antibodies and/or viral RNA. All current measles vaccines contain a live attenuated strain of MeV, and great progress has been made to increase global vaccination coverage to drive down the incidence of measles. However, endemic transmission continues in many parts of the world. Measles remains a considerable cause of childhood mortality worldwide, with estimates that >100,000 fatal cases occur each year. Case fatality ratio estimates vary from <0.01% in industrialized countries to >5% in developing countries. All six WHO regions have set goals to eliminate endemic transmission of MeV by achieving and maintaining high levels of vaccination coverage accompanied by a sensitive surveillance system. Because of the availability of a highly effective and relatively inexpensive vaccine, the monotypic nature of the virus and the lack of an animal reservoir, measles is considered a candidate for eradication.


First evidence of neonicotinoid residues in a long-distance migratory raptor, the European honey buzzard (Pernis apivorus).
The evidence of negative impacts of agricultural pesticides on non-target organisms is constantly growing. One of the most widely used group of pesticides are neonicotinoids, used in treatments of various plants, e.g. oilseed crops, corn and apples, to prevent crop damage by agricultural insect pests. Treatment effects have been found to spill over to non-target insects, such as bees, and more recently also to other animal groups, among them passerine birds. Very little is known, however, on the presence of neonicotinoids in other wild species at higher trophic levels. We present results on the presence of neonicotinoid residues in blood samples of a long-distant migratory food-specialist raptor, the European honey buzzard. Further, we investigate the spatial relationship between neonicotinoid residue prevalence in honey buzzards with that of crop fields where neonicotinoids are typically used. A majority of all blood samples contained neonicotinoids, thiacloprid accounting for most of the prevalence. While neonicotinoid residues were detected in both adults and nestlings, the methodological limit of quantification was exceeded only in nestlings. Neonicotinoids were present in all sampled nests. Neonicotinoid presence in honey buzzard nestlings' blood matched spatially with the presence of oilseed plant fields. These are the first observations of neonicotinoids in a diurnal raptor. For better understanding the potential negative sub-lethal of neonicotinoids in wild vertebrates, new (experimental) studies are needed.


Inlay-fixed partial dentures adhesively retained and reinforced by glass fibers: clinical and scanning electron microscopy analysis after five years.
Fifty-three posterior glass fibre-reinforced composite inlay-fixed partial dentures (IFPDs) in 36 patients were followed for 5 yr. For statistical analysis, one IFPD per patient was randomly selected. The survival rate and influence of discrete predictors (gender, location) and continuous variables (age, abutment surfaces) were determined. Clinical observations were recorded by using modified United States Public Health System (USPHS) criteria. Replicas of 17 randomly selected abutments were analysed by scanning electron microscopy (SEM) for marginal adaptation and the results were compared by using a repeated-measures analysis of variance (anova). The main reason for failure was veneering material delamination from the framework. The cumulative survival rate after 5 yr was 73% (95% confidence interval: 57-89%) for not delaminating and 96% (95% confidence interval: 88-100%) for not debonding. No significant influence of the tested predictors was found. Significant changes between baseline USPHS criteria and counterparts recorded at recall were fractures of the veneering material (chipping), wear, surface texture, and staining. Significant margin changes were only found between baseline and 1 yr. Thereafter, marginal adaptation remained stable. After 5 yr, 90% of the margins were termed as perfect. It was concluded that hard-tissue saving IFPDs with the current design maintained acceptable retention and marginal integrity. Future studies should aim at reducing delaminations by searching for improved framework designs and materials.


A clinical evaluation of anorectal pressure studies in the diagnosis of Hirschsprung's disease.
Stimulation of the rectum by stretch results, in the normally innervated bowel, in the reflex relaxation of the internal anal sphincter. The absence of this rectosphincteric reflex in Hirschsprung's disease forms the basis of a simple and safe diagnostic test. Our experience over two years using a simplified air-filled pressure probe system is described, based on the examination of 267 infants and children with abnormal bowel function, of whom 114 were suffering from Hirschsprung's disease.A review of the last 100 consecutive patients examined shows an overall diagnostic reliability of 85%. This was of the same order as that of a barium enema in these patients, and indeed of obtaining the correct diagnosis on the first rectal biopsy. It has proved easier to exclude the disease (90.8%) than to confirm its presence (74.3%), and has been found to be more reliable than the barium enema in the diagnosis of ultrashort segment disease. The commoner pitfalls in the interpretation of the trace are described. We consider that this investigation justifies a place in the routine investigation of Hirschsprung's disease alongside the barium enema and rectal biopsy, and is of particular value as a simple screening test in outpatients.


Depletion of Uric Acid Due to SLC22A12 (URAT1) Loss-of-Function Mutation Causes Endothelial Dysfunction in Hypouricemia.
Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with hypouricemia. Twenty-six patients with hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with hypouricemia, and not in the other 5. In the hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of hypouricemia. Thirteen of 16 hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function. Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients.


Risk of bladder cancer in patients with spina bifida: case reports and review of the literature.
This article presents four cases of patients with spina bifida who developed bladder cancer while under our care and provides a literature review on the incidence, initial presentation, possible etiologies, and role for screening for bladder cancer in the neurogenic bladder population. Case reports of four patients are presented followed by a literature review of the current available studies. Patients with spina bifida present with bladder cancer at an atypically young age with very advanced disease. The dire prognosis associated with bladder cancer in these patients demands that we provide better treatment, diagnosis, and prevention modalities. However, the potential morbidity, financial burden, and lack of proven benefit discourage cystoscopic screening in this patient population. Until we have more data on how to best serve spina bifida patients, this population should receive careful and regular urologic follow-up. Given the atypical young age of presentation and very advanced nature of bladder cancer in the spina bifida population, the authors strongly recommend that any new bladder changes, such as including increased urinary leakage, pain, recurrent infections, or increased gross hematuria, prompt immediate urologic referral for endoscopic evaluation and biopsy as indicated.


The watercolor illusion and neon color spreading: a unified analysis of new cases and neural mechanisms.
Coloration and figural properties of neon color spreading and the watercolor illusion are studied using phenomenal and psychophysical observations. Coloration properties of both effects can be reduced to a common limiting condition, a nearby color transition called the two-dot limiting case, which clarifies their perceptual similarities and dissimilarities. The results are explained by the FACADE neural model of biological vision. The model proposes how local properties of color transitions activate spatial competition among nearby perceptual boundaries, with boundaries of lower-contrast edges weakened by competition more than boundaries of higher-contrast edges. This asymmetry induces spreading of more color across these boundaries than conversely. The model also predicts how depth and figure-ground effects are generated in these illusions.


Nosocomial infections in patients with spontaneous intracerebral hemorrhage.
Nosocomial infections are frequent complications in patients with intracerebral hemorrhage. To determine the prevalence, risk factors, and outcomes of nosocomial infections in patients with intracerebral hemorrhage. Prospectively collected data on patients with spontaneous intracerebral hemorrhage between January 2009 and June 2012 were retrospectively reviewed. Patients who had nosocomial infection during the hospital stay were compared with patients who did not. Poor outcome was defined as death or discharge to a long-term nursing facility. At least 1 nosocomial infection developed in 26% of 202 patients with intracerebral hemorrhage. The most common infections were pneumonia (18%), urinary tract infection (12%), meningitis or ventriculitis (3%), and bacteremia (1%). On univariate analysis, independent predictors of nosocomial infection were intraventricular hemorrhage, hydrocephalus, low score on the Glasgow Coma Scale at admission, hyperglycemia at admission, and treatment with mechanical ventilation. On multivariate regression analysis, the only significant predictor of nosocomial infection was intraventricular hemorrhage (odds ratio, 5.4; 95% CI, 1.2-11.4; P = .02). Patients with nosocomial infection were more likely than those without to require a percutaneous gastrostomy tube (odds ratio, 33.1, 95% CI, 23.3-604.4; P < .001) and to have a longer stay in the intensive care unit or hospital without a significant increase in mortality. Patients with nosocomial pneumonia were also more likely to have a poor outcome (P < .001). Pneumonia was the most common infection among patients with intracerebral hemorrhage.


Aging and Neurocognitive Functioning in HIV-Infected Women: a Review of the Literature Involving the Women's Interagency HIV Study.
HIV-infected women may be particularly vulnerable to certain types of neurocognitive impairments which may be exacerbated by aging and other predictors. Within the context of cognitive reserve, this article examines issues surrounding women as they age with HIV. For this, a review of 12 recent studies (2013-2016) using data from the Women's Interagency HIV Study (WIHS), the largest cohort study comparing HIV-infected and demographically matched uninfected women, is presented that specifically examines neurocognition. In general, HIV-infected women are more vulnerable to developing neurocognitive impairments than uninfected women; other factors that may contribute to these neurocognitive impairments include recent illicit drug use, reading level (educational quality/cognitive reserve), stress, PTSD, insulin resistance, liver fibrosis, and age. Surprisingly, when examined in some analyses, age × HIV interactions were not observed to impact neurocognitive performance, findings largely consistent in the literature; however, longitudinal analyses of these data have yet to be performed which may yield future insights of how cognitive reserve may be compromised over time. Yet, with insulin resistance, liver fibrosis, stress, and other known predictors of poorer neurocognition also occurring more with advanced age, in time, the synergistic effect of age and HIV may be more robust and observable as this population ages.


Evolution of Self-Organized Task Specialization in Robot Swarms.
Division of labor is ubiquitous in biological systems, as evidenced by various forms of complex task specialization observed in both animal societies and multicellular organisms. Although clearly adaptive, the way in which division of labor first evolved remains enigmatic, as it requires the simultaneous co-occurrence of several complex traits to achieve the required degree of coordination. Recently, evolutionary swarm robotics has emerged as an excellent test bed to study the evolution of coordinated group-level behavior. Here we use this framework for the first time to study the evolutionary origin of behavioral task specialization among groups of identical robots. The scenario we study involves an advanced form of division of labor, common in insect societies and known as "task partitioning", whereby two sets of tasks have to be carried out in sequence by different individuals. Our results show that task partitioning is favored whenever the environment has features that, when exploited, reduce switching costs and increase the net efficiency of the group, and that an optimal mix of task specialists is achieved most readily when the behavioral repertoires aimed at carrying out the different subtasks are available as pre-adapted building blocks. Nevertheless, we also show for the first time that self-organized task specialization could be evolved entirely from scratch, starting only from basic, low-level behavioral primitives, using a nature-inspired evolutionary method known as Grammatical Evolution. Remarkably, division of labor was achieved merely by selecting on overall group performance, and without providing any prior information on how the global object retrieval task was best divided into smaller subtasks. We discuss the potential of our method for engineering adaptively behaving robot swarms and interpret our results in relation to the likely path that nature took to evolve complex sociality and task specialization.


Significance of megamitochondria in alcoholic liver disease.
The significance of megamitochondria in the alcoholic liver injury of humans was investigated as part of a large Veterans Administration cooperative study of the natural history of alcoholic hepatitis. Two hundred twenty patients were clinically stratified into the following three groups according to disease severity using serum bilirubin and prothrombin time as indicators: Group 1 (mild disease), serum bilirubin levels less than 5 mg/dl and prothrombin time prolonged for less than 4 s; group 2 (moderate disease), serum bilirubin levels greater than 5 mg/dl but prothrombin time prolonged for less than 4 s; and group 3 (severe disease), serum bilirubin levels greater than 5 mg/dl and prothrombin time prolonged for greater than 4 s. Megamitochondria were observed in 20% of the patients (45 of 220). Of these, 43 patients were in groups 1 and 2 of severity and only 1 patient belonged in group 3. The association of megamitochondria with cirrhosis was infrequent (33%, 15 of 45 patients). The differences in severity correlated with the differences in mortality: in patients with megamitochondria, only 1 had died at 6 mo compared with 40 deaths in patients without megamitochondria. By 12 mo, there were two deaths in patients with megamitochondria versus 51 deaths in those patients without. No complications were present in 72% of patients with megamitochondria versus 39% for those without. Infection, gastrointestinal bleeding, pancreatitis, hyperglycemia, azotemia, delirium tremens, seizures, and hepatic encephalopathy were all more common in patients without megamitochondria. The patients with megamitochondria appear to represent a subcategory of alcoholic hepatitis with a milder degree of clinical severity, lower incidence of cirrhosis, fewer complications, and good long-term survival.


Nutrition and physical activity for the prevention and treatment of age-related sarcopenia.
Sarcopenia, defined as loss of skeletal muscle mass and function, is associated with adverse outcomes such as physical disability, impaired quality of life and increased mortality. Several mechanisms are involved in the development of sarcopenia. Potentially modifiable factors include nutrition and physical activity. Protein metabolism is central to the nutritional issues, along with other potentially modifying nutritional factors as energy balance and vitamin D status. An increasing but still incomplete knowledge base has generated recent recommendations on an increased protein intake in the elderly. Several factors beyond the total amount of protein consumed emerge as potentially important in this context. A recent summit examined three hypotheses: (1) A meal threshold; habitually consuming 25-30 g protein at breakfast, lunch and dinner provides sufficient protein to effectively stimulate muscle protein anabolism; (2) Protein quality; including high-quality protein at each meal improves postprandial muscle protein synthesis; and (3) performing physical activity in close temporal proximity to a high-quality protein meal enhances muscle anabolism. Optimising the potential for muscle protein anabolism by consuming an adequate amount of high-quality protein at each meal, in combination with physical activity, appears as a promising strategy to prevent or delay the onset of sarcopenia. However, results of interventions are inconsistent, and well-designed, standardised studies evaluating exercise or nutrition interventions are needed before guidelines can be developed for the prevention and treatment of age-related sarcopenia.


[Effect of angelica polysaccharides co-erythropoietin on JAK2/STAT5 signal transduction pathway in hematopoietic stem/progenitor cells].
To investgate the signal transduction and regulation in erythropoiesis by angelica polysaccharides (APS) to clarify the mechanism for APS promoting hematopoiesis. The mononuclear cells were isolated from foetus umbilic cord blood (mononuclear cells, MNCs), after MNCs were incubated in the presence of APS group (APS 200 mg x L(-1)) and control group for 24 h, the cells were stimulated with Epo (5 U x mL(-1)) for 0, 2, 5, 30 min, respectively. STAT5 was measured by ICC and laser confocal scanning microscope. JAK2, STAT5 in nucleus and cytoplasm were measured by western-blotting-ECL. Angelica polysaccharide cooperated with Epo has significant impact on the expression of STAT5. The expression of STAT5 has significant difference between APS group and the control group at 4 time points. JAK2, STAT5 expressed in cytoplasm and nuclear of APS group significantly increased as compared to those of control group, and they expressed the strongest at 5 min. JAK2, STAT5 signal transduction molecule plays an important role in the effect of APS cooperated with Epo on promoting hematopoiesis.


Are children presenting with non-IMCI complaints at greater risk for suboptimal screening? An analysis of outpatient visits in Afghanistan.
To determine if children presenting without complaints related to the Integrated Management of Childhood Illness (IMCI) are at greater risk for suboptimal screening for IMCI conditions. Cross-sectional study. Thirty-three provinces in Afghanistan. Observation of 3072 sick child visits selected by systematic random sampling. A 10 point IMCI assessment index. One hundred and thirty-one (4.3%) of the 3072 sick child visits involved no IMCI-related complaints. The mean assessment index for all sick child visits was 4.81 (SD 2.41). Visits involving any IMCI-related complaint were associated with a 1.02 point higher mean assessment index than those without IMCI-related complaints (95% CI, 0.52-1.53; P < 0.001). After adjusting for relevant covariates including patient age, caretaker gender, provider type, provider gender, provider IMCI training status and IMCI guideline availability, we found that children with IMCI-related presenting complaints had a significantly better quality of IMCI screening, than those without IMCI presenting complaints (by 0.75 points; 95% CI, 0.25-1.26; P = 0.003). Our study indicates that children with non-IMCI presenting complaints are at greater risk of suboptimal screening compared to children with IMCI-related presenting complaints. The premise of IMCI is to routinely screen all children for conditions responsible for the major burden of childhood disease in countries like Afghanistan. The study illustrates an important finding that facility and provider capacity needs to be improved, particularly during training, supervision and guideline dissemination to ensure that all children receive routine screening for common IMCI conditions.


Chest wall volume changes during inspiratory loaded breathing.
We assessed the effect of inspiratory loaded breathing (ILB) on respiratory muscle strength and investigated the extent to which respiratory muscle fatigue is associated with chest wall volume changes during ILB. Twelve healthy subjects performed ILB at 76 ± 11% of maximal inspiratory mouth pressure (MIP) for 1h. MIP and breathing pattern during 3 min of normocapnic hyperpnea (NH) were measured before and after ILB. Breathing pattern and chest wall volume changes were assessed by optoelectronic plethysmography. After ILB, six subjects decreased MIP significantly (-16 ± 10%; p < 0.05), while the other six subjects did not (0 ± 7%, p = 0.916). Only subjects with decreased MIP after ILB lowered end-expiratory rib cage volume (volume at which inspiration is initiated) below resting values during ILB. During NH after ILB, tidal volume was smaller in subjects with decreased MIP (-19 ± 16%, p < 0.05), while it remained unchanged in the other group (-3 ± 11%, p = 0.463). These results suggest that respiratory muscle fatigue depends on the lung volume from which inspiratory efforts are made during ILB.


[A hierarchical model for analysis of socio-economic variables and water contact patterns associated with the hepatosplenic form of schistosomiasis].
A study of factors associated with the hepatosplenic clinical form of schistosomiasis was carried out in an endemic area (Comercinho, Minas Gerais) where prevalence of Schistosoma mansoni infection was 70.4%. Of the 1,408 inhabitants aged two years and over, 1,162 (82.5%) participated in the study. Socio-demographic characteristics and reasons for water contacts of individuals with the hepatosplenic form (n = 73) were compared to those who did not present splenomegaly and eliminated (positive controls; n + 804) or did not eliminate S. mansoni eggs in stools (negative controls; n = 285). Multivariate analysis was performed, considering the existence of colinearity among socio-economic status of the family, running water in the household, and bathing in streams. The hepatosplenic form in children was strongly associated with occupation of the head of the family (manual workers) (OR = 11.4; 95% CI = 1.4 - 91.8), absence of running water in the household (OR = 7.7; 95% CI = 2.6 - 23.1), and bathing in streams (OR and 95% CI 7.6; 2.5-22.9 and 5.7; 1.3-25.5 for frequencies > weekly and <= weekly, respectively); bathing in streams, which implies intense contacts, was a consequence of the first two factors. Our results suggest that running water in the household can decrease morbidity from schistosomiasis because it reduces the need for intense contacts with streams.


Prevalence of depressive symptoms in older nursing home residents with intact cognitive function in Taiwan.
The investigators aimed to explore the prevalence of depressive symptoms and associated factors among older residents with intact cognitive function in nursing homes in Taiwan. A cross-sectional descriptive and correlational research design was used. A convenience sample of 178 older residents without cognitive impairment was recruited from 36 nursing homes in Southern Taiwan. The questionnaires included demographic data; the Barthel Index, which assesses the ability to perform activities of daily living; and the Geriatric Depression Scale Short Form. Among older residents in nursing homes with intact cognitive function, 39.3% had depressive symptoms. Age, religion, previous living status, previous working status, being totally dependent in physical function, and being severely dependent in physical function were significant predictors of depressive symptoms among cognitively intact older residents. The findings highlight the critical mental healthcare issues among older residents with intact cognitive function in nursing homes. Practical strategies for preventing the occurrence of depressive symptoms and caring for those who have depressive symptoms should be developed, especially for younger or dependent older residents or residents who have never been employed, have no religious beliefs, or have lived alone before they moved into an institution.


The influence of the indicator arm on end point distribution in proprioceptive localization with multi-joint arms.
The present study attempted to demonstrate that the indicator arm influences end point distribution in contralateral multi-joint proprioceptive tasks and also that intrinsic physical characteristics of multi-joint arms (arm stiffness) may predict the error pattern. For this purpose, we carried out two types of contralateral localization tasks with multi-jointed arm movements. In the concurrent localization task, the end point distribution was significantly more elongated in the direction of the lower stiffness at each target position when based on the indicator stiffness, while in the remembered localization task, there was no significant difference between the axes. The best-fit ellipse for the end point distribution also confirmed those results. These findings may support the idea that a large part of the configuration of end point distribution could be determined by the characteristics of arm stiffness of the indicator arm in the condition without memory decay of position representation. Further, error bias of proprioceptive localization may be influenced by the combined effect between movement direction and orientation of the lower stiffness. In conclusion, this study suggests that error patterns largely reflect indicator factors such as the elastic property of the arm in multi-joint proprioceptive tasks, which have been assumed to assess the proprioceptive sense of the reference arm.


[HIV/AIDS and middle aged: knowledge assessment of people from Vale do Sinos, Rio Grande do Sul State, Brazil].
The objective of this article is to assess the knowledge about HIV/aids in middle aged acquaintance group participants from the Vale do Sinos, Rio Grande do Sul State, Brazil. A prospective cross-sectional study with 168 individuals (9.5% male and 90.5% female) between 40 and 59 years of age was performed. A questionnaire comprising questions about the concept, transmission, vulnerability, prevention, and treatment domains on HIV issues was constructed. It was observed that 61.3% of the sample had finished elementary education and 45.2% had a monthly income ranging from 1 to 3 minimum wages. In the conceptual domain, 65.2% did not know that HIV infection has an asymptomatic phase and 34.5% believed HIV could be transmitted by a mosquito bite. In prevention and vulnerability domains, 19.5% had no knowledge about female condoms and 29.2% believed that the disease was confined to specific groups. Regarding to antiretroviral treatment, 12.5% had no idea about its existence. According to findings, middle aged participants from acquaintance groups in Vale do Sinos had misconceptions about HIV/aids which might enhance the risk of infection. Therefore it is necessary to provide public health programs directed to this population group in order to prevent or decrease the risk of HIV transmission.


PEGylation of human serum albumin: reaction of PEG-phenyl-isothiocyanate with protein.
Successful and cost-effective PEGylation protocols require pure functionalized PEG reagents, which can be synthesized by simple and efficient procedures, exhibit high stability against hydrolysis, and maintain a level of reactivity with protein functional groups under mild reaction conditions. PEG-phenyl-isothiocyanate (PIT-PEG) is a new functionalized PEG having these characteristics, and has been synthesized by condensation of the bifunctional reagent 4-isothiocyanato phenyl isocyanate with monomethoxy PEG (mPEG). The data of (1)H NMR and colormetric analysis of the new PEG reagent establish that the mPEG has been quantitatively functionalized. The t 1/4 values for the hydrolysis of PIT-PEG5K in 100 mM phosphate solution at pH 6.5 and 9.2 are about 95 and 40 h, respectively. Incubation of human serum albumin (HSA, 0.5 mM) with a 10-fold molar excess of PIT-PEG (3K or 5K) at pH 6.5 and 9.2 generated PEG-HSA conjugates with average of 3.5 and 6.0 PEG chains per HSA molecule, respectively. The circular dichroism spectra of the conjugates showed that PEGylation of HSA has little influence on the secondary structure of HSA. The hexaPEGylated HSA, (TCP-PEG5K) 6-HSA, exhibited very high hydrodynamic volume, and the molecular radius of HSA increased from 3.95 to 6.57 nm on hexaPEGylation. The hexaPEGylation also increased the viscosity of 4% HSA from 1.05 to 2.10 cP, and the colloid osmotic pressure from 15.2 to 48.0 mmHg. The large increase in the hydrodynamic volume and the solution properties of (TCP-PEG5K) 6-HSA suggest that it could be a potential candidate as a plasma volume expander. PIT-PEG is a useful addition to the spectrum of functionalized PEG reagents available for surface decoration of proteins with PEG.


Evaluation of the Pleasure Scale in the assessment of anhedonia in children.
The Pleasure Scale for Children, a measure developed to assess anhedonia in school-age children, was evaluated. Psychometric properties and concurrent validity of the scale were evaluated with 232 child psychiatric inpatient children (ages 6-13) and their parents. Based on prior research with adults, predictions were made that children with a diagnosis of major depression would evince greater anhedonia on the scale and that anhedonic children (low Pleasure Scale scores) would show a negative attributional style in relation to rewarding experiences. The results indicated that the Pleasure Scale was internally consistent, yielded moderate to high item-total score correlations, appeared to reflect a single dimension, and correlated positively and significantly with other measures of pleasurable affect. Depressed children showed greater anhedonia, as reflected in lower total Pleasure Scale scores and in their pattern of responding to individual items on the scale. Children high in anhedonia, independently of their diagnosis, showed less active involvement in seeking rewards, were higher in their expectations of negative outcomes, and were more likely to attribute unrewarding outcomes to their own behavior than to external causes. Overall, the results provide initial support for the construct validity of the scale. Further research to evaluate nonclinic samples, to develop alternative assessment strategies, to examine developmental differences in reporting pleasurable experiences, and to study the relation of anhedonia to subtypes and clinical course of depression is briefly discussed.


Virus-like particles (VLP) in prophylaxis and immunotherapy of allergic diseases.
Apart from active allergen avoidance, immunotherapy is regarded as the most effective form of treatment available for type I allergies. Such treatments involve the administration of allergen preparations in various forms and by various routes. Virus-like particles (VLPs) offer a very effective platform for immunization with the allergen and are characterized by high immunogenicity, low allergenicity and high clinical efficacy. Formulations that include Toll-like receptor ligands, T cell stimulatory epitopes and/or depot-forming adjuvants appear to enhance activation of the relevant immune cells. Short nucleotide sequences including CpG motifs have also been intensively explored as potent stimulators of dendritic cells and B cells. The present paper is based on a systematic literature search in PubMed and MEDLINE, and focuses on the pertinent immunological processes and on clinical data relating to use of VLPs and CpG motifs for the treatment of allergic rhinitis (AR). Many published studies have reported positive clinical results following administration of VLPs, either alone or in combination with CpG motifs and, in some cases, even in the absence of the allergen-specific allergen. These results indicate that VLPs modulate immune responses in ways which underline their exceptional promise as a platform for the immunotherapy of allergic disorders. However, clinical evaluations remain limited, and further large-scale and longer-term studies will be necessary to substantiate the efficacy and safety of these novel therapies.


Do maternal concerns at delivery predict parenting stress during infancy?
In a previous study, we found that new mothers could and would express concerns about their parenting, including concerns about maltreatment and poor care. In this study, we examine the utility of early maternal concerns for predicting parenting stress in the first year. Parenting stress is important because it has been shown to be related to maltreatment and poor parent-child relationships. A sample of 246 mothers were interviewed shortly after delivery in a publicly funded hospital about their parenting concerns, and 93% were reinterviewed in their homes about their parenting when the infants were 6 to 12 months old. Standardized measures with demonstrated psychometric properties were employed, including a measure of parenting stress due to the demands of the parenting role, characteristics of the child that make him or her difficult to care for, and stress due to difficult interactions. Multiple regression results indicate that both mothers concerns at delivery and sociodemographic variables are significant predictors of all three types of parenting stress in infancy. Maternal concerns were more powerful than sociodemographics in predicting stress related to the demands of parenting, while sociodemographics were more powerful for the prediction of stress related to difficult child characteristics and difficult mother-infant interaction. These findings suggest that knowledge of new mothers' parenting concerns might be useful for predicting parenting problems, as well as for engaging mothers' in and enhancing the effectiveness of parenting services.


A metallacage encapsulating chloride as a probe for a solvation scale in ionic liquids.
With the purpose of assessing the reactivity of chloride ions dissolved in ionic liquids (ILs), a relative scale for the solvation of chloride is given for a series of ILs based on the bis(trifluoromethane)sulfonimide ([Tf(2)N]) anion and different cations, 1-butyl-3-methylimidazolium ([bmim]), 1-butyl-2,3-dimethylimidazolium ([bdmim]), 1-butyl-1-methylpyrrolidinium ([bmpy]), 1-butylpyridinium ([bpy]), 1-pentyl-1,1,1-triethylammonium ([C(5)e(3)am]), and 1-(2-hydroxy)ethyl-3-methylimidazolium ([mimeOH]). Insights into the solvation of chloride are achieved by the thermodynamic study of the reaction of dissociation of a chloride-templated nickel(II) metallacage performed at various temperatures by UV-visible spectroscopy in each IL. The order of chloride solvation [C(5)e(3)am][Tf(2)N] < [bmpy][Tf(2)N] < [bmim][Tf(2)N] <or= [bdmim][Tf(2)N] < [bpy][Tf(2)N] < [mimeOH][Tf(2)N] was ascertained from the reaction enthalpies determined in the different ILs. The reaction entropies display a concentration-dependent behavior, which has highlighted a correlated motion of the ions in these ILs.


Prevalence of chronic obstructive pulmonary disease and tobacco use in veterans at Boise Veterans Affairs Medical Center.
Although its prevalence is still debated, chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the United States, and smoking cessation remains the only intervention that can significantly improve the prognosis of COPD. To determine the prevalence of COPD in a typical population seeking care at a Veterans Affairs Medical Center; the impact of smoking, age, and sex on the prevalence of COPD in this population; and how often spirometry is done in patients at risk for COPD, we extracted data from the Veterans Integrated Service Network 20 Consumer Health Information and Performance Sets database, on patients seen at the Boise Veterans Affairs Medical Center between January 1, 1999, and May 30, 2006. Approximately 8.8% (2,556/28,983) of all patients and 14.1% (1,152/8,149) of smokers were reported to have COPD. The odds of COPD in smokers, after adjusting for age and sex, was 3.18 (95% confidence interval 2.88-3.50) times greater than in nonsmokers. Males were 1.48 times more likely to have COPD than females, and there was an increasing risk of COPD with age. Thirty-nine percent of all veterans and 54% of those with COPD were active smokers. 273 (60%) of the 455 symptomatic smokers without a prior diagnosis of COPD were not evaluated with spirometry. The prevalence of COPD in patients at the Boise Veterans Affairs Medical Center was consistent with that in other United States surveys, although the underutilization of screening spirometry in those at risk for COPD may have caused underestimation of the prevalence. Smoking, age, and male sex were identified as significant risk factors for COPD, and the prevalence of active smoking remains high in this population of veterans.


Phaeobacter aquaemixtae sp. nov., isolated from the junction between the ocean and a freshwater spring.
A Gram-reaction-negative, aerobic, non-spore-forming, non-motile and rod-shaped or ovoid bacterial strain, designated SSK6-1(T), was isolated from the zone where the ocean and a freshwater spring meet at Jeju island, South Korea. Strain SSK6-1(T) grew optimally at 30 °C, at pH 7.0-7.5 and in the presence of 2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that strain SSK6-1(T) clustered with Phaeobacter daeponensis TF-218(T) and Phaeobacter caeruleus LMG 24369(T), exhibiting sequence similarities of 98.6 and 98.3 %, respectively. The novel strain exhibited sequence similarities of 94.6-97.8 % to the type strains of other recognized species of the genera Phaeobacter and Leisingera. Strain SSK6-1(T) contained Q-10 as the predominant ubiquinone and C18 : 1ω7c and 11-methyl C18 : 1ω7c as the major fatty acids. The major polar lipids of strain SSK6-1(T) were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminolipid and one unidentified lipid. The DNA G+C content of strain SSK6-1(T) was 64.6 mol% and its DNA-DNA relatedness values with P. daeponensis TF-218(T) and P. caeruleus were 21 and 25 %, respectively. The differential phenotypic properties, together with phylogenetic and genetic distinctiveness, revealed that strain SSK6-1(T) is separate from recognized Phaeobacter species. On the basis of the data presented, strain SSK6-1(T) is considered to represent a novel species of the genus Phaeobacter, for which the name Phaeobacter aquaemixtae sp. nov. is proposed. The type strain is SSK6-1(T) ( = KCTC 32538(T) = CECT 8399(T)).


Evaluation of surveillance bias and the validity of the venous thromboembolism quality measure.
Postoperative venous thromboembolism (VTE) rates are widely reported quality metrics soon to be used in pay-for-performance programs. Surveillance bias occurs when some clinicians use imaging studies to detect VTE more frequently than other clinicians. Because they look more, they find more VTE events, paradoxically worsening their hospital's VTE quality measure performance. A surveillance bias may influence VTE measurement if (1) greater hospital VTE prophylaxis adherence fails to result in lower measured VTE rates, (2) hospitals with characteristics suggestive of higher quality (eg, more accreditations) have greater VTE prophylaxis adherence rates but worse VTE event rates, and (3) higher hospital VTE imaging utilization use rates are associated with higher measured VTE event rates. To examine whether a surveillance bias influences the validity of reported VTE rates. 2010 Hospital Compare and American Hospital Association data from 2838 hospitals were merged. Next, 2009-2010 Medicare claims data for 954,926 surgical patient discharges from 2786 hospitals who were undergoing 1 of 11 major operations were used to calculate VTE imaging (duplex ultrasonography, chest computed tomography/magnetic resonance imaging, and ventilation-perfusion scans) and VTE event rates. The association between hospital VTE prophylaxis adherence and risk-adjusted VTE event rates was examined. The relationship between a summary score of hospital structural characteristics reflecting quality (hospital size, numbers of accreditations/quality initiatives) and performance on VTE prophylaxis and risk-adjusted VTE measures was examined. Hospital-level VTE event rates were compared across VTE diagnostic imaging rate quartiles and with a quantile regression. Greater hospital VTE prophylaxis adherence rates were weakly associated with worse risk-adjusted VTE event rates (r2 = 4.2%; P = .03). Hospitals with increasing structural quality scores had higher VTE prophylaxis adherence rates (93.3% vs 95.5%, lowest vs highest quality quartile; P < .001) but worse risk-adjusted VTE rates (4.8 vs 6.4 per 1000, lowest vs highest quality quartile; P < .001). Mean VTE diagnostic imaging rates ranged from 32 studies per 1000 in the lowest imaging use quartile to 167 per 1000 in the highest quartile (P < .001). Risk-adjusted VTE rates increased significantly with VTE imaging use rates in a stepwise fashion, from 5.0 per 1000 in the lowest quartile to 13.5 per 1000 in the highest quartile (P < .001). Hospitals with higher quality scores had higher VTE prophylaxis rates but worse risk-adjusted VTE rates. Increased hospital VTE event rates were associated with increasing hospital VTE imaging use rates. Surveillance bias limits the usefulness of the VTE quality measure for hospitals working to improve quality and patients seeking to identify a high-quality hospital.


DNA polymerase switching: I. Replication factor C displaces DNA polymerase alpha prior to PCNA loading.
An important not yet fully understood event in DNA replication is the DNA polymerase (pol) switch from pol alpha to pol delta. Indirect evidence suggested that the clamp loader replication factor C (RF-C) plays an important role, since a replication competent protein complex containing pol alpha, pol delta and RF-C could perform pol switching in the presence of proliferating cell nuclear antigen (PCNA). By using purified pol alpha/primase, pol delta, RF-C, PCNA and RP-A we show that: (i) RF-C can inhibit pol alpha in the presence of ATP prior to PCNA loading, (ii) RF-C decreases the affinity of pol alpha for the 3'OH primer ends, (iii) the inhibition of pol alpha by RF-C is released upon PCNA loading, (iv) ATP hydrolysis is required for PCNA loading and subsequent release of inhibition of pol alpha, (v) under these conditions a switching from pol alpha/primase to pol delta is evident. Thus, RF-C appears to be critical for the pol alpha to pol delta switching. Based on these results, a model is proposed in which RF-C induces the pol switching by sequestering the 3'-OH end from pol alpha and subsequently recruiting PCNA to DNA.


Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features.
Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features (MD-Psy). We assessed the extent to which the pharmacotherapy received by patients with MD-Psy under usual care conforms to these recommendations. We assessed the pharmacotherapy received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD (Study of the Pharmacotherapy of Psychotic Depression), a 12-week randomized, controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo. Our assessment took place from January 2003 to May 2004. The strength of antidepressant trials was rated using the Antidepressant Treatment History Form (ATHF). The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF. We also determined whether the strength of antipsychotic or combination trials was associated with age, the duration of the current depressive episode, medical burden, cognitive status, or the severity of depressive or psychotic symptoms. Most patients with MD-Psy were treated with antidepressants (N = 82, 82%) or antipsychotics (N = 65, 65%). About half of the patients (N = 48, 48%) received therapeutic doses of an antidepressant; 10% (N = 10) received an intermediate dose of an antipsychotic, and 6% (N = 6) received a high dose. Overall, only 5% (N = 5) received a combination of an adequate dose of an antidepressant and a high dose of an antipsychotic. The strength of both antipsychotic trials (p = .021) and combination trials (p = .039) was significantly associated only with a longer duration of the current depressive episode. These findings show a persisting low use of antipsychotics in the treatment of MD-Psy. Given the high morbidity rates associated with MD-Psy, it is important to continue to educate clinicians regarding its identification and treatment. ClinicalTrials.gov identifier NCT00056472.


Synovial Fluid Fatty Acid Profiles Differ between Osteoarthritis and Healthy Patients.
Free fatty acids (FAs) may influence cartilage metabolism and osteoarthritis (OA) disease progression. It is not clearly studied which FAs are present in the synovial fluid of knee joints and whether there are differences in FA content between nonsymptomatic and OA knee joints. The aim of this study was to investigate the presence of different types of FAs in synovial fluid of both OA- and nonsymptomatic control joints, and to analyze differences between both groups. A total of 23 synovial fluid samples were collected from patients with end-stage knee OA undergoing total knee replacement, with approval of the medical ethical committee. As controls, 6 synovial fluid samples were obtained from postmortem donors without any history of joint disease or arthritis. Measurement of free FA concentration was done by mass spectrometry for saturated FAs (SFA), monounsaturated FAs (MUFA), and omega-3 and omega-6 polyunsaturated FAs (n-3 PUFAs and n-6 PUFAs). Our measurements demonstrated the presence of SFAs, MUFAs, n-3 and n-6 PUFAs in synovial fluid of both nonsymptomatic and OA knee joints. The n-6/n-3 ratio was significantly lower in the OA group (P = 0.0005). Arachidonic acid (n-6 PUFA) concentrations were also lower in OA synovial fluid (P = 0.01), while tetracosadienoic acid (P = 0.0001) and nervonic acid (P = 0.001) (MUFAs) were higher in synovial fluid of patients with knee OA. Synovial fluid contains a broad spectrum of free FAs. The FAs profile differs between OA and control subjects, including a tendency for less n-6 FAs in OA joints.


Measurements of conduction times with catheter electrodes during pacing from different ventricular sites.
Filtered bipolar catheter electodes, I mm apart, were used to pace and record from the high right atrium, right ventricular apex, right ventricular outflow tract, right ventricular inflow tract, middle cardiac vein, great cardiac vein, and endocardium of the left ventricular septal surface. Right ventricular apex to middle cardiac vein and the middle cardiac vein to right ventricular apex conduction intervals gave a rough estimate of anteroposterior and posteroanterior "transseptal plus free left ventricular wall" conduction times, respectively. On the other hand, the right ventricular apex to left ventricular septal surface and left ventricular septal surface to right ventricular apex intervals represented pure "transseptal" conduction times, since both sets of electrodes were in contact with the respective septal surface. During stimulation of the intermediately located right ventricular inflow tract propagation to the right ventricular apex and right ventricular outflow tract was longer than between these two sites. Moreover, conduction was almost as delayed to the right ventricular apex and right ventricular outflow tract as it was to the left ventricular septal surface. These findings were attributed to the peculiar electrophysiological behaviour of the right ventricular inflow tract muscle. Pacing from different segments of the great cardiac vein produced QRS morphologies and arrival of excitation patterns consistent with the relation between the anatomical location of this structure and the recording electrodes. However, from this study no inferences could be drawn regarding the conduction velocity or specific conduction pathways used by the stimulus in its journey from stimulating to recording areas.


Is coracohumeral distance associated with pain-function, and shoulder range of movement, in chronic anterior shoulder pain?
The aim of this study was twofold: (i) to assess the intrarater reliability of coracohumeral distance; (ii) to investigate the level of association between coracohumeral distance measured by ultrasonography, and pain-disability and shoulder range of movement, in patients suffering from chronic anterior shoulder pain. An observational, cross sectional study was carried out. A convenience sample comprised of 87 patients with chronic anterior shoulder pain was assessed from 3 primary care centres. Main outcomes as pain and function were measured through the shoulder pain and disability index. Furthermore, shoulder range of movement-free of pain in shoulder elevation, as well as coracohumeral distance at both 0 and 60 degrees, were collected. Absence of any correlation was found between coracohumeral distance and shoulder pain and disability index at both 0 and 60 degrees of shoulder elevation. Furthermore, absence of any correlation was found between coracohumeral distance measurements and active shoulder range of movement -free of pain. There was poor association between coracohumeral distance and shoulder pain and function, as well as with shoulder range of movement, in patients with chronic anterior shoulder pain. Hence, clinicians should consider, not only increasing this space, but also other possibilities in their therapies, when patients with anterior shoulder pain are treated. ACTRN12614000144617 . Registered: 1st March 2014.


Human pDCs preferentially sense enveloped hepatitis A virions.
Unlike other picornaviruses, hepatitis A virus (HAV) is cloaked in host membranes when released from cells, providing protection from neutralizing antibodies and facilitating spread in the liver. Acute HAV infection is typified by minimal type I IFN responses; therefore, we questioned whether plasmacytoid dendritic cells (pDCs), which produce IFN when activated, are capable of sensing enveloped virions (eHAV). Although concentrated nonenveloped virus failed to activate freshly isolated human pDCs, these cells produced substantial amounts of IFN-α via TLR7 signaling when cocultured with infected cells. pDCs required either close contact with infected cells or exposure to concentrated culture supernatants for IFN-α production. In isopycnic and rate-zonal gradients, pDC-activating material cosedimented with eHAV but not membrane-bound acetylcholinesterase, suggesting that eHAV, and not viral RNA exosomes, is responsible for IFN-α induction. pDC activation did not require virus replication and was associated with efficient eHAV uptake, which was facilitated by phosphatidylserine receptors on pDCs. In chimpanzees, pDCs were transiently recruited to the liver early in infection, during or shortly before maximal intrahepatic IFN-stimulated gene expression, but disappeared prior to inflammation onset. Our data reveal that, while membrane envelopment protects HAV against neutralizing antibody, it also facilitates an early but limited detection of HAV infection by pDCs.


Intrinsic acid-base properties of purine derivatives in aqueous solution and comparison of the acidifying effects of platinum(II) coordinated to N1 or N7: acidifying effects are reciprocal and the proton "outruns" divalent metal ions.
The effect of Pt(2+) coordination, in particular of (dien)Pt(2+) or cis-(NH(3))(2)Pt(2+), on the acid-base properties of the purine ligands 9-ethylguanine (9EtG), 9-methylhypoxanthine (9MeHx), inosine (Ino), 9-methyladenine (9MeA), and N6',N6',N9-trimethyladenine (TriMeA) is quantitatively evaluated. The corresponding acidity constants of the complexes are calculated by curve-fitting procedures using previously published (1)H NMR shift data which had been measured in aqueous solution (D(2)O) in dependence on pH (pD). Comparison of the pK(a) values of the ligands with those of the Pt(2+) complexes reveals the expected behavior for the (N7)-platinated complexes; i.e., the (N1)H(0/+) sites are acidified due to charge repulsion. However, Pt(2+) coordination at (N1)(-)(/0) sites leads to an (already previously observed) apparent increase in the basicity of the N7 sites for the guanine, hypoxanthine, and adenine residues; this is also the case if Pt(2+) is bound to N3. Coordination of Pt(2+) to both the (N1)(-) and N7 sites of 9EtG results apparently in an enhanced basicity of N3 if compared with the release of the proton from the (N3)H(+) site in H(2)(9EtG)(2+). For the former cases in aqueous solution (H(2)O) it is now proven for a comprehensive set of data (seven examples), by taking into account the intrinsic basicities of the various N7 sites via micro acidity constants, that the acidifications are reciprocal and identical. This means Pt(2+) coordinated to (N1)(-)(/0) sites in guanine, hypoxanthine, or adenine residues acidifies the (N7)H(+) unit to the same extent as (N7)-coordinated Pt(2+) acidifies the (N1)H(0/+) site. In other words, the apparently increased basicity of N7 upon Pt(2+) coordination at (N1)(-)(/0) sites disappears if the micro acidity constants of the appropriate isocharged tautomers of the ligand are properly taken into account. It is further proven, on the basis of the evaluations of the nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), that these given conclusions are also valid for nucleotides. In addition, it is shown that the mentioned apparent basicity increase, which results from the use of macro acidity constants, has its origin in the fact that the proton-metal ion (Pt(2+)) interaction (the extent of which depends on the kind of metal ion involved) is less pronounced than the proton-proton interaction. Finally, the proven reciprocal behavior will now allow one to determine micro acidity constants of ligands by studying complexes formed with kinetically inert metal ions. A further result of interest is the proof that the competition of Pt(2+) (or Pd(2+)) with the proton for the (N1)(-) and N7 binding sites of inosinate results in the isomer where the metal ion is at N7 with the proton relegated to (N1)(-); this isomer is favored by a factor of about 2000 compared with the one having the metal ion at (N1)(-) and the proton at N7.


Al₂C monolayer: the planar tetracoordinate carbon global minimum.
Inspired by our theoretical finding that C₂Al₆(2-) has a planar D₂h minimum with two planar tetracoordinate carbons (ptCs), we computationally designed a new two-dimensional (2D) inorganic material, an Al₂C monolayer. All carbons in this monolayer are ptC's, stabilized inductively by binding to four electropositive Al atoms in the same plane. The Al₂C monolayer is semiconducting with an indirect minimum band gap and a slightly larger direct band gap. Good persistence of the Al₂C monolayer is indicated by its moderate cohesive energy, the absence of imaginary modes in its phonon spectrum, and the high melting point predicted by molecular dynamics (MD) simulations. Moreover, a particle-swarm optimization (PSO) global minimum search found the Al₂C monolayer to be the lowest-energy 2D structure compared to other Al₂C alternatives. Dividing the Al₂C monolayer results in one-dimensional (1D) Al₂C nanoribbons, which are computed to have quite rich characteristics such as direct or indirect band gaps with various values, depending on the direction of the division and the resulting edge configuration.


Trends in the Development of Diagnostic Tools for Red Blood Cell-Related Diseases and Anemias.
In the recent years, the progress in genetic analysis and next-generation sequencing technologies have opened up exciting landscapes for diagnosis and study of molecular mechanisms, allowing the determination of a particular mutation for individual patients suffering from hereditary red blood cell-related diseases or anemia. However, the huge amount of data obtained makes the interpretation of the results and the identification of the pathogenetic variant responsible for the diseases sometime difficult. Moreover, there is increasing evidence that the same mutation can result in varying cellular properties and different symptoms of the disease. Even for the same patient, the phenotypic expression of the disorder can change over time. Therefore, on top of genetic analysis, there is a further request for functional tests that allow to confirm the pathogenicity of a molecular variant, possibly to predict prognosis and complications (e.g., vaso-occlusive pain crises or other thrombotic events) and, in the best case, to enable personalized theranostics (drug and/or dose) according to the disease state and progression. The mini-review will reflect recent and future directions in the development of diagnostic tools for red blood cell-related diseases and anemias. This includes point of care devices, new incarnations of well-known principles addressing physico-chemical properties, and interactions of red blood cells as well as high-tech screening equipment and mobile laboratories.


Types of falls and strategies for maintaining stability on an unstable surface.
Falls constitute an important health issue. They cause significant morbidity, mortality and have marked psychological effects on the individual, too. The aim of this study has been to determine parameters describing human movement strategies for balance and the reaction if balance is lost as a result of an unstable ground, and to attempt to describe the types of falls. The study group comprised 20 volunteers. Kinematic parameters of falling and dynamic stability were measured using the Vicon Motion System and the Biodex Balance System SD. During the test, subjects stood for 20 s on the tilting platform. The analysis was conducted based on the first recordings, when the participants were not prepared for the event and their reactions were natural. A cluster analysis tool was applied to divide the behavior of people during the test. Based on motion range for kinematic parameters, the cluster analysis revealed 2 types of human behavior: falling (stepping) and restoring balance. Two types of falls were also observed: side and back falls. Moreover, on the basis of angular values for tilting plate, 4 zones were determined. The frequency of access to these zones by each joint revealed 3 strategies to maintain balance: ankle, knee and hip strategy. A set of initial conditions that may be used for future numerical simulations was also determined. Furthermore, the results presented in this study are likely to support the analysis of the effects and the falling patterns. Med Pr 2018;69(3):245-252.


An anisotropic pore-network model to estimate the shale gas permeability.
The permeability of shale is a significant and important design parameter for shale gas extraction. The shale gas permeability is usually obtained based on Darcy flow using standard laboratory permeability tests done on core samples, that do not account for different transport mechanisms at high pressures and anisotropic effects in shales due to nano-scale pore structure. In this study, the permeability of shale is predicted using a pore network model. The characteristics of pore structure can be described by specific parameters, including porosity, pore body and pore throat sizes and distributions and coordination numbers. The anisotropy was incorporated into the model using a coordination number ratio, and an algorithm that was developed for connections of pores in the shale formation. By predicting hydraulic connectivity and comparing it with several high-pressure permeability tests, the proposed three-dimensional pore network model was verified. Results show that the prediction from the anisotropic pore network model is closer to the test results than that based on the isotropic pore network model. The predicted permeability values from numerical simulation using anisotropic pore network model for four shales from Qaidam Basin, China are quite similar to those measured from laboratory tests. This study confirmed that the developed anisotropic three-dimensional pore network model could reasonably represent the natural gas flow in the actual shale formation so that it can be used as a prediction tool.


Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae.
Saccharomyces cerevisiae is able to adapt to a wide range of external oxygen conditions. Previously, oxygen-dependent phenotypes have been studied individually at the transcriptional, metabolite, and flux level. However, the regulation of cell phenotype occurs across the different levels of cell function. Integrative analysis of data from multiple levels of cell function in the context of a network of several known biochemical interaction types could enable identification of active regulatory paths not limited to a single level of cell function. The graph theoretical method called Enriched Molecular Path detection (EMPath) was extended to enable integrative utilization of transcription and flux data. The utility of the method was demonstrated by detecting paths associated with phenotype differences of S. cerevisiae under three different conditions of oxygen provision: 20.9%, 2.8% and 0.5%. The detection of molecular paths was performed in an integrated genome-scale metabolic and protein-protein interaction network. The molecular paths associated with the phenotype differences of S. cerevisiae under conditions of different oxygen provisions revealed paths of molecular interactions that could potentially mediate information transfer between processes that respond to the particular oxygen availabilities.


A comparison of two approaches to text processing: facilitating chart reviews of radiology reports in electronic medical records.
Chart review is central to health services research. Text processing, which analyzes free-text fields through automated methods, can facilitate this process. We compared precision and accuracy of NegEx and SQLServer 2008 Free-Text Search in identifying acute fractures in radiology reports.The term "fracture" was included in 23,595 radiology reports from the Veterans Aging Cohort Study. Four hundred reports were randomly selected and manually reviewed for acute fractures to establish a gold standard. Reports were then processed by SQLServer and NegEx. Results were compared to the gold standard to determine accuracy, precision, recall, and F-statistic.NegEx and the gold standard identified acute fractures in 13 reports. SQLServer identified 2 in a report-based analysis (precision: 1.00; accuracy: 0.97; recall: 0.15; F-statistic: 0.26), and 12 in a sentence-by-sentence analysis (precision: 1.00; recall: 0.92; accuracy: 0.92; F-statistic: 0.96).Text-processing tools utilizing basic database or programming skills are comparable, precise, and accurate in identifying reports for review.


Exposure-response estimates for diesel engine exhaust and lung cancer mortality based on data from three occupational cohorts.
Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen. We derived a meta-exposure-response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios. We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios and also calculated the fractions of annual lung cancer deaths attributable to DEE. We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m3-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 μg/m3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m3 EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures, we estimated that approximately 6% of annual lung cancer deaths may be due to DEE exposure. Combined data from three U.S. occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above the usually acceptable limits in the United States and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively.


Protective effect of Lysimachia christinae against acute alcohol-induced liver injury in mice.
Lysimachia christinae Hance (Primulaceae) is a medicinal plant. The present study was undertaken to investigate protection of L. christinae against acute alcohol-induced liver injury in mice, the related mechanism of oxidative stress and its hepatoprotective chemical compound for the first time. Mice were orally administered alcohol at 6 g/kg 2 h after a 75% ethanol extract of L. christinae (ET) (100, 200, 400 mg/kg), quercetin (2, 4, 8 mg/kg) isolated from L. christinae, or bifendate (150 mg/kg) for seven consecutive days by intragastric administration (i.g.) except the normal group. Serum and liver tissue samples were collected 6 h after alcohol administration and the amount of quercetin in ET was analyzed by high-performance liquid chromatography (HPLC) with a diode array detector (DAD). The results showed that alcohol-induced elevated serum alanine transferase (ALT) and aspartate transaminase (AST) activities were significantly reduced by ET (200, 400 mg/kg), quercetin (4, 8 mg/kg) and bifendate (150 mg/kg), respectively. Further analysis demonstrated that lipid peroxidation (LPO) levels significantly decreased, while glutathione amounts, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities all increased in livers of ET-, quercetin-, and bifendate-treated mice. Besides, amount of quercetin in ET was 1.03%. Taken together, our results indicate that L. christinae can protect against acute alcohol-induced liver injury in mice, the potential mechanism can be related to inhibiting liver oxidative stress injury, and its main hepatoprotective compound is quercetin, for the first time.


Magnetic resonance elastography for the detection and staging of liver fibrosis in chronic hepatitis B.
We measured the accuracy of magnetic resonance elastography (MRE) for the detection and staging of liver fibrosis in chronic hepatitis B (CHB) and compared it with serum fibrosis markers. Prospective comparison of MRE and routine serum fibrosis markers, namely serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), ALT/AST ratio (AAR), AST to platelet ratio index (APRI) and prothrombin index (PI), was performed in 63 consecutive CHB patients who underwent MRE and histological confirmation of liver fibrosis within a 6-month interval. Diagnostic performance of MRE and serum markers for staging fibrosis (≥F1), significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) was compared. The study group comprised 63 patients (19 female; mean age ± SD, 50 ± 11.9 years). MRE (ρ = 0.94, P < 0.0001), APRI (ρ = 0.42, P = 0.0006), PI (ρ = 0.42, P = 0.0006) and AST (ρ = 0.28, P = 0.028) results correlated significantly with fibrosis stage. MRE was significantly more accurate than serum fibrosis markers for the detection of significant fibrosis (0.99 vs. 0.55-0.73) and cirrhosis (0.98 vs. 0.53-0.77). Sensitivity, specificity, positive predictive and negative predictive values for MRE for significant fibrosis and cirrhosis were 97.4 %, 100 %, 100 % and 96 %, and 100 %, 95.2 %, 91.3 % and 100 %, respectively. MRE is an accurate non-invasive technique for the detection and staging of liver fibrosis in CHB. • Magnetic resonance elastography is accurate for liver fibrosis detection and staging. • MR elastography is more accurate than serum tests for staging liver fibrosis. • MR elastography can potentially replace liver biopsy in chronic hepatitis B.


Effect of estrogen-progestin and estrogen on mammographic density.
To assess the different effects between non-treatment, estrogen and estrogen-progestin regimens on changes in mammographic density in postmenopausal women. A historical cohort of 105 postmenopausal women who attended the Menopause Clinic, Srinagarind Hospital, Khon Kaen, Thailand, and received 1 of 3 regimens: nontreatment, estrogen or estrogen-progestin (35 in each group). Mammographic examinations were done before and after a 12-24-month period of hormone therapy. Breast density (mammographic density, recorded in the medical records) between the 2 examinations in each group were compared. An increase in mammographic density occurred among women receiving hormone therapy: 40% (14 of 35) in the estrogen-progestin group and 20% (7 of 35) in the estrogen-only group, but no variation in density was observed in the nontreatment group. The increase in mammographic density occurring in women on hormone therapy, as compared to the nontreatment group, was statistically significant (estrogen-progestin, 95% CI 20.91-59.09; estrogen, 95% CI 3.89-36.11). When the different treatment types were compared, the estrogen-progestin group tended to have a higher prevalence of mammographic density change than the estrogen-only group, but the difference was not statistically significant (95% CI -3.81-43.81). Hormone therapy was associated with increased mammographic density. Apparently the estrogen-progestin regimen affects breast density more than estrogen-only does.


Treatment of Nonsyndromic Cleft Lip and/or Palate in Brazil: Existing Consensus and Legislation, Scope of the Unified Health System, Inconsistencies and Future Perspectives.
Cleft lip and/or palate (CL/P) are the most prevalent craniofacial birth defects in humans, affecting around ten and a half million people across the world and over three hundred thousand in Brazil. Of that, about 70% of the cases occur as a nonsyndromic form, while the remaining 30% are syndromic. In turn, individuals with nonsyndromic CL/P (NSCL/P) often have anatomic deformities involving the lip, alveolar ridge and palate. In this case, the treatments generally require multiple surgeries and various other health interventions throughout childhood, adolescence and adulthood. Another relevant point is that various problems regarding the treatment of NSCL/P in Brazil through the Unified Health System (SUS) have been reported. There are also many inconsistencies in this scenario, including the territorial coverage of healthcare assistance from the craniofacial centres across the country. However, very little data can be found in the scientific literature about the current situation for the treatment of NSCL/P in Brazil. Thus, the present article discusses the existing consensus and legislation, the scope of the SUS, as well as inconsistencies and future perspectives related to the treatment of these craniofacial abnormalities at a national level.


Rhodococcus aetherivorans sp. nov., a new species that contains methyl t-butyl ether-degrading actinomycetes.
The taxonomic positions of two actinomycetes, strains Bc663 and 10bc312T, provisionally assigned to the genus Rhodococcus were determined using a combination of genotypic and phenotypic properties. The organisms have phenotypic properties typical of members of the genus Rhodococcus and were assigned to the 16S rRNA subgroup which contains Rhodococcus rhodochrous and closely related species. The two strains, which have many phenotypic features in common, belong to the same genomic species albeit one readily separated from Rhodococcus ruber with which they form a distinct phyletic line. The organisms were also distinguished from all of the species classified in the R. rhodochrous subgroup, including R. ruber, using a combination of phenotypic properties. The genotypic and phenotypic data show that strains Bc663 and 10bc312T merit recognition as a new species of Rhodococcus. The name proposed for the new species is Rhodococcus aetherivorans (10bc312T = DSM 44752T = NCIMB 13964T).


Comparison of FDTD numerical computations and analytical multipole expansion method for plasmonics-active nanosphere dimers.
This paper describes a comparative study of finite-difference time-domain (FDTD) and analytical evaluations of electromagnetic fields in the vicinity of dimers of metallic nanospheres of plasmonics-active metals. The results of these two computational methods, to determine electromagnetic field enhancement in the region often referred to as "hot spots" between the two nanospheres forming the dimer, were compared and a strong correlation observed for gold dimers. The analytical evaluation involved the use of the spherical-harmonic addition theorem to relate the multipole expansion coefficients between the two nanospheres. In these evaluations, the spacing between two nanospheres forming the dimer was varied to obtain the effect of nanoparticle spacing on the electromagnetic fields in the regions between the nanostructures. Gold and silver were the metals investigated in our work as they exhibit substantial plasmon resonance properties in the ultraviolet, visible, and near-infrared spectral regimes. The results indicate excellent correlation between the two computational methods, especially for gold nanosphere dimers with only a 5-10% difference between the two methods. The effect of varying the diameters of the nanospheres forming the dimer, on the electromagnetic field enhancement, was also studied.


Structure-function analysis of the tobacco mosaic virus resistance gene N.
The tobacco N gene is a member of the Toll-interleukin-1 receptor/nucleotide-binding site/leucine-rich repeat (TIR-NBS-LRR) class of plant resistance (R) genes and confers resistance to tobacco mosaic virus (TMV). We investigated the importance of specific domains of N in inducing TMV resistance, by examining various N deletion and point mutations that introduce single amino acid substitution mutants in vivo. Our deletion analysis suggests that the TIR, NBS, and LRR domains play an indispensable role in the induction of resistance responses against TMV. We show that amino acids conserved among the Toll/IL-1R/plant R gene TIR domain and NBS-containing proteins play a critical role in N-mediated TMV resistance. Some loss-of-function N alleles such as the TIR deletion and point mutations in the NBS (G216A/E/V/R, G218R, G219D, K222E/N, and T223A/N) interfere with the wild-type N function and behave like dominant negative mutations. These F(1) plants mount a hypersensitive response (HR) that is indistinguishable from that of the wild-type N plants, yet TMV was able to move systemically, causing a systemic hypersensitive response (SHR). Many amino acid substitutions in the TIR, NBS, and LRR domains of N lead to a partial loss-of-function phenotype. These mutant plants mount delayed HR compared with the wild-type N plants and fail to contain the virus to the infection site. In addition, some partial loss-of-function alleles (W82S/A, W141S/A, G218V/S, and G219V) interfere with the wild-type N function, leading to SHR. The partial loss-of-function and dominant negative mutant alleles described in this report will be useful in furthering our understanding of the TIR-NBS-LRR class of R genes.