Quality of life after upper third molar removal: A prospective longitudinal study.
Third molar extraction is a very common procedure in Dentistry. The aim of this study was to evaluate the quality of life (QoL) and satisfaction of patients undergoing extraction of an upper third molar under local anesthesia. A second objective was to describe the evolution of self-reported pain measured in a visual analogue scale (VAS) in the 7 days after surgery and its relationship with pre- and intraoperative factors. A prospective longitudinal cohort study was made. Fifty-five patients received a questionnaire assessing social and working isolation, eating and speaking ability, diet modifications, sleep impairment, physical appearance, discomfort at suture removal and overall satisfaction. Pain was registered daily on a VAS scale. A descriptive and bivariate analysis of the data was performed. Forty-seven patients were included. Pain decreased lineally across the 7 days, and relief was significant between days 2 and 3. Intraoperative complications were significantly associated with pain. The complication that showed the highest pain score was the tuberosity fracture. Upper third molar removal significantly affects the patient's quality of life, particularly during the first 2 days after extraction.


Nearshore larval retention in a region of strong upwelling and recruitment limitation.
The ability of miniscule larvae to control their fate and replenish populations in dynamic marine environments has been a long-running topic of debate of central importance for managing resources and understanding the ecology and evolution of life in the sea. Larvae are considered to be highly susceptible to offshore transport in productive upwelling regions, thereby increasing dispersal, limiting onshore recruitment, and reducing the intensity of community interactions. We show that 45 species of nearshore crustaceans were not transported far offshore in a recruitment-limited region characterized by strong upwelling. To the contrary, 92% of these larvae remained within 6 km from shore in high densities throughout development along two transects sampled four times during the peak upwelling season. Larvae of most species remained nearshore by remaining below a shallow Ekman layer of seaward-flowing surface waters throughout development. Larvae of other species migrated farther offshore by occurring closer to the surface early in development. Postlarvae evidently returned to nearshore adult habitats either by descending to shoreward-flowing upwelled waters or rising to the sea surface where they can be transported shoreward by wind relaxation events or internal waves. Thus wind-driven offshore transport should not limit recruitment, even in strong upwelling regions, and larvae are more likely to recruit closer to natal populations than is widely believed. This study poses a new challenge to determine the true cause and extent of recruitment limitation for a more diverse array of species along upwelling coasts, and thus to further advance our understanding of the connectivity, dynamics, and structure of coastal populations.


Novel method for assessing postantibiotic effect by using the Coulter counter.
To study postantibiotic effect, viable counts are routinely acquired by the pour plate technique. However, this technique is laborious and time-consuming; the required sample dilutions also cause excessive errors and material wastage. A new total cell counting technique in which a Coulter counter is used to obtain more efficient postantibiotic effect measurements has been developed.


Kombucha Reduces Hyperglycemia in Type 2 Diabetes of Mice by Regulating Gut Microbiota and Its Metabolites.
Kombucha, which is rich in tea polyphenols and organic acid, is a kind of acidic tea soup beverage fermented by acetic acid bacteria, yeasts, lactic acid bacteria. Kombucha has been reported to possess anti-diabetic activity, but the underlying mechanism was not well understood. In this study, a high-fat, high-sugar diet combined with streptozotocin (STZ) injection was used to induce T2DM model in mice. After four weeks of kombucha intervention, the physiological and biochemical index were measured to determine the diabetes-related indicators. High-throughput sequencing technology was used to analyze the changes in gut microbiota from the feces. The results showed that four weeks of kombucha intervention increased the abundance of SCFAs-producing bacteria and reduced the abundance of gram-negative bacteria and pathogenic bacteria. The improvement in gut microbiota reduced the damage of intestinal barrier, thereby reducing the displacement of lipopolysaccharide (LPS) and inhibiting the occurrence of inflammation and insulin resistance in vivo. In addition, the increased levels of SCFAs-producing bacteria, and thus increasing the SCFAs, improved islet β cell function by promoting the secretion of gastrointestinal hormones (GLP-1/PYY). This study methodically uncovered the hypoglycemic mechanism of kombucha through gut microbiota intervention, and the result suggested that kombucha may be introduced as a new functional drink for T2DM prevention and treatment.


GM2D gangliosidosis B1 variant in a boy of German/Hungarian descent.
After the introduction of 4-methylumbelliferyl-2-acetamido-2-deoxy-beta A-D-glucopyranoside (4MUG) and its sulfated form (4MUGS) in the pre- and postnatal diagnosis and carrier identification of gangliosidosis genotypes, infrequent forms of the GM2 gangliosidosis Type B (Tay-Sachs disease) have been observed which show normal activity of Hexosaminidase A (Hex A) isoenzyme with the substrate 4MUG but absent or deficient activity against the sulfated form 4MUGS. Here we report the observation of a German/Hungarian boy aged 12 when he died with a prolonged course of a neurodegenerative disorder, later biochemically identified as a GM2 gangliosidosis B1-variant which is characterized by a deficient Hex A activity only against 4MUGS. The first clinical symptoms had occurred after the age of 14 months with a clear manifestation of the disease at age 3, when he presented disturbances of movement and tended to fall down. The slowly progressive course with brain atrophy, seizures and severe mental deterioration resulted in death after almost 9 years. At autopsy, the typical light microscopic neuronal changes of a "lysosomal storage disorder" were found, with multilamellar concentric bodies (MCB) and Zebra bodies in the neuronal cytoplasm at the electron microscopic level.


Light-Addressable Potentiometric Sensors in Microfluidics.
The light-addressable potentiometric sensor (LAPS) is an electrochemical sensor based on the field-effect principle of semiconductors. It is able to sense the change of Nernst potential on the sensor surface, and the measuring area can be controlled by the illumination of a movable light. Due to the unique light-addressable ability of the LAPS, the chemical imaging system constructed with the LAPS can realize the two-dimensional image distribution detection of chemical/biomass. In this review, the advantages of the LAPS as a sensing unit of the microelectrochemical analysis system are summarized. Then, the most recent advances in the development of the LAPS analysis system are explained and discussed. In particular, this review focused on the research of ion diffusion, enzymatic reaction, microbial metabolism, and droplet microfluidics using the LAPS analysis system. Finally, the development trends and prospects of the LAPS analysis system are illustrated.


[Effect of the content of crude plant protein in the ration on the utilization of urea in dairy cattle. 2. 15N-urea metabolism].
The metabolism of 15N-urea in the rations of dairy cows was investigated in dependence on the crude protein content of the rations. With energy concentration remaining unchanged, the rations contained 10.7 (I), 13.7 (II) and 17.1 (III)% plant crude protein and, after the supplementation of 150 g urea per animal and day, a total of 13.8, 16.7 and 20.2% crude protein in the dry matter. The urea was intraruminally infused during the feeding in the morning and the evening. In the morning feeding of each 1st measuring day it was labelled with 27.5 atom-% 15N-excess (15N'). The degree of labelling with 15N' of the N-fraction of rumen fluid, contents of the duodenum, faeces and milk, precipitable with trichloric acetic acid (TCA) decreased with the rising protein level of the ration. This effect was bigger than could be expected considering the low 15N'-quota in the total-N of the ration. In the sequence I ... III, 52.7, 32.2 and 30.6% of the 15N'-amount taken in passed the duodenal re-entrant cannula in TCA-precipitable form within 72 hours after the 15N-application. 33.3, 21.9 and 22.6% were apparently absorbed in the intestines as TCA-precipitable N within 120 h after the 15N'-application. In the same period 31.7, 43.1 and 72.8% of the 15N' taken in were excreted in urine. 12.3, 9.6 and 5.8% of the applied 15N' were found in milk protein. One can conclude that the utilisation of urea-N decreases with the rising level of crude protein in the ration and that, however, urea-N is still biochemically utilised when there is an excess of plant-N in the ration.


Serum levels of mullerian inhibiting substance in boys throughout puberty and in the first two years of life.
Serum levels of Mullerian inhibiting substance (MIS) have been measured in 91 boys throughout normal pubertal development. MIS levels fell sharply after pubertal stage 1 and were mostly undetectable at pubertal stage 6. The relationship between MIS concentration and pubertal stage was similar when compared with age. Seven patients with precocious puberty and 12 with delayed puberty were also investigated and found to have MIS levels consistent with their degree of pubertal development. Precocious puberty was associated with MIS levels that were abnormally low for age, while delayed puberty resulted in persistence of high MIS levels. Serum MIS levels were also measured in 29 boys less than 2 yr of age undergoing minor surgery. High levels were found throughout this time period, which is consistent with previous reports. MIS levels appear to be inversely related to levels of gonadotropins, steroids, and inhibin, which fall in the first 2 yr of life and rise throughout puberty.


[Comparative analysis of experimental data about the effects of various polyphenols on lifespan and aging.]
To analyze experimental data on the effect of various polyphenolic compounds on lifespan of mice, we approximated survival curves with the Gompertz model in its minimal form, which does not account for the heterogeneity of samples and the age-independent mortality. The plots of regressions of log0 (logarithm of the initial mortality) on  (the rate of aging) in series of control samples were used to assess the deviations of vectors directed from control to experimental data from the slopes of the control regressions. The analysis of published data suggests that resveratrol, polyphenol-containing grape skin extract, metformin, tocopherol, and the antioxidant SkQ1 do not produce changes beyond those possible upon comparing of different samples of a control population. The effect of the polyphenolic composition BP-C3 on female SHR mice is unique in being associated with a significant decrease in the rate of aging. The effect may be partly contributed to by the antioxidant properties of BP-C3. Its antioxidant capacity determined in vitro is comparable with that of established antioxidants, such as dihydroquercetin. Its effects in vivo include the ability to ameliorate reduction in the peroxide-decomposing activity of RBC lysates from male BALB/c mice treated with 5-fluorouracil.


Metagenomic evidence for sulfur lithotrophy by Epsilonproteobacteria as the major energy source for primary productivity in a sub-aerial arctic glacial deposit, Borup Fiord Pass.
We combined free enenergy calculations and metagenomic analyses of an elemental sulfur (S(0)) deposit on the surface of Borup Fiord Pass Glacier in the Canadian High Arctic to investigate whether the energy available from different redox reactions in an environment predicts microbial metabolism. Many S, C, Fe, As, Mn, and [Formula: see text] oxidation reactions were predicted to be energetically feasible in the deposit, and aerobic oxidation of S(0) was the most abundant chemical energy source. Small subunit ribosomal RNA (SSU rRNA) gene sequence data showed that the dominant phylotypes were Sulfurovum and Sulfuricurvum, both Epsilonproteobacteria known to be capable of sulfur lithotrophy. Sulfur redox genes were abundant in the metagenome, but sox genes were significantly more abundant than reverse dsr (dissimilatory sulfite reductase)genes. Interestingly, there appeared to be habitable niches that were unoccupied at the depth of genome coverage obtained. Photosynthesis and [Formula: see text] oxidation should both be energetically favorable, but we found few or no functional genes for oxygenic or anoxygenic photosynthesis, or for [Formula: see text] oxidation by either oxygen (nitrification) or nitrite (anammox). The free energy, SSU rRNA gene and quantitative functional gene data are all consistent with the hypothesis that sulfur-based chemolithoautotrophy by Epsilonproteobacteria (Sulfurovum and Sulfuricurvum) is the main form of primary productivity at this site, instead of photosynthesis. This is despite the presence of 24-h sunlight, and the fact that photosynthesis is not known to be inhibited by any of the environmental conditions present. This is the first time that Sulfurovum and Sulfuricurvum have been shown to dominate a sub-aerial environment, rather than anoxic or sulfidic settings. We also found that Flavobacteria dominate the surface of the sulfur deposits. We hypothesize that this aerobic heterotroph uses enough oxygen to create a microoxic environment in the sulfur below, where the Epsilonproteobacteria can flourish.


Glucocorticoid hormones upregulate interleukin 2 receptor alpha gene expression.
We present evidence that glucocorticoid hormones increase expression of IL-2Rec alpha chain on T cells by regulating IL-2Rec alpha gene transcription. We have previously reported that glucocorticoids can upregulate IL-2Rec alpha mRNA and protein expression in some T cell hybrids. In the present study we show that the glucocorticoid analogue dexamethasone increases mRNA levels of the endogenous IL-2Rec alpha gene and the expression of plasmids containing 5'-flanking sequences of the IL-2Rec alpha gene linked to CAT reporter genes transiently transfected into different cell lines. We show that the dexamethasone effect depends on cis-acting regulatory elements in a segment (-1835/-802) of the mouse gene that also contains cytokine response elements and a inducible DNase I-hypersensitive site. Dexamethasone responses of IL-2Rec alpha-CAT reporter gene constructs were observed in a CTL line, in an IL-3-dependent bone marrow-derived cell line, and in COS7 monkey kidney cells. In the latter the response depended on cotransfection of a glucocorticoid receptor expression vector. The biological relevance of the glucocorticoid-mediated upregulation of the IL-2Rec alpha gene is discussed.


[Intermittent assisted ventilation in neuromuscular diseases: course and quality of life].
Intermittent non-invasive home ventilation is expected to improve the quality of life, but progression of underlying neuromuscular diseases may lead to a deterioration. We observed after 82-1085 days of such home mechanical ventilation (7 patients with muscular dystrophy (age [mean/std.) 33 +/- 15 years), 8 patients with amyotrophic lateral sclerosis (ALS. age 60 +/- 8 years) a nonsignificant decrease of vital capacity (1.6 +/- 0.4 rp. 1.2 +/- 0.4 l) and an improvement of hypercapnia (49.3 +/- 8.5 rp. 43 +/- 18.5 mmHg). Quality of life (SF-36, Medical Outcomes Trust, Boston, USA) increased significantly only for mental health in patients with ALS (55 +/- 13 rp. 64 +/- 17%). Despite progression of the underlying disease the quality of life remained stable under home mechanical ventilation and mental health improved.


Nitronyl and imino nitroxides: improvement of Ullman's procedure and report on a new efficient synthetic route.
The synthesis of nitronyl and imino nitroxides has been reexamined with the aim of both increasing yields and of offering opportunities for new structures. The conditions for the formation of 2,3-bis(hydroxyamino)-2,3-dimethylbutane, the key intermediate of Ullman's route, have been carefully studied, and a new procedure is proposed, which affords the free base in a very pure form and up to 60% yield. Full characterization of this intermediate including an X-ray crystal structure is presented. An alternative synthetic route through 2,3-diamino-2,3-dimethylbutane and the corresponding imidazolidines which bypasses the delicate synthesis of the bis(hydroxyamino) compound is described. It is shown that 3-chloroperbenzoic acid is an effective oxidant for the transformation of adequately substituted imidazolidines into nitronyl nitroxides, which are obtained in high yield. An illustration of the potentialities of this new route, a new nitronyl nitroxide with two ethyl substituents in positions 4 and 5 of the imidazoline ring, is reported. The scope and limitations of the two routes are discussed.


Synthesis of highly substituted pyrroles via nucleophilic catalysis.
A nucleophilic catalysis method providing a concise synthesis of di-, tri-, and tetrasubstituted pyrroles is described. This regioselective one-pot method relies on nucleophilic catalysis of the intermolecular addition of oximes to activated alkynes and thermal rearrangement of the in situ generated O-vinyl oximes to form pyrroles that contain a functional group handle at the C3/C4 position.


Pulmonary Hyalinising Granuloma: A report of two cases.
Pulmonary hyalinising granuloma (PHG) is a rare fibrosclerosing inflammatory lung condition of unknown aetiology. It is characterised by solitary or multiple pulmonary nodules that are usually found incidentally while imaging the chest for other reasons. We report two cases of histologically proven PHG diagnosed at the Royal Hospital, Muscat, Oman. The first case was a 71-year-old male patient who presented in 2010 with a dry cough, weight loss and bilateral pulmonary nodules. The second case was a 58-year-old male patient who presented in 2012 and was found to have incidental bilateral pulmonary nodules on chest X-ray. Both patients were started on prednisolone and on follow-up the PHG nodules remained stable. Although there is no definitive treatment, PHG generally has an excellent prognosis.


Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution.
Using the differential display method to analyze mRNA expression in hepatocellular carcinoma (HCC) and nontumor livers, we cloned a full-length cDNA of 2263 bp, which was designated GTR2-2 and was identical with MXR7. The MXR7 mRNA was detected in 143 of 191 (74.8%) primary and recurrent HCCs taken from 154 patients but only in 5 (3.2%) nontumor livers. MXR7 mRNA was detected in one of two hepatoblastomas but not in hepatocellular adenoma, cholangiocarcinoma, or metastatic carcinomas to the liver. In human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric adenocarcinomas but not in several other types of cancer and 21 nonhepatocellular human tumor cell lines examined. MXR7 mRNA was expressed in high levels in the placenta, fetal liver, lung, and kidney, but it was undetectable in adult liver and was expressed in very low levels in adult lung and kidney. Our observations suggest that the MXR7 gene is regulated developmentally and expressed preferentially in HCC. To study its potential biological significance, we selected 113 patients who had unicentric primary HCC and had been followed for more than 4 years for further analysis. The MXR7 mRNA expression correlated closely with elevated serum alpha-fetoprotein (AFP) levels (88 versus 55%; P = 0.0001) and with expression of AFP mRNA (87 versus 55%; P = 0.005) and CD24 mRNA in HCC (80 versus 50%; P < 0.04), high tumor grade (76 versus 56%; P = 0.05), and tumor invasion (76 versus 55%; P < 0.05), but not with patient outcome. In HCC < or =3 cm, the frequency (77%) of MXR7 mRNA expression was significantly higher than that of elevated serum AFP (43%; P < 0.007) and AFP mRNA expression in HCC (41%; P < 0.004). Thus, MXR7 may serve as a sensitive early tumor marker for HCC and warrants more study to better understand its biological function.


Prevalence of genotype D in chronic liver disease patients with occult HBV infection in northern region of India.
Etiology of nearly 30% cases of chronic viral hepatitis remains undetected. Occult HBV infection (OBI) has emerged as an important clinical entity in this scenario. Apart from prevalence and clinical outcome of OBI patients genotype was determined in northern region of India. A total of 847 patients with chronic liver disease (CLD) were screened for common viral etiologies and others serological markers of HBV. Amplification of surface, precore and polymerase genes of HBV was performed in patients negative for other etiologies. Genotyping and sequencing of the precore region was performed for OBI cases. Twenty-nine (7.61%) cases of OBI were identifiedof which 9 had chronic liver disease (CHD), 11 liver cirrhosis (LC) and 9 hepatocellular carcinoma (HCC). Majority of OBI cases were detected by amplification of surface gene 26 (89.6%), followed by pre-core gene 12 (41.3%). Their liver functions tests were significantly deranged in comparison to overt HBV cases. IgG anti HBc was present in 8 (27.6%) OBI cases. Mutation was observed in 8 (32%) in pre-core region at nt. 1896 of overt HBV cases. Genotype D was the predominant genotype. OBI in our study was characterized by predominance of genotype D and more severe clinical and biochemical profile in comparison to overt HBV. IgG anti HBc positivity could be utilized as a marker of OBI. We recommend use of sensitive nested PCR for diagnosis of OBI, amplifying at least surface and precore gene.


Hydrogel-Assisted Transfer of Graphene Oxides into Nonpolar Organic Media for Oil Decontamination.
In this work, graphene oxide (GO)-loaded agarose hydrogel was transferred into oil such as hexadecane via stepwise solvent exchange with no chemical modification of the GO hydrophilic surface and the agarose network. After transfer, the GOs, loaded in the agarose network, could effectively and efficiently adsorb lipophilic dyes in oil via hydrogen bonding between the polar groups of the GOs and the dyes. The maximum adsorption capacity was 355.9 mg g(-1) for Nile red for instance, which is substantially larger than that of pristine agarose hydrogel and hydrophilic GO powder. The dye concentration for effective adsorption can be as low as 0.5 ppm. Thus, the present work demonstrates the promising potential of using hydrophilic adsorbents for efficient removal of polar impurities from oil.


Effect of insulin-like growth factor (IGF)-I and Des (1-3) IGF-I on the level of IGF binding protein-3 and IGF binding protein-3 mRNA in cultured porcine embryonic muscle cells.
Insulin-like growth factor binding protein (IGFBP)-3 effects proliferation and differentiation of numerous cell types by binding to insulin-like growth factors (IGF) and attenuating their activity or by directly affecting cells in an IGF-independent manner. Consequently, IGFBPs produced by specific cells may affect their differentiation and proliferation. In this study we show that embryonic porcine myogenic cells, unlike murine muscle cell lines, produce significant quantities of a binding protein immunologically identified as IGFBP-3. Nonfusing cells subcultured from highly fused porcine myogenic cell cultures do not produce detectable IGFBP-3 protein or mRNA, thus suggesting the IGFBP-3 is produced by muscle cells in the porcine myogenic cell cultures. Treatment of porcine myogenic cultures with 20 ng of IGF-I or 20 ng of Des (1-3) IGF-I/ml serum-free media for 24 h results in a threefold reduction in the level of IGFBP-3 in conditioned media. This reduction is not affected by cell density over a sixfold range. Additionally, treatment for 24 h with 20 ng of IGF-I/ml media results in a sevenfold decrease in the steady-state level of IGFBP-3 mRNA. This IGF-I-induced decrease in IGFBP-3 mRNA level appears to be relatively unique to myogenic cells. IGF-I treatment also causes a fourfold increase in the steady-state level of myogenin mRNA. This increase in myogenin mRNA suggests that, as expected, IGF-I treatment accelerates differentiation of myogenic cells. The simultaneous decrease in IGFBP-3 mRNA and protein that accompanies IGF-I-induced myogenin expression suggests that differentiation of myogenic cells may be preceded or accompanied by decreased production of IGFBP-3.


Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score.
This study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer. This retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting long-term outcomes. Of the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001). Stratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.


Measurement of serum granulocyte colony-stimulating factor in a patient with congenital agranulocytosis (Kostmann's syndrome).
A 12-month-old boy with Kostmann's syndrome was admitted with cavitary pulmonary disease. He had also had bacterial conjunctivitis, periorbital cellulitis, pneumonitis, and otitis media since the age of 10 days. His umbilical cord had not fallen off until he was 3 weeks old. Neutropenia was diagnosed at 4 weeks of age. Antineutrophil antibody studies were negative. A bone marrow aspirate showed granulocytic hypoplasia and a maturation arrest at the promyelocyte stage. Hematopoietic cell culture showed normal numbers of colony-forming units-granulocyte macrophage. Serum granulocyte-macrophage colony-stimulating factor level, was 0.24 ng/mL (normal, greater than 0.05 ng/mL). Serum granulocyte colony-stimulating factor levels, measured by enzyme immunoassay, were undetectable. The patient was successfully treated with filgrastim (granulocyte colony-stimulating factor), with an increase in the absolute neutrophil count to 10.0 x 10(9)/L. Thus, our case of Kostmann's syndrome appears to represent a defect in regulation or production of granulocyte colony-stimulating factor.


Evaluation and comparison of the electrostatic dust print lifter and the electrostatic detection apparatus on the development of footwear impressions on paper.
The Electrostatic Dust Print Lifter (EDPL) and the Electrostatic Detection Apparatus(2) (ESDA(2)) were compared to determine if both processes could be used to develop footwear impressions of the same or similar quality and in what order they should be used to develop the highest quality footwear impression. The sensitivity of each technique was also evaluated. The quality of the footwear impressions developed was determined by comparing 25 individual characteristics present on the known shoe to the footwear impressions developed using each technique. The footwear impressions were made by stepping on paper placed over several different surfaces, which included: linoleum, industrial Berber carpet, nylon carpet placed over a (3/8)-in. pad, ceramic tile, cardboard, 1-in. foam, 4-in. foam, cement, asphalt, grass, and mulch. Each of the papers placed on these surfaces was developed using the EDPL before the ESDA(2) and vice versa. The sensitivity test for the ESDA(2) was conducted by processing 10 sheets of stacked paper that were stepped on with the known shoe, beginning with the top sheet. The sensitivity test for the EDPL was conducted by processing 10 sheets of paper stepped on with the known shoe in succession. This study determined the footwear impressions developed using the EDPL were of better comparative value than impressions developed with the ESDA(2). On average, 72.4% of the individual characteristics from the known impression were identified on images developed when the EDPL was used first compared with an average of 38.9% when the ESDA(2) was used first. Therefore, if only one technique is used, the EDPL should be chosen. The sensitivity test determined the ESDA(2) develops high-quality footwear impressions on only the top sheet of paper. No footwear impressions were developed on any sheets under the top sheet of paper. The sensitivity test also determined the EDPL results increase in quality as the amount of dust residue decreases on the surface.


Brief communication: Effect of size biases in the coefficient of variation on assessing intraspecific variability in the prosimian skeleton.
This study examines the effect of a measurement size bias in coefficients of variation on the evaluation of intraspecific skeletal variability in a sample of eight prosimian species (Eulemur fulvus, Hapalemur griseus, Lemur catta, Varecia variegata, Galago senegalensis, Otolemur crassicaudatus, Nycticebus coucang, and Tarsius syrichta). Measurements with smaller means were expected to have higher coefficients of variation (CVs) due to the impact of instrumental precision on the ability to assess variability. This was evaluated by testing for a negative correlation between CVs and means in the total sample, within each species, and within each measurement, and by testing for the leveraging impact of small measurements on the significance of comparisons of variability between regions of the prosimian skeleton. Three comparisons were made: cranial versus postcranial variability, epiphysis versus diaphysis variability, and forelimb versus hindlimb variability. CVs were significantly negatively correlated with means within the total sample (r(2) = 0.208, P < 0.0001) and within each species. CVs and means were significantly correlated within only three of the measurements, which may reflect the relatively low body size range of the species studied. As predicted by the higher variability of smaller measurements, removing the smallest measurements from comparisons of variable classes containing measurements of different mean magnitudes pushed the comparisons below significance. These results indicate caution should be exercised when using CVs to assess variability across sets of measurements with different means.


Mutations in human papillomavirus type 16 L1 hypervariable surface-exposed loops affect L2 binding and DNA encapsidation.
Prophylactic vaccines against human papillomavirus (HPV) based on virus-like particles (VLP) induce type-specific neutralizing antibodies against a small number of hypervariable residues positioned in surface-exposed loops of the major capsid protein L1. To investigate the importance of these residues for neutralization, cross-neutralization, L2 incorporation and genome encapsidation, ten surface-exposed amino acid residues in four hypervariable loops of L1 were mutated. VLPs containing mutated or WT L1, with or without WT L2, were produced in 293TT cells using pseudovirion expression vectors. The mutations reduced the ability to induce neutralizing antibodies and to incorporate the L2 protein in the capsid. Ability to induce cross-neutralizing antibodies and to encapsidate pseudogenomes were completely abrogated. In summary, the surface-exposed L1 loops are important for the function of the HPV particle.


Capturing all of the costs in NICE appraisals: the impact of inflammatory rheumatic diseases on productivity.
Inflammatory rheumatic diseases are common. It is estimated that ∼2.1% of the population has an inflammatory rheumatic disease (Andrianakos A, Trontzas P, Christoyannis F et al. Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study. J Rheumatol 2003;30:1589-601). For diseases such as RA, PsA and AS, onset is most frequent between the ages of 30 and 50 years. The impact of inflammatory rheumatic diseases on physical functioning can be significant. Patients can suffer from swollen joints that cause pain and disability. This can reduce sufferers' ability to lead fully productive lives. This has major financial consequences for sufferers and their families and there is an economic impact on society. The National Institute for Health and Clinical Excellence (NICE) technology appraisal process has typically ignored any improvements in productivity that may result from treatment. There have been calls to extend the perspective of economic evaluations to include productivity costs as one aspect of wider social effects. However, there are a number of issues that must be resolved before productivity costs can become a routine input into the calculation of cost-effectiveness of treatments. First, there is limited agreement regarding the practical details and appropriate methods for their inclusion in economic evaluation. Second, there are issues that must be addressed regarding society's preference for equity. This issue arises when considering individual's economic productivity, that is to say, how we weigh individuals who are more productive (e.g. those in employment) against those who are less so (e.g. the unemployed). Finally, it is important to consider cross-budgetary effects, since productivity has cost and benefit implications outside of health.


Nonequilibrium stochastic processes: time dependence of entropy flux and entropy production.
Based on the Fokker-Planck and the entropy balance equations we have studied the relaxation of a dissipative dynamical system driven by external Ornstein-Uhlenbeck noise processes in the absence and presence of nonequilibrium constraint in terms of the thermodynamically inspired quantities such as entropy flux and entropy production. The interplay of nonequilibrium constraint, dissipation, and noise reveals some interesting extremal nature in the time dependence of entropy flux and entropy production.


Metabolism of tetramethrin isomers in rat: IV. Tissues responsible for formation of reduced and hydrated metabolites.
1. To identify the sites of formation of the reduced metabolites, 3-hydroxy-cyclohexane-1,2-dicarboximide (3-OH-HPI-1 and -2), 1,2-cyclohexanedicarboxylic acid (TCDA) and 1-hydroxy-1,2-cyclohexanedicarboxylic acid (1-OH-HPA), in rat treated with 14C-labelled (1RS, trans)-tetramethrin, [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate], bile-duct cannulated animals were orally or intravenously administered 14C-labelled 3,4,5,6-tetrahydrophthalimide (TPI) or 3,4,5,6-tetrahydrophthalic acid (THPA), precursors of these metabolites, and bile, urine and faeces were collected for analysis. 2. 3-OH-HPI-1 and 3-OH-HPI-2, which are cis-form reduced metabolites, and 1-OH-HPA were detected in bile and urine samples of the bile-cannulated rat treated intravenously and orally with 14C-labelled TPI, indicating their formation in tissues or blood. TCDA, a trans-form reduced metabolite, was not detected in bile, urine or faeces of the bile-cannulated rat treated intravenously with 14C-THPA, but was found in the faeces after oral application, indicating formation in the gastrointestinal tract. 3. To clarify whether 1-OH-HPA is produced from THPA via TCDA (hydroxylation via reduction) or by direct addition of H2O to its double bond (hydration), rats were orally administered 14C-labelled TCDA, and metabolites in urine and faeces were analysed. The observed lack of 1-OH-HPA indicated formation by direct addition of H2O to the double-bond of THPA. 4. To specify which tissues form reduced and hydrated metabolites, in vitro metabolism studies were carried out. Reduction to the cis-form was found to take place in blood cells, reduction to the trans-form took place in the gastrointestinal tract contents, and hydration took place in the liver and the intestinal tract contents.


Surface shape evaluation with a corneal topographer based on a conical null-screen with a novel radial point distribution.
In order to measure the shape of fast convex aspherics, such as the corneal surface of the human eye, we propose the design of a conical null-screen with a radial point distribution (spots similar to ellipses) drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact array of circular spots if the surface is perfect. Any departure from this geometry is indicative of defects on the evaluated surface. We present the target array design and the surface evaluation algorithm. The precision of the test is increased by performing an iterative process to calculate the surface normals, reducing the numerical errors during the integration. We show the applicability of the null-screen based topographer by testing a spherical calibration surface of 7.8 mm radius of curvature and 11 mm in diameter. Here we obtain an rms difference in sagitta between the evaluated surface and the best-fitting sphere less than 1 μm.


Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex.
Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1) and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs) which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET) and wild-type (WT) mice using [(3)H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV) and the dentate gyrus (DG) of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL) subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However, in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.


Detection of circulating released platelets after renal transplantation.
In recipients of renal transplants, the biochemical defect(s) that underlies increased deposition of platelets in the graft and their shortened survival in the circulation are poorly understood. Forty-six recipients of kidney allografts, with and without rejection signs (13 acute rejections (ARs), 15 chronic rejections (CRs), and 18 functioning transplants (FTs), had lower platelet serotonin (5HT) and higher plasma beta-thromboglobulin than normal controls (NCs). These abnormalities were more pronounced in patients with ARs than with CRs but were also present in patients with FTs. All groups of transplant recipients showed an abnormal metabolism of platelet arachidonate, as expressed by low serum levels of thromboxane B2. In AR, plasma fibrinopeptide A (FPA) was significantly high whereas FPA levels were unchanged in CR and in FT. These findings suggest that in patients with renal transplants, the platelet release reaction has occurred in vivo, resulting in the secretion of granule-bound substances and the circulation of partially empty platelets. Vasoactive, mitogenic, and proaggregatory substances released from platelets might damage the graft and aggravate the rejection process.


Free and ATP-bound structures of Ap4A hydrolase from Aquifex aeolicus V5.
Asymmetric diadenosine tetraphosphate (Ap(4)A) hydrolases degrade the metabolite Ap(4)A back into ATP and AMP. The three-dimensional crystal structure of Ap(4)A hydrolase (16 kDa) from Aquifex aeolicus has been determined in free and ATP-bound forms at 1.8 and 1.95 A resolution, respectively. The overall three-dimensional crystal structure of the enzyme shows an alphabetaalpha-sandwich architecture with a characteristic loop adjacent to the catalytic site of the protein molecule. The ATP molecule is bound in the primary active site and the adenine moiety of the nucleotide binds in a ring-stacking arrangement equivalent to that observed in the X-ray structure of Ap(4)A hydrolase from Caenorhabditis elegans. Binding of ATP in the active site induces local conformational changes which may have important implications in the mechanism of substrate recognition in this class of enzymes. Furthermore, two invariant water molecules have been identified and their possible structural and/or functional roles are discussed. In addition, modelling of the substrate molecule at the primary active site of the enzyme suggests a possible path for entry and/or exit of the substrate and/or product molecule.


Temporal lobe epilepsy in early childhood.
To explore the electroclinical features of temporal lobe epilepsy (TLE) in early childhood, we studied results of video-EEG and other tests of 14 children aged 16 months to 12 years selected by seizure-free outcome after temporal lobectomy. Four children had mesiotemporal sclerosis, 1 had cortical dysplasia, and 9 had low-grade temporal neoplasms. The children had complex partial seizures (CPS) with symptomatology similar to that of adults with TLE, including decreased responsiveness and automatisms. Automatisms tended to be simpler in the younger children, typically limited to lip smacking and fumbling hand gestures. Scalp/sphenoidal EEG showed anterior/inferior temporal interictal sharp waves and unilateral temporal seizure onset in the 4 children with mesiotemporal sclerosis and in the child with cortical dysplasia, but EEG findings in 9 children with low-grade temporal tumors were complex, including multifocal interictal sharp waves or poorly localized or falsely lateralized EEG seizure onset. In children without tumors, video-EEG was critical to localization of the epileptogenic zone for resection, but in patients with tumors video-EEG was less localizing and its main value was to confirm that the reported behaviors were epileptic seizures with semiology typical of temporal lobe onset.


[The content of pepsinogen in the blood plasma of growing fallow deer (Dama dama L.) raised helminth free and under natural conditions in captivity].
Pepsinogen values were determined in helminth free (n = 12) and naturally raised farmed fallow deer (n = 10-12) from birth (June 1992) to 11 (May 1993) and 15 months (September 1993) of age respectively in 4 weekly intervals. At birth the plasma pepsinogen value was 0.708 +/- 0.197 U Tyrosin/l and decreased thereafter until 14 weeks of age to 0.139 +/- 0.061 U Tyrosin/l in both groups. From the 18th week of age the naturally raised fallow deer, infected with gastrointestinal nematodes, had significantly higher pepsinogen values than the helminth free kept animals. Maximum pepsinogen levels in the naturally raised fallow deer were determined in November 1992 (0.813 +/- 0.336 U Tyrosin/l) and in June 1993 (1.050 +/- 0.163 U Tyrosin/l). In helminth free animals no further decrease of plasma pepsinogen values was seen from 14th week of age onwards: it was 0.202 +/- 0.110 U Tyrosin/l. There was no influence of sex on the plasma pepsinogen values in both groups.


Interchangeability of a semiadjustable articulator.
The purpose of this study was to investigate whether the interchangeability of new Hanau semiadjustable articulators fulfills the manufacturer's criterion (102 microns) in the mediolateral direction and the defined 166-micron criterion three dimensionally and whether the articulators maintain the same interchangeability as new articulators after a period of function. The spatial deviations in three dimensions of ten new, ten 18-month-old, and ten 30-month-old Hanau articulators were measured with a field-inspection gauge and compared to those of a master articulator. Compared to the master articulator, nine of 10 new articulators met the manufacturer's criterion of articulator interchangeability in the mediolateral direction. However, only four of the 10 articulators fulfilled the criterion for three-dimensional interchangeability. The articulators were found to be interchangeable among the groups when the spatial deviations of test articulators from the master articulator at the position of the lingual cusp of the right maxillary first premolar were compared. However, using the geometric mean deviations of test articulators, the 30-month group was not interchangeable with the new and the 18-month articulator groups. This limited study revealed that most of the articulators tested met the manufacturer's criterion of articulator interchangeability, but most did not pass the three-dimensional interchangeability test. Clinicians should be aware of the amount of occlusal error in the range of 0.2 mm that may result from interchanging dental casts on the articulator system. The articulator system might be able to maintain the same level of interchangeability for up to 18 months of routine use.


Proliferative and cytotoxic immune functions in ageing mice. I. Sequence of decline of reactivities measured under optimal and suboptimal sensitization conditions.
Individual young adult, middle-aged, and old C57BL/6J male mice were tested for in vitro generated proliferative and cytotoxic responses to H-2 alloantigens under a variety of sensitization conditions. Proliferation in mixed lymphocyte culture (MLC) had decreased by 14 months of age (middle-aged), whether measured by directly assaying cultures in microtitre plates (micro MLC) or by labelling aliquots taken from large culture tubes (macro MLC). Cytotoxicity did not decline until a later age if sensitization was done in large tubes (macro cell-mediated lympholysis, CML). When cytotoxic activity was assayed by measuring lysis after addition of chromated cells to MLCs in microtitre plates (micro CML), differences were revealed between young and middle-aged animals. However, these conditions were suboptimal for generation of cytotoxicity even in young controls and showed even lower responses in the middle-aged group. It was concluded that proliferation showed an earlier, more severe decline than cytotoxicity with age as the proliferative response had declined by middle-age under all sensitization conditions used. With optimal sensitization conditions, senescent mice (26--30 months) showed a four- to ten-fold decrease in cytotoxicity compared with young adult mice.


A variant translocation t(2;18) in follicular lymphoma involves the 5' end of bcl-2 and Ig kappa light chain gene.
We have examined three cases of human lymphoma bearing a t(2;18)(p11;q21) chromosome translocation. The bcl-2 gene appeared to be rearranged in all three cases and breakpoints were clustered in the 5' flanking region of the gene. In all three cases, bcl-2 was juxtaposed to J segments of the Ig kappa gene. This juxtaposition of the bcl-2 and Ig kappa genes is very similar to the variant chromosome translocations of Burkitt lymphoma that juxtapose the c-myc locus to IgL genes.


Effects of Interferon-Tau and Steroids on Cytochrome P450 Activity in Bovine Endometrial Epithelial Cells.
The objective of the current study was to examine cyclooxygenase (COX), cytochrome P450 1A (CYP1A) and 2C (CYP2C) activity in bovine endometrial cell cultures following exposure to oxytocin (OT), interferon-τ (IFN), estradiol (E2) and/or progesterone (P4). Bovine endometrial epithelial cells were treated with OT, IFN, a combination of OT+IFN or control (CON) media for 24 h. For the second experiment, cells were treated with E2, P4, a combination of E2 + P4 or CON media for 24 h. Treatments were performed in triplicate, and the experiment was repeated four times (n = 12 per treatment). Treatment with OT alone increased (p < 0.01) activity of COX compared with CON; however, OT alone did not alter activity of CYP1A (p = 0.55) or CYP2C (p = 0.46) compared with CON. Activity of CYP1A and CYP2C was decreased in cells exposed to IFN (p < 0.01) or OT+IFN (p < 0.01) compared with CON. Treatment with E2 alone did not alter activity of CYP1A (p = 0.64) or CYP2C (p = 0.06) compared with CON. Activity of CYP1A and CYP2C was decreased (p < 0.01) in P4 vs CON. In summary, IFN exposure, irrespective of OT treatment, decreased the activity of CYP1A and CYP2C. Activity of CYP1A was decreased following P4 treatment alone, while that of CYP2C was decreased following both P4 and E2 + P4 treatment. The mixed function monooxygenase enzymes, CYP1A and CYP2C, have been implicated in synthesizing embryotoxic compounds; therefore, downregulation in the endometrium may be necessary during maternal recognition of pregnancy.


[Revision operations in retinal redetachment].
We analyzed retrospectively 239 consecutive patients who had undergone reoperation for repeat retinal detachment; 441 repeat operations were performed. The average follow-up was 2.1 years, and on average we noted 1.8 retinal redetachments per patient. At the last follow-up examination in 173 eyes (72.4%), the retina was reattached; 10.5% of the eyes had a partially detached retina and in 15.9% the retina was again completely detached. Enucleation was necessary in 3 eyes (1.2%). Visual improvement occurred in 45% of the eyes with reattachment of the retina. When the first retinal detachment occurred, 74 eyes were aphakic. Compared to the other 165 eyes there was no difference in anatomic or visual outcome. Aphakic eyes needed fewer additional reoperations (39%) compared to the phakic group (50%, p less than 0.01). One important reason for the surgery being unsuccessful was poor placement of the scleral buckle. In both groups equatorial placement of the scleral buckle led to anatomical success in more than 50%. The eyes in the aphakic group required more vitrectomies (47%) compared to the phakic eyes (34%, p less than 0.01).


Electromagnetic scattering by arbitrarily oriented ice cylinders.
The scattering of electromagnetic waves by arbitrarily oriented, infinitely long circular cylinders is solved by following the procedures outlined by van de Hulst. The far-field intensities for two cases of a linearly polarized incident wave are derived. The scattering coefficients involve the Bessel functions of the first kind, the Hankel functions of the second kind, and their first derivatives. Calculations are made for ice cylinders at three wavelengths: 0.7 micro, 3 micro, and 10 micro. The numerical results of intensity coefficients are presented as functions of the observation angle ø. A significant cross-polarized component for the scattered field, which vanishes only at normal incidence, is obtained. It is also shown that the numerous interference maxima and minima of the intensity coefficients due to single-particle effects depend on the size parameter x as well as on the oblique incident angle alpha. Since cylinder-type particles are often observed in ice clouds, the light-scattering calculations performed for a cir ular cylinder in this paper should be of use in the study of cloud microstructure.


Comprehensive assessment of coronary artery stenoses: computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina.
We sought to determine the diagnostic accuracy of noninvasive visual (computed tomography coronary angiography [CTCA]) and quantitative computed tomography coronary angiography (QCT) to predict the hemodynamic significance of a coronary stenosis, using intracoronary fractional flow reserve (FFR) as the reference standard. It has been demonstrated that CTCA provides excellent diagnostic sensitivity for identifying coronary stenoses, but may lack accurate delineation of the hemodynamic significance. We investigated 79 patients with stable angina pectoris who underwent both 64-slice or dual-source CTCA and FFR measurement of discrete coronary stenoses. CTCA and conventional coronary angiography (CCA), and QCT and quantitative coronary angiography (QCA), were performed to determine the severity of a stenosis that was compared with FFR measurements. A significant anatomical or functional stenosis was defined as >/=50% diameter stenosis or an FFR <0.75. Stented segments and bypass grafts were not included in the analysis. A total of 89 stenoses were evaluated of which 18% (16 of 89) had an FFR <0.75. The diagnostic accuracy of CTCA, QCT, CCA, and QCA to detect a hemodynamically significant coronary lesion was 49%, 71%, 61%, and 67%, respectively. Correlation between QCT and QCA with FFR measurement was weak (R values of -0.32 and -0.30, respectively). Correlation between QCT and QCA was significant, but only moderate (R = 0.53; p < 0.0001). The anatomical assessment of the hemodynamic significance of coronary stenoses determined by visual CTCA, CCA, or QCT or QCA does not correlate well with the functional assessment of FFR. Determining the hemodynamic significance of an angiographically intermediate stenosis remains relevant before referral for revascularization treatment.


Advances in the establishment of defined mouse models for the study of fracture healing and bone regeneration.
The availability of a broad spectrum of antibodies and gene-targeted animals caused an increasing interest in mouse models for the study of molecular mechanisms of fracture healing and bone regeneration. In most murine fracture models, the tibia or the femur is fractured using a 3-point bending device (closed models) or is osteotomized using an open surgical approach (open models). For fracture studies in mice, the tibia has to be considered less appropriate compared with the femur because the stabilization of the fracture is more difficult due to its triangular, distally declining caliber and its bowed longitudinal axis. Biomechanical factors critically influence the bone healing process. Thus, the use of stable osteosynthesis techniques is also of interest in murine fracture models. To achieve stable fixation, several biomechanically standardized implants have recently been introduced, including a locking nail and an intramedullary compression screw. Other implants, such as a pin-clip, an external fixator, and a locking plate, additionally allow the stabilization of fractures with distinct gap sizes. This enables the study of healing of critical size defects and nonunions. The use of these implants further allows a rigid fixation of fractures in bridle bones, which is essential for fracture studies in animals suffering from metabolic bone diseases like osteoporosis. In general, the analysis of bone healing in these models includes different imaging techniques and histologic, immunohistochemical, biomechanical, and molecular methods. To evaluate the impact of different osteosynthesis techniques on physical activity and rehabilitation, gait analysis may additionally be performed. By this, the gait of the animals can be visualized and quantitatively analyzed using modified running wheels and dynamic high-resolution radiography systems. Taken together, a variety of different murine femur fracture models have become available, providing defined biomechanical conditions for fracture research. The use of these mouse models may now allow studying the influence of fracture stabilization techniques on molecular mechanisms of bone healing.


The Influence of Endogenous Testosterone Density on Unfavorable Disease and Tumor Load at Final Pathology in Intermediate-Risk Prostate Cancer: Results in 338 Patients Treated with Radical Prostatectomy and Extended Pelvic Lymph Node Dissection.
The aim of this study is to evaluate the influence of endogenous testosterone density (ETD) on features of aggressive prostate cancer (PCa) in intermediate-risk disease treated with radical prostatectomy and extended pelvic lymph node dissection. Density measurements included the ratio of endogenous testosterone (ET), prostate-specific antigen (PSA), and percentage of biopsy positive cores (BPC) on prostate volume (ETD, PSAD, and BPCD, respectively). The ratio of percentage of cancer invading the gland (tumor load, TL) on prostate weight (TLD) was also calculated. Unfavorable disease (UD) was defined as tumor upgrading (ISUP >3) and/or upstaging (pT >2) and/or lymph node invasion (LNI). Associations of ETD with features of aggressive PCa, including UD and TLD, were evaluated by logistic and linear regression models. Evaluated cases were 338. Subjects with upgrading, upstaging, and LNI were 61/338 (18%), 73/338 (21%), and 25/338 (7.4%), respectively. TLD correlated with UD (Pearson's correlation coefficient, r = 0.204; p < 0.0001), PSAD (r = 0.342; p < 0.0001), BPCD (r = 0.364; p < 0.0001), and ETD (r = 0.214; p < 0.0001), which also correlated with BMI (r = -0.223; p < 0.0001), PSAD (r = 0.391; p < 0.0001), and BPCD (r = 0.407; p < 0.0001). TLD was the strongest independent predictor of UD (OR = 2.244; 95% CI = 1.146-4.395; p = 0.018). In the multivariate linear regression model predicting BPCD, ETD was an independent predictor (linear regression coefficient, b = 0.026; 95% CI: 0.016-0.036; p < 0.0001) together with PSAD (b = 1.599; 95% CI: 0.863-2.334; p < 0.0001) and TLD (b = 0.489; 95% CI: 0.274-0.706; p < 0.0001). According to models, TLD increased as ETD increased accordingly, but mean ET levels were significantly lower for patients with UD. As ETD measurements incremented, the risk of large tumors extending beyond the prostate increased accordingly, and patients with lower ET levels were more likely to occult UD. The influence of ETD on PCa biology should be addressed by prospective studies.


Thrombosis of the greater saphenous vein in a collegiate football place kicker.
The greater saphenous vein is vulnerable in its superficial course overlying the distal tibia in the zone of impact of a kicker's foot. Minor repetitive trauma or a single traumatic event to this area may subject the vein to intimal trauma or other irregularities that may lead to vein thrombosis.


[Samples in Coagulation Test].
An understanding and ability to develop a strategy to prevent pre-analytical errors of laboratory tests in the hemostasis area are two of the most important skills of medical technologists and related doctors. Recently, the working group for standardization of sampling in coagulation tests is working towards a consensus. This article reviews a summary of the consensus: (1) The anticoagulant for coagulation tests is 3.13-3.2% sodium citrate at a ratio of 1:9 to whole blood and the accuracy of the ratio is within 10%. (2) Blood sampling is achieved with the use of a 21-23G needle and coagulation. Blood sampling can be achieved by both a syringe and vacuum tube system. After taking blood, laboratory tests such as of the prothrombin time (PT) and activated partial thromboplastin time (APTT) should be completed within one hour and the storage temperature should be at room temperature, not ice-cold conditions. 3) To prepare a plasma sample, citrated blood is centrifuged at 1,500 x g for 15 min at room temperature to minimize the remaining platelets in plasma (below 10,000/microL at least).


Iron status in diffuse telogen hair loss among women.
The relationship between iron body status and different types of hair loss has been investigated in a number of studies, however, with relatively discrepant findings. Therefore we conducted an analytical case-control study to assess whether diffuse telogen hair loss in women of childbearing age (15 to 45 years old) is associated with iron deficiency. Using the analytical case-control methodology, we studied 30 consecutive women with documented diffuse telogen hair loss in comparison with 30 women without hair loss. Study subjects had no history of nutritional supplement intake or chronic underlying diseases, and had normal thyroid function and inflammatory profiles. Biochemical investigations were performed in all study women. The mean ferritin level and trasferrin saturation was statistically significantly lower in patients with diffuse telogen hair loss than in subjects without hair loss (16.3+/-12.6 vs. 60.3+/-50.1, ng/mL; P<0.0001 and 20.3+/-9.7 vs. 28.3+/-11.8 percent; P=0.006, respectively). Also, total iron binding capacity was significantly higher in patients than in control group (367.8+/-58.2 vs. 319.2+/-60.1 microg/dL; P=0.004). Of nine patients with iron deficiency anemia (Hb <12 g/dL), eight patients had telogen hair loss (odds ratio: 10.5, 95%CI: 1.2-90.7; P=0.013). Odds ratio (95% confidence interval) for diffuse telogen hair loss was 21.0 (4.2-105.0) at serum ferritin levels < or =30 ng/mL. Women with iron deficiency status are at a risk of telogen hair loss. The important role of serum ferritin in hair loss is becoming more evident. In women without systemic inflammation or other underlying disorders, serum ferritin levels below or equal to 30 ng/mL are strongly associated with telogen hair loss.


The relationship between beta-catenin and apoptosis: A cytological and immunocytochemical examination.
Disruption of the adhesive role of beta-catenin by caspases has been reported; however, the relationship between the Wnt/beta-catenin signaling pathway and apoptosis remains unclear. Therefore, we aimed to evaluate squamous epithelial cells in cervicovaginal smears by using cytological and immunocytochemical methods to observe changes in the presence and localization of beta-catenin during apoptosis, death receptor-, and mitochondria-mediated apoptosis. We investigated 224 cervicovaginal smears using the Papanicolaou method. Anti-beta-catenin and anti-cleaved caspase 3, 8, and 9 antibodies were used for immunocytochemical staining. Apoptotic cells were negative for beta-catenin. This showed that the Wnt/beta-catenin signaling pathway was inactive in apoptotic cells. However, beta-catenin showed intense positivity in the membrane, cytoplasm, and nucleus of non-apoptotic epithelial cells around these apoptotic cells. Therefore, the Wnt/beta-catenin signaling pathway was active in non-apoptotic epithelial cells, and this activity in non-apoptotic cells may have been induced by apoptotic cells. A highly significant association between the presence of death receptor-mediated apoptosis and the activity of the Wnt/beta-catenin signaling pathway was also found (P<0.001). In conclusion, the Wnt/beta-catenin signaling pathway was found to be inactive in apoptotic cells, but apoptotic cells may induce the Wnt/beta-catenin signaling pathway in non-apoptotic cells to compensate for a decrease in epithelial cells because of apoptosis in order to maintain epithelial tissue integrity.


Associations of socio-demographic, perceived environmental, social and psychological factors with active travel in Hong Kong adolescents: the iHealt(H) cross-sectional study.
Adolescent active travel (AT) can contribute to health-enhancing physical activity, sense of community, social interactions, spatial and navigational skills and is a sustainable form of transport. Data analysed were from surveys with validated scales, translated and adapted for Chinese speaking Hong Kong adolescents and their parents, and administered to 1,299 adolescent/parent dyads. Using hierarchical modelling, this study examined independent associations of socio-demographic, perceived environmental, social and psychological factors (in that order) with adolescent AT to/from school (ATS) and AT to other destinations in Hong Kong. Moderation by gender and age on perceived environmental and social factors and number of household vehicles on proximity to destinations with AT were also estimated. The adolescents participating in ATS (58%), averaged 7.93 trips and 139.79 min per week. Adolescents averaged 7.68 trips/week to destinations other than school. Perceived proximity of school to home and social support for PA from peers were independently associated with higher odds of engaging in ATS. Social support for PA from household adults was associated with lower odds of engaging in ATS, especially in older adolescents. Trip frequency in those who engaged in ATS was positively associated with perceived proximity of school, access to services and parental transport-related PA. Perceived proximity of school was negatively associated with weekly minutes of ATS. Gender modified the association between social support for PA from peers and ATS frequency, and that of perceived proximity to public transport from home with weekly minutes of ATS. Perceived environmental, social and psychological factors were independently associated with AT to destinations other than school. In conclusion, Hong Kong adolescents appear to have high frequencies of ATS and AT to other destinations than reported elsewhere. Social support from peers, parental AT and having schools and other destinations within walking distance from home may independently contribute to adolescents' AT.


Magneto-optical properties of one-dimensional orderly nanocorrugation made from magnetic quadrilayer films.
Magneto-optical (MO) Kerr effect and optical reflectance are investigated in the visible light region for one-dimensional orderly nanocorrugation of magnetic quadrilayer films. We find that the MO enhancement originates from the combined action between cavity effect and surface plasmon resonance. The coupling between surface plasmon polaritions and localized surface plasmons cannot only enhance the magnitude of Kerr angle, but also alter the sign of Kerr rotation. In addition, the MO properties on the nanocomposite films can be tuned by the thickness of the intermediate HfO2 layer due to the cavity effect in multilayer.


Recognition of transition metal ions by peptides. Identification of specific metal-binding peptides in proteolytic digest maps by UV laser desorption time-of-flight mass spectrometry.
Metal-binding peptides in proteolytic digest maps have been identified by matrix-assisted UV laser desorption time-of-flight mass spectrometry (LDTOF-MS). The plasma and milk metal transport protein chosen to demonstrate this process, histidine-rich glycoprotein (HRG), was purified and then digested with trypsin; the cleavage products were analyzed by LDTOF-MS with dihydroxybenzoic acid as the matrix. The selective interaction of specific peptides with one or more Cu atoms was observed when Cu(II) ions were added to the digest mixture. At least one specific metal-binding peptide was identified by computerized sequence analysis using the molecular mass data and available cDNA sequence. These results demonstrate the first direct observation by mass spectrometry of differential peptide-metal ion interactions in protein digest maps. The ability to evaluate peptide-metal ion interactions, including stoichiometry, with less than 1 pmol of sample improves significantly our ability to identify metal binding domains in metal-binding proteins.


Transgenic insertion of the cyanobacterial membrane protein ictB increases grain yield in Zea mays through increased photosynthesis and carbohydrate production.
The C4 crop maize (Zea mays) is the most widely grown cereal crop worldwide and is an essential feedstock for food and bioenergy. Improving maize yield is important to achieve food security and agricultural sustainability in the 21st century. One potential means to improve crop productivity is to enhance photosynthesis. ictB, a membrane protein that is highly conserved across cyanobacteria, has been shown to improve photosynthesis, and often biomass, when introduced into diverse C3 plant species. Here, ictB from Synechococcus sp. strain PCC 7942 was inserted into maize using Agrobacterium-mediated transformation. In three controlled-environment experiments, ictB insertion increased leaf starch and sucrose content by up to 25% relative to controls. Experimental field trials in four growing seasons, spanning the Midwestern United States (Summers 2018 & 2019) and Argentina (Winter 2018 & 2019), showed an average of 3.49% grain yield improvement, by as much as 5.4% in a given season and up to 9.4% at certain trial locations. A subset of field trial locations was used to test for modification of ear traits and ФPSII, a proxy for photosynthesis. Results suggested that yield gain in transgenics could be associated with increased ФPSII, and the production of longer, thinner ears with more kernels. ictB localized primarily to the microsome fraction of leaf bundle-sheath cells, but not to chloroplasts. Extramembrane domains of ictB interacted in vitro with proteins involved in photosynthesis and carbohydrate metabolism. To our knowledge, this is the first published evidence of ictB insertion into a species using C4 photosynthesis and the largest-scale demonstration of grain yield enhancement from ictB insertion in planta. Results show that ictB is a valuable yield gene in the economically important crop maize, and are an important proof of concept that transgenic manipulation of photosynthesis can be used to create economically viable crop improvement traits.


Microangiopathic Hemolytic Anemia Due to Malignancy in Pregnancy.
Microangiopathic disorders during pregnancy remain a diagnostic challenge because these conditions often imitate more common obstetric diseases. A 31-year-old multigravid woman delivered at term with a postpartum course complicated by laboratory indices consistent with hemolysis, elevated liver enzymes, and low platelet count syndrome. After clinical recovery, she was readmitted 2 weeks after delivery with presumptive pyelonephritis. Persistent hemolysis and worsening thrombocytopenia suggested a diagnosis of thrombotic microangiopathy, which did not respond to plasma exchange. Directed bone biopsy revealed metastatic signet ring cell adenocarcinoma. Microangiopathic hemolytic anemia is rarely the initial clinical manifestation of malignancy. Given the similar features of several common obstetric complications, additional diagnostic measures may be necessary to refine the diagnosis in cases unresponsive to standard obstetric management.


Lower limb lymphedema: experiences and perceptions of cancer patients in the late palliative stage.
Lower limb lymphedema (LLL) is a common but neglected problem in palliative cancer patients. No studies have focused on these patients' experiences of lymphedema. The aims of this study were to explore patients' experiences regarding LLL and how they manage to deal with this in the late palliative stage. Thirteen patients with cancer-related LLL were included to satisfy a maximum variation sampling strategy. Interviews were analyzed using a qualitative phenomenographic method. LLL influenced the patients' thoughts about the future. Body image was often strongly influenced. Interactions with other persons were perceived as both positive and negative, and a range of coping strategies were expressed. LLL can exert a considerable influence on the physical experiences and the psychosocial situation of cancer patients in palliative care. Areas in need of increased education, attention, and further research are highlighted.


Human cytomegalovirus IE1 protein disrupts interleukin-6 signaling by sequestering STAT3 in the nucleus.
In the canonical STAT3 signaling pathway, binding of agonist to receptors activates Janus kinases that phosphorylate cytoplasmic STAT3 at tyrosine 705 (Y705). Phosphorylated STAT3 dimers accumulate in the nucleus and drive the expression of genes involved in inflammation, angiogenesis, invasion, and proliferation. Here, we demonstrate that human cytomegalovirus (HCMV) infection rapidly promotes nuclear localization of STAT3 in the absence of robust phosphorylation at Y705. Furthermore, infection disrupts interleukin-6 (IL-6)-induced phosphorylation of STAT3 and expression of a subset of IL-6-induced STAT3-regulated genes, including SOCS3. We show that the HCMV 72-kDa immediate-early 1 (IE1) protein associates with STAT3 and is necessary to localize STAT3 to the nucleus during infection. Furthermore, expression of IE1 is sufficient to disrupt IL-6-induced phosphorylation of STAT3, binding of STAT3 to the SOCS3 promoter, and SOCS3 gene expression. Finally, inhibition of STAT3 nuclear localization or STAT3 expression during infection is linked to diminished HCMV genome replication. Viral gene expression is also disrupted, with the greatest impact seen following viral DNA synthesis. Our study identifies IE1 as a new regulator of STAT3 intracellular localization and IL-6 signaling and points to an unanticipated role of STAT3 in HCMV infection.


Translational coregulation of 5'TOP mRNAs by TIA-1 and TIAR.
The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post-transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 5'-terminal oligopyrimidine tracts (5'TOP). However, the responsible trans-factors and the mechanism by which they coregulate 5'TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 5'TOP mRNA regulation, which upon amino acid starvation assemble onto the 5' end of 5'TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 5'TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5'TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment.


Transformation of immortalized woodchuck hepatic cell lines with the c-Ha-ras proto-oncogene.
Woodchuck hepatocytes were immortalized with the simian virus 40 T antigen (SV40 T-ag) oncogene and utilized in an oncogenic transformation assay. Transfection of these cell lines with an activated C-Ha-ras oncogene (EJ6.6) resulted in the transformation of cells to a phenotype characterized by anchorage-independent growth in soft agar. Colonies of transformed cells were subcloned and up to 80% were positive for oncoprotein expression detected by immunoblot and Northern blot procedures. When compared with the parental cell lines, ras-transformed derivatives were altered both morphologically and in growth rate. The tumorigenic potential of c-Ha-ras transformed cells was demonstrated in severe combined immunodeficient (SCID) mice. There was a latency period of 1 to 4 weeks before tumors were detectable and a period of 7 weeks was required for tumors to reach a diameter of 1 cm. Histologically, tumors derived from cell lines fully transformed by the SV40 T-ag had the appearance of well-differentiated hepatocellular carcinoma (HCC) while tumors derived from c-Ha-ras transformed cell lines had the appearance of poorly differentiated HCC. The capacity to induce oncogenic transformation events in immortalized woodchuck hepatic cell lines should provide the opportunity to study the cooperative effects of hepadnaviral genes in hepatocarcinogenesis in vitro.


How does Conditional Regard Impact Well-being and Eagerness to Learn? An Experimental Study.
Conditional regard refers to regard dependent upon the receiver's fulfillment of certain expectations. Using an experimental design, we examined the effect of conditional negative and positive regard on well-being and eagerness to learn in university freshmen (N = 131). Participants experienced either failure or success followed by conditional vs. unconditional regard. As expected, success and failure had opposite effects on well-being and eagerness to learn. More importantly, there was an increase in positive affect following success in the context of conditional regard, but not in the context of unconditional regard. Additionally, the decrease in positive affect following failure was more pronounced when accompanied by conditional as compared to unconditional regard. Conditional regard thus magnified the impact of success versus failure on students' emotional experiences.


Haemoglobin A1c is a predictor of COVID-19 severity in patients with diabetes.
Poor outcomes of coronavirus disease 2019 (COVID-19) have been linked to diabetes, but its relation to pre-infection glycaemic control is still unclear. To address this question, we report here the association between pre-infection Haemoglobin A1c (HbA1c) levels and COVID-19 severity as assessed by need for hospitalization in a cohort of 2068 patients with diabetes tested for COVID-19 in Leumit Health Services (LHSs), Israel, between 1 February and 30 April 2020. Using the LHS-integrated electronic medical records system, we were able to collect a large amount of clinical information including age, sex, socio-economic status, weight, height, body mass index, HbA1c, prior diagnosis of ischaemic heart disease, depression/anxiety, schizophrenia, dementia, hypertension, cerebrovascular accident, congestive heart failure, smoking, and chronic lung disease. Of the patients included in the cohort, 183 (8.85%) were diagnosed with COVID-19 and 46 were admitted to hospital. More hospitalized patients were female, came from higher socio-economic background and had a higher baseline HbA1c. A prior diagnosis of cerebrovascular accident and chronic lung disease conferred an increased risk of hospitalization but not obesity or smoking status. In a multivariate analysis, controlling for multiple prior clinical conditions, the only parameter associated with a significantly increased risk for hospitalization was HbA1c ≥ 9%. Using pre-infection glycaemic control data, we identify HbA1c as a clear predictor of COVID-19 severity. Pre-infection risk stratification is crucial to successfully manage this disease, efficiently allocate resources, and minimize the economic and social burden associated with an undiscriminating approach.


Focussed extracorporeal pyrotherapy: experimental results.
A new device made of piezoelectric ceramic placed in a semispherical dish and focussed at 320 mm was developed in order to generate heat and cavitation responsible for coagulative necrosis of deep tissues. The target to be treated is located with a central ultrasound probe of 3.5 MHz. In vitro studies with polyurethane phantoms showed that the ultrasound melted a surface of 2 x 12 mm within 1 s. The temperature recorded at the focus was 270 degrees C. In tissue samples (prostate cancer and benign prostate hyperplasia), the temperature rose to 85 degrees C in vitro and a hyperechoic zone appeared at the focus during shots. In vivo 8-mm plastic spheres, introduced surgically into the bladder of pigs, were melted by repeat shots without burning of crossed tissues. These studies were performed in the kidney and the liver. Autopsy performed on day 0 showed congestion, autopsy performed between day 6 and day 11 showed necrosis, whereas at 3 months the focussed area was fibrosed. This technique, which we called 'focussed extracorporeal pyrotherapy', combines phenomena of cavitation and high heat at the focus. Prostate tumors, bladder tumors, kidney tumors and liver metastases are potential indications for pyrotherapy.


Medical Emergencies During the COVID-19 Pandemic.
In this study, we investigate the number of emergency room consultations during the COVID-19 pandemic of 2020 in Germany compared to figures from the previous year. Case numbers from calendar weeks 1 through 22 of the two consecutive years 2019 and 2020 were obtained from 29 university hospitals and 7 non-university hospitals in Germany. Information was also obtained on the patients' age, sex, and urgency, along with the type of case (outpatient/inpatient), admitting ward, and a small number of tracer diagnoses (I21, myocardial infarction; J44, COPD; and I61, I63, I64, G45, stroke /TIA), as well as on the number of COVID-19 cases and of tests performed for SARS-CoV-2, as a measure of the number of cases in which COVID-19 was suspected or at least included in the differential diagnoses. A total of 1 022 007 emergency room consultations were analyzed, of which 546 940 took place in 2019 and 475 067 in 2020. The number of consultations with a positive test for the COVID-19 pathogen was 3122. The total number of emergency room consultations in the observation period was 13% lower in 2020 than in 2019, with a maximum drop by 38% coinciding with the highest number of COVID-19 cases (calendar week 14; 572 cases). After the initiation of interpersonal contact restrictions in 2020, there was a marked drop in COVID-19 case numbers, by a mean of -240 cases per week per emergency room (95% confidence interval [-284; -128]). There was a rise in case numbers thereafter, by a mean of 17 patients per week [14; 19], and the number of cases of myocardial infarction returned fully to the level seen in 2019. In Germany, the COVID-19 pandemic led to a significant drop in medical emergencies of all kinds presenting to the nation's emergency departments. A recovery effect began to be seen as early as calendar week 15, but the levels seen in 2019 were not yet reached overall by calendar week 22; only the prevalence of myocardial infarction had renormalized by then. The reasons for this require further investigation.


Gold-catalyzed reactions between alkenyldiazo carbonyl species and acetals.
In the presence of catalyst IPrAuSbF6 catalyst (IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene), alkenyldiazo carbonyl species react with organic acetals to give E-configured alkyl 3,5-dimethoxy-5-pent-2-enoates stereoselectively. This reaction sequence comprises an initial Prins-type reaction, followed by gold carbene formation.


Blood issues update: minimizing the risk of transfusion-associated HIV infection. American Hospital Association Technical Advisory Task Force on Blood Resources.
In March 1987, the Centers for Disease Control (CDC) (Atlanta), identified individuals who received multiple transfusions collected in high risk areas before April 1985 (when a blood screening test became available) as a group at risk for acquired immunodeficiency syndrome (AIDS). The exact number of individuals in this risk group is unknown but thought to be small. Nevertheless, this problem has attracted the attention of the President's Commission on the HIV Epidemic which, in its final report, issued June 24, 1988, recommended notification of every patient who received a blood transfusion since 1977 of their potential exposure to human immunodeficiency virus (HIV). The White House response to the report appeared to support the recommendation, as did the subsequently dropped William Dannemeyer amendment to the Waxman AIDS Testing/Confidentially Bill (HR 4757). In addition, some hospitals in high risk areas implemented such programs on their own initiative. To date there is no regulatory requirement for hospitals to notify past blood recipients. Unknowing transmission of pre-HIV test transfusion-related AIDS is a public health issue that in most cases is best assessed and resolved on an individual basis by patients and their physicians. The purpose of this communication is to inform hospitals about the existence of the risk group, to provide historical perspective on the issue, and to suggest ways in which hospitals can cooperate with and support medical staff in routinizing protection of this risk group and their contacts.


LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.
A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 μg/mL in plasma and 0.05-300.00 μg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.


A distributed cerebellar-inspired learning model for robotic arm control.
The cerebellum plays a big role in motor control and motor coordination in mammals, especially for limbs control. Therefore, many cerebellar models were proposed to be applied in the field of robotic arm control. However, some problems exist in the current cerebellar modeling approach, such as lack of the expression of bio-characteristics, limited learning ability et al. Therefore, a distributed cerebellar-inspired learning model was proposed to mimic the physiology and anatomy features of the cerebellum. Meanwhile, this model could learn to adjust the motor command according to the error information provided by the inferior olive to achieve control goal. To test the performance of the cerebellar model, a robotic arm control system was implemented. The results showed that our model was able to complete the robotic arm control tasks successfully.


[Lifestyle-related hip fracture risk].
Proximal femoral fracture (PFF) has long become a target for intervention with pharmacologic agents and pharmacologic intervention has been shown to reduce the fracture risk at least by half, compared to placebo, but PFF still continues to increase in incidence. Causes of fracture include bone-related and other factors but data remains yet to be accumulated on the relationship between these causes and lifestyle-related factors, such as nutrition, exercise and lifestyle preferences, which should be essential to establishing osteoporosis as a lifestyle-related disease. Furthermore, despite the paucity of evidence on the relationship between PFF and lifestyle habits, consideration should be given to developing preventive measures against PFF which take into account the potential impact of lifestyle-related factors on the occurrence of PFF to produce positive results.


The Utility of a Point-of-Care Transcranial Doppler Ultrasound Management Algorithm on Outcomes in Pediatric Asphyxial Out-of-Hospital Cardiac Arrest - An Exploratory Investigation.
Transcranial Doppler ultrasound is a sensitive, real time tool used for monitoring cerebral blood flow; it could provide additional information for cerebral perfusion in cerebral resuscitation during post cardiac arrest care. The aim of the current study was to evaluate the utility of a point-of-care transcranial Doppler ultrasound management algorithm on outcomes in pediatric asphyxial out-of-hospital cardiac arrest. This retrospective cohort study was conducted in two tertiary pediatric intensive care units between January 2013 and June 2018. All children between 1 month and 18 years of age with asphyxial out-of-hospital cardiac arrest and a history of at least 3 min of chest compressions, who were treated with therapeutic hypothermia and survived for 12 h or more after the return of circulation were eligible for inclusion. Twenty-one patients met the eligibility criteria for the study. Sixteen (76.2%) of the 21 children were male, and the mean age was 2.8 ± 4.1 years. Seven (33.3%) of the children had underlying disorders. The overall 1-month survival rate was 52.4%. Twelve (57.1%) of the children received point-of-care transcranial Doppler ultrasound. The 1-month survival rate was significantly higher (p = 0.03) in the point-of-care transcranial Doppler ultrasound group (9/12, 75%) than in the non-point-of-care transcranial Doppler ultrasound group (2/9, 22.2%). Point-of-care transcranial Doppler ultrasound group was associated with a significantly better 1-month survival rate compared with no point-of-care transcranial Doppler ultrasound group in pediatric asphyxial out-of-hospital cardiac arrest.


Psychometric properties of a Spanish version of the UPPS-P impulsive behavior scale: reliability, validity and association with trait and cognitive impulsivity.
Impulsivity is a multifaceted construct central to several forms of psychopathology. Recently, Lynam, Smith, Whiteside, and Cyders (2006) developed the UPPS-P scale, a multidimensional inventory that assesses 5 personality pathways contributing to impulsive behavior: negative urgency, lack of perseverance, lack of premeditation, sensation seeking, and positive urgency. In this study, we aimed (a) to analyze the psychometric properties of a Spanish version of the UPPS-P scale and (b) to explore the relationship between the different dimensions of the UPPS-P scale and conceptually related constructs including trait measures derived from different models of impulsive personality (the Gray's [1987] and Plutchik's [1984] models) and a state measure of cognitive impulsivity, the Delay-Discounting Test (Kirby, Petry, & Bickel, 1999). We administered the UPPS-P scale along with the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001), the Plutchik Impulsivity Scale (Plutchik & Van Praag, 1989), and the Delay-Discounting Test to a sample of 150 undergraduate students. Results showed that the Spanish adaptation of the UPPS-P scale have appropriate psychometric properties. Different dimensions of the UPPS-P were differentially associated with predicted conceptually related constructs. We conclude that the Spanish adaptation of the UPPS-P scale is a useful instrument for fine-grained assessment of impulsivity in Spanish-speaking adult population.


[Diagnosis of small peripheral lung cancers using spiral computed tomography lung cancer screening].
Small peripheral lung cancers can be detected by spiral or helical computed tomography (CT). We applied mobile spiral CT as the first step in further examination (or secondary screening) for lung cancer. We detected 86 lung cancers per 100,000 persons without spiral CT, and 102 patients with spiral CT. Using the latter method, the resection rate and the rate of early-stage lung cancer increased significantly from 48.6% to 67.3% (p < 0.01) and from 21.1% to 35.1% (p < 0.05), respectively. Good results were obtained with mobile CT, especially in women. The mean tumor size of lung cancer detectable with CT was 7 mm smaller than that detected by the previous method. The mean tumor size was only less than 20 mm in females. Overall 787 lung cancers per 100,000 persons were detected using spiral CT for primary screening (1,039 lung cancers/100,000 in men). We must investigate whether the new CT screening system for lung cancer really leads to a lower mortality rate compared with the previous methods. When small nodular lesions with ground-glass opacity could not be diagnosed, the subsequent period up to 10 months can be used to obtain a final diagnosis, regardless of their malignancy. This paper reports specific findings of small peripheral lung cancers, and review the methods of diagnosis for small-sized tumors.


A study on the experimental envenomation in mice with the venom of Tityus trivitattus Kraepelin 1898 (Scorpiones, Buthidae) captured in Argentina.
Although Tityus trivitattus is the only scorpion species reported to cause severe human envenomation in Argentina, no previous studies on its venom have been done. Telson homogenates from T. trivitattus specimens collected in Santiago del Estero, Cordoba, and Buenos Aires were employed to study their protein composition and toxicity to mice. Regardless of the site of collection, electrophoretic analysis showed bands at 205, 150, 100, 40, 32, and 13 kDa or smaller. FPLC gel filtration showed three major peaks and 6-8 minor peaks with similar elution volumes. One of the minor peaks from FPLC containing a component of approximately 8 kDa was lethal to mice. Mice injected intravenously with different doses of homogenates presented severe autonomic signs like tachypnea, tachycardia, sialorrhea, lacrimation, profuse sweating, diarrhea, dyspnea, and death. Pathology studies of lungs showed severe congestion of alveolar capillaries, pulmonary edema, and hemorrhagic areas. The kidneys showed glomerular as well as tubular lesions and exocrine glands showed areas of necrosis. The calculated LD50 was 0.38 +/- 0.08 telsons per 20 g mouse, which suggests a lethal potency similar to that of T. serrulatus venom. The lethal potency of 5.0 LD50 of T. trivitattus telson homogenate was neutralized by both an anti-T. trivitattus and a heterologous anti Tityus with ED50 values of 41 +/- 19 and 170 +/- 42 microl, respectively.


Float and compress: honeycomb-like array of a highly stable protein scaffold.
Organizing nano-objects, proteins in particular, on surfaces is one of the primary goals of bio/chemical nanotechnology. A highly stable protein scaffold (6His-SP1) was organized into a hexagonal 2D array by a new, versatile method. The protein was expelled from solution into the air/water interface and compressed in a Langmuir trough into a closely packed monolayer without the use of phospholipids or other surfactants at the interface. The 2D arrays formed at the air/water interface were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM).


Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons.
The basis for selective death of specific neuronal populations in neurodegenerative diseases remains unclear. Parkinson's disease (PD) is a synucleinopathy characterized by a preferential loss of dopaminergic neurons in the substantia nigra (SN), whereas neurons of the ventral tegmental area (VTA) are spared. Using intracellular patch electrochemistry to directly measure cytosolic dopamine (DA(cyt)) in cultured midbrain neurons, we confirm that elevated DA(cyt) and its metabolites are neurotoxic and that genetic and pharmacological interventions that decrease DA(cyt) provide neuroprotection. L-DOPA increased DA(cyt) in SN neurons to levels 2- to 3-fold higher than in VTA neurons, a response dependent on dihydropyridine-sensitive Ca2+ channels, resulting in greater susceptibility of SN neurons to L-DOPA-induced neurotoxicity. DA(cyt) was not altered by alpha-synuclein deletion, although dopaminergic neurons lacking alpha-synuclein were resistant to L-DOPA-induced cell death. Thus, an interaction between Ca2+, DA(cyt), and alpha-synuclein may underlie the susceptibility of SN neurons in PD, suggesting multiple therapeutic targets.


Incidence, clinical features, treatment and outcome of primary central nervous system lymphoma in Norway.
The incidence of primary central nervous system lymphoma (PCNSL) has been reported to increase in some parts of the world, while being stable in other regions. In an attempt to characterize the incidence rate, clinical features, treatment, outcome, and prognostic factors of PCNSL in Norway, we report our experience in a large unselected series of patients. Clinical features, histological diagnosis, radiological findings, treatment, and outcome of all patients diagnosed with PCNSL in Norway in the years 1989-1998 were registered. During the 10-year period 58 new cases of histologically verified PCNSL were registered in Norway. The annual incidence rate of PCNSL was on average 1.34 cases per million people with a non-significant increasing trend (p=0.069). For patients diagnosed before death (n=45) the estimated survival following histological diagnosis was 55%, 47%, and 23% at 1, 2, and 5 years, respectively. In Cox-regression analysis age, WHO performance status and treatment had independent prognostic impact on survival. In the studied decade, there was a non-significant trend towards increased incidence of PCNSL, perhaps due to increased availability of diagnostic imaging, especially magnetic resonance imaging.