Polyglycidol, Its Derivatives, and Polyglycidol-Containing Copolymers-Synthesis and Medical Applications.
Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a ⁻CH₂OH reactive side group in every structural unit. The hydroxyl groups in polyglycidol not only increase the hydrophilicity of this polymer but also allow for its modification, leading to polymers with carboxyl, amine, and vinyl groups, as well as to polymers with bonded aliphatic chains, sugar moieties, and covalently immobilized bioactive compounds in particular proteins. The paper describes the current state of knowledge on the synthesis of polyglycidols with various topology (linear, branched, and star-like) and with various molar masses. We provide information on polyglycidol-rich surfaces with protein-repelling properties. We also describe methods for the synthesis of polyglycidol-containing copolymers and the preparation of nano- and microparticles that could be derived from these copolymers. The paper summarizes recent advances in the application of polyglycidol and polyglycidol-containing polymers as drug carriers, reagents for diagnostic systems, and elements of biosensors.


Comparison of Vital Statistics Definitions of Suicide against a Coroner Reference Standard: A Population-Based Linkage Study.
We sought to determine the utility of health administrative databases for population-based suicide surveillance, as these data are generally more accessible and more integrated with other data sources compared to coroners' records. In this retrospective validation study, we identified all coroner-confirmed suicides between 2003 and 2012 in Ontario residents aged 21 and over and linked this information to Statistics Canada's vital statistics data set. We examined the overlap between the underlying cause of death field and secondary causes of death using ICD-9 and ICD-10 codes for deliberate self-harm (i.e., suicide) and examined the sociodemographic and clinical characteristics of misclassified records. Among 10,153 linked deaths, there was a very high degree of overlap between records coded as deliberate self-harm in the vital statistics data set and coroner-confirmed suicides using both ICD-9 and ICD-10 definitions (96.88% and 96.84% sensitivity, respectively). This alignment steadily increased throughout the study period (from 95.9% to 98.8%). Other vital statistics diagnoses in primary fields included uncategorised signs and symptoms. Vital statistics records that were misclassified did not differ from valid records in terms of sociodemographic characteristics but were more likely to have had an unspecified place of injury on the death certificate ( P < 0.001), more likely to have died at a health care facility ( P < 0.001), to have had an autopsy ( P = 0.002), and to have been admitted to a psychiatric hospital in the year preceding death ( P = 0.03). A high degree of concordance between vital statistics and coroner classification of suicide deaths suggests that health administrative data can reliably be used to identify suicide deaths.


[Rehabilitative therapy after removal of parasagittal meningiomas].
A complex of restorative treatment measures applied for promoting the process of motor function restoration in patients who underwent removal of parasagittal meningiomas includes drug therapy, physiotherapy, and therapeutic exercises. The lapse of time after the operation and the specific features of the motor defect must be taken into account. The suggested complex was used in 87 patients. Motor activity was restored in 23 patients completely and to a satisfactory degree in 49 patients. The causes of poor outcomes are analysed. Optimum rehabilitation of neurosurgical patients can be achieved only with complex and stage-by-stage restorative treatment.


Case Report: Repeated Intralesional Injections of Autologous Mesenchymal Stem Cells Combined With Platelet-Rich Plasma for Superficial Digital Flexor Tendon Healing in a Show Jumping Horse.
In the present case report a show jumping 10-year-old Sella Italiano gelding, presented with severe lameness, swelling and pain at palpation of the mid-metacarpal region of the left forelimb. Clinical and ultrasound examination diagnosed a chronic tendonitis of the central region of the superficial digital flexor tendon (SDFT). The lesion was a reoccurrence since it developed from a previously healed injury. The horse had to stop competing and was unresponsive to gold-standard treatments as Non-steroidal anti-inflammatory drugs (NSAIDs) and conservative management after 6 months of therapy. The animal was subjected to repeated intralesional injections of autologous adipose-derived mesenchymal stem cells (AD-MSCs) combined with autologous platelet-rich plasma (PRP). The combined treatment was administered twice in a 1-month interval. The healing process was assessed through clinical examination, ultrasound imaging and quantification of oxidative stress products and inflammatory mediators in blood plasma. After 2 weeks from first injection, a reduction of concentration of oxidative-derived products was observed, together with an increase of anti-inflammatory cytokines and pro-mitotic growth factors. These results were reflected clinically as the horse showed a reduction of lameness along with swelling and pain after 4 weeks. At the 1-year follow-up, the horse showed no signs of lameness and swelling. The ultrasonographic examination highlighted a compact fiber alignment with a normal echogenic tendon as observed in the sound contralateral limb. Moreover, the horse went back to the previous level of competition. Our results suggest the positive effects of a repeated intralesional injection of AD-MSCs and PRP for the treatment of a chronic tendonitis with long-term effects and an improvement for both equine quality of life and athletic performance.


Enhanced intelligent driver model to access the impact of driving strategies on traffic capacity.
With an increasing number of vehicles equipped with adaptive cruise control (ACC), the impact of such vehicles on the collective dynamics of traffic flow becomes relevant. By means of simulation, we investigate the influence of variable percentages of ACC vehicles on traffic flow characteristics. For simulating the ACC vehicles, we propose a new car-following model that also serves as the basis of an ACC implementation in real cars. The model is based on the intelligent driver model (IDM) and inherits its intuitive behavioural parameters: desired velocity, acceleration, comfortable deceleration and desired minimum time headway. It eliminates, however, the sometimes unrealistic behaviour of the IDM in cut-in situations with ensuing small gaps that regularly are caused by lane changes of other vehicles in dense or congested traffic. We simulate the influence of different ACC strategies on the maximum capacity before breakdown and the (dynamic) bottleneck capacity after breakdown. With a suitable strategy, we find sensitivities of the order of 0.3, i.e. 1 per cent more ACC vehicles will lead to an increase in the capacities by about 0.3 per cent. This sensitivity multiplies when considering travel times at actual breakdowns.


A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s.
N-nitrosamines are a well-established group of environmental carcinogens, which require cytochrome P450 oxidation to exhibit activity. The accepted mechanism of metabolic activation involves formation of α-hydroxynitrosamines that spontaneously decompose to DNA alkylating agents. Accumulation of DNA damage and the resulting mutations can ultimately lead to cancer. New evidence indicates that α-hydroxynitrosamines can be further oxidized to nitrosamides processively by cytochrome P450s. Because nitrosamides are generally more stable than α-hydroxynitrosamines and can also alkylate DNA, nitrosamides may play a role in carcinogenesis. In this report, we describe a general protocol for evaluating nitrosamide production from in vitro cytochrome P450-catalyzed metabolism of nitrosamines. This protocol utilizes a general approach to the synthesis of the relevant nitrosamides and an in vitro cytochrome P450 metabolism assay using liquid chromatography-nanospray ionization-high resolution tandem mass spectrometry for detection. This method detected N'-nitrosonorcotinine as a minor metabolite of N'-nitrosonornicotine in the example study. The method has high sensitivity and selectively due to accurate mass detection. Application of this method to a wide variety of nitrosamine-cytochrome P450 systems will help determine the generality of this transformation. Because cytochrome P450s are polymorphic and vary in activity, a better understanding of nitrosamide formation could aid in individual cancer risk assessment.


Education, survival and avoidable deaths in cancer patients in Finland.
Relative survival after cancer in Finland is at the highest level observed in Europe and has, in general, been on a steady increase. The aim of this study is to assess whether the high survival is equally shared by different population subgroups and to estimate the possible gains that might be achieved if equity prevailed. The educational level and occupation before the cancer diagnosis of patients diagnosed in Finland in 1971-2005 was derived from an antecedent population census. The cancers were divided into 27 site categories. Cancer (cause)-specific 5-year survival proportions were calculated for three patient categories based on the educational level and for an occupational group of potentially health-conscious patients (physicians, nurses, teachers etc.). Proportions of avoidable deaths were derived by assuming that the patients from the two lower education categories would have the same mortality owing to cancer, as those from the highest educational category. Estimates were also made by additionally assuming that even the mortalities owing to other causes of death were all equal to those in the highest category. For almost all the sites considered, survival was consistently highest for patients with the highest education and lowest for those with only basic education. The potentially health-conscious patients had an even higher survival. The differences were, in part, attributable to less favourable distributions of tumour stages in the lower education categories. In 1996-2005, 4-7% of the deaths in Finnish cancer patients could have potentially been avoided during the first 5-year period after diagnosis, if all the patients had the same cancer mortality as the patients with the highest educational background. The proportion would have also been much higher, 8-11%, if, in addition, the mortality from other causes had been the same as that in the highest educational category. Even in a potentially equitable society with high health care standards, marked inequalities persist in cancer survival. Earlier cancer diagnosis and the ability to cope within the health care system may be a partly relevant explanation, but personal habits and lifestyles also have a role, particularly for the cancer patients' mortality from other causes of death than cancer.


Antioxidant enzymes in renal cell carcinoma.
The aim of the study was to estimate the significance of oxidative/nitrosative damage and expression of antioxidant enzymes in renal cell carcinomas (RCC). For this we investigated immunohistochemically six antioxidant enzymes (AOEs) including MnSOD, ECSOD, thioredoxin, thioredoxin reductase, and gammaglutamyl cysteine synthetase heavy and light chain in 138 RCCs. As an indicator of oxidative/nitrosative damage, sections were stained with an antibody to nitrotyrosine. The extent of apoptosis was evaluated by TUNEL method and proliferation by immunohistochemistry to Ki67. Variable expression of all AOEs could be seen in RCC with expression of MnSOD being strongest. Nitrotyrosine was significantly associated with high grade tumors. MnSOD was associated with tumors of a lower stage. Cases showing ECSOD reactivity had higher and cases expressing thioredoxin lower apoptotic index than other tumors. No association with patient prognosis was observed. According to the results renal cell carcinomas show oxidative/nitrosative damage which, according to nitrotyrosine staining, was higher in high grade tumors. Of AOEs, MnSOD was more abundantly expressed in low stage tumors suggesting that its antioxidant function could play a main role to prevent development of oxidative damage leading to more aggressive tumors.


Bioavailability and the mechanisms of intestinal absorption of iron from ferrous ascorbate and ferric polymaltose in experimental animals.
The comparative bioavailability from matching quantities of iron in the form of ferrous ascorbate or ferric polymaltose was defined in rats. Studies were carried out in the intact animals under basal conditions and also when requirements for this metal were either increased or decreased by manipulating stores or erythropoietic activity. No significant difference was found in the total quantity of iron absorbed from either salt or complex under any of these circumstances, suggesting that the mucosal mechanism regulating the overall process was common to both. However, the rate of transfer from the lumen into portal blood was distinctive, reaching a maximum with salt at 30 min compared to 24 h for the complex. To explore the possibility that iron from the two sources was initially handled by different subcellular pathways, the radiolabeled compounds were instilled into loops of bowel that had been isolated between ligatures in vivo. Enterocytes were harvested and fractionated, and incorporation into ferritin and transferrin was determined using RIA. From salt, iron appeared rapidly in duodenal but not ileal ferritin, whereas mucosal transferrin increased under conditions of stimulated absorption, suggesting that this protein may act as a shuttle for the metal. In contrast, iron from polymaltose showed a cumulative incorporation into duodenal ferritin over time that correlated with iron absorption, defined by the appearance of radiolabel in the serum and in the carcass; a similar pattern was demonstrable in ileal mucosal cells. Conversely, binding of iron to transferrin was minimal. No iron polymaltose was found within the mucosal cells. It is suggested that the low rate of iron transfer from this ferric complex may reflect its extracellular breakdown in the lumen of the gastrointestinal tract.


Case Report: Community-Acquired Legionella gormanii Pneumonia in an Immunocompetent Patient Detected by Metagenomic Next-Generation Sequencing.
Legionella spp. has been well-recognized as an important cause of community-acquired pneumonia. Current community-acquired pneumonia guidelines recommended covering the treatment of Legionella because of the high mortality associated with inadequate antibiotic treatments. However, the symptom of Legionella pneumonia is non-specific, and routine diagnostic tests exhibit low sensitivity for Legionella spp., especially for non-Legionella pneumophila serogroup 1 strains. We report a 53-year-old man without underlying diseases admitted to respiratory intensive care unit because of severe community-acquired pneumonia and respiratory failure. Although, the results of routine culture of bronchoalveolar lavage fluid and the Legionella urinary antigen test were all negative, metagenomic next-generation sequencing (mNGS) identified a great amount of DNA and RNA sequences of Legionella gormanii in bronchoalveolar lavage fluid while negative in blood sample. The presence of Legionella gormanii in bronchoalveolar lavage fluid was further confirmed by polymerase-chain-reaction and Sanger sequencing. Legionella gormanii has rarely been reported in patients with community-acquired pneumonia mainly due to lack of diagnostic test for non-Legionella pneumophila serogroup 1 strains. This is the first report of Legionella gormanii pneumonia in an immunocompetent patient detected by mNGS, which indicates that mNGS is a high-resolution and sensitive assay for the diagnosis and surveillance of Legionella infection.


New World Orders: Continuities and Changes in Latin American Migration.
Although migration from Mexico to the United States is more than a century old, until recently most other countries in Latin America did not send out significant numbers of migrants to foreign destinations. Over the past thirty years, however, emigration has emerged as an important demographic force throughout the region. This article outlines trends in the volume and composition of the migrant outflows emanating from various countries in Latin America, highlighting their diversity with respect to country of destination; multiplicity of destinations; legal auspices of entry; gender and class composition; racial, ethnic, and national origins; and the mode of insertion into the receiving society. The review underscores the broadening of international migration away from unidirectional flows toward the United States to new streams going to Europe, Canada, Australia, and Japan, as well as to other countries in Latin America itself.


Self-Powered Filterless On-Chip Full-Stokes Polarimeter.
The detection of polarization states of light is essential in photonic and optoelectronic devices. Currently, the polarimeters are usually constructed with the help of waveplates or a comprehensive metasurface, which will inevitably increase the fabrication complexity and unnecessary energy loss. Here, we have successfully demonstrated a self-powered filterless on-chip full-Stokes polarimeter based on a single-layer MoS2/few-layer MoS2 homojunction. Combining the built-in electric field enhanced circular photogalvanic effect with the intrinsic optical anisotropy of MoS2 between in-plane and out-of-plane directions, the device is able to conveniently sense four Stokes parameters of incident light at zero bias without requiring an extra filtering layer and can function in the wavelength range of 650-690 nm with acceptable average errors. Besides, this homojunction device is easy to integrate with silicon-based chips and could have much smaller sizes than metasurface based polarimeters. Our study thus provides an excellent paradigm for high-performance on-chip filterless polarimeters.


Development of a class-specific immunochromatographic strip test for the rapid detection of organophosphorus pesticides with a thiophosphate group.
In recent decades, organophosphorus (OP) pesticides are widely used in agricultural and domestic fields. There is increasing demand for more rapid and economical methods of detecting pesticide residues. We have developed a gold immunochromatography assay (GICA) strip test for detecting a group of OP pesticides based on monoclonal antibodies (MAb) against a generic hapten, O,O-diethyl O-(4-carboxy-3-methylphenyl) phosphorothioate. The MAb showed desirable properties for use in indirect competitive ELISA, and the minimum IC50 value (93 ng/mL) was observed in chlorpyrifos-ethyl curve. The partially purified monoclonal antibodies were conjugated with colloidal gold particles. The conjugation of the colloidal gold and antibodies was monitored by ultraviolet-visible (UV-vis) spectroscopy and fluorescence spectroscopy, while the transmission electron microscopy (TEM) images were used to characterize the particle size and shape of the conjugates. Dynamic light scattering (DLC) was applied as a less expensive and faster method to substitute TEM. The colloidal gold and antibody conjugates were used for the production of a GICA strip test to detect OP pesticides. Preliminary assessment suggests that the OP pesticide, chlorpyrifos-ethyl (CE), in environmental samples could be detected by the GICA strip. This assay could potentially be used for screening large volume of samples and on-spot monitoring before the precise analysis. But the homogeneity of the detection needs to be improved further.


[[(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl) acetamide for imaging the sigma receptor status of tumors: comparison with [(18)F]FDG, and [(125)I]IUDR.
A series of biodistribution studies were conducted with the radiotracer, [(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl)acetamide, [(18)F]1 in nude mice bearing tumor xenografts of the mouse mammary adenocarcinoma, line 66. This radiotracer has a high affinity for both sigma(1) and sigma(2) receptors. In vivo studies were also conducted in order to assess the effect of blocking sigma(1) receptors on tumor uptake and the tumor:background ratio of this radiotracer. The results of these studies revealed that blocking the sigma(1) receptor so that only the sigma(2) receptors are labeled in vivo, results in a higher tumor:background ratio with only a small reduction in the tumor uptake of the radiotracer relative to the no-carrier-added (i.e., nonselective) conditions. Comparative in vivo studies were also conducted with the anatomic and metabolic imaging agent, [(18)F]FDG, and a radiolabeled DNA precursor, [(125)I]IUdR. Both of these radiolabeled compounds represent classes of agents that have been proposed for imaging the proliferative status of solid tumors. The results of these studies indicated that a sigma(2)-selective imaging agent may be, 1) a better anatomic imaging agent for breast cancer than [(18)F]FDG, and 2) a better functional imaging agent than the radiolabeled DNA precursors, [(123/124)I]IUdR and [(11)C]thymidine, for measuring the proliferative status of breast tumors with PET and SPECT. However, additional studies will be needed to compare sigma(2)-selective imaging agents with [(18)F]FLT in order to determine which is the more appropriate imaging agent for measuring the proliferative status of breast tumors with PET.


AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts.
Activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is indispensable for somatic hypermutation (SHM), class switch recombination, and gene conversion of immunoglobulin genes, which indicates a common molecular mechanism for these phenomena. Here we show that ectopic expression of AID alone can induce hypermutation in an artificial GFP substrate in NIH 3T3 murine fibroblast cells. The frequency of mutations was closely correlated with the level of transcription of the target gene, and the distribution of mutations in NIH 3T3 cells was similar to those of SHM in B lymphocytes. These results indicate that AID is sufficient for the generation of SHM in an actively transcribed gene in fibroblasts, as well as B cells, and that any of the required cofactors must be present in these fibroblasts.


A cytotoxic electronegative LDL subfraction is present in human plasma.
By using fast protein liquid chromatography, we isolated from human plasma a minor electronegative LDL subfraction designated LDL(-). After immunoaffinity chromatography against apolipoprotein (apo)(a) and apo A-I, LDL(-) represented 6.7 +/- 0.9% (mean +/- SD; n = 18) of total LDL. Compared with the major LDL subfraction, designated LDL(+), LDL(-) contained similar amounts of thiobarbituric acid-reactive substances, conjugated dienes, and vitamin E and had a similar lipid/protein ratio and mean density. Moreover, the apo B of LDL(-) was not aggregated and its LDL receptor-binding activity was slightly increased. These results were consistent with the nonoxidized nature of LDL(-). LDL(-) showed increased contents of sialic acid (38.1 +/- 5.2 versus 28.9 +/- 3.3 nmol/mg protein; n = 7; P < .01), apo C-III (1.43 +/- 0.21% versus 0.14 +/- 0.04%; n = 7; P < .01), and apo E (1.64 +/- 0.26% versus 0.10 +/- 0.05%; n = 7; P < .0005). Compared with LDL(+), LDL(-) displayed enhanced cytotoxic effects on cultured human umbilical vein endothelial cells, as shown by lactate dehydrogenase assay (P < .003; n = 6), neutral red uptake (P < .02; n = 6), and morphological studies. We also studied the relationship of LDL(-) to age and plasma lipid levels in 133 subjects. The percentage of contribution of LDL(-) to total plasma LDL correlated with age (P < .05), total cholesterol (P < .05), and LDL cholesterol (P < .003). In conclusion, this study shows that LDL(-), a circulating human plasma LDL, is an electronegative native LDL subfraction with cytotoxic effects on endothelial cells. This subfraction, which correlates positively with common atherosclerotic risk factors, might induce atherogenesis by actively contributing to alteration of the vascular endothelium.


Factors contributing to endobronchial intubation in neonates.
To assess neonatologists' practices, knowledge, and opinions regarding the prevention of endobronchial intubation. Anonymous survey. Program Directors of Neonatology Fellowship Programs in the United States, surveyed by mail, and neonatologists who volunteered to respond while attending the Vermont-Oxford Network Annual Meeting. None. Program directors (response rate 66%) and other practitioners contributed equally to the 132 survey responses, which were statistically indistinguishable between groups. Deep intubation frequency was estimated at greater than 5% by 39% of respondents, and 38% believed that it contributes to neonatal morbidity equally or more than medication errors. Quality assurance surveillance of intubations was uncommon. Neonatologists had remarkably varied responses when identifying the recommended vocal cord-level marking from a triple set of distal safety markings on a commonly used endotracheal tube; most had never seen recommendations or package insert directions for the use of such markings, and 86% desired improvements in endotracheal tube features to promote safer intubations. Neonatologists perceive endobronchial intubation as a consequential but underreported complication. Most are uncertain about the use of common vocal cord markings on endotracheal tubes, and few have seen specific instructions on this feature. We suggest that standardizing endotracheal tube safety features and making clear directions available to users may decrease the risk of endobronchial intubation in neonates.


Variations in labeling protocol influence incorporation, distribution and retention of iron oxide nanoparticles into human umbilical vein endothelial cells.
Various studies have shown that various cell types can be labeled with iron oxide particles and visualized by magnetic resonance imaging (MRI). However, reported protocols for cell labeling show a large variation in terms of labeling dose and incubation time. It is therefore not clear how different labeling protocols may influence labeling efficiency. Systematic assessment of the effects of various labeling protocols on labeling efficiency of human umbilical vein endothelial cells (HUVEC) using two different types of iron oxide nanoparticles, i.e. super paramagnetic iron oxide particles (SPIOs) and microparticles of iron oxide (MPIOs), demonstrated that probe concentration, incubation time and particle characteristics all influence the efficiency of label incorporation, label distribution, label retention and cell behavior. For SPIO the optimal labeling protocol consisted of a dose of 12.5 µg iron/2 ml/9.5 cm(2) and an incubation time of 24 h, resulting in an average iron load of 12.0 pg iron/per cell (uptake efficiency of 9.6%). At 4 h many SPIOs are seen sticking to the outside of the cell instead of being taken up by the cell. For MPIO optimal labeling was obtained with a dose of 50 µg iron/2 ml/9.5 cm(2). Incubation time was of less importance since most of the particles were already incorporated within 4 h with a 100% labeling efficiency, resulting in an intracellular iron load of 626 pg/cell. MPIO were taken up more efficiently than SPIO and were also better tolerated. HUVEC could be exposed to and contain higher amounts of iron without causing significant cell death, even though MPIO had a much more pronounced effect on cell appearance. Using optimal labeling conditions as found for HUVEC on other cell lines, we observed that different cell types react differently to identical labeling conditions. Consequently, for each cell type separately an optimal protocol has to be established.


[Corrigendum] Emerging roles of non‑coding RNAs in the response of rectal cancer to radiotherapy (Review).
Following the publication of the above review article, the authors have realized that they overlooked including the funding information in the Declarations section. Therefore, the following text should also have been included with the review: Funding: The present review was supported by the National Research Foundation of Korea grant funded by the Korean government (grant no. 2020R1F1A1061122) and Gachon University Research fund of 2018 (GCU-2018-0670) to SH. The authors regret their oversight, apologize to the funding bodies concerned, and regret any inconvenience caused. [the original article was published in International Journal of Oncology 58: 344‑358, 2021; DOI: 10.3892/ijo.2021.5175].


Residue of gutta-percha and a glass ionomer cement sealer following root canal retreatment.
A previous report indicates that root canals obturated with a new glass ionomer cement endodontic sealer (Ketac-Endo, Espe, Germany) and laterally condensed gutta-percha can be retreated by ultrasonic instrumentation. To address the possibility of Ketac-Endo being used without condensation of gutta-percha, the purpose of this study was to evaluate the efficacy of ultrasonic retreatment in canals obturated with single-cone gutta-percha and Ketac-Endo. Thirty root canals were prepared in a standardized way to ISO size 40 and obturated with gutta-percha and Ketac-Endo. Either a size 40 gutta-percha cone was used with and without lateral condensation, or a size 25 single cone, without condensation. After 14 days, the canals were retreated using chloroform and ultrasonic instrumentation. The roots were split vertically, and the amount of residual debris on the canal walls was assessed by three examiners using a dissecting microscope. Debris was recorded in the apical, middle and coronal canal levels according to a preset evaluation scale. The mean scores for each group were compared by ANOVA and Mann-Whitney U-test, with a 5% level of significance. In the roots obturated with lateral condensation the amounts of residual debris in the coronal and middle canal levels was lower than in the other two groups, whereas in the apical level it was higher. Statistically, only the differences in the apical level were significant (P < 0.03). It was concluded that ultrasonic retreatment may be performed effectively in root canals obturated with single-cone gutta-percha and Ketac-Endo.


Association between Physical Activity and Non-Alcoholic Fatty Liver Disease in Adults with Metabolic Syndrome: The FLIPAN Study.
Background: A lifestyle with regular PA (physical activity) and Mediterranean diet has benefits on NAFLD (non-alcoholic fatty liver disease) and MetS (metabolic syndrome). Objectives: To assess the association between physical activity and NAFLD in adults with MetS. Design: Cross-sectional study in 155 participants (40−60 years old) from Balearic Islands and Navarra (Spain) with diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 Kg/m2. Methods: PA level was categorized into two groups according to weekly METs (metabolic equivalents of tasks). PA was assessed using a validated Minnesota questionnaire and accelerometers. MetS parameters were assessed by blood collection analysis and NAFLD by abdominal MRI (magnetic resonance imaging). Results: Participants with high PA showed more energy expenditure and expended more calories than ingested (−143.9 Kcal/day; p < 0.001). PA was a risk factor for AST (aspartate aminotransferase) (adjusted OR: 7.26; 95% CI: 1.79−29.40) and a protective factor for ALT (alanine aminotransferase) (adjusted OR: 0.24; 95% CI: 0.12−0.48), GGT (gamma-glutamyl transferase) (adjusted OR: 0.52; 95% CI: 0.29−0.94) and IFC-NMR (intrahepatic fat content by nuclear magnetic resonance) (adjusted OR: 0.26; 95% CI: 0.12−0.56) when sociodemographic confounders were considered. Conclusions: NAFLD patients with high PA showed more positive relationship on MetS parameters and liver profile (ALT, GGT, IFC-NMR) than subjects with low PA, but not for AST. Difference between calories ingested and expended influenced this relationship.


Phylogenetic relationships of the Acanthocephala inferred from 18S ribosomal DNA sequences.
Phylogenetic relationships within the Acanthocephala have remained unresolved. Past systematic efforts have focused on creating classifications with little consideration of phylogenetic methods. The Acanthocephala are currently divided into three major taxonomic groups: Archiacanthocephala, Palaeacanthocephala, and Eoacanthocephala. These groups are characterized by structural features in addition to the taxonomy and habitat of hosts parasitized. In this study the phylogenetic relationships of 11 acanthocephalan species are examined with 18S rDNA sequences. Maximum parsimony, minimum evolution, and maximum likelihood methods are used to estimate phylogenetic relationships. Within the context of sampled taxa, all phylogenetic analyses are consistent with monophyly of the major taxonomic groups of the Acanthocephala, suggesting that the current higher order classification is natural. The molecular phylogeny is used to examine patterns of character evolution for various structural and ecological characteristics of the Acanthocephala. Arthropod intermediate host distributions, when mapped on the phylogeny, are consistent with monophyletic groups of acanthocephalans. Vertebrate definitive host distributions among the Acanthocephala display independent radiations into similar hosts. Levels of uncorrected sequence divergence among acanthocephalans are high; however, relative-rate tests indicate significant departure from rate uniformity among acanthocephalans, arthropods, and vertebrates. This precludes comparison of 18S divergence levels to assess the relative age of the Acanthocephala. However, other evidence suggests an ancient origin of the acanthocephalan-arthropod parasitic association.


Phase and rheological behavior of the hexadecyl(trimethyl)azanium; 2-hydroxybenzoate/water system.
The phase and rheological behavior of hexadecyl(trimethyl)azanium; 2-hydroxybenzoate (CTAS), and water as a function of surfactant concentration and temperature are investigated here. The critical micellization concentration (cmc(1)) and the concentration at which the structure of aggregates changes (cmc(2)) as well as the Krafft temperature (T(K)) are reported. A large micellar solution region exhibiting high viscosity, as well as hexagonal- and lamellar-phase regions were identified. In the dilute region, below the overlapping entanglement concentration (C*), the micellar solutions exhibit shear thickening. Above C*, wormlike micelles form and the solutions show strong viscoelasticity with Maxwell behavior in the linear regime and shear banding flow in the non-linear regime. The linear viscoelastic regime was analyzed with the Granek-Cates model, showing that the relaxation is controlled by the kinetics of reformation-and-scission of the micelles. The steady response in the non-linear regime is compared with the predictions of the Bautista-Manero-Puig (BMP) and the Giesekus models.


Unexpected Discovery of Thelypteris palustris (Thelypteridaceae) in Sicily (Italy): Morphological, Ecological Analysis and Habitat Characterization.
Thelypteris palustris Schott (Thelypteridaceae), known as "marsh fern", is infrequent in the Mediterranean area. The occurrence of this species is known for almost all the Italian regions (except for Sardinia and Sicily), but with rare and declining populations. During floristic fieldwork on the Sicilian wetlands, a new unknown population was found. The aim of this paper is to analyze the morphological traits of the species, as well as its ecological features and the floristic composition of the plant communities where it lives. According to IUCN guidelines, here we provide the regional assessment (Sicily) of T. palustris. To analyze its morphological features, many living plants were examined, with particular attention to the spore structure. A total of 179 plots (110 species) and 34 pools were sampled. Our results highlight the relic character of the species which is at the southernmost border of its distribution range. The micro-morphological investigations on the spores show that the Sicilian population belongs to the subsp. palustris. The floristic analysis confirms the clear dominance of perennial temperate-cold zones Eurasian taxa. Finally, a new association, Thelypterido palustris-Caricetum paniculatae, within the Caricion gracilis alliance (Phragmito-Magnocaricetea class) is described.


Implications for the ligase chain reaction in gastroenterology.
The ligase chain reaction (LCR) is a new DNA detection method that uses thermostable ligase to discriminate exquisitely and amplify single base changes in genes of medical interest. This enzyme specifically links two adjacent oligonucleotides when hybridized to a complementary target only when the nucleotides are perfectly base-paired at the junction. Oligonucleotide products are exponentially amplified by thermal cycling of the ligation reaction in the presence of a second set of adjacent oligonucleotides, complementary to the first set and the target. A single-base mismatch prevents ligation and amplification, thus distinguishing a single base mutation from the normal allele. The use of a thermostable ligase allows the enzyme to survive thermal cycling in a fashion analogous to Taq polymerase in the polymerase chain reaction. The assay is compatible with nonradioactive detection and has the potential for automation. Although still in its early stages of development, LCR is expected to find many uses in the field of gastroenterology and in medicine in general. In this review we briefly describe how LCR works and discuss potential areas of application in gastroenterology.


Effects of feeding and body weight loss on the 1H-NMR-based urine metabolic profiles of male Wistar Han rats: implications for biomarker discovery.
For almost two decades, 1H-NMR spectroscopy has been used as an 'open' system to study the temporal changes in the biochemical composition of biofluids, including urine, in response to adverse toxic events. Many of these in vivo studies have reported changes in individual metabolites and patterns of metabolites that correlated with toxicological changes. However, many of the proposed novel biomarkers are common to a number of different types of toxicity. These may therefore reflect non-specific effects of toxicity, such as weight loss, rather than a specific pathology. A study was carried out to investigate the non-specific effects on urinary metabolite profiles by administering four hepatotoxic compounds, as a single dose, to rats at two dose levels: hydrazine hydrate (0.06 or 0.08 g kg (1)), 1,2-dimethylhydrazine (0.1 or 0.3 g kg (-1)), alpha-napthylisothiocyanate (0.1 or 0.15 g kg(-1)) and carbon tetrachloride (1.58 or 3.16 g kg(-1)). The study included weight-matched control animals along with those that were dosed, which were then 'pair-fed' with the treated animals so they achieved a similar weight loss. The urinary metabolite profiles were investigated over time using 1H-NMR spectroscopy and compared with the pathology from the same animals. The temporal changes were analysed statistically using multivariate statistical data analysis including principal component analysis, partial least squares, parallel factor analysis and Fisher's criteria. A number of metabolites associated with energy metabolism or which are partially dietary in origin, such as creatine, creatinine, tricarboxylic acid (TCA) cycle intermediates, phenylacetylglycine, fumarate, glucose, taurine, fatty acids and N-methylnicotinamide, showed altered levels in the urine of treated and pair-fed animals. Many of these changes correlated well with weight loss. Interestingly, there was no increase in ketone bodies (acetate and beta-hydroxybutyrate), which might be expected if energy metabolism was switched from glycolysis to fatty acid beta-oxidation. In some instances, the metabolites that changed were considered to be non-specific markers of toxicity, but were also identified as markers of a specific type of toxicity. For example, taurine was raised significantly in carbon tetrachloride-treated animals but reduced in the pair-fed group. However, raised urinary bile acid levels were only seen after alpha-napthylisothiocyanate treatment. The methodology, statistical analysis used and the data generated will help improve the identification of specific markers or patterns of urinary markers of specific toxic effects.


[Bone abnormalities in diabetic hemodialysis patients].
In patients with end stage renal disease, metabolic bone abnormalities are frequently seen. Diabetes may affect bone metabolism through various mechanisms, including hyperglycemia, insulin deficiency, and accumulation of advanced glycation end-products. Bone disease in hemodialysis patients with diabetes mellitus is characterized by low bone turnover, resulting from either impaired secretion of parathyroid hormone or osteoblast dysfunction. The prevalence rate of vertebral fractures in diabetic hemodialysis patients was 32%, which was greater than that of non-diabetic hemodialysis patients (13%). In non-diabetic hemodialysis patients, those with vertebral fracture showed significantly lower bone mineral density in either lumbar spine or distal one third of radius than the respective value in those without fracture. However, in diabetic hemodialysis patients, neither bone mineral density in lumbar spine nor distal one third of radius was significantly lower in those with vertebral fracture than in those without.


The effect of changes in visible area on facial recognition.
The proportion of a human face which needs to be visible for correct identification was investigated. Photographs of familiar public faces were presented under two conditions: (i) the facial photographs were original photographs with local information; and (ii) the facial photographs were blurred, with high spatial frequencies removed and with no local information. Subjects could scan the face as they wished through a moveable window generated by a TV system and had to identify the depicted person as quickly as possible. Window size was varied systematically. The main study showed that, in spite of including only its local features, a familiar facial photograph could be perfectly identified when the visual window covered one-fifth of the whole face, and that a global image of the whole face was obtained when nearly half of the whole face was processed simultaneously. The structure of the memory image of the face is discussed in the light of the results obtained.


Jaundice and cholestasis. Some common and uncommon causes.
Jaundiced patients may not always be as sick as they look, and cholestatic patients may be quite ill but not yet jaundiced. There is variability in presentation of cholestasis, and jaundice may be intrahepatic or extrahepatic and acute or chronic. Even though the diagnosis of jaundice can be elusive, an unnecessarily exhaustive search for a cause should be avoided, because some tests are not without dangers. Dr Gordon describes many possible causes, some of which are rare but are still worth consideration.


The Fusarium graminearum genome reveals more secondary metabolite gene clusters and hints of horizontal gene transfer.
Fungal secondary metabolite biosynthesis genes are of major interest due to the pharmacological properties of their products (like mycotoxins and antibiotics). The genome of the plant pathogenic fungus Fusarium graminearum codes for a large number of candidate enzymes involved in secondary metabolite biosynthesis. However, the chemical nature of most enzymatic products of proteins encoded by putative secondary metabolism biosynthetic genes is largely unknown. Based on our analysis we present 67 gene clusters with significant enrichment of predicted secondary metabolism related enzymatic functions. 20 gene clusters with unknown metabolites exhibit strong gene expression correlation in planta and presumably play a role in virulence. Furthermore, the identification of conserved and over-represented putative transcription factor binding sites serves as additional evidence for cluster co-regulation. Orthologous cluster search provided insight into the evolution of secondary metabolism clusters. Some clusters are characteristic for the Fusarium phylum while others show evidence of horizontal gene transfer as orthologs can be found in representatives of the Botrytis or Cochliobolus lineage. The presented candidate clusters provide valuable targets for experimental examination.


Timing of Tourniquet Release in Total Knee Arthroplasty.
EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Describe the available tourniquet application strategies for patients treated with total knee arthroplasty (TKA). 2. Differentiate the potential strengths and limitations of tourniquet release before and after wound closure in TKA. 3. Cite the available evidence regarding tourniquet release before and after wound closure in TKA. 4. Recognize the optimal tourniquet application strategy in TKA based on the available evidence. The authors conducted a meta-analysis to determine the optimal tourniquet application strategy in total knee arthroplasty (TKA). Fourteen high-quality randomized, controlled trials were retrieved. The results showed tourniquet release before wound closure for hemostasis could significantly increase not only the total measured blood loss but also the calculated blood loss in patients treated with TKA, regardless of fixation type. With proper control of the amount of pressure (less than 293 mm Hg) and the duration of application (less than 150 minutes), tourniquet release after wound closure can reduce blood loss in patients treated with primary TKA without increasing the risk of complications. [Orthopedics. 2015; 38(7):445-451.].


Deep focus light-field camera for handheld 3D intraoral scanning using crosstalk-free solid immersion microlens arrays.
3D in vivo imaging techniques facilitate disease tracking and treatment, but bulky configurations and motion artifacts limit practical clinical applications. Compact light-field cameras with microlens arrays offer a feasible option for rapid volumetric imaging, yet their utilization in clinical practice necessitates an increased depth-of-field for handheld operation. Here, we report deep focus light-field camera (DF-LFC) with crosstalk-free solid immersion microlens arrays (siMLAs), allowing large depth-of-field and high-resolution imaging for handheld 3D intraoral scanning. The siMLAs consist of thin PDMS-coated microlens arrays and a metal-insulator-metal absorber to extend the focal length with low optical crosstalk and specular reflection. The experimental results show that the immersion of MLAs in PDMS increases the focal length by a factor of 2.7 and the transmittance by 5.6%-27%. Unlike conventional MLAs, the siMLAs exhibit exceptionally high f-numbers up to f/6, resulting in a large depth-of-field for light-field imaging. The siMLAs were fully integrated into an intraoral scanner to reconstruct a 3D dental phantom with a distance measurement error of 82 ± 41 μm during handheld operation. The DF-LFC offers a new direction not only for digital dental impressions with high accuracy, simplified workflow, reduced waste, and digital compatibility but also for assorted clinical endoscopy and microscopy.


Low measured auto-positive end-expiratory pressure during mechanical ventilation of patients with severe asthma: hidden auto-positive end-expiratory pressure.
To describe the occurrence of low measured auto-end-expiratory pressure (auto-PEEP) during mechanical ventilation of patients severe asthma. Observational clinical study. Medical intensive care unit of a university-affiliated county hospital. Four mechanically ventilated patients with severe asthma who had low measured auto-PEEP despite marked increase in both peak and plateau airway pressures. None. Peak pressure, plateau pressure, and auto-PEEP were measured at an early time point, when airflow obstruction was most severe, and again at a later time after clinical improvement. Auto-PEEP was measured by the method of end-expiratory airway occlusion. From the early to the late point, there was a marked decrease in peak pressure (76 +/- 7 to 53 +/- 6 cm H2O; p<.001) and in plateau pressure (28 +/- 2 to 18 +/- 3 cm H2O; p<.001), but only minimal change in auto-PEEP (5 +/- 3 to 4 +/- 3 cm H2O). The difference between plateau pressure and auto-PEEP decreased between the early and late time points (23 +/- 1 to 14 +/- 1 cm H2O; p<.01), even though tidal volume was larger at the late time point. In three patients, low auto-PEEP and a large difference between plateau pressure and auto-PEEP was only seen after expiratory time was prolonged. In these three patients, prolongation of expiratory time resulted in a large decrease in measured auto-PEEP (14 +/- 4 to 5 +/- 4 cm H2O), but a much smaller change in plateau pressure (31 +/- 3 to 29 +/- 3 cm H2O). We conclude that measured auto-PEEP may underestimate end-expiratory alveolar pressure in severe asthma, and that marked pulmonary hyperinflation may be present despite low measured auto-PEEP, especially at low respiratory rates. This phenomenon may be due to widespread airway closure that prevents accurate assessment of alveolar pressure at end-expiration.


Socioeconomic disparities in maternity care among Indian adolescents, 1990-2006.
India, with a population of more than 1.21 billion, has the highest maternal mortality in the world (estimated to be 56000 in 2010); and adolescent (aged 15-19) mortality shares 9% of total maternal deaths. Addressing the maternity care needs of adolescents may have considerable ramifications for achieving the Millennium Development Goal (MDG)-5. This paper assesses the socioeconomic differentials in accessing full antenatal care and professional attendance at delivery by adolescent mothers (aged 15-19) in India during 1990-2006. Data from three rounds of the National Family Health Survey of India conducted during 1992-93, 1998-99, and 2005-06 were analyzed. The Cochran-Armitage and Chi-squared test for linear and non-linear time trends were applied, respectively, to understand the trend in the proportion of adolescent mothers utilizing select maternity care services during 1990-2006. Using pooled multivariate logistic regression models, the probability of select maternal healthcare utilization among women by key socioeconomic characteristics was appraised. After adjusting for potential socio-demographic and economic characteristics, the likelihood of adolescents accessing full antenatal care increased by only 4% from 1990 to 2006. However, the probability of adolescent women availing themselves of professional attendance at delivery increased by 79% during the same period. The study also highlights the desolate disparities in maternity care services among adolescents across the most and the least favoured groups. Maternal care interventions in India need focused programs for rural, uneducated, poor adolescent women so that they can avail themselves of measures to delay child bearing, and for better antenatal consultation and delivery care in case of pregnancy. This study strongly advocates the promotion of a comprehensive 'adolescent scheme' along the lines of 'Continuum of Maternal, Newborn and Child health Care' to address the unmet need of reproductive and maternal healthcare services among adolescent women in India.


Kinetics and mathematical model of killer/sensitive interaction under different physicochemical conditions of must/wine: a study from a biological point of view.
Fermentation of grape must to wine is carried out by a complex microbial mixture, which also involves spoilage yeasts of wine. The latter yeasts produce organoleptic changes that cause significant economic losses to the wine industry. SO2 is traditionally used to control this spoilage populations, but because of its harmful effects on human health, biocontrol has emerged as an alternative treatment. Although studies have been carried out to select biocontroller yeasts and examine their underlying mechanisms of action, reports on their application have not been published yet. To better understand the interaction and the successful application of biocontrol, the use of mathematical models, among other methods, is important, as they facilitate the prediction of success or failure of the antagonist. The objective of the present study was to use an existing mathematical model to obtain information about the yeast's interaction assayed and to validate its predictive use under different physicochemical conditions during the wine fermentation, and eventually predict biocontrol kinetics. The mathematical model was applied to the fermentation conditions and provided information on the kinetic parameters of the biocontrol interaction and allowed interpretations about other parameters. The model was applied in the different physicochemical conditions for the biocontrol and did not fit correctly to experimental data, and therefore an improvement was proposed which was successful and presented new hypotheses.


Flow fingerprinting fecal pollution and suspended solids in stormwater runoff from an urban coastal watershed.
Field studies were conducted to characterize the concentration vs streamflow relationships (or "flow fingerprints") of fecal pollution and suspended solids in stormwater runoff from the Santa Ana River watershed, the largest watershed in southern California. The concentrations of fecal indicator bacteria and F+ coliphages (viruses infecting E. coli) exhibit little-to-no dependence on streamflow rates, whereas the concentrations of total suspended solids (TSS) exhibit a very strong (power-law) dependence on streamflow rates. The different flow fingerprints observed for fecal pollutants, on one hand, and TSS, on the other hand, reflect different sources and transport pathways for these stormwater constituents. The flow-independent nature of fecal indicator bacteria and F+ coliphages is consistent with the idea that these contaminants are ubiquitously present on the surface of the urban landscape and rapidly partition into the surface water as the landscape is wetted by rainfall. The flow-dependent nature of TSS, on the other hand, is usually ascribed to the shear-induced erosion of channel bed sediments and/or the expansion of drainage area contributing to runoff. The apparent ubiquity of fecal indicator bacteria and F+ coliphages, together with the very high storm-loading rates of fecal indicator bacteria and the low detection frequency of human adenovirus and human enterovirus, suggest that fecal pollution in stormwater runoff from the Santa Ana River watershed is primarily of nonhuman waste origin.


[Identification of the minimal zinc-binding center in natural isoforms of amyloid-beta domain 1-16 using ESI-MS].
Alzheimer's disease, is a lethal neurodegenerative pathology, characterized by the formation of soluble neurotoxic oligomers of the human amyloid-beta peptide Abeta which get accumulated forming polymeric extracellular aggregates (so-called amyloid plaques). The isomerized at aspartate 7 isoform of the human Abeta (isoAbeta) is the main component of these plaques and is considered as the potential pathogenic agent of AD. Besides this, there is a possible generation mechanism for this isoform from a genetically deficient D7N Abeta variant (Tottori mutation). On the contrary the rodent Abeta (rat Abeta), which has three amino acid substitutions in its metal-binding domain, is not susceptible to pathogenic aggregation in vivo, unlike the other known natural isoforms of Abeta. Interactions with zinc ions play a crucial role in the aggregation of monomeric human Abeta in vitro and in vivo. In the presented article using high resolution ESI-MS methods it was shown that domains 1-16 of isoAbeta and D7NAbeta bind zinc ions in the exactly the same manner as the normal human Abeta1-16, whereas ratAbeta has significant differences in structure of its minimal zinc binding center. These results confirm the overall interaction mechanism between zinc ions and the humanAbeta isoforms and allows to suppose that perhaps modulation of the structure of region 6-14 of Abeta can be used as a promising therapeutic approach to AD treatment.


Transcriptional responses, metabolic activity and mouthpart deformities in natural populations of Chironomus riparius larvae exposed to environmental pollutants.
Biomarkers are an important tool in laboratory assays that link exposure or effect of specific toxicants to key molecular and cellular events, but they have not been widely used in invertebrate populations exposed to complex mixtures of environmental contaminants in their natural habitats. The present study focused on a battery of biomarkers and their comparative analysis in natural populations of the benthic larvae of Chironomus riparius (Diptera), sampled in three differentially polluted rivers (the Con, Sar, and Louro in Galicia, Spain). In our study, some parameters were identified, such as hsp70 gene activity, GST enzymatic activity, total glycogen content and mouthpart deformities, which showed significant differences among populations from the three rivers that differed in the levels and types of sedimentary contaminants analyzed (metals, organic-chlorine pesticides, alkylphenols, pharmaceutical, and personal care products). In contrast to these sensitive biomarkers, other parameters showed no significant differences (hsc70 gene, EcR gene, P450 gene, RNA:DNA ratio, total protein content), and were stable even when comparing field and nonexposed laboratory populations. The hsp70 gene seems to be particularly sensitive to conditions of pollutant exposure, while its constitutive counterpart hsc70 showed invariable expression, suggesting that the hsc70/hsp70 ratio may be a potential indicator of polluted environments. Although further studies are required to understand the correlation between molecular responses and the ecological effects of pollutants on natural populations, the results provide new data about the biological responses to multiple-stressor environments. This field study adds new molecular endpoints, including gene expression, as suitable tools that, complementing other ecotoxicological parameters, may help to improve the methodologies of freshwater monitoring under the increasing burden of xenobiotics.


Mepore Ultra and Alldress: primary and secondary dressings.
Expenditure on wound care continues to rise in the UK as new products and innovations are introduced. Nurse specialists in tissue viability are at the forefront of many of these advances and therefore it is vital that they consider both the clinical and economic benefits of each new treatment. In this article, the authors use a case study methodology to evaluate primary and secondary wound dressings. The aim was to focus on the opportunity for reducing overall costs in wound management without compromising clinical outcomes. Given the initial results observed there appears to be ample scope for a debate within the tissue viability specialty with regard to achieving best value for money in wound care. The authors suggest that the time has come to consider this area in greater detail and depth.


[Management of trauma to the male external genitalia].
Male genital injury, although rarely life-threatening, demands prompt, appropriate management to prevent long-term sexual and psychological damage. However, because of the rarity and disparity of severe genital injuries, there is still no universal therapeutic strategy. Urethral injury, although rare, may be associated with substantial long-term morbidity such as fistulas and strictures. Injuries to the scrotum and its contents may cause impaired fertility, chronic pain, hypogonadism, and altered self-image. Penile injury may lead to pain, curvature, and erectile dysfunction. This article concentrates on reviewing the major etiologies and mechanisms of urethral and genital injuries in men and summarizes principles and strategies of treatment based on the guidelines of the European Association of Urology.


Bicalutamide: clinical pharmacokinetics and metabolism.
Bicalutamide is a nonsteroidal pure antiandrogen given at a dosage of 150 mg once daily as monotherapy for the treatment of early (localised or locally advanced) nonmetastatic prostate cancer. It is used at a dosage of 50 mg once daily in combination with a luteinising hormone-releasing hormone analogue or surgical castration for the treatment of advanced prostate cancer. Bicalutamide is a racemate and its antiandrogenic activity resides almost exclusively in the (R)-enantiomer, with little, if any, activity in the (S)-enantiomer. (R)-Bicalutamide is slowly and saturably absorbed, but absorption is unaffected by food. It has a long plasma elimination half-life (1 week) and accumulates about 10-fold in plasma during daily administration. (S)-Bicalutamide is much more rapidly absorbed and cleared from plasma; steady-state concentrations (Css) of (R)-bicalutamide are 100-fold higher than those of (S)-bicalutamide. Css increases linearly with doses up to 50 mg, but nonlinearly at higher doses, reaching a plateau above 300 mg. Css is higher in Japanese than in Caucasians, but no relationship with degree of renal impairment, bodyweight or age exists. Although mild-to-moderate hepatic impairment does not affect pharmacokinetics, there is evidence for slower elimination of (R)-bicalutamide in subjects with severe hepatic impairment. Bicalutamide metabolites are excreted almost equally in urine and faeces with little or no unchanged drug excreted in urine; conversely, unchanged drug predominates in plasma. Bicalutamide in faeces is thought to arise from hydrolysis of bicalutamide glucuronide and from unabsorbed drug. Bicalutamide appears to be cleared almost exclusively by metabolism; this is largely mediated by cytochrome P450 (CYP) for (R)-bicalutamide, but glucuronidation is the predominant metabolic route for (S)-bicalutamide. (S)-Bicalutamide is metabolised in vitro by CYP3A4, and it is probable that this isoenzyme is also responsible for the metabolism of (R)-bicalutamide. In vitro data suggest that (R)-bicalutamide has the potential to inhibit CYP3A4 and, to a lesser extent, CYP2C9, 2C19 and 2D6. However, using midazolam as a specific CYP3A4 marker, no clinically relevant inhibition is observed in vivo with bicalutamide 150mg. Although bicalutamide is a CYP inducer in laboratory animals, dosages < or = 150 mg/day have shown no evidence of enzyme induction in humans. Daily administration of bicalutamide increases circulating levels of gonadotrophins and sex hormones; although testosterone increases by up to 80%, concentrations in most patients remain within the normal range. Bicalutamide produces a dose-related decrease in prostate-specific antigen (PSA) at dosages < or = 150 mg/day. However, little relationship is observed between median PSA reduction and (R)-bicalutamide Css.


Effect of light intensity on the formation of the photochemical apparatus in the green bacterium Chloropseudomonas ethylicum.
Holt, Stanley C. (Dartmouth Medical School, Hanover, N.H.), S. F. Conti, and R. C. Fuller. Effect of light intensity on the formation of the photochemical apparatus in the green bacterium Chloropseudomonas ethylicum. J. Bacteriol. 91:349-355. 1966.-When the green bacterium Chloropseudomonas ethylicum was grown at various light intensities, the formation of the photosynthetic vesicles was found to be an inverse function of the light intensity at which the cells were grown. The specific chlorophyll content of isolated vesicles varied as the light intensity was changed over a wide range. Thus, the regulation of chlorophyll content in C. ethylicum in response to a change in light intensity is achieved both by a change in the number of vesicles that are formed and by a change in the specific chlorophyll content of these vesicles.


Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols.
The abundance of polyphenols in edible plants makes them an important component of human nutrition. Considering the ongoing COVID-19 pandemic, a number of studies have investigated polyphenols as bioactive constituents. We applied in-silico molecular docking as well as molecular dynamics supported by in-vitro assays to determine the inhibitory potential of various plant polyphenols against an important SARS-CoV-2 therapeutic target, the protease 3CLpro. Of the polyphenols in initial in-vitro screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC50 values of 11.8 µM to 23.4 µM. In-silico molecular dynamics simulations indicated stable interactions with the 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CLpro in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CLpro by natural plant polyphenols, and suggest further research into the development of these novel 3CLpro inhibitors or biochemical probes.


[Analysis of the guarantee and enjoyment of patients with occupational pneumoconiosis in Gansu Province].
Objective: To analyze the security situation of patients with occupational pneumoconiosis in Gansu Province to lay the foundation for strengthening the security measures for patients with pneumoconiosis. Methods: In August 2020, a follow-up survey was conducted on the current patients with occupational pneumoconiosis diagnosed and surviving in Gansu Province from 1949 to 2019, to obtain the information of industrial injury insurance, employer compensation, medical insurance, subsistence allowance and so on, and analyze their distribution characteristics. The proportion of patients enjoying various security, medical insurance reimbursement and subsistence allowances was tested by chi square. Results: Among the current patients with occupational pneumoconiosis in Gansu Province, 72.0% (5335/7410) enjoyed the benefits of work-related injury insurance, 8.2% (609/7410) enjoyed the compensation paid by the employer, 91.5% (6780/7410) had medical insurance, and 2.8% (204/7410) had no guarantee. Among the patients with occupational pneumoconiosis, 374 enjoyed the minimum living allowance, accounting for 5.05% (374/7410) ; the first diagnosis period with a high proportion of minimum living allowance was phase Ⅲ, accounting for 15.14% (43/284) . Conclusion: The proportion of medical insurance outpatient and inpatient reimbursement of occupational pneumoconiosis patients in Gansu Province is still at a low level. It is suggested that relevant departments should introduce relevant security policies for workers without fixed employers to reduce the economic burden of patients.


Inter-Institutional Collaboration Between Quaternary and Tertiary Hospitals: Cardiac Surgery Impact.
An inter-institutional collaboration between a quaternary hospital (QH) with a high volume of cardiac surgery and a community-based, tertiary hospital (TH) with a newly established cardiac surgery program was established. We retrospectively reviewed data of patients admitted to the TH between September 2015 and June 2017 for cardiac surgery. The decision to transfer a patient to the QH was based on a Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score of ≥ 3%, the potential need for hemodialysis, and other risk factors. The same team of surgeons performed operations at both hospitals. We analyzed the perioperative outcomes of the patients and the referral pattern. A total of 116 patients met eligibility criteria; 105 underwent surgery at the TH, while 11 were transferred to the QH. Among the 11 patients transferred to the QH, eight had a score of 3% (median = 8.2 [IQR 5.7-25.0]). The patients transferred to the QH prior to surgery had a significantly higher STS-PROM score (P = ≤ .001). Overall, the mortality of patients who underwent surgery at the TH was 0.9% (1/105); while surgeries at the QH had a mortality rate of 0% (0/11). The collaborative effort between high-volume cardiac surgery programs and emerging community-based hospitals showed acceptable outcomes in perioperative cardiac surgical mortality. Elevated STS-PROM scores (>3%), previous sternotomy and anticipation of coagulopathy, and low left ventricular ejection fraction or dilated ventricles are factors that influenced the need to transfer from a TH to QH.


Measurement of isovolumic relaxation: comparison of echocardiographic mitral valve opening and Doppler mitral valve flow.
The relation between mitral valve opening and transmitral blood flow was investigated by M-mode echocardiography and Doppler ultrasound in 50 normal subjects to allow the measurement of the timing of the end of isovolumic relaxation. Standard parasternal M-mode echocardiograms of the mitral valve to show the onset of cusp separation were recorded with a simultaneous electrocardiogram and phonocardiogram. Pulse wave Doppler ultrasound using both amplitude and spectral analysis was recorded with a transducer at the apex, and the initial diastolic blood flow towards the transducer was taken as the onset of flow. For each subject five cardiac cycles of similar length were measured using the three methods. Isovolumic relaxation could be measured with a high degree of reliability (retest reliability coefficient greater than 0.94). The echocardiographic measurement of isovolumic relaxation ranged from 52 to 82 ms (mean(SD) 67(9) ms). Isovolumic relaxation measured by Doppler was 52-83 ms (mean(SD) 67(9) ms) using amplitude analysis and 54-89 ms (mean(SD) 72(11) ms) using spectral analysis. There was a strong correlation between the echocardiographic isovolumic relaxation and measurements made using spectral analysis (r = 0.93, slope 0.97) and amplitude analysis (r = 0.97, slope 0.98). Therefore in normal subjects the end of isovolumic relaxation can be reliably measured by echocardiographic and Doppler methods, and whereas the amplitude signal is coincidental with that measured by echocardiography that measured by spectral analysis is delayed by approximately 5 ms.


Melanotic neuroectodermal tumor of infancy presenting in the subcutaneous soft tissue of the thigh.
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare and diagnostically challenging neoplasm typically presenting in the bones of the maxilla, skull, or mandible. Only 6 of approximately 357 reported cases have involved the subcutis. We describe a case of MNTI presenting as a palpable, subcutaneous, thigh mass in a 5-month-old girl. By ultrasound, the mass was round with well-defined borders, minimal vascularity, and heterogeneous echogenicity. Microscopically, the tumor consisted of nested foci of primitive-appearing small round blue cells with an increased nuclear to cytoplasmic ratio, stippled chromatin, and occasional mitotic figures. A larger and more epithelioid second cell population exhibited eosinophilic cytoplasm and sparse pigmented granules. The background stroma was fibrous and densely sclerotic. The differential diagnosis of soft tissue MNTI can include melanoma, neuroblastoma, rhabdomyosarcoma, desmoplastic small round cell tumor, and other pediatric "small round cell" neoplasms. The tumor had the characteristic immunophenotype of MNTI: cytokeratin+, HMB-45+, neuron-specific enolase+, and synaptophysin+. MNTI should be considered in the differential diagnosis of pigmented soft tissue lesions in children. Our patient remains disease-free 40 months after excision, although these tumors can locally recur (10%-20%) and rarely metastasize.


Carbon Oxysulfide Is an Inhibitor of Both CO(2) and HCO(3) Uptake in the Cyanobacterium Synechococcus PCC7942.
Carbon oxysulfide (COS) was reinvestigated as an inhibitor of active inorganic carbon transport in cells of Synechococcus PCC7942 adapted to growth at low inorganic carbon. COS inhibited both CO(2) and HCO(3) (-) transport processes in a reversible (in the short term) and mixed competitive manner. The inhibition of COS was established using both silicone oil centrifugation experiments and O(2)-evolution studies. The K(i) for COS inhibition was 29 micromolar for CO(2) transport and 110 micromolar for HCO(3) (-) transport. These results support a model of inorganic carbon transport with a central CO(2) pump and an inducible HCO(3) (-) utilizing accessory protein which supplies CO(2) to the primary pump.


Sarcoma of the proximal portion of the tibia in a dog 5.5 years after tibial plateau leveling osteotomy.
Osseous neoplasia was identified in the proximal portion of the tibia and distal portion of the femur in an 11.75-year-old spayed female German Shepherd Dog. A tibial plateau leveling osteotomy, followed by application of a metal plate, had been performed on the affected limb 5.5 years earlier. Areas of osteolysis and periosteal proliferation were seen radiographically, with an intense area of osteolysis directly beneath the metal plate. Histologically, the tumor was identified as a poorly differentiated sarcoma. Extracellular and intracellular debris was seen histologically, and energy-dispersive x-ray analysis confirmed that this debris was metallic. On visual examination, areas of the underside of the metal plate that had been in contact with bone had a dull, roughened appearance, and scanning electron microscopy of these areas revealed multiple corrosion pits. The plate was strongly magnetic, suggesting that it contained ferrite, and metallographic examination of the plate revealed substantial differences in the chemical makeup of various parts of the plate. Microstructure analysis revealed that the plate consisted of an austenite matrix with a large fraction of ferrite. The plate was determined to be a cast 316L stainless steel implant, but it did not meet American Society for Testing Materials standards for implant-grade materials. The possibility that implant corrosion might have played a role in tumor development is of concern; however, a definitive association was not established.


Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER).
Statins are the most commonly prescribed agents for lowering levels of low-density lipoprotein (LDL) cholesterol. Although dose-dependent reductions in levels of atherogenic lipids are observed with all statins, the impact of increasing dose has not been fully elucidated. An individual patient data pooled analysis was performed of 32,258 patients in studies comparing the efficacy of rosuvastatin with that of atorvastatin or simvastatin. The impact of increasing dose on lowering LDL cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B was investigated. Doubling the dose of each statin was accompanied by a 4% to 7% greater degree of lowering of all atherogenic lipids. A stronger correlation was observed between changes in LDL cholesterol and non-HDL cholesterol (r = 0.92, p <0.001) or apolipoprotein B (r = 0.76, p <0.001) than triglycerides (r = 0.14, p <0.001). On multivariate analysis, baseline lipid level (p <0.0001) and increasing statin dose (p <0.0001) were strong predictors of achieving treatment goals in high-risk patients. Increasing age was a strong independent predictor of achieving goal for all atherogenic lipids (p <0.0001). Achieving LDL cholesterol goals was also more likely in women (p <0.0001), patients with diabetes (p <0.0001), and patients without atherosclerotic disease (p = 0.0002). In contrast, normal triglyceride levels were more often observed in men (p <0.0001) and patients without diabetes mellitus (p = 0.03). In conclusion, doubling statin dose was associated with greater lowering of LDL cholesterol by 4% to 6% and non-HDL cholesterol by 3% to 6%. Greater lipid goal achievement with increasing dose supports the use of high-dose statin therapy for more effective cardiovascular prevention.


Caprine articular, meniscus and intervertebral disc cartilage: an integral analysis of collagen network and chondrocytes.
Cartilage is a tissue with only limited reparative capacities. A small part of its volume is composed of cells, the remaining part being the hydrated extracellular matrix (ECM) with collagens and proteoglycans as its main constituents. The functioning of cartilage depends heavily on its ECM. Although it is known that the various (fibro)cartilaginous tissues (articular cartilage, annulus fibrosus, nucleus pulposus, and meniscus) differ from one each other with respect to their molecular make-up, remarkable little quantitative information is available with respect to its biochemical constituents, such as collagen content, or the various posttranslational modifications of collagen. Furthermore, we have noticed that tissue-engineering strategies to replace cartilaginous tissues pay in general little attention to the biochemical differences of the tissues or the phenotypical differences of the (fibro)chondrocytes under consideration. The goal of this paper is therefore to provide quantitative biochemical data from these tissues as a reference for further studies. We have chosen the goat as the source of these tissues, as this animal is widely accepted as an animal model in orthopaedic studies, e.g. in the field of cartilage degeneration and tissue engineering. Furthermore, we provide data on mRNA levels (from genes encoding proteins/enzymes involved in the synthesis and degradation of the ECM) from (fibro)chondrocytes that are freshly isolated from these tissues and from the same (fibro)chondrocytes that are cultured for 18 days in alginate beads. Expression levels of genes involved in the cross-linking of collagen were different between cells isolated from various cartilaginous tissues. This opens the possibility to include more markers than the commonly used chondrogenic markers type II collagen and aggrecan for cartilage tissue-engineering applications.


Discovery of Icotinib-1,2,3-Triazole Derivatives as IDO1 Inhibitors.
Tumor immunotherapy is considered to be a highlight in cancer treatment in recent years. Indoleamine 2,3-dioxygenase 1 (IDO1) is closely related to the over expression of many cancers, and is therefore a promising target for tumor immunotherapy. To search for novel IDO1-targeting therapeutic agents, 22 icotinib-linked 1,2,3-triazole derivatives were prepared and evaluated for their inhibitory activity against IDO1. The structures of the prepared compounds were confirmed with1H NMR, 13C NMR and HR MS. IDO1 inhibitory activity assay results indicated that 10 of those compounds showed remarkable inhibitory activity against IDO1, among which compound a17 was the most potent with IC50value of 0.37 μM. The binding model between the prepared compounds and IDO1 was studied with molecular modeling study. The current study suggested that icotinib-1,2,3-triazole derivatives could be used as potential inhibitors that preferentially bind to the ferrous form of IDO1 through the formation of coordinate bond with the haem iron.


Optimal recycle price game theory model for second-hand mobile phone recycling.
Human societies develop rapidly through the advancement of technology; however, with these advancements, many problems are emerging. The topic chosen for this study surrounds the e-waste, which has become a major problem around the world. Second-hand and unused mobile phones are a big part of globally generated e-waste. If these devices are properly recycled, they can generate substantial economic and resource value. Yet if they are indiscriminately discarded, they cause a profound environmental impact. Given the current low recovery rate of mobile phones, an increase in recovery rates becomes critical in lessening economic and environmental impacts. Based on the status quo of second-hand mobile phone recycling processes in China, this article analyzes the behavior of individuals and recyclers through a comprehensive static information game theory and finds ways to increase the recycling rate of second-hand mobile phones. The study helps the customers, to clearly identify the recycle price. In case of market, the government policy can be introduced with a reward and punishment mechanism. Furthermore, under the ideological guidance of game theory, this paper also establishes a corresponding price model of second-hand mobile phone recycling based on best response dynamics like search, variable neighborhood search, and hybrid meta-heuristic method. This model shows that the recovery time differences have a significant impact on the recovery price. Moreover, to an extent, this model can promote the possibility and initiative of customers choosing cell phone recycling.


Experiences of Stigma and Health Service Utilization among Young Rural-to-urban Migrants in China: The Mediation Role of Social Capital.
Previous studies revealed that experiences of stigma may negatively affect health service utilization (HSU) among young rural-to-urban migrants. Existing literature also suggested social factors including social capital may mediate such negative effect. However, data are limited regarding the mediation role of social capital among this vulnerable population. Therefore, the current study aimed to examine the associations among experiences of stigma, social capital, and HSU among young rural-to-urban migrants in China. A sample of 641 young rural-to-urban migrants was recruited through a venue-based sampling approach in Beijing, China. Participants were assessed on sociodemographic characteristics, experiences of stigma, and social capital in their urban communities. Self-reported frequency of physical examinations (regularly, irregularly, none) was used as an indicator of HSU. Structural equation modeling (SEM) was performed to examine the direct effect of stigma on HSU as well as the mediation effect of social capital. Among the 641 young rural-to-urban migrants, 32.3% (195/603) reported never having physical examinations while 50.6% (305/603) reported having them irregularly. The final model showed a goodness of fit (χ 2/df=1.7, CFI=0.98, RMSEA=0.03, WRMR=0.74). Results of SEM revealed that both of the direct and indirect paths from experiences of stigma on HSU were statistically significant. There was a partial mediation effect of social capital on the association between experiences of stigma and HSU (delta z score=-5.49, p<0.01). Rural-to-urban migrants have a low rate of regular HSU. Experiences of stigma is associated with decreased likelihood of HSU. Social capital in the urban communities can mediate the negative effect of stigma on HSU and plays a mediation role between experiences of stigma and HSU. Therefore, to increase HSU among migrants, targeted interventions to reduce stigma and increase social capital at the migration destinations are needed.


Falling televisions: The hidden danger for children.
The United States Consumer Product Safety Commission (USCPSC) recently has reported a significant number of injuries and deaths in the home related to televisions (TV) falling on children. To date, little is known regarding the significance of this mechanism of injury in childhood trauma. The current investigation was designed to examine the risk factors, spectrum of injuries, and operative intervention required in children injured by falling televisions. The records of all patients 0 to 16 years of age with television-related injuries and entered in the Pennsylvania Trauma Outcome Study (PTOS) between 1989 and 1999 were reviewed. The authors examined Glascow coma scale (GCS), injury severity score (ISS), length of hospital stay (LOS), major injuries sustained, and operative procedures performed. Fourteen of the children in the PTOS were seen at the Benedum Pediatric Trauma Center at the Children's Hospital of Pittsburgh. In these 14 children, a review of the medical records was performed for a detailed description of the accident scenario. Forty-three children sustained television-related injuries during this period. Nearly 56% of these children were </= years; 60% were boys. The mortality rate was 11% with 80% of the deaths occurring in children </= years. Furthermore, these children sustained the highest ISS and LOS and lowest GCS. The majority of injuries sustained were head injuries followed by extremity fractures. Dressers and standard television stands were common supportive structures from which the television fell and injured the child. These data show that the majority of television-related injuries occur in toddlers (1 to 3 years) who were left unattended at home. The mortality rate was surprisingly high, especially in children </= years from subsequent head injuries. Prevention focused on improved public awareness of this danger, and modified design of the standard support structures can decrease the number of injuries, which will benefit children overall.


Probe-Based Confocal Laser Endomicroscopy for Imaging TRAIL-Expressing Mesenchymal Stem Cells to Monitor Colon Xenograft Tumors In Vivo.
Mesenchymal stem cells (MSCs) can serve as vehicles for therapeutic genes. However, little is known about MSC behavior in vivo. Here, we demonstrated that probe-based confocal laser endomicroscopy (pCLE) can be used to track MSCs in vivo and individually monitor tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) gene expression within carcinomas. Isolated BALB/c nu/nu mice MSCs (MSCs) were characterized and engineered to co-express the TRAIL and enhanced green fluorescent protein (EGFP) genes. The number of MSCs co-expressing EGFP and TRAIL (TRAIL-MSCs) at tumor sites was quantified with pCLE in vivo, while their presence was confirmed using immunofluorescence (IF) and quantitative polymerase chain reaction (qPCR). The therapeutic effects of TRAIL-MSCs were evaluated by measuring the volumes and weights of subcutaneous HT29-derived xenograft tumors. Intravital imaging of the subcutaneous xenograft tumors revealed that BALB/c mice treated with TRAIL-MSCs exhibited specific cellular signals, whereas no specific signals were observed in the control mice. The findings from the pCLE images were consistent with the IF and qPCR results. The pCLE results indicated that endomicroscopy could effectively quantify injected MSCs that homed to subcutaneous xenograft tumor sites in vivo and correlated well with the therapeutic effects of the TRAIL gene. By applying pCLE for the in vivo monitoring of cellular trafficking, stem cell-based anticancer gene therapeutic approaches might be feasible and attractive options for individualized clinical treatments.


The influence of diets and gut microflora on lectin binding patterns of intestinal mucins in rats.
The mechanisms responsible for the biosynthesis, storage, secretion, or degradation of intestinal mucins are still unclear. Little is known about the carbohydrate composition of mucins in response to changes in the intestinal lumen, so lectin histochemical techniques were used to study the alterations in glycoconjugate synthesis of mucins in rats under different diets and microfloras. Nine-week-old germ-free and conventional rats were given either a purified diet of finely powdered ingredients, including cellulose as a source of fiber, or a more coarsely ground commercial diet of natural ingredients containing crude fiber of cereal origin. To mimic the human situation more closely, a group of rats born germ-free, inoculated with a suspension of human feces, and fed a purified diet were used as an experimental model. In rats fed a commercial diet, the surface goblet cells in the small intestine were more intensely labeled with N-acetyl-glucosamine and sialic acid-linked D-galactose-specific lectins than in rats fed the purified diet. A similar increased staining with a N-acetylgalactosamine-specific lectin was observed in the large intestine of rats fed a commercial diet. The microbial flora modified the crypt-surface glycosylation of fucosyl and sialic acid residues in the large intestine. The human flora specifically altered the goblet cell glycoconjugates in the surface epithelium. The significant changes in goblet cell glycoconjugates reflect the adaptation of the intestinal mucosa to different diets and microbial populations. An overall reduction in sialic acid-linked D-galactose residues in conventional rats and a loss of crypt-to-surface gradient of fucosyl expression in the large intestine of human flora rats are likely to be due to differing strains of glycosidases in the two microflora.


Successful treatment of two patients with gestational trophoblastic neoplasm presenting with emergent neurologic symptoms.
The objective of this study is to present the successful treatment of two young patients with gestational trophoblastic neoplasms (GTN) presenting with emergent neurologic symptoms without any gynecological problems. Case 1, a 22-year-old patient, was admitted to an infectious disease ward, with admitting diagnosis of encephalitis due to neurologic symptoms. Case 2, a 33-year-old patient, underwent craniotomy due to hemorrhagic brain tumor in the neurosurgery department. The diagnosis of GTN should be considered in any woman of reproductive age who has neurologic symptoms. It seems that multiagent chemotherapy in conjunction with whole-brain irradiation results in acceptable survival rate in brain metastatic GTN patients. Craniotomy is often necessary in fulminant cases.


Two new sesquiterpene dimers isolated from the roots of Saussurea lappa (Yunmuxiang).
Two new sesquiterpene dimers, lappadimers A and B, were isolated from the roots of Saussurea lappa (Yunmuxiang). Their structures were established on the basis of spectroscopic methods. They were found to have potential anti-inflammatory activity at 10 µM and could reduce LPS-induced NO levels in murine macrophage, with inhibitory rates of 67% and 47%, respectively.


Different regulated expression of the tyrosine phosphatase-like proteins IA-2 and phogrin by glucose and insulin in pancreatic islets: relationship to development of insulin secretory responses in early life.
IA-2 and phogrin are tyrosine phosphatase-like proteins that may mediate interactions between secretory granules and cytoskeleton in islets and neuroendocrine tissues. We investigated factors that regulate IA-2 and phogrin expression and their relationship to maturation of insulin secretory responses that occur after birth. Islet content of IA-2, but not phogrin, increased during the first 10 days of life in rats, when insulin secretion in response to glucose increased to adult levels. In cultured 5-day-old rat islets, IA-2 protein and mRNA was increased by glucose and agents that potentiate insulin secretion by the cAMP pathway. Addition of insulin increased IA-2 protein levels and insulin biosynthesis without affecting IA-2 mRNA. Blocking insulin secretion with diazoxide or insulin action with insulin receptor antibodies inhibited glucose-induced increases in IA-2 protein, but not those of mRNA. Phogrin expression was unchanged by all agents. Thus, IA-2 is regulated at the mRNA level by glucose and elevated cAMP, whereas locally secreted insulin modulates IA-2 protein levels by stimulating biosynthesis. In contrast, phogrin expression is insensitive to factors that modify beta-cell function. These results demonstrate differential regulation of two closely related secretory granule components and identify IA-2 as a granule membrane protein subject to autocrine regulation by insulin.


NMDA receptors and fear extinction: implications for cognitive behavioral therapy.
Based primarily on studies that employ Pavlovian fear conditioning, extinction of conditioned fear has been found to be mediated by N-methyi-D-aspartate (NMDA) receptors in the amygdala and medial prefrontal cortex. This led to the discovery that an NMDA partial agonist, D-cycloserine, could facilitate fear extinction when given systemically or locally into the amygdala. Because many forms of cognitive behavioral therapy depend on fear extinction, this led to the successful use of D-cycloserine as an adjunct to psychotherapy in patients with so-called simple phobias (fear of heights), social phobia, obsessive-compulsive behavior, and panic disorder. Data in support of these conclusions are reviewed, along with some of the possible limitations of D-cycloserine as an adjunct to psychotherapy.


Dating violence at three time periods: 1976, 1992, and 1996.
Data collected over the past 10 years were used to investigate whether there have been changes in the incidence of violence when dating reported at a large university. Responses to Straus's 1979 Conflict Tactics Scale in 1986 (n = 603), 1992 (n = 414), and 1996 (n = 571) were compared. Analyzes indicated that there has been a reduction in both verbal aggression and violence scores over the 10-yr. period. In addition, the percentage of respondents who reported being in nonviolent relationships increased while the percentage of respondents in the three categories of relationship that include violence (mutual, perpetrator, and victim) decreased. These findings indicate that there may be an over-all reduction in both verbal aggression and violence between dating partners as they attempt to resolve conflicts.


A systematic review and meta-analysis of velamentous cord insertion among singleton pregnancies and the risk of preterm delivery.
Observational studies have reported varying results about the association of velamentous cord insertion (VCI) with adverse pregnancy outcomes. To evaluate the risk of preterm delivery among singleton pregnancies complicated by VCI. Various databases were searched for English-language articles published up to February, 28, 2017, using keywords including VCI; abnormal placentation; abnormal cord insertions; adverse perinatal outcomes; and preterm birth. Outcome measures included preterm delivery; pre-eclampsia; cesarean delivery; fetal demise in utero (FDIU); and small for gestational age (SGA). Only studies involving VCI were included in the meta-analysis. Analyses were performed using RevMan version 5.3.5 (The Nordic Cochrane Centre, Copenhagen, Denmark). There were six studies included in the analysis. The VCI and control groups comprised 16 295 and 1 366 485 women, respectively. An increased incidence of preterm delivery was found for the VCI group compared with the control group (11.8% vs 7.0%; adjusted odds ratio [aOR] 1.95, 95% confidence interval [CI] 1.85-2.04). A diagnosis of VCI was also associated with cesarean delivery (aOR 1.17, 95% CI 1.12-1.23), SGA (aOR 1.93, 95% CI 1.83-2.04), and FDIU (aOR 3.96, 95% CI 3.21-4.89). The presence of VCI was associated with adverse pregnancy outcomes.


Clinics in diagnostic imaging (28).
A 44-year-old man presented with sudden headache and neck stiffness. Computed tomography (CT) demonstrated subarachnoid haemorrhage. CT and magnetic resonance (MR) angiography showed the cause to be a ruptured anterior communicating artery aneurysm. These findings were confirmed by digital subtraction angiogram and at surgery. The role of imaging in detection of cerebral aneurysms is briefly discussed.


Folin-Ciocalteu Reaction Alternatives for Higher Polyphenol Quantitation in Colombian Passion Fruits.
Passiflora edulis Flavicarpa, Passiflora edulis Sims, and Passiflora ligularis Juss are Colombian fruits (passion fruits) of important exportation value. They act efficiently as antioxidants, antifungal, and antimicrobial compounds due to their high polyphenol content. Polyphenols can be quantified by the Folin-Ciocalteu (F-C) reaction. Food matrices, solvent polarity, and several different reacting conditions are critical for the optimum extraction and quantification of polyphenols. Chromatographic identification and quantitation are satisfactory with access to a vast number of reference standards considering the availability of abundant phenolic compounds in crude extracts. The purpose of this study was to evaluate alternatives and specific F-C reacting conditions aiming at determining the highest total phenolic content (TPC) in three Colombian Passifloras. Among optimum reacting conditions, reduced reaction time and diluted alkali conditions yielded desirable positive results highlighting lower working time and minimum reagent waste production. For higher extraction yield, acetone 70% was the best solvent to capture more phenolics from the seedless pulp of these Colombian passion fruits.


[Exploring the stem cell surface markers expressed in human dental pulp stem cells].
To explore the stem cell surface markers expressed in human dental pulp stem cells which were selected and isolated by magnetic beads. Human dental pulp cells (hDPCs) were separated and cultured from dental pulp of healthy third molars for orthodontic purpose. HDPSCs were isolated from cultured hDPCs by magnetic-activated cell sorting's (MACS) indirect magnetic cell labeling and positive selection strategy with antibody STRO-1 in the 2nd generation. Then the stem cell surface markers (CD73, CD90, CD105, CD166 and STRO-1) were respectively detected in 3, 4, 5, 6, 7 and 8 generation of dental pulp stem cells. HDPSCs were induced to differentiation by adipogenic medium and osteogenic medium in the 3rd generation. Adipogenic differentiation was assessed by oil red O staining in day 21, and osteogenic differentiation was assessed by alizarin red staining in day 21. HDPSCs could differentiate into adipocyte and osteoblasts. Oil red O staining and alizarin red staining were positively expressed after induction of HDPSCs. STRO-1's expression was decreased with the increase of generation. The expressions of CD73, CD90, CD105 and CD166 were relatively stable. The expression of STRO-1 is declined with the increase of generation, and the expressions of CD73, CD90, CD105 and CD166 are relatively stable with the changes of generation. Supported by National Natural Science Foundation of China (81070826/81371143) and Shanghai Rising-Star Program (12QH1401400).