Phytochemical characterization of various St. John's Wort extracts.
Hypericum perforatum is used for its beneficial effects on the nervous system, especially as an antidepressant. Owing to the fast-growing St. John's Wort market in the United States, more and more products (herb and extract) are sold at different quality levels. The amount of well-dried H. perforatum plant material is limited and other species with differing composition and no proof of efficacy are sold. The generally used method for standardization--spectrophotometric determination of naphthodianthrones--is not as selective as a high-performance liquid chromatographic (HPLC) method and can be manipulated (eg, by adding colorants). The different analytical methods used for characterization of St. John's Wort are discussed and a combined spectrophotometric and HPLC method is proposed. Qualitative and quantitative ranges for pharmaceutically relevant compounds of St. John's Wort extracts are cited and the composition of European, US, and Far East extracts is detailed. The influence of the production process, which involves extraction solvents, on phytochemical composition is also described.


Temperature: a driving factor for Meloidogyne floridensis migration toward different hosts.
The peach root-knot nematode, Meloidogyne floridensis, is an emerging species and may become a threat to peach growers if contamination and spread are not avoided. The influence of temperature and two plants - tomato (Solanum lycopersicum) and French marigold (Tagete patula) - on the vertical migration of second-stage juveniles (J2) of M. floridensis was studied using 14-cm long segmented soil columns. Plants were transplanted into cups attached to the top of each column. Nylon meshes were placed between cups and columns to prevent downward root growth. About 1,000 freshly hatched J2 were injected into the base of the columns and then the columns were transferred to growth chambers at 20 and 26°C under a completely randomized block design with four replicates. The number of J2 in each ring of the columns as well as inside tomato or marigold roots was recorded at 3, 6, 9, and 12 days after injection (DAI). Nematode data were subjected to a repeated measures MANOVA. The presence of plants did not improve J2 migration as compared to control. M. floridensis migration was best at 20°C at first, with J2 migrating more than 13 cm as soon as 3 DAI, while it took 9 DAI for J2 to migrate long distances at 26°C. The distribution of J2 along the columns was similar at both temperatures at 12 DAI. Temperature had no influence on J2 penetration. French marigold did not hinder J2 migration, but fewer J2 penetrated its roots.


Comparison of risk factors for cardiovascular mortality in black and white adults.
Recent attention to racial and ethnic disparities in health outcomes highlights the excess coronary heart disease mortality in black patients compared with white patients. We investigated whether traditional cardiovascular disease (CVD) risk factors were similarly associated with CVD mortality in black and white men and women. Participants included 3741 black and 33,246 white men and women (44%) without a history of myocardial infarction, aged 18 to 64 years at baseline (1967-1973) from the Chicago Heart Association Detection Project in Industry study. Blood pressure, total cholesterol level, body mass index, cigarette smoking, and physician-diagnosed diabetes were assessed at baseline using standard methods. Through 2002, there were 107, 1586, 177, and 2866 deaths from CVD in black women, white women, black men, and white men, respectively. In general, the magnitude and direction of associations between traditional risk factors and CVD mortality were similar by race. However, in black women the multivariable-adjusted hazard ratio (HR) per 12 mm Hg of diastolic blood pressure was 1.08 (95% confidence interval [CI], 0.90-1.29), whereas it was 1.31 in white women (95% CI, 1.25-1.38). There was no association between higher cholesterol level (per 40 mg/dL [1.04 mmol/L]) and CVD mortality in black men (HR, 0.94; 95% CI, 0.80-1.10), whereas the risk was elevated in white men (HR, 1.21; 95% CI, 1.16-1.26). Most traditional risk factors demonstrated similar associations with mortality in black and white adults of the same sex. Small differences were primarily in the strength, not the direction, of association.


SFTG international collaborative study on in vitro micronucleus test II. Using human lymphocytes.
This study on the in vitro micronucleus assay, comprising 11 laboratories using human lymphocytes, was coordinated by an organizing committee supported by the SFTG (the French branch of the European Environmental Mutagen Society). Nine coded substances were assessed for their ability to induce micronuclei in human lymphocytes in vitro, mitomycin C being used as a positive control. Cultures were exposed to the test substances for a short (early or late) time or for a long time, followed by a short or long recovery period, in the presence of cytochalasin B. Each chemical was evaluated, generally in two laboratories, using three treatment schedules at least twice. The data were assessed for acceptability, and then classified as negative, positive or equivocal. Two of seven genotoxic compounds, namely colchicine and bleomycin, clearly induced micronuclei. Reproducible results were difficult to obtain for some substances, which tended to be those acting at specific stages of the cell cycle. Cytosine arabinoside, diethylstilboestrol and 5-fluorouracil were classified as equivocal. Urethane and thiabendazole were classified as negative. The two presumed non-genotoxic compounds, mannitol and clofibrate, did not induce micronuclei. Repeat testing, exposing cells at both an early and late time after mitogenic stimulation, was needed to detect substances classified as equivocal. These results show the importance of achieving sufficient inhibition of nuclear division to avoid the possibility of missing an effect. The evaluation of micronuclei in mononucleated as well as binucleated cells was particularly useful to detect aneugens. There were no false positive results using lymphocytes, indicating a high specificity. It is concluded that the clastogenic or aneugenic potential in vitro of the substances tested was correctly identified in this study, but that refining the protocol to take into account factors such as the stages of the cell cycle exposed to the compound, or the duration of recovery would be likely to improve the sensitivity of detection using lymphocytes.


Persistent contaminants as potential constraints on the recovery of urban river food webs from gross pollution.
Urban areas contribute substantially to xenobiotic contaminant loads in rivers, but their effects have been investigated more for individual organisms and sensitive taxa, rather than through the emergent properties of communities. Here, we use replicated, catchment-scale sampling of benthic invertebrates and novel multivariate techniques to assess whether urban wastewater contaminants affected the structure and function of river food webs. We postulated that the continued occurrence of selected contaminants in river systems might explain the incomplete recovery of urban rivers from legacy gross pollution. Benthic invertebrate communities were sampled monthly over a year (2016-2017) at 18 sites across 3 river systems in South Wales (United Kingdom). Contaminant sources were characterised using remote sensing, water quality data from routine monitoring and measured concentrations of selected persistent xenobiotic pollutants (polychlorinated biphenyls and polybrominated diphenyl ethers). Urban wastewater discharges had relatively limited effects on river water quality, with small increases in nitrate, phosphate, temperature, conductivity and total dissolved solids in urban systems. Concentrations of polychlorinated biphenyls and polybrominated diphenyl ethers in invertebrates, however, were significantly higher under greater urban land cover and wastewater discharge. Food webs at the most highly contaminated urban sites were characterised by: (i) reduced taxonomic and functional diversity; (ii) simplified food web structure with reduced network connectance; and (iii) reductions in the abundance of prey important for apex predators such as the Eurasian dipper (Cinclus cinclus). Although correlative and partially confounded by other effects, these data provide support for the hypothesis that impairment to food webs resulting from urban pollutants might explain population, community and ecosystem-level effects in urban river systems, and hence incomplete recovery from past pollution.


What are the demographic and radiographic characteristics of patients with symptomatic extraarticular femoroacetabular impingement?
Extraarticular femoroacetabular impingement (FAI) can result in symptomatic hip pain, but preoperative demographic, radiographic, and physical examination findings have not been well characterized. The purposes of this study were to (1) define the demographic characteristics of patients with symptomatic extraarticular FAI; and (2) identify relevant radiographic and physical examination findings that are associated with intraoperative locations of extraarticular FAI. For purposes of this study, we defined extraarticular FAI as abnormal contact between the extraarticular regions of the proximal femur (greater trochanter, lesser trochanter, extracapsular femoral neck) and the ilium or ischium. The diagnosis was suspected preoperatively, but it was confirmed at the time of surgery by direct visualization of extraarticular impingement after surgical hip dislocation. A prospective single-center hip preservation registry was used to retrospectively characterize patients presenting between October 2010 and November 2013 with symptomatic hip pain and intraoperative findings of extraarticular FAI (N = 75 patients, 86 hips). Detailed demographic data were recorded. Radiographs, CT, and MRI scans were reviewed for all patients by two of the authors (BFR, ELS). Outcome instruments including modified Harris hip score (mHHS), Hip Outcome Score (HOS), and International Hip Outcome Tool (iHOT-33) were assessed preoperatively. A comparison group of all patients (N = 1690 patients, 1989 hips) undergoing surgery for intraarticular FAI over the study period were included for demographic comparisons. Cases with extraarticular FAI accounted for 4% (75 of 1765 patients) of our cohort over the study time period. Patients with extraarticular FAI were more likely to be younger (mean ± SD, 24 ± 7 years versus 30 ± 11 years; difference [95% confidence interval {CI}], -7 [-9 to -4]; p < 0.001), female (85% versus 49%; odds ratio [95% CI], 6 [3 to 12]; p < 0.001), to have undergone prior hip surgery (44% versus 10%; odds ratio [95% CI], 9 (6 to 15); p < 0.001), and have lower preoperative outcome scores after adjustment for age, sex, and revision status (mHHS 55 ± 15 versus 63 ± 15; adjusted difference [95% CI], -4 (-8 to -1); p = 0.017; HOS ADL 64 ± 19 versus 73 ± 18; adjusted difference [95% CI], -7 (-11 to -3); p = 0.002) than patients undergoing surgery for intraarticular FAI. Within the extraarticular FAI group, preoperative femoral version on CT was different among patients with anterior versus posterior extraarticular impingement (median [first quartile, third quartile], 8° [2, 18] versus 21° [20, 30], respectively; p = 0.005) and anterior versus complex extraarticular impingement (median [first quartile, third quartile], 8° [2, 18] versus 20° [10, 30], respectively; p = 0.007]. Preoperative external rotation in extension was increased in patients with anterior versus complex extraarticular FAI (median [first quartile, third quartile], 70° [55, 75] versus 40° [20, 60]; p < 0.001). Extraarticular FAI is an uncommon source of impingement symptoms. We suspect the diagnosis often is missed, because many of these patients had prior hip surgery before the procedure that diagnosed the extraarticular impingement source. This diagnosis seems more common in younger, female patients. Radiographic and physical examination findings correspond to locations of intraoperative extraarticular impingement. Future studies will need to determine whether surgical treatment of extraarticular impingement pathology improves pain and function in this subset of patients.


Assessing the resistance and bioremediation ability of selected bacterial and protozoan species to heavy metals in metal-rich industrial wastewater.
Heavy-metals exert considerable stress on the environment worldwide. This study assessed the resistance to and bioremediation of heavy-metals by selected protozoan and bacterial species in highly polluted industrial-wastewater. Specific variables (i.e. chemical oxygen demand, pH, dissolved oxygen) and the growth/die-off-rates of test organisms were measured using standard methods. Heavy-metal removals were determined in biomass and supernatant by the Inductively Couple Plasma Optical Emission Spectrometer. A parallel experiment was performed with dead microbial cells to assess the biosorption ability of test isolates. The results revealed that the industrial-wastewater samples were highly polluted with heavy-metal concentrations exceeding by far the maximum limits (in mg/l) of 0.05-Co, 0.2-Ni, 0.1-Mn, 0.1-V, 0.01-Pb, 0.01-Cu, 0.1-Zn and 0.005-Cd, prescribed by the UN-FAO. Industrial-wastewater had no major effects on Pseudomonas putida, Bacillus licheniformis and Peranema sp. (growth rates up to 1.81, 1.45 and 1.43 d-1, respectively) compared to other test isolates. This was also revealed with significant COD increases (p < 0.05) in culture media inoculated with living bacterial isolates (over 100%) compared to protozoan isolates (up to 24% increase). Living Pseudomonas putida demonstrated the highest removal rates of heavy metals (Co-71%, Ni-51%, Mn-45%, V-83%, Pb-96%, Ti-100% and Cu-49%) followed by Bacillus licheniformis (Al-23% and Zn-53%) and Peranema sp. (Cd-42%). None of the dead cells were able to remove more than 25% of the heavy metals. Bacterial isolates contained the genes copC, chrB, cnrA3 and nccA encoding the resistance to Cu, Cr, Co-Ni and Cd-Ni-Co, respectively. Protozoan isolates contained only the genes encoding Cu and Cr resistance (copC and chrB genes). Peranema sp. was the only protozoan isolate which had an additional resistant gene cnrA3 encoding Co-Ni resistance. Significant differences (p < 0.05) observed between dead and living microbial cells for metal-removal and the presence of certain metal-resistant genes indicated that the selected microbial isolates used both passive (biosorptive) and active (bioaccumulation) mechanisms to remove heavy metals from industrial wastewater. This study advocates the use of Peranema sp. as a potential candidate for the bioremediation of heavy-metals in wastewater treatment, in addition to Pseudomonas putida and Bacillus licheniformis.


Gastrointestinal illness linked to incidents in drinking water distribution networks in Sweden.
During recent years, knowledge gaps on drinking water-related gastrointestinal illness have been identified, especially for non-epidemic cases. Pathogen contamination of drinking water during distribution has been suggested to contribute to these cases, but the risk factors are not yet fully understood. During 2014-2015, we conducted an epidemiological study in five municipalities in Sweden, to assess whether incidents in the drinking water distribution system influence the risk of gastrointestinal illness. Telephone interviews were conducted in the affected areas and in reference areas 7-14 days after a reported incident. Symptoms of gastrointestinal illness occurring during the period were documented for each household member. The results showed a significantly elevated risk of vomiting and acute gastrointestinal illness (AGI) in the affected areas, compared to the reference areas (ORvom. = 2.0, 95% CI: 1.2-3.3; ORAGI = 1.9, 95% CI: 1.2-3.0). Certain conditions, or risk factors, during the incidents, such as sewage and drinking water pipelines at the same level in the trench, were associated with an elevated risk of AGI and vomiting. Safety measures taken during repair work, like flushing, were also associated with an elevated risk of AGI and vomiting. These results show that incidents in the drinking water distribution network contribute to endemic gastrointestinal illness, especially AGI and vomiting, and that external pathogen contamination of the drinking water is a likely cause of these cases of gastrointestinal illness. The results also indicate that safety measures used today may not be sufficient for eliminating the risk of gastrointestinal illness.


Measurement of maximal coronary flow reserve: a technique for assessing the physiologic significance of coronary arterial lesions in humans.
Recent studies suggest that angiographic measurements of coronary arterial stenosis are poorly correlated with direct measurements of the capacity of the artery to conduct hyperemic blood flow. Direct measurement of coronary blood flow and the flow reserve capacity of individual coronary vessels in conscious humans, however, has been hampered by methodologic limitations. We have developed and validated a coronary Doppler catheter capable of subselectively measuring coronary blood flow velocity at the time of cardiac catheterization. Studies in seven calves demonstrated that measurements of the change in coronary blood flow velocity assessed using the Doppler catheter were highly correlated with simultaneous measurements of the change in coronary sinus blood flow (r = 0.97, slope = 1.06) and changes in blood flow velocity assessed using an epicardial Doppler probe (r = 0.95, slope = 1.04). Additional studies demonstrated that the catheter did not produce physiologically significant obstruction to coronary blood flow. Subsequent studies in 215 humans undergoing catheterization have shown that acceptable signals of phasic coronary blood flow velocity could be recorded in 176 patients. Subsequent dose response kinetic studies demonstrated that intracoronary administration of papaverine can rapidly produce maximal coronary hyperemia, equivalent in magnitude to intravenous dipyridamole, but short enough in duration to permit multiple measurements of coronary flow reserve during a single catheterization. Measurements of coronary flow reserve in patients with obstructive coronary artery disease have permitted characterization of the physiologic significance of individual obstructive coronary lesions. The development of this coronary Doppler catheter system and technique for measurement of maximal coronary flow reserve should facilitate characterization of the physiologic impact of coronary arterial lesions on coronary blood flow and studies of the coronary circulation in conscious humans.


Attempted transmission of Toxoplasma gondii infection from pregnant cats to their kittens.
Sixteen 1- to 7-week-old pregnant specific-pathogen free cats were inoculated orally with Toxoplasma gondii cysts. Fetuses and neonatal kittens were examined for toxoplasma infection by inoculating suspensions of their tissues into mice. Toxoplasma gondii was not isolated from 23 fetuses and 16 newborn kittens from 13 queens. Six (3 litters) of the 15 kittens from the 3 remaining queens were killed on the day of or a day after birth, and the remaining 9 kittens were housed with their mothers for 7 to 33 days. None of the 9 kittens from the 2 litters examined between 0 and 33 days of age was infected with T gondii. In the other litter, T gondii was isolated from 3 kittens killed at 9, 16, and 22 days of age but not from 3 littermates killed on days 1, 1, and 22. Internal organs from the 3 kittens with proved toxoplasma infectivity in mice were examined histologically. Multifocal granulomatous encephalitis, hepatitis, nephritis, myocarditis, myositis, and interstitial pneumonia were found in all 3 kittens. Toxoplasma forms were demonstrated histologically in the tissues of 2 of these kittens. The mode of toxoplasma infection in newborn kittens was not determined but did not appear to be either transplacental or via fecal contamination from oocysts excreted by the mother cat. Evidence obtained in these experiments suggests that transplacental toxoplasma infection in the cat is not an important epidemiologic factor in perpetuation of the disease in the feline population.


Use of Digital Educational Technologies among Nursing Students and Teachers: An Exploratory Study.
The emergence of digital educational technologies (DET) raises questions regarding the personalization of both teaching and care. DET use implies profound changes with consequences in nursing care and in nursing teaching-learning process. With the purpose of contributing to the improvement of the teaching-learning process through the use of DET, an exploratory-descriptive, cross-sectional, and observational study, with a quantitative approach (descriptive and inferential statistics), was developed. Online questionnaires were applied (n = 140 students and n = 23 teachers) after ethics committee approval. Results point to low cost and access without time/space limits as the main benefits, and decreased interaction, less physical contact, and technical difficulties as constraints. Globally, there was no difference between students and teachers in the use of DET. Still, men report more constraints than women. In this sample, the use of DET is still at an early stage. Both students and teachers are still unfamiliar with the scope and possibilities of these tools, not taking full advantage of the potential they have to offer. The impact of DET used in personalized nursing care is still yet to be understood.


Nonionizing Electromagnetic Irradiations; Biological Interactions, Human Safety.
Human is usually exposed to environmental radiation from natural and man-made sources. Therefore, it is important to investigate the effects of exposure to environmental radiation, partly related to understanding and protecting against the risk of exposure to environmental radiation with beneficial and adverse impacts on human life. The rapid development of technologies causes a dramatic enhancement of radiation in the human environment. In this study, we address the biological effects caused by different fractions of non-ionizing electromagnetic irradiation to humans and describe possible approaches for minimizing adverse health effects initiated by radiation. The main focus was on biological mechanisms initiated by irradiation and represented protection, and safety approaches to prevent health disorders.


SASA-Net: A Spatial-aware Self-attention Mechanism for Building Protein 3D Structure Directly from Inter-residue Distances.
Protein functions are tightly related to the fine details of their 3D structures. To understand protein structures, computational prediction approaches are highly needed. Recently, protein structure prediction has achieved considerable progresses mainly due to the increased accuracy of inter-residue distance estimation and the application of deep learning techniques. Most of the distance-based ab initio prediction approaches adopt a two-step diagram: constructing a potential function based on the estimated inter-residue distances, and then build a 3D structure that minimizes the potential function. These approaches have proven very promising; however, they still suffer from several limitations, especially the inaccuracies incurred by the handcrafted potential function. Here, we present SASA-Net, a deep learning-based approach that directly learns protein 3D structure from the estimated inter-residue distances. Unlike the existing approach simply representing protein structures as coordinates of atoms, SASA-Net represents protein structures using pose of residues, i.e., the coordinate system of each individual residue in which all backbone atoms of this residue are fixed. The key element of SASA-Net is a spatial-aware self-attention mechanism, which is able to adjust a residue's pose according to all other residues' features and the estimated distances between residues. By iteratively applying the spatial-aware self-attention mechanism, SASA-Net continuously improves the structure and finally acquires a structure with high accuracy. Using the CATH35 proteins as representatives, we demonstrate that SASA-Net is able to accurately and efficiently build structures from the estimated inter-residue distances. The high accuracy and efficiency of SASA-Net enables an end-to-end neural network model for protein structure prediction through combining SASA-Net and an neural network for inter-residue distance prediction. Source code of SASA-Net is available at https://github.com/gongtiansu/SASA-Net/.


A Unified attentional bottleneck in the human brain.
Human information processing is characterized by bottlenecks that constrain throughput. These bottlenecks limit both what we can perceive and what we can act on in multitask settings. Although perceptual and response limitations are often attributed to independent information processing bottlenecks, it has recently been suggested that a common attentional limitation may be responsible for both. To date, however, evidence supporting the existence of such a "unified" bottleneck has been mixed. Here, we tested the unified bottleneck hypothesis using time-resolved fMRI. Experiment 1 isolated brain regions involved in the response selection bottleneck that limits speeded dual-task performance. These same brain regions were not only engaged by a perceptual encoding task in Experiment 2, their activity also tracked delays to a speeded decision-making task caused by concurrent perceptual encoding (Experiment 3). We conclude that a unified attentional bottleneck, including the inferior frontal junction, superior medial frontal cortex, and bilateral insula, temporally limits operations as diverse as perceptual encoding and decision-making.


Computer simulations of speckle in B-scan images.
The granularity or speckle in medical ultrasound images tends to mask the presence of small lesions. As well, artifactual filling in of anechoic regions such as cysts, reduces the diagnostic potential of the images. These effects depend not only on the acoustic properties of the tissue but also are strongly influenced by the imaging system, especially the transducer geometry. To study the effect of the transducer on the final B-scan image, a computer model has been developed simulating the interaction of ultrasound with a simple scattering medium. This model, incorporating the position dependence of the point response of the transducer, is based on single scattering from a collection of points positioned randomly in a three-dimensional volume. Using this approach, B-scan images showing speckle have been generated for different transducer geometries. Inclusion of a 2.6 mm void mimicking a cyst within the three-dimensional scattering volume has allowed us to predict the cyst contrast in the image for the different transducer systems. Experimental B-scan images of a scattering phantom were obtained using the different pulse echo systems. Quantitative assessment using first and second order statistics of the images shows good agreement between experiment and theory.


Fall Rates in Urban and Rural Nursing Units: Does Location Matter?
Patient falls remain a leading adverse event in hospitals. In a study of 65 rural hospitals with 222 nursing units and 560 urban hospitals with 4274 nursing units, we found that geographic region, unit type, and nurse staffing, education, experience, and outcomes were associated with fall rates. Implications include specific attention to fall prevention in rehabilitation units, creating better work environments that promote nurse retention, and provide RN-BSN educational opportunities.


Identification of a cryptic lethal mutation in the mouse t(w73) haplotype.
t haplotypes are naturally occurring, variant forms of the t complex on mouse chromosome 17, characterized by the presence of four inversions with respect to wild-type. They harbour mutations causing male sterility, male transmission ratio distortion (TRD) and embryonic lethality. Mice carrying t haplotypes have been found throughout the world, and genetic studies of the lethal mutations have identified at least 16 complementation groups. The embryonic lethal phenotypes of many t haplotypes have been characterized in detail, and are thought to be the consequence of homozygosity for single gene mutations. However, the existence of additional mutations in genes that function at later stages of development would be obscured. Here we investigated the possibility of multiple mutations in t haplotypes by screening the t(w73) haplotype for the presence of novel mutations. Since genetic analysis of t haplotype mutations is hindered by recombination suppression due to the inversions, deletion complexes covering the proximal two-thirds of the t complex were used to uncover the presence of any new lethal alleles. This analysis revealed a novel mutation between D17Jcs41 and D17Mit100, causing mice carrying both t(w73) and selected deletions to die at birth, prior to feeding. The finding of a new, cryptic lethal mutation in t haplotypes is an indication that these recombinationally isolated chromosomes, which already contain at least one lethal mutation that prevents homozygosity, may serve as sinks for the accumulation of additional recessive mutations.


Impaired antioxydative Keap1/Nrf2 system and the downstream stress protein responses in the motor neuron of ALS model mice.
The Kelch-like ECH-associated protein 1 (Keap1)/Nuclear erythroid 2-related factor 2 (Nrf2) system is the major cellular defense mechanism under oxidative stress, but the role in motor neuron degeneration under amyotrophic lateral sclerosis (ALS) pathology has not yet been fully elucidated. Here we examined temporal and spatial changes of Keap1, Nrf2, and their downstream stress response proteins heme oxgenase-1 (HO-1), glutathione, thioredoxin (TRX), and heat shock protein 70 (HSP70) throughout the course of motor neuron (MN) degeneration in the spinal cord of ALS model mice. Keap1 protein levels progressively decreased in the MN and anterior lumbar cord of ALS mice to 63% at early symptomatic 14 weeks and 58% at end symptomatic 18 weeks, while Nrf2 dramatically increased in the anterior lumbar cord with accumulation in the MN nucleus to 229% at 14 weeks and 471% at 18 weeks when glial like cells became also positive. In contrast, downstream stress response proteins such as HO-1, glutathione, TRX, and HSP70 showed only a small increase in MN with a significant increase to 149% to 280% in the number of glial-like cells after symptomatic 14 weeks. Our present observation suggests that MN selectively lost inductions of these important downstream protective proteins without regard to the Keap1/Nrf2 system activation, which could be a pivotal mechanism of neurodegenerative processes of ALS.


Expression of keratin 19 is related to high recurrence of hepatocellular carcinoma after radiofrequency ablation.
Keratin (K) 19 positivity has been reported to be a useful predictive marker for recurrence in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection. We investigated the clinical usefulness of K19 positivity in patients who had received curative radiofrequency ablation (RFA). We retrospectively evaluated the clinicopathological features, including imaging and K19 expression, in 246 patients with HCC who were within the Milan criteria and had received curative RFA. Using a two-step insertion method, tumor biopsies were obtained just prior to RFA and were evaluated histologically. Tumor seeding due to liver biopsy and RFA was not observed. Ten patients (4.1%) had K19-positive HCC. Imaging findings were similar between K19-positive and -negative HCC (p = 0.187). Nine out of 10 patients (90%) who had K19-positive HCC had recurrence of HCC after RFA, and intrahepatic recurrences were observed within 12 months in 6 out of 10 (60.0%). K19 positivity was a significant risk factor for recurrence (p < 0.0001) and early recurrence (<1 year after RFA; p =0.012). K19 expression (p = 0.016) was an independent risk factor for tumor status exceeding the Milan criteria after RFA. Expression of K19 is related to high recurrence of HCC after curative RFA.


Effect of irrigation on needle morphology, shoot and stem growth in a drought-exposed Pinus sylvestris forest.
In Valais, Switzerland, Scots pines (Pinus sylvestris L.) are declining, mainly following drought. To assess the impact of drought on tree growth and survival, an irrigation experiment was initiated in 2003 in a mature pine forest, approximately doubling the annual precipitation. Tree crown transparency (lack of foliage) and leaf area index (LAI) were annually assessed. Seven irrigated and six control trees were felled in 2006, and needles, stem discs and branches were taken for growth analysis. Irrigation in 2004 and 2005, both with below-average precipitation, increased needle size, area and mass, stem growth and, with a 1-year delay, shoot length. This led to a relative decrease in tree crown transparency (-14%) and to an increase in stand LAI (+20%). Irrigation increased needle length by 70%, shoot length by 100% and ring width by 120%, regardless of crown transparency. Crown transparency correlated positively with mean needle size, shoot length and ring width and negatively with specific leaf area. Trees with high crown transparency (low growth, short needles) experienced similar increases in needle mass and growth with irrigation than trees with low transparency (high growth, long needles), indicating that seemingly declining trees were able to 'recover' when water supply became sufficient. A simple drought index before and during the irrigation explained most of the variation found in the parameters for both irrigated and control trees.


Interactions between hydrophobic and ionic solutes in aqueous guanidinium chloride and urea solutions: lessons for protein denaturation mechanism.
In order to clarify the mechanism of denaturant-induced unfolding of proteins we have calculated the interactions between hydrophobic and ionic species in aqueous guanidinium chloride and urea solutions using molecular dynamics simulations. Hydrophobic association is not significantly changed in urea or guanidinium chloride solutions. The strength of interaction between ion pairs is greatly diminished by the guanidinium ion. Although the changes in electrostatic interactions in urea are small, examination of structures, using appropriate pair functions, of urea and water around the solutes show strong hydrogen bonding between urea's carbonyl oxygen and the positively charged solute. Our results strongly suggest protein denaturation occurs by the direct interaction model according to which the most commonly used denaturants unfold proteins by altering electrostatic interactions either by solvating the charged residues or by engaging in hydrogen bonds with the protein backbone. To further validate the direct interaction model we show that, in urea and guanidinium chloride solutions, unfolding of an unusually stable helix (H1) from mouse PrPC (residues 144-153) occurs by hydrogen bonding of denaturants to charged side chains and backbone carbonyl groups.


A novel mutation in leukocyte adhesion deficiency type II/CDGIIc.
Leukocyte adhesion deficiencies (LAD) are autosomal recessive immunodeficiency syndromes characterized by severe and recurrent bacterial infections, impaired wound healing and leukocytosis. Block in different steps in the leukocyte adhesion cascade causes different types of leukocyte adhesion deficiencies, LAD type I, II and III. In LAD type II, the rolling phase of the leukocyte adhesion cascade is affected due to mutations in the specific fucose transporter GFTP (GDP fucose transporter), causing defect in the biosynthesis of selectin ligands on leukocytes. Thus this syndrome is also called congenital disorder of glycosylation IIc (CGDIIc). LAD II/CGDIIc is very rare and has been diagnosed in nine children to date. Fever, leukocytosis, typical dysmorphic features, growth, psychomotor retardation and the Bombay blood group, are characteristic findings in patients. Here, we describe two Turkish siblings with a novel mutation in GFTP. They both have the characteristic features of the syndrome. The older sibling died of severe bacterial pneumonia at the age of 3 years. The younger sibling, diagnosed at the age of 3 months, responded to high dose oral fucose supplementation. Secundum atrial septal defect which was not described in previously reported patients, but present in both of our patients, may primarily related to the defect in fucosylation.


Successful priority setting in low and middle income countries: a framework for evaluation.
Priority setting remains a big challenge for health managers and planners, yet there is paucity of literature on evaluating priority setting. The purpose of this paper is to present a framework for evaluating priority setting in low and middle income countries. We conducted a qualitative study involving a review of literature and Delphi interviews with respondents knowledgeable of priority setting in low and middle income countries. Respondents were asked to identify the measures of successful priority setting in low and middle income countries. Responses were grouped as: immediate internal or external/delayed internal or external. We also identified some pre-requisites for successful priority setting. The immediate internal measures included increased efficiency in decision making, improved quality of decisions and fairer priority setting. Immediate External measures included-improved public understanding and acceptance of decisions, increased public participation, increased trust. Delayed Internal measures included increased satisfaction, understanding, compliance, balanced budget, achievement of organization goals, and improved internal accountability. Delayed External measures include impact on policy and practice, improved population health and reduction of health inequalities, achievement of health system goals and strengthening of health care systems. Identified pre-requisites for successful priority setting included; the presence of credible priority setting institutions, incentives for participation and implementation and resources, capacity and political will to implement. These would be augmented in a conducive political, social and economic context. This framework, although not exhaustive, provides a practical basis for planning and evaluating priority setting in low and middle income countries.


Rescreening in gynecologic cytology. Rescreening of 3762 previous cases for current high-grade squamous intraepithelial lesions and carcinoma--a College of American Pathologists Q-Probes study of 312 institutions.
To quantitate, characterize, and analyze errors identified in the rescreening of previous gynecologic cytology specimens with original diagnoses of "within normal limits" or "benign cellular changes" for current cases diagnosed as carcinoma or high-grade squamous intraepithelial lesion. College of American Pathologists Q-Probes laboratory quality improvement study in 312 laboratories. False-negative rate in cases rescreened as a result of a current cytologic diagnosis of carcinoma or high-grade squamous intraepithelial lesion. During the examination and reporting of 1,741,515 current Papanicolaou smear cases, participating laboratories rescreened a total of 3762 previous cases that were originally diagnosed, during the 5 years prior to the current case, as being within normal limits or having benign cellular changes. For the rescreened cases, the overall false-negative rates were 10.1% using a narrow definition and 19.7% using a broad definition. The majority of errors for cases originally diagnosed as within normal limits were screening errors, while interpretive errors predominated in those cases originally diagnosed as having benign cellular changes. Eighty-six percent of all false negatives were identified in those previous cases that were originally diagnosed and reported in the 3 years prior to the current case. Rescreening of previously reported smears, in patients with current abnormal findings, as one component of a complete quality improvement program, identifies errors that may provide information that will enable a laboratory to improve future performance.


Hypertension.
Systemic arterial hypertension is the most important modifiable risk factor for all-cause morbidity and mortality worldwide and is associated with an increased risk of cardiovascular disease (CVD). Fewer than half of those with hypertension are aware of their condition, and many others are aware but not treated or inadequately treated, although successful treatment of hypertension reduces the global burden of disease and mortality. The aetiology of hypertension involves the complex interplay of environmental and pathophysiological factors that affect multiple systems, as well as genetic predisposition. The evaluation of patients with hypertension includes accurate standardized blood pressure (BP) measurement, assessment of the patients' predicted risk of atherosclerotic CVD and evidence of target-organ damage, and detection of secondary causes of hypertension and presence of comorbidities (such as CVD and kidney disease). Lifestyle changes, including dietary modifications and increased physical activity, are effective in lowering BP and preventing hypertension and its CVD sequelae. Pharmacological therapy is very effective in lowering BP and in preventing CVD outcomes in most patients; first-line antihypertensive medications include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, dihydropyridine calcium-channel blockers and thiazide diuretics.


Carbohydrate effect: hormone and oxidative changes.
Carbohydrate administration during exercise diminishes stress hormone release, but the relationship of these hormones with oxidative stress has not been examined. Fifteen subjects functioned as their own controls and ingested carbohydrate (6 %) or placebo in a randomized design while cycling for 2.5-h ( approximately 75 % V.O (2peak)). Blood and skeletal muscle samples were collected 30 min pre-exercise, immediately post-exercise, and 12-h post-exercise and analyzed for F (2)-isoprostanes, ferric reducing ability of plasma, glucose, insulin, cortisol, epinephrine, and muscle glycogen, respectively. Statistical design was a 2 (treatment) x 3 (time) repeated measures analysis of variance. Glucose, insulin, and ferric reducing ability of plasma were significantly higher and F (2)-isoprostanes, cortisol, and epinephrine significantly lower in carbohydrate versus placebo. The decrease in muscle glycogen was not different. During cycling exercise, oxidative stress appears to be heavily influenced by carbohydrate ingestion and increased stress hormones.


C-terminal domain phosphorylation of ERK3 controlled by Cdk1 and Cdc14 regulates its stability in mitosis.
ERK3 (extracellular-signal-regulated kinase 3) is an atypical MAPK (mitogen-activated protein kinase) that is suggested to play a role in cell-cycle progression and cellular differentiation. However, it is not known whether the function of ERK3 is regulated during the cell cycle. In the present paper, we report that ERK3 is stoichiometrically hyperphosphorylated during entry into mitosis and is dephosphorylated at the M-->G1 transition. The phosphorylation of ERK3 is associated with the accumulation of the protein in mitosis. In vitro phosphorylation of a series of ERK3-deletion mutants by mitotic cell extracts revealed that phosphorylation is confined to the unique C-terminal extension of the protein. Using MS analysis, we identified four novel phosphorylation sites, Ser684, Ser688, Thr698 and Ser705, located at the extreme C-terminus of ERK3. All four sites are followed by a proline residue. We have shown that purified cyclin B-Cdk1 (cyclindependent kinase 1) phosphorylates these sites in vitro and demonstrate that Cdk1 acts as a major Thr698 kinase in vivo. Reciprocally, we found that the phosphatases Cdc14A and Cdc14B (Cdc is cell-division cycle) bind to ERK3 and reverse its C-terminal phosphorylation in mitosis. Importantly, alanine substitution of the four C-terminal phosphorylation sites markedly decreased the half-life of ERK3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase. The results of the present study identify a novel regulatory mechanism of ERK3 that operates in a cell-cycle-dependent manner.


Physical and psychomotor development in the offspring born to mothers with epilepsy.
Psychomotor development of 71 children born to mothers with epilepsy was prospectively studied and compared to those of 99 controls matched for age, maternal educational level and age, and socioeconomic status. Intrauterine growth retardation disappeared before age 3 years. Assessment at age 1.5 years revealed that exposure to seizures, high dose of antiepileptic drugs (AEDs) in utero, and small head circumference at birth affected development quotient (DQ) scores of motor or linguistic abilities or both. DQ scores of motor ability of children of mothers with complex partial seizures were lower than those with simple partial seizures when assessed at age 3 years. Assessments at age 1.5 years revealed that the total daily dose of AEDs correlated negatively with DQ scores of motor ability, and at age 3 years, maternal educational level affected DQ scores of some fields, including linguistic ability. The effects of AED exposure in utero and the occurrence of maternal seizures on the development of offspring were found to matter more at the younger age, but later on, the child care environment and, in particular, maternal ability of child-rearing, became more important. Our findings indicate that careful and regular follow-ups are needed to monitor the developmental stages of children of mothers with epilepsy, and the introduction of a day nursery should be suggested if necessary.


[Effect of reduced N application on soil N residue and N loss in maize-soybean relay strip intercropping system].
A field experiment was conducted in 2012, including three planting pattern (maize-soybean relay strip intercropping, mono-cultured maize and soybean) and three nitrogen application level [0 kg N x hm(-2), 180 kg N x hm(-2) (reduced N) and 240 kg N x hm(-2) (normal N)]. Fields were assigned to different treatments in a randomized block design with three replicates. The objective of this work was to analyze the effects of planting patterns and nitrogen application rates on plant N uptake, soil N residue and N loss. After fertilization applications, NH4(+)-N and NO3(-)-N levels increased in the soil of intercropped maize but decreased in the soil of intercropped soybean. Compared with mono-crops, the soil N residue and loss of intercropped soybean were reduced, while those of intercropped maize were increased and decreased, respectively. With the reduced rate of N application, N residue rate, N loss rate and ammonia volatilization loss rate of the maize-soybean intercropping relay strip system were decreased by 17.7%, 21.5% and 0.4% compared to mono-cultured maize, but increased by 2.0%, 19.8% and 0.1% compared to mono-cultured soybean, respectively. Likewise, the reduced N application resulted in reductions in N residue, N loss, and the N loss via ammonia volatilization in the maize-soybean relay strip intercropping system compared with the conventional rate of N application adopted by local farmers, and the N residue rate, N loss rate and ammonia volatilization loss rate reduced by 12.0%, 15.4% and 1.2%, respectively.


Fourier-Engineered Plasmonic Lattice Resonances.
Resonances in optical systems are useful for many applications, such as frequency comb generation, optical filtering, and biosensing. However, many of these applications are difficult to implement in optical metasurfaces because traditional approaches for designing multiresonant nanostructures require significant computational and fabrication efforts. To address this challenge, we introduce the concept of Fourier lattice resonances (FLRs) in which multiple desired resonances can be chosen a priori and used to dictate the metasurface design. Because each resonance is supported by a distinct surface lattice mode, each can have a high quality factor. Here, we experimentally demonstrate several metasurfaces with flexibly placed resonances (e.g., at 1310 and 1550 nm) and Q-factors as high as 800 in a plasmonic platform. This flexible procedure requires only the computation of a single Fourier transform for its design, and is based on standard lithographic fabrication methods, allowing one to design and fabricate a metasurface to fit any specific, optical-cavity-based application. This work represents a step toward the complete control over the transmission spectrum of a metasurface.


Cross-cultural adaptation and validation of the Portuguese version of the Oxford Shoulder Score (OSS).
To translate and culturally adapt the Oxford Shoulder Score (OSS) to the European Portuguese language, and to test its reliability (internal consistency, reproducibility and measurement error) and validity (construct validity). The OSS Portuguese version was obtained through translations, back-translations, consensus panels, clinical review and cognitive pre-test. Portuguese OSS, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires, and the visual analogue scales of pain at rest [VAS rest] and during movement [VAS movement] were applied to 111 subjects with shoulder pain (degenerative or inflammatory disorders) and recommended for physical therapy. A clinical and sociodemographic questionnaire was also applied. The reliability was good, with a Cronbach's alpha coefficient of 0.90, an intraclass correlation coefficient (ICC) of 0.92, a standard error of measurement (SEM) of 2.59 points and a smallest detectable change (SDC) of 7.18 points. Construct validity was supported by the confirmation of three initial hypotheses involving expected significant correlation between OSS and other measures (DASH, VAS rest and VAS movement) and between OSS and the number of days of work absenteeism. The Portuguese OSS version presented suitable psychometric properties, in terms of reliability (internal consistency, reproducibility and measurement error) and validity (construct validity).


Fiber and diabetes.
Plant fibers have important influences on gastrointestinal physiology and the absorption of many nutrients. Certain fibers delay the absorption of carbohydrates and result in less postprandial hyperglycemia. Because the intake of plant fibers lowers plasma glucose concentrations and decreases glycosuria, high-fiber foods may be useful in the management of diabetes mellitus. Consumption of selected fibers and fiber-rich foods lowers serum cholesterol values and may lower triglyceride concentrations. Plant fiber intake may lead to mineral depletion or vitamin deficiency, but this has not been observed in several long-term studies. Further work is required to delineate the therapeutic utility of plant fibers in the diet of persons with diabetes and to assess the undesirable effects of fiber intake. In our opinion, persons with diabetes who are eating very low-fiber diets would benefit from an increase in plant fiber intake from whole grains, legumes, and vegetables.


Phase-shifting whole-field speckle photography technique for the measurement of in-plane deformations in real time.
A new real-time phase-shifting readout system is developed for quantitative evaluation of full-field correlation fringes obtained by means of Fourier filtering in speckle photography. The proposed method, which uses photorefractive crystals as the recording medium, is capable of mapping the whole-field displacement data from the recorded phase-shifted fringe patterns. Experimental results are presented on a diffuse surface subjected to rotation in its own plane.


Ischaemia/reperfusion enhances phenylephrine-induced contraction of rabbit aorta due to impairment of neuronal uptake.
We studied the effect of ischaemia and reperfusion on vasoconstrictor and vasodilator mechanisms. Anaesthetized rabbits were subjected to 4-h abdominal aortic occlusion and 1-h reperfusion in vivo. Segments of the abdominal (ischaemic-reperfused) and thoracic (control) aorta were then removed for in vitro studies. Ischaemia/reperfusion had no significant effect on relaxant responses to either acetylcholine (ACh:endothelium-dependent) or sodium nitroprusside (SNP:endothelium-independent). The sensitivity of the aorta to contraction by phenylephrine was significantly increased in aortic rings with or without endothelium (by 2.2- and 3.7-fold, respectively), but was not different after 4-h ischaemia without reperfusion. In contrast, responses to methoxamine, serotonin, and U46619 were not affected by ischaemia/reperfusion. Moreover, the relative increase in aortic sensitivity to phenylephrine was prevented by treatment of control and ischaemic-reperfused aortic rings with the neuronal uptake inhibitor cocaine (10(-5) M). These results suggest that after 4-h ischaemia, reperfusion damages sympathetic neuronal uptake mechanisms in rabbit aorta. As a result, phenylephrine, an agonist normally susceptible to neuronal uptake, may exert more potent contractile effects. Endothelium-dependent and endothelium-independent relaxant mechanisms in the aorta appear to be resistant to acute ischaemia and reperfusion.


Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy.
Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.


1,25-Dihydroxyvitamin D3 modulates the phenotype and function of Monocyte derived dendritic cells in cattle.
The active form of the vitamin D3, 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to have major effects not only on physiological processes but also on the regulation of the immune system of vertebrates. Dendritic cells are specialised antigen presenting cells which are in charge of the initiation of T-cell dependant immune responses and as such are key regulators of responses towards pathogens. In this study we set out to evaluate the effects of 1,25-(OH)2D3 on the phenotype of cattle monocyte-derived dendritic cells (MoDCs) and how the conditioning with this vitamin affects the function of these myeloid cells. MoDCs were generated from CD14+ monocytes with bovine IL-4 and GM-CSF with or without 1,25-(OH)2D3 supplementation for 10 days. Vitamin D conditioned MoDCs showed a reduced expression of co-stimulatory and antigen presenting molecules, as well as a reduced capability of endocytose ovalbumin. Furthermore, the capacity of MoDCs to induce proliferation in an allogeneic mixed leukocyte reaction was abolished when MoDCs were generated in presence of 1,25-(OH)2D3. LPS induced maturation of 1,25-(OH)2D3conditioned MoDCs resulted in lower secretion of IL-12 and higher IL-10 than that observed in MoDCs. The typical immunotolerant phenotype observed in cattle DCs after exposure to 1,25-(OH)2D3 has a significant effect on the functionality of these immune cells, inhibiting the T-cell stimulatory capacity of MoDCs. This could have profound implications on how the bovine immune system deals with pathogens, particularly in diseases such as tuberculosis or paratuberculosis.


The Correlation between Infarct Size and the QRS Axis Change after Thrombolytic Therapy in ST Elevation Acute Myocardial Infarction.
Electrocardiography (ECG) may be a practical guiding tool for prognostic infarct sizing in ST elevation acute myocardial infarction (STEAMI). In this study, we sought to find a relation between the infarct size and the change in the QRS axis after thrombolytic therapy. Patients with STEAMI who received thrombolytic therapy were selected retrospectively. The mean QRS axes of two ECGs (before and 90 minutes after thrombolytic therapy) were calculated. Creatinine kinase MB (CKMB) was used as the marker of infarct size. We did not detect any correlation between infarct size and change in the QRS axis with respect to any myocardial infarction MI localizations (p=0.80). However, in the isolated inferior MI group, there was a good correlation between CKMB and change in the QRS axis (r=-0.52 p=0.049). The change in the QRS axis is rarely emphasized, providing a practical and promising tool for evaluating both the efficiency of the thrombolytic therapy and prognostic infarct sizing.


Cellular distribution of 125I-endothelin-1 binding in rat kidney following in vivo labeling.
Endothelin-1 (ET-1) receptors have previously been demonstrated in the rat kidney by in vitro autoradiography and in cultured renal cell lines by radioreceptor assay, but the precise cellular localization of these receptors under in vivo conditions remains to be determined. We performed electron microscopic autoradiography on rat kidney following intravenous administration of 125I-labeled ET-1. In vivo autoradiographs revealed binding patterns identical to those previously demonstrated following in vitro labeling. Light microscopic autoradiography showed that silver grains occurred exclusively overlaying glomeruli and peritubular capillaries in the cortex, inner stripe of the outer medulla, and the inner medulla. At the electron microscopic level, ET-1 binding was specifically localized to the fenestrated endothelium of glomerular and peritubular capillaries, and to a lesser extent to the vasa recta. No significant grains were seen on mesangial or visceral epithelial cells; nor were any seen on the cells of proximal tubule, the thick and thin limbs of the loop of Henle, the medullary collecting ducts, and renal interstitial cells. These results indicate that the endothelial cells of glomerular and peritubular capillaries are the primary target for the circulating ET-1 in the rat kidney and suggest an autocrine and/or paracrine function of locally synthesized ET-1 in vivo in both physiological and pathophysiological states.


Virtual tool for bilaterally controlled forceps robot--for minimally invasive surgery.
Bilateral control enables an operator to be placed away from the working environment. A slave manipulator usually works at a remote site or in a hazardous environment while the master operator senses the environment through the slave manipulator. Bilateral control can be used in surgeries. Usually doctors are very sensitive to the tactile sensation they feel through medical tools. If bilateral control is used in a surgery, ideally the doctor should perceive the sensation of both the body tissue and the reaction force from the specialized tool. Many surgical instruments are essentially similar at the tool tip while showing some structural differences at the gripping end. Therefore, it is advantageous for an expensive tool to be replaced by a virtual tool together with a simple tool. With the virtual tool, the surgeon should be able to perceive the feeling of the actual tool together with the reaction force coming from the body tissue; this may also reduce the time taken for a tool change during the surgery. In this study, above ideas were implemented in a bilaterally controlled forceps robot and experiments were carried out to test the applicability of the concept. Bilateral control is used as the method of tactile feedback. Disturbance observer is used for robust control. Reaction force observer is used in place of a force sensor. Virtual model is used in place of the special tool properties. A virtual spring acting at the end of the forceps, was implemented to a bilateral control system, so that the operator at the master side could perceive the feeling of the spring together with reaction forces from the surgical environment. Operator could feel the vivid sensation of the environment through the master manipulator. The virtual model adds a load to the system. The master and slave responses are slightly different, but the result is good enough for the application. This novel approach could be used in many master-slave applications.


Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line.
CD63 belongs to the transmembrane 4 superfamily of membrane proteins and is expressed in several normal tissues as well as in melanoma cells. Previous reports have suggested that CD63 may play an important role in inhibiting melanoma progression, and this was supported by our studies showing that CD63 was associated with suppression of the growth of melanoma in nude mice. Recently, we and others have shown that CD63 may form noncovalent associations with beta1 integrins, which suggests that the function of CD63 may be related to that of integrins. To further explore the role of CD63 in melanoma, we transfected CD63 into a highly motile, CD63-negative melanoma cell line, KM3, which was shown to express alpha(v)beta5 as the predominant integrin with only trace amounts of beta1 integrins. Following transfection, CD63 was shown to associate with beta1 integrins, and beta1 expression appeared to be up-regulated. Cell motility in serum-containing media was markedly suppressed following transfection of CD63. This inhibition was potentiated by mAbs to CD63, and correlated with the level of CD63 expression. The CD63-transfected, but not the untransfected, melanoma cells showed increased adhesion and migration on the beta1 substrates, fibronectin, laminin, and collagen, whereas rates of migration were similar on the beta5 substrate, vitronectin. These results show that CD63 is involved in regulation of the motility of melanoma cells and their adhesion and migration on substrates associated with beta1 integrins. We suggest they provide further insights into the role of CD63 in tumor progression.


Expression of HERV-K proviruses in human leukocytes.
HERV-K is a 50-copy, human endogenous, class 1 retroviral element that contains some polycistrons with gag, pol, and env open reading frames. Although expression of HERV-K proviruses has been shown in cultured human cell lines, expression of these elements has not been shown in human blood leukocytes. Using both reverse transcriptase-polymerase chain reaction and ribonuclease protection techniques, we show HERV-K pol gene expression in human blood leukocytes. Expression in blood leukocytes from 7 normal individuals was from a variety of different HERV-K proviruses, while restricted expression was observed in blood cells of 5 leukemia patients and 3 polycythemia vera patients. Evidence is presented suggesting that the restricted expression in leukemia blood cells is a result of gene regulation, not gene amplification.


Second messenger effects on the myosin phosphorylation system in smooth muscle.
It has been shown that with initial and tonic contractions stimulated by a cholinergic muscarinic agonist in tracheal smooth muscle, the extent of myosin heavy chain phosphorylation remains low. Cholinergic stimulation of tracheal smooth muscle results in formation of both monophosphorylated and diphosphorylated myosin light chain, although the amount of diphosphorylated light chain is substantially less than monophosphorylated light chain. Phosphorylation of the single serine site on myosin light chain by myosin light chain kinase is the primary phosphorylation that is associated with activation of smooth muscle contraction. A general scheme for the physiological regulation of smooth muscle contractility can be proposed. Upon activation of cell surface receptors by neurotransmitters or hormones, phosphoinositide metabolism is stimulated to form InsP3. The InsP3 rapidly releases Ca2+ from sarcoplasmic reticulum which then binds to calmodulin. The Ca2+/calmodulin complex binds to myosin light chain kinase which then phosphorylates myosin light chain. It appears that the rate of conversion of myosin light chain kinase from an inactive to an active enzyme may be a significant rate limiting step for the initiation of myosin light chain phosphorylation. Once the kinase is activated, phosphorylation of myosin light chain may reach maximal values within 2 s with neural stimulation, followed by the slower rate of force development. Protein kinase C does not phosphorylate myosin light chain or heavy chain during the initial or tonic phases of contraction. However, this general scheme for smooth muscle contraction does not exclude the possibility of other regulatory processes involved in sustained contractions.


Map locations of five transcripts homologous to TR-DNA in tobacco and sunflower crown gall tumors.
Polyadenylated RNA from two octopine type tumor lines (E1, PSCG-15955) was analyzed by RNA blot hybridization and shown to contain five major transcripts homologous to TR DNA. In tobacco E1 tissue, the molecular weights of the TR homologous RNAs are 1.65 kb, 1.55 kb, 1.45 kb, 1.05 kb, and 0.78 kb. The 5' - and 3'-termini of each of the five E1 tumor transcripts were determined by S1 nuclease hybrid protection mapping. The polarity of transcription for the 0.78, 1.05 and 1.65 kb RNAs is from left to right, while the 1.55 and 1.45 kb RNAs are transcribed from right to left. Although we see the same size transcripts in sunflower PSCG-15955 tissue (with the exception of a 0.89 kb RNA in place of the 1.55 kb transcript of E1) there is an apparent difference in the relative abundance of the various RNAs between the two tumor lines.


[Post-aggression metabolism: attempt at a status determination].
Selection of important results in pathophysiology and pathobiochemistry of the surgical patient. Anglo-American and German literature since 1988. Importance of reported results for the understanding of superior interactions. The term 'postaggression' syndrome was introduced on the basis of earlier observations regarding the pathophysiology of the surgical patient. More recent results which addressed pathobiochemistry, and which had been obtained by methods of molecular biology, led to the new definition as systemic inflammatory response syndrome (SIRS). Knowledge on metabolic changes which are associated with SIRS increased significantly in the field of protein and carbohydrate metabolism. Concerning the clinically important phenomenon of protein catabolism, it is possible today to differentiate between changes in protein synthesis and protein degradation. The time period which had passed since the underlying trauma and the variable responses of different organ systems were recognized as important variables of catabolism. The ongoing question regarding possible mediators of protein catabolism still remains unanswered. Release of cytokines which can be observed in SIRS appears to play only an indirect role. The small bowel, which is important for the general pathophysiology of SIRS, gained a central position in amino acid metabolism (especially glutamine metabolism). A new aspect of carbohydrate metabolism was found in the liver. The accelerated cycling of glucose molecules between glucose, glucose-6-phosphate, and glucose (glucose cycling) seems to contribute to the increased energy expenditure found in SIRS. Use of new methods in in vivo and in vitro research significantly expanded the knowledge on pathophysiological and pathobiochemical mechanisms in SIRS. Future research activities should tie together these individual mechanisms into the complex network as it presents to the physician during clinical routine.


Rapid detection of human immunodeficiency virus types 1 and 2 by use of an improved piezoelectric biosensor.
Disasters can create situations in which blood donations can save lives. However, in emergency situations and when resources are depleted, on-site blood donations require the rapid and accurate detection of blood-borne pathogens, including human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Techniques such as PCR and antibody capture by an enzyme-linked immunosorbent assay (ELISA) for HIV-1 and HIV-2 are precise but time-consuming and require sophisticated equipment that is not compatible with emergency point-of-care requirements. We describe here a prototype biosensor based on piezoelectric materials functionalized with specific antibodies against HIV-1 and HIV-2. We show the rapid and accurate detection of HIV-1 and HIV-2 in both simple and complex solutions, including human serum, and in the presence of a cross-confounding virus. We report detection limits of 12 50% tissue culture infective doses (TCID50s) for HIV-1 and 87 TCID50s for HIV-2. The accuracy, precision of measurements, and operation of the prototype biosensor compared favorably to those for nucleic acid amplification. We conclude that the biosensor has significant promise as a successful point-of-care diagnostic device for use in emergency field applications requiring rapid and reliable testing for blood-borne pathogens.


[Affection of central nervous system in hemorrhagic fever with renal syndrome].
The authors report results of comparative analysis of 897 cases of hemorrhagic fever with renal syndrome diagnosed in the Upper Amur region in 1960-2005. All the patients were grouped by 5-year intervals depending on the severity of clinical condition. The frequency of CNS affection accompanied by acute psychic disorders, convulsive and meningeal syndromes varied significantly in different years. Pituitary hemorrhage was revealed at autopsy in 36.8% of the patients, pituitary necrosis in 5.2%, brainstem hemorrhage in 68.4%. A case of severe hemorrhagic fever with renal syndrome is described characterized by acute renal insufficiency and eclamptic convulsions with moderately manifest hemorrhagic syndrome preceding the favourable outcome.


A scalable admission control scheme based on time label.
Resource reservation protocols allow communicating hosts to reserve resources such as bandwidth to offer guaranteed service. However, current resource reservation architectures do not scale well for a large number of flows. In this paper, we present a simple reservation protocol and a scalable admission control algorithm, which can provide QoS guarantees to individual flows without per-flow management in the network core. By mapping each flow to a definite time, this scheme addresses the problems that limit the effectiveness of current endpoint admission control schemes. The overall admission control process is described. Analysis is used to explain the reasonability of our scheme and simulation validates its performance.


Establishing the thermal window for aerobic scope in New Zealand geoduck clams (Panopea zelandica).
Geoduck clams (Panopea spp.) are the longest-lived and largest deep burrowing bivalve. Their unique morphology allows them to live buried in the sediment at depths of up to 1 m. The endemic New Zealand geoduck (Panopea zelandica Quoy and Gaimard, 1835) has recently been identified as a potential species for aquaculture. However, very little is known about the biology and physiology of this entirely subtidal geoduck species. Currently, the New Zealand geoduck fishery relies entirely upon wild harvests, but farms are expected to emerge as cultivation protocols are established. A key step in the optimization of cultivation procedures is the identification of optimal temperature and food rations. One method for establishing thermal optima is to identify the temperature window that supports the widest aerobic scope: the degree to which metabolic rate can be increased to support elevated activity demands. Thus, we investigated the aerobic scope for activity at five different temperatures representative of typical environmental conditions (8, 11, 15, 19, and 23 °C) for juvenile and young adult P. zelandica. Clearance rate was also measured at all temperatures. Comparisons of aerobic scope for activity and clearance rates between size classes revealed that juvenile geoducks had a narrower thermal optimum than young adults (15-19 versus 11-19 °C, respectively). Temperatures higher than 19 °C resulted in a reduction of aerobic scope for activity and clearance rate for both juvenile and young adults, which may lead to reduced performance and elevated mortality. These findings provide the first measures of aerobic scope in P. zelandica, a key step towards a meaningful understanding of the ecophysiology of this unusual species.


Development of a polymerase chain reaction assay for the detection of antibiotic resistance genes in community DNA.
Many methods are used to detect antibiotic resistance genes in samples. The objective of the study reported here was to compare polymerase chain reaction (PCR) analysis of community DNA with fecal culturing for detecting antibiotic resistance genes in cattle samples. In the laboratory-based portion of this study, known concentrations of an Escherichia coli strain with 3 antibiotic resistance genes (cmy-2, flo, and cat) were added to feces from dairy cattle. These genes were used to assess the effect of various primer pairs, chromosomally versus plasmid-encoded genes, and gene copy number on the sensitivity of PCR amplification. Gene-specific PCR amplification was performed on the community DNA extracted from the feces. Feces were cultured for the inoculated strain. In the field-based portion of the study, 80 cattle fecal samples of unknown gene status were compared by use of similar methods. Culture and PCR amplification from community DNA extractions produced variable results, and this variability was most noticeable at dilutions that approached the detection limit of the assay. Typically, PCR amplification had a higher sensitivity than did culture for detecting the gene of interest. However, the sensitivity of culture was improved by plating on selective media containing antibiotics. The community DNA approach enables assessment of bacterial communities in complex samples such as feces, a task that can be prohibitive by budget or time constraints associated with culture methods. Through a strategic combination of culture and community DNA approaches, the relationship between specific selection pressures and the persistence and dissemination of specific resistance genes can be elucidated.


Increased 27-hydroxycholesterol production during luteolysis may mediate the progressive decline in progesterone secretion.
Does 27-hydroxycholesterol (27OH) actively facilitate the progression of luteolysis? There is increased mRNA expression of the enzyme that produces 27OH during luteolysis in vivo in rhesus macaques and sheep, and 27OH reduces progesterone secretion from human luteinized granulosa cells. There is an increase in mRNA expression of liver x receptor (LXR) and a decrease in sterol regulatory element binding protein 2 (SREBP2) target genes during spontaneous luteolysis in primates, which could result in reduced cholesterol availability for steroidogenesis. Concentrations of 27OH are also increased in primate corpora lutea (CL) during luteolysis, and 27OH is a dual LXR agonist and SREBP2 inhibitor. This was an in vitro study using primary human luteinized granulosa cells in a control versus treatment(s) design. Analyses of CL from sheep undergoing induced or spontaneous luteolysis were also performed, along with database mining of microarray data from rhesus macaque CL. Primary luteinizing granulosa cells were obtained from 37 women aged 24-44 who were undergoing oocyte donation or IVF for male factor or idiopathic infertility, and cells were further luteinized in vitro using human chorionic gonadotropin. Three approaches to test the effect of 27OH produced via CYP27A1 (cytochrome p450, family 27, subfamily A, polypeptide 1) on luteinized granulosa cells were used: (i) direct 27OH supplementation, (ii) induction of endogenous CYP27A1 activity via pharmacologic inhibition of steroidogenesis, and (iii) siRNA-mediated knockdown to directly inhibit CYP27A1 as well as cholesterol transport into the mitochondria via the steroidogenic acute regulatory protein (STAR). Endpoints included: progesterone (P4) secretion into culture media determined by enzyme immunoassay, cholesterol efflux and uptake assays using fluorescent lipid analogs, and mRNA expression determined via semi-quantitative real-time PCR (QPCR). An additional experiment involved QPCR analysis of 40 CL collected from ewes undergoing induced or spontaneous luteolysis, as well as database mining of microarray data generated from 16 rhesus macaque CL collected during spontaneous luteolysis and 13 macaque CL collected during a luteinizing hormone ablation and replacement protocol. The mRNA expression of CYP27A1 was significantly increased during luteolysis in rhesus macaques and sheep in vivo, and CYP27A1 transcription was suppressed by luteinizing hormone and hCG. There was a significant decrease in hCG-stimulated P4 secretion from human luteinized granulosa cells caused by 27OH treatment, and a significant increase in basal and hCG-stimulated P4 synthesis when endogenous 27OH production was inhibited via CYP27A1 knockdown, indicating that 27OH inhibits steroidogenesis. Pharmacologic inhibition of steroidogenesis by aminoglutethimide significantly induced LXR and inhibited SREBP2 target gene mRNA expression, indicating that increased oxysterol production occurs when steroidogenesis is suppressed. Inhibiting cholesterol delivery into the mitochondria via knockdown of STAR resulted in reduced SREBP2 target gene mRNA expression, indicating that STAR function is necessary to maintain SREBP2-mediated transcription. The effects of 27OH treatment on markers of LXR and SREBP2 activity were moderate, and knockdown of CYP27A1 did not prevent aminoglutethimide-induced changes in LXR and SREBP2 target gene mRNA expression. These observations indicate that 27OH inhibits P4 secretion partially via mechanisms separate from its role as an LXR agonist and SREBP2 inhibitor, and also demonstrate that other oxysterols are involved in modulating LXR and SREBP2-mediated transcription when steroidogenesis is suppressed. None. Luteinized granulosa cells may differ from luteal cells, and the effect on luteal function in vivo was not directly tested. The mechanisms that cause the initial rise in CYP27A1 mRNA expression during luteolysis are also not clear. The factors causing luteolysis in primates have not yet been determined. This study provides functional evidence of a novel mechanism via increased 27OH synthesis during luteolysis, which subsequently represses progesterone secretion. Increased 27OH may also facilitate the progression of luteolysis in domestic animal species. The authors have nothing to disclose. Support was provided by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) of the National Institutes of Health (NIH), award number R00HD067678 to R.L.B.


[Valvular diseases of the right heart].
Recently, the development of diagnostic and operative interventional techniques has contributed to the successful treatment of congenital valve lesions of the right heart. The clinical picture, diagnostic approaches, and therapeutic outcome are presented. In pulmonic valve stenosis the fusion of leaflets is most common. Stenosis severity corresponds to the intensity of the systolic murmur. Pressure gradients can be quantitated by Dopplersonography. Balloon valvuloplasty is the method of choice for treatment. Residual gradients (24-36 mmHg) are not significantly different from surgical results. In Tetralogy of Fallot the ventricular outflow tract obstruction and a subaortic septal defect are most characteristic, both of which can be visualized by echocardiography. Cyanosis and the pulmonary systolic murmur are typical findings. Complications due to hypoxemia are reduced by corrective surgery in early childhood. Arrhythmias and ventricular dysfunction may complicate the long-term prognosis. Pulmonary insufficiency mostly results from surgical relief of stenoses. It can be quantitated by densitometry and MNR. Even severe pulmonary insufficiency is well tolerated for decades; on the long-term its prognosis remains uncertain. In Ebstein's anomaly the leaflet attachment of the tricuspid valve is displaced into the right ventricle, which is best diagnosed by echocardiography. Symptomatology ranges from heart failure (infancy) to a systolic murmur only (childhood). Plastic recontruction of the tricuspid valve has become technically feasible.


Microvascular thrombosis and multiple organ dysfunction syndrome.
This paper will review the involvement of disseminated intravascular coagulation-induced microvascular thrombosis in the pathogenesis of multiple organ dysfunction syndrome and the interaction between disseminated intravascular coagulation and systemic inflammatory response syndrome in critically ill patients. The published literature on clinical and experimental studies are the data sources of the study. Histologic evidence of microvascular thrombosis and tissue injury in disseminated intravascular coagulation has been reported in clinical, experimental, and autopsy findings. Proinflammatory cytokine-evoked neutrophil-endothelial activation and interplay between inflammation and coagulation through protease-activated receptors contribute to enhanced microvascular fibrin deposition in organs. In a clinical setting, systemic inflammatory response syndrome and disseminated intravascular coagulation synergistically play pivotal roles in the development of multiple organ dysfunction syndrome and in the poor prognosis of critical illness. Disseminated intravascular coagulation contributes to microvascular thrombosis and subsequent multiple organ dysfunction syndrome. Recent knowledge on the relationship between disseminated intravascular coagulation and systemic inflammatory response syndrome gives further insight into the pathogenic mechanisms of multiple organ dysfunction syndrome in critically ill patients.


Effect of red grapes co-winemaking in polyphenols and color of wines.
The red grapes co-winemaking effect on phenolic fraction and wine color has been studied for the first time, where Monastrell was comacerated and cofermentated with Cabernet Sauvignon and Merlot. Changes in the relative abundance of anthocyanins were observed as well as hyperchromic shifts at 530 and 620 nm; these effects remain constant after aging. Co-winemaking also favored copigmentation, giving way to more stable anthocyanins and facilitating their polymerization. With regard to color evolution, the mixture of Monastrell with Merlot grapes was more appropriate than with Cabernet Sauvignon for aging wines in oak barrels. The extent of copigmentation was more important in young wines than in aged wines. This is mainly due to the self-anthocyanin monomer reactions in the case of young wines, whereas in aged wines copigmentation is mainly due to the reaction between the anthocyanins and other polyphenolic cofactors. Discriminant analysis showed the possibility of differentiating wines according to the aging time and the type of wine, with color parameters (color intensity, OD 620 nm, and OD 520 nm) being the most important discrimination variables in the first case and petunidin-3-glucoside and peonidin-3-glucoside contents in the second case.


Dual Role of a C-Terminally Truncated Isoform of Large Tumor Suppressor Kinase 1 in the Regulation of Hippo Signaling and Tissue Growth.
The considerable amount of experimental evidence has defined the Hippo pathway as a tumor suppressive pathway and increased expression and/or activity of its oncogenic effectors is frequently observed in cancer. However, clinical studies have failed to attribute cancer development and progression to mutations in the pathway. In explaining this conundrum, we investigated the expression and functions of a C-terminally truncated isoform of large tumor suppressor kinase 1 (LATS1) called short LATS1 (sLATS1) in human cell lines and Drosophila. Intriguingly, through overexpression of sLATS1, we demonstrated that sLATS1 either activates or suppresses the activity of Yes-associated protein (YAP), one of the effectors of the Hippo pathway, in a cell type-specific manner. The activation is mediated through inhibition of full-length LATS1, whereas suppression of YAP is accomplished through sLATS1-YAP interaction. In HEK293T cells, the former mechanism may affect the cellular response more dominantly, whereas in U2OS cells and developing tissues in Drosophila, the latter mechanism may be solely carried out. Finally, to find the clinical relevance of this molecule, we examined the expression of sLATS1 in breast cancer patients. The transcriptome analysis showed that the ratio of sLATS1 to LATS1 was increased in tumor tissues comparing to their adjacent normal tissues.


The role of cross-reactive immunity to emerging coronaviruses: Implications for novel universal mucosal vaccine design.
Host immune response to coronaviruses and the role of cross-reactivity immunity among different coronaviruses are crucial for understanding and combating the continuing COVID-19 outbreak and potential subsequent pandemics. This review paper explores how previous exposure to common cold coronaviruses and more pathogenic coronaviruses may elicit a protective immune response against SARS-CoV-2 infection, and discusses the challenges posed by some variants of concern that may escape current vaccines. It also highlights the need for a mucosal universal vaccine that can induce long-term protection against current and emerging coronaviruses by leveraging cross-reactive immunity. We propose a novel mucosal universal vaccine that consists of cross-reactive antigenic peptides with highly conserved epitopes among coronaviruses, conjugated with an immunostimulant adjuvant cytokine, including B-cell activating factor (BAFF). This vaccine may enhance the local mucosal adaptive response, induce tissue-resident memory cells, and inhibit viral replication and clearance. However, further research is required to evaluate its safety and efficacy.


The role of hippocampal glial glutamate transporter (GLT-1) in morphine-induced behavioral responses.
Opioid abuse modifies synaptic plasticity, which leads to behavioral changes, such as morphine dependence, but the mechanism remains poorly understood. Glial cells play an important role in the modulation of synaptic plasticity and are involved in addictive-like behaviors. The indisputable role of glutamate in opiate addiction has been shown. Astrocytes, a type of glial cells, which are integral functional elements of synapses, modulate the concentration of glutamate in the synaptic space. One of the most important mechanisms for glutamate concentration regulation is its uptake from the synaptic cleft. In this study, we evaluated the role of hippocampal glial glutamate transporter (GLT-1) in morphine dependence. Male rats received subcutaneous (s.c.) morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. In order to activate GLT-1, animals received an intrahippocampal injection of ceftriaxone (0.5 mmol/0.5 μl) in the CA1 region of the hippocampus, 30 min before each morphine administration. Rats were assessed for morphine dependence by monitoring naloxone hydrochloride-induced morphine withdrawal. Our results showed that hippocampal microinjection of ceftriaxone, as an activator of GLT-1, reduced some signs of morphine withdrawal, such as activity, diarrhea, head tremor, freezing, and ptosis. It seems that hippocampal GLT-1 can be affected by chronic morphine administration and involved in morphine dependence. Therefore, its activation may reduce morphine side effects by reducing hippocampal glutamate.


Epizootiologic association between feline immunodeficiency virus infection and feline leukemia virus seropositivity.
Five hundred twenty-one feline serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Nov 1, 1988, and Jan 31, 1989 were tested for antibody to feline immunodeficiency virus (FIV) by use of an ELISA. The prevalence of FIV infection in this population was 11.3% (95% confidence interval: 8.6 to 14.0%). Serologic test results for FeLV were available for 156 of the 521 cats. A significant (P = 0.008) association between FIV infection and FeLV seropositivity was observed; FeLV-positive cats were nearly 4 times more likely to be seropositive for FIV than were FeLV-negative cats. The association remained statistically significant (P = 0.021) after adjusting for age and gender, using multiple-logistic regression analysis.


Skin manifestations of athletes competing in the summer olympics: what a sports medicine physician should know.
Olympic athletes are vulnerable to traumatic, environmental and infectious skin manifestations. Although dermatological complaints are frequent among Olympians, there is a scarcity of literature that reviews sports-related dermatoses among Olympic athletes. A comprehensive review of PREMEDLINE and MEDLINE searches of all available literature through to January 2011 was conducted, focusing on sports-related dermatological presentations as well as the key words 'Olympic athletes' and 'skin diseases'. Common skin conditions can be harmful and even prohibitive for competition. Common aetiologies of dermatological conditions related to sports include: skin infections with dermatophytes such as tinea pedis and tinea corporis, bacteria such as pitted keratolysis, and folliculitis and viruses such as herpes gladiatorum. Frictional dermatoses occur commonly and include athlete's nodules, jogger's itch, frictional blisters, callosities and talon noir. Trauma can cause haematomas such as auricular haematomas. Due to long training hours in the sun, many endurance athletes experience high levels of UV radiation and a higher risk for both melanoma and non-melanoma skin cancer. Pre-existing dermatoses can also be aggravated with practice and competition; in particular, atopic eczema and physical urticarias. Infrequent dermatoses are susceptible to misdiagnosis, delay in treatment and needless biopsies. This review highlights the diagnosis and management of sports-related dermatoses by the following general categories of Olympic sport: endurance, resistance, team sport, and performing arts.


Depletion of slow-cycling PDGFRα+ADAM12+ mesenchymal cells promotes antitumor immunity by restricting macrophage efferocytosis.
The capacity to survive and thrive in conditions of limited resources and high inflammation is a major driver of tumor malignancy. Here we identified slow-cycling ADAM12+PDGFRα+ mesenchymal stromal cells (MSCs) induced at the tumor margins in mouse models of melanoma, pancreatic cancer and prostate cancer. Using inducible lineage tracing and transcriptomics, we demonstrated that metabolically altered ADAM12+ MSCs induced pathological angiogenesis and immunosuppression by promoting macrophage efferocytosis and polarization through overexpression of genes such as Gas6, Lgals3 and Csf1. Genetic depletion of ADAM12+ cells restored a functional tumor vasculature, reduced hypoxia and acidosis and normalized CAFs, inducing infiltration of effector T cells and growth inhibition of melanomas and pancreatic neuroendocrine cancer, in a process dependent on TGF-β. In human cancer, ADAM12 stratifies patients with high levels of hypoxia and innate resistance mechanisms, as well as factors associated with a poor prognosis and drug resistance such as AXL. Altogether, our data show that depletion of tumor-induced slow-cycling PDGFRα+ MSCs through ADAM12 restores antitumor immunity.


Molecular Mechanisms of the SLC13A5 Gene Transcription.
Citrate is a crucial energy sensor that plays a central role in cellular metabolic homeostasis. The solute carrier family 13 member 5 (SLC13A5), a sodium-coupled citrate transporter highly expressed in the mammalian liver with relatively low levels in the testis and brain, imports citrate from extracellular spaces into the cells. The perturbation of SLC13A5 expression and/or activity is associated with non-alcoholic fatty liver disease, obesity, insulin resistance, cell proliferation, and early infantile epileptic encephalopathy. SLC13A5 has been proposed as a promising therapeutic target for the treatment of these metabolic disorders. In the liver, the inductive expression of SLC13A5 has been linked to several xenobiotic receptors such as the pregnane X receptor and the aryl hydrocarbon receptor as well as certain hormonal and nutritional stimuli. Nevertheless, in comparison to the heightened interest in understanding the biological function and clinical relevance of SLC13A5, studies focusing on the regulatory mechanisms of SLC13A5 expression are relatively limited. In this review, we discuss the current advances in our understanding of the molecular mechanisms by which the expression of SLC13A5 is regulated. We expect this review will provide greater insights into the regulation of the SLC13A5 gene transcription and the signaling pathways involved therein.


Impact of perfusion strategy on neurologic recovery in acute type A aortic dissection.
The optimal perfusion strategy during surgery of acute type A aortic dissection is controversial. The purpose of this study was to determine the impact of retrograde cerebral perfusion during hypothermic circulatory arrest on short-term and long-term outcome in this specific patient population. Between 1984 and 2005, 175 consecutive patients underwent repair of an acute type A dissection. Three different surgical approaches were used: aortic cross-clamping without hypothermic circulatory arrest in 50 (29%), hypothermic circulatory arrest alone in 69 (39%), and hypothermic circulatory arrest with supplemental retrograde cerebral perfusion in 56 (32%). Operative mortality was 18% +/- 3% (+/- 70% confidence interval), and adverse outcomes (death or cerebrovascular accident) occurred in 21% +/- 3% of patients (p = 0.97 between groups). Multivariate analysis identified valve replacement (p = 0.04), preoperative flow complications (p = 0.03), and non-Marfan syndrome (p = 0.04) as predictors of operative mortality. Intraoperative dissection (p < 0.001) and history of cerebrovascular disease (p = 0.02) were predictors for permanent neurologic deficit, and retrograde cerebral perfusion was shown to have a protective effect on transient neurologic deficits (p = 0.008). Kaplan-Meier survival was 75% +/- 3% at 1 year (131 patients at risk), 63% +/- 4% at 5 years (87 patients at risk), and 49% +/- 4% at 10 years (48 patients at risk) and was independent of surgical approach (p = 0.37). Long-term survival was diminished with increased age (p < 0.001), earlier operative year (p < 0.001), and coronary artery disease (p = 0.02). The current investigation suggests improved neurologic recovery with circulatory arrest and supplemental retrograde cerebral perfusion. Operative mortality and long-term survival were comparable among groups.


Nationwide public-access defibrillation in Japan.
It is unclear whether dissemination of automated external defibrillators (AEDs) in public places can improve the rate of survival among patients who have had an out-of-hospital cardiac arrest. From January 1, 2005, through December 31, 2007, we conducted a prospective, population-based, observational study involving consecutive patients across Japan who had an out-of-hospital cardiac arrest and in whom resuscitation was attempted by emergency responders. We evaluated the effect of nationwide dissemination of public-access AEDs on the rate of survival after an out-of-hospital cardiac arrest. The primary outcome measure was the 1-month rate of survival with minimal neurologic impairment. A multivariate logistic-regression analysis was performed to assess factors associated with a good neurologic outcome. A total of 312,319 adults who had an out-of-hospital cardiac arrest were included in the study; 12,631 of these patients had ventricular fibrillation and had an arrest that was of cardiac origin and that was witnessed by bystanders. In 462 of these patients (3.7%), shocks were administered by laypersons with the use of public-access AEDs, and the proportion increased, from 1.2% to 6.2%, as the number of public-access AEDs increased (P<0.001 for trend). Among all patients who had a bystander-witnessed arrest of cardiac origin and who had ventricular fibrillation, 14.4% were alive at 1 month with minimal neurologic impairment; among patients who received shocks from public-access AEDs, 31.6% were alive at 1 month with minimal neurologic impairment. Early defibrillation, regardless of the type of provider (bystander or emergency-medical-services personnel), was associated with a good neurologic outcome after a cardiac arrest with ventricular fibrillation (adjusted odds ratio per 1-minute increase in the time to administration of shock, 0.91; 95% confidence interval, 0.89 to 0.92; P<0.001). The mean time to shock was reduced from 3.7 to 2.2 minutes, and the annual number of patients per 10 million population who survived with minimal neurologic impairment increased from 2.4 to 8.9 as the number of public-access AEDs increased from fewer than 1 per square kilometer of inhabited area to 4 or more. Nationwide dissemination of public-access AEDs in Japan resulted in earlier administration of shocks by laypersons and in an increase in the 1-month rate of survival with minimal neurologic impairment after an out-of-hospital cardiac arrest.