Mentalising and social problem solving in adults with Asperger's syndrome.
It is well established that autistic spectrum disorder is linked to difficulties with mentalising, but the ways in which this affects everyday behaviour is less well understood. This study explored the nature and extent of difficulties in everyday social functioning in adults with Asperger's syndrome (AS), since increased understanding can enhance the development of more effective intervention strategies. Individuals with AS (n=21) were compared with healthy control participants (n=21) on three tests of social cognition: the Mentalistic Interpretation task, which assesses interpretation of sarcasm and actions; the Social Problem Fluency task, which assesses ability to generate problem solutions; and the Social Problem Resolution task, which assesses judgement in selecting problem solutions. Comprehension of both sarcastic remarks and actions was impaired in those with AS on the mentalistic interpretation task. Participants with AS showed difficulties in identifying the awkward elements of everyday social scenarios, and they were also impaired in generating problem solutions but not in judging alternative solutions on the social problem fluency and resolution tasks. These tasks potentially provide a means of profiling strengths and weaknesses in social processing, which in turn has implications for informing clinical evaluation and training.


Hepatic Radiofrequency Ablation-induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition.
To elucidate how hepatic radiofrequency (RF) ablation affects distant extrahepatic tumor growth by means of two key molecular pathways. Rats were used in this institutional animal care and use committee-approved study. First, the effect of hepatic RF ablation on distant subcutaneous in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly assigned to standardized RF ablation, sham procedure, or no treatment. Tumor growth rate was measured for 3½ to 7 days. Then, tissue was harvested for Ki-67 proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation was performed for hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and c-Met receptor expression measurement in periablational rim, serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant tumor growth and growth factor levels. Finally, hepatic RF ablation was performed in rats with c-Met-negative R3230 tumors for comparison with the native c-Met-positive line. Tumor size and immunohistochemical quantification at day 0 and at sacrifice were compared with analysis of variance and the two-tailed Student t test. Tumor growth curves before and after treatment were analyzed with linear regression analysis to determine mean slopes of pre- and posttreatment growth curves on a per-tumor basis and were compared with analysis of variance and paired two-tailed t tests. After RF ablation of normal liver, distant R3230 tumors were substantially larger at 7 days compared with tumors treated with the sham procedure and untreated tumors, with higher growth rates and tumor cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF ablation predominantly increased periablational and serum HGF and downstream distant tumor VEGF levels. Compared with RF ablation alone, RF ablation combined with adjuvant PHA-665752 or semaxanib reduced distant tumor growth, proliferation, and microvascular density. For c-Met-negative tumors, hepatic RF ablation did not increase distant tumor growth, proliferation, or microvascular density compared with sham treatment. RF ablation of normal liver can stimulate distant subcutaneous tumor growth mediated by HGF/c-Met pathway and VEGF activation. This effect was not observed in c-Met-negative tumors and can be blocked with adjuvant c-Met and VEGF inhibitors.


Binding of N-substituted anthracenecarboxamides to double-stranded DNA: an electronic spectral study.
The electronic absorption and fluorescence spectra of two isomeric anthracenecarboxamides substituted with quaternary alkyl ammonium groups were studied as a function of solvent polarity, solvent rigidity, and state of protonation. These relatively simple environmental perturbations of the electronic spectra were employed to interpret spectral shifts caused by complexation with the bases or base pairs of DNA. The exocyclic side chains of the compounds studied have some freedom of movement when the spectroscopic probes are bound to double-stranded DNA.


The QT and Tp-e intervals in left and right chest leads: comparison between patients with systemic and pulmonary hypertension.
Action potential duration in the right ventricle is normally shorter than that in the left. We tested the hypothesis that there may be intrinsic differences in the QT and Tp-e (an interval from the peak to the end of the T wave) intervals between the left and right chest leads that can be exaggerated by systemic hypertension but attenuated by pulmonary hypertension in humans. Electrocardiograms in the left (V4L-V6L) and right (V4R-V6R) chest leads were obtained in 40 healthy individuals, 29 patients with systemic hypertension and left ventricular hypertrophy, and 15 patients with pulmonary hypertension. In healthy individuals, the corrected QT (QTc) and corrected Tp-e [T(p-e)c] intervals were 421+/-5 and 86+/-3 milliseconds in V4L through V6L, respectively, significantly longer than those recorded from V4R through V6R (383+/-5 and 62+/-4 milliseconds, respectively; P<.01). Left ventricular hypertrophy prolonged the QTc interval in V4L through V6L (456+/-5 milliseconds), exaggerating the difference in the QTc interval between the left and right chest leads (61+/-4 vs 40+/-3 milliseconds in healthy control subjects; P<.01). Left ventricular hypertrophy also resulted in a small but significant increase in the T(p-e)c interval in V4L through V6L (97+/-3 vs 86+/-3 milliseconds in control subjects; P<.05) but exerted no significant effect on the T(p-e)c interval in the right. In contrast, pulmonary hypertension lengthened the QTc interval in the right chest leads, reducing the difference in the QTc interval between the left and right chest leads (3+/-8 vs 40+/-3 milliseconds in control subjects; P<.01). There are intrinsic differences in the QT and Tp-e intervals between V4L-V6L and V4R-V6R that are significantly amplified by systemic hypertension but markedly attenuated by pulmonary hypertension.


Immunoanalysis methods for the detection of dioxins and related chemicals.
With the development of biotechnology, approaches based on antibodies, such as enzyme-linked immunosorbent assay (ELISA), active aryl hydrocarbon immunoassay (Ah-I) and other multi-analyte immunoassays, have been utilized as alternatives to the conventional techniques based on gas chromatography and mass spectroscopy for the analysis of dioxin and dioxin-like compounds in environmental and biological samples. These screening methods have been verified as rapid, simple and cost-effective. This paper provides an overview on the development and application of antibody-based approaches, such as ELISA, Ah-I, and multi-analyte immunoassays, covering the sample extraction and cleanup, antigen design, antibody preparation and immunoanalysis. However, in order to meet the requirements for on-site fast detection and relative quantification of dioxins in the environment, further optimization is needed to make these immuno-analytical methods more sensitive and easy to use.


Rapid Microwave-Assisted Synthesis of ZnIn2S4 Nanosheets for Highly Efficient Photocatalytic Hydrogen Production.
In this study, a facile and rapid microwave-assisted synthesis method was used to synthesize In2S3 nanosheets, ZnS nanosheets, and ZnIn2S4 nanosheets with sulfur vacancies. The two-dimensional semiconductor photocatalysts of ZnIn2S4 nanosheets were characterized by XRD, FESEM, BET, TEM, XPS, UV-vis diffuse reflectance, and PL spectroscopy. The ZnIn2S4 with sulfur vacancies exhibited an evident energy bandgap value of 2.82 eV, as determined by UV-visible diffuse reflectance spectroscopy, and its energy band diagram was obtained through the combination of XPS and energy bandgap values. ZnIn2S4 nanosheets exhibited about 33.3 and 16.6 times higher photocatalytic hydrogen production than In2S3 nanosheets and ZnS nanosheets, respectively, under visible-light irradiation. Various factors, including materials, sacrificial reagents, and pH values, were used to evaluate the influence of ZnIn2S4 nanosheets on photocatalytic hydrogen production. In addition, the ZnIn2S4 nanosheets revealed the highest photocatalytic hydrogen production from seawater, which was about 209.4 and 106.7 times higher than that of In2S3 nanosheets and ZnS nanosheets, respectively. The presence of sulfur vacancies in ZnIn2S4 nanosheets offers promising opportunities for developing highly efficient and stable photocatalysts for photocatalytic hydrogen production from seawater under visible-light irradiation.


A structured model for simulation of cultures of the cyanobacterium Spirulina platensis in photobioreactors: I. Coupling between light transfer and growth kinetics.
The study of the interactions between physical limitation by light and biological limitations in photobioreactors leads to very complex partial differential equations. Modeling of light transfer and kinetics and the assessment of radiant energy absorbed in photoreactors require an equation including two parameters for light absorption and scattering in the culture medium. In this article, a simple model based on the simplified, monodimensional equation of Schuster for radiative transfer is discussed. This approach provides a simple way to determine a working illuminated volume in which growth occurs, therefore allowing identification of kinetic parameters. These parameters might then be extended to the analysis of more complex geometries such as cylindrical reactors. Moreover, this model allows the behavior of batch or continuous cultures of cyanobacteria under light and mineral limitations to be predicted.


Quantifying local characteristics of velocity, aggregation and hematocrit of human erythrocytes in a microchannel flow.
The effect of erythrocyte aggregation on blood viscosity and microcirculatory flow is a poorly understood area of haemodynamics, especially with relevance to serious pathological conditions. Advances in microfluidics have made it possible to study the details of blood flow in the microscale, however, important issues such as the relationship between the local microstructure and local flow characteristics have not been investigated extensively. In the present study an experimental system involving simple brightfield microscopy has been successfully developed for simultaneous, time-resolved quantification of velocity fields and local aggregation of human red blood cells (RBC) in microchannels. RBCs were suspended in Dextran and phosphate buffer saline solutions for the control of aggregation. Local aggregation characteristics were investigated at bulk and local levels using statistical and edge-detection image processing techniques. A special case of aggregating flow in a microchannel, in which hematocrit gradients were present, was studied as a function of flowrate and time. The level of aggregation was found to strongly correlate with local variations in velocity in both the bulk flow and wall regions. The edge detection based analysis showed that near the side wall large aggregates are associated with regions corresponding to high local velocities and low local shear. On the contrary, in the bulk flow region large aggregates occurred in regions of low velocity and high erythrocyte concentration suggesting a combined effect of hematocrit and velocity distributions on local aggregation characteristics. The results of this study showed that using multiple methods for aggregation quantification, albeit empirical, could help towards a robust characterisation of the structural properties of the fluid.


Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma.
The use of neuronal nuclear antigen (NeuN) as a reliable neuronal marker in the differential diagnosis of clear cell neoplasms of the central nervous system was determined in a biopsy series of 23 cases. Immunohistochemical analyses were carried out by antisera against neuronal nuclear antigen, synaptophysin, neuron-specific enolase, microtubule-associated protein 2, and glial fibrillary acidic protein. All eight central neurocytomas were characteristically immunolabeled by NeuN. NeuN immunoreactivity was uniformly strong and basically located in the nuclei of neurocytes. Despite this uniform staining pattern of central neurocytomas, 12 cases of oligodendrogliomas and three cases of ependymoma were negative for NeuN. As the diagnostic criteria for central neurocytoma include immunohistochemical and/or ultrastructural evidence for neuronal differentiation, NeuN as a sensitive and specific neuronal marker in formalin-fixed, paraffin-embedded tissues may greatly facilitate the differential diagnosis of central neurocytomas.


Protein translocation by the Sec61/SecY channel.
The conserved protein-conducting channel, referred to as the Sec61 channel in eukaryotes or the SecY channel in eubacteria and archaea, translocates proteins across cellular membranes and integrates proteins containing hydrophobic transmembrane segments into lipid bilayers. Structural studies illustrate how the protein-conducting channel accomplishes these tasks. Three different mechanisms, each requiring a different set of channel binding partners, are employed to move polypeptide substrates: The ribosome feeds the polypeptide chain directly into the channel, a ratcheting mechanism is used by the eukaryotic endoplasmic reticulum chaperone BiP, and a pushing mechanism is utilized by the bacterial ATPase SecA. We review these translocation mechanisms, relating biochemical and genetic observations to the structures of the protein-conducting channel and its binding partners.


Colloids in food: ingredients, structure, and stability.
This article reviews progress in the field of food colloids with particular emphasis on advances in novel functional ingredients and nanoscale structuring. Specific aspects of ingredient development described here are the stabilization of bubbles and foams by the protein hydrophobin, the emulsifying characteristics of Maillard-type protein-polysaccharide conjugates, the structural and functional properties of protein fibrils, and the Pickering stabilization of dispersed droplets by food-grade nanoparticles and microparticles. Building on advances in the nanoscience of biological materials, the application of structural design principles to the fabrication of edible colloids is leading to progress in the fabrication of functional dispersed systems-multilayer interfaces, multiple emulsions, and gel-like emulsions. The associated physicochemical insight is contributing to our mechanistic understanding of oral processing and textural perception of food systems and to the development of colloid-based strategies to control delivery of nutrients during food digestion within the human gastrointestinal tract.


Estimates of cost-effectiveness of prehospital continuous positive airway pressure in the management of acute pulmonary edema.
To estimate the cost-effectiveness of continuous positive airway pressure (CPAP) in managing prehospital acute pulmonary edema in an urban EMS system. Using estimates from published reports on prehospital and emergency department CPAP, a cost-effectiveness model of implementing CPAP in a typical urban EMS system was derived from the societal perspective as well as the perspective of the implementing EMS system. To assess the robustness of the model, a series of univariate and multivariate sensitivity analyses was performed on the input variables. The cost of consumables, equipment, and training yielded a total cost of $89 per CPAP application. The theoretical system would be expected to use CPAP 4 times per 1000 EMS patients and is expected to save 0.75 additional lives per 1000 EMS patients at a cost of $490 per life saved. CPAP is also expected to result in approximately one less intubation per 6 CPAP applications and reduce hospitalization costs by $4075 per year for each CPAP application. Through sensitivity analyses the model was verified to be robust across a wide range of input variable assumptions. Previous studies have demonstrated the clinical effectiveness of CPAP in the management of acute pulmonary edema. Through a theoretical analysis which modeled the costs and clinical benefits of implementing CPAP in an urban EMS system, prehospital CPAP appears to be a cost-effective treatment.


Biochemical properties and kinetic parameters of monoamine oxydase in human seminal plasma.
The present study demonstrates that monoamine oxydase (MAO) is present in the human seminal plasma and that its activity was higher in infertile than in fertile men. The Km and Vmax of the enzyme were, respectively, 3.0 X 10(-3) M and 625 eta mol of deaminated 5-HT mg of prot-1 min-1. The enzyme was activated by pyridoxal-5' phosphate but inhibited by usual MAO inhibitors such as pargyline-HCl, iproniazid-PO4 and clorgyline. These findings suggest a relationship between the synthesis and degradation of biogenic amines and testicular function.


Soy isoflavones increase quinone reductase in hepa-1c1c7 cells via estrogen receptor beta and nuclear factor erythroid 2-related factor 2 binding to the antioxidant response element.
Soy protein and isoflavones (genistein and daidzein) have been demonstrated to increase quinone reductase (QR) activity, protein, and mRNA in animal and cell culture models. However, their mechanism of action has not been completely characterized. Additionally, it has not been determined if equol, a daidzein metabolite, can modulate QR activity and expression. Estrogen receptor beta (ERβ) is thought to be involved in stimulating QR gene transcription by anti-estrogens and phytoestrogens, along with nuclear factor erythroid 2-related factor 2 (Nrf2). This study tested the hypothesis that genistein, daidzein and equol increase quinone reductase activity, protein and mRNA via ERβ and Nrf2 binding to the QR antioxidant response element (ARE). QR expression and activity were determined using TaqMan polymerase chain reaction, protein immunoblots and activity assays. Molecular events were investigated using luciferase reporter gene assays and chromatin immunoprecipitation (ChIP). Hepa-1c1c7 cells were treated with control [0.1% (v:v) dimethyl sulfoxide (DMSO)]; 1 μmol/L β-naphthoflavone (positive control); 5 μmol/L resveratrol (ChIP positive control for ERβ binding) and 1, 5 and 25 μmol/L genistein, daidzein or equol. Treatment durations were 1 h (ChIP), 24 h (mRNA and luciferase assays) and 24 and 48 h (protein and activity). Genistein, daidzein and equol increased QR activity, protein and mRNA, with daidzein and equol having more of an impact at physiologic concentrations (1 and 5 μmol/L) compared to genistein. Furthermore, the study results demonstrate that genistein, daidzein and equol interact with the QR ARE and that daidzein and equol act via both ERβ and Nrf2 binding strongly to the QR ARE.


Nicotinic acid action on gastrointestinal smooth muscle.
The mechanism of nicotinic acid action in smooth muscle was studied by testing the drug in rat stomach fundus and descending colon using either the superfusion or perfusion technique. In the rat stomach strips nicotinic acid (or Na-nicotinate) induces concentration-dependent contractions that are drastically antagonized by indomethacin but not by the other inhibitors tested (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine, imidazole, anacardic acid). Reduced glutathione, on the contrary, clearly potentiates the contractile effect of nicotinic acid in the tissue. The response of the rat stomach strips to different prostanoids (PGE1, PGE2 alpha, PGF2 alpha, and PGI2) shows that only PGE2 (at a very low concentration: 14 nM) induces muscle contraction similar to that evoked by Na-nicotinate (34.4 nM). In segments of rat descending colon Na-nicotinate induces concentration-dependent contractions that are abolished by scopolamine, by hemicholinium-3 or incubation at low temperature (20 degrees C). These results provide evidence that nicotinic acid influences gastrointestinal smooth muscle by indirect mechanisms, i.e. by release of endogenous autacoids, namely prostaglandins in the stomach fundus and cholinergic transmitter in the descending colon.


A Rapid Method for the Quantitative Determination of 34 Pesticides in Nonalcoholic Carbonated Beverages Using Liquid-Liquid Extraction Coupled to Dispersive Solid-Phase Cleanup Followed by Gas Chromatography with Tandem Mass Spectrometry.
An economical, rapid, and sensitive multiresidue method using liquid-liquid extraction (LLE) coupled with dispersive SPE (dSPE) cleanup was developed for the quantitative determination of 34 multiclass multiresidue (MCMR) pesticides (14 organochlorines, eight organophosphates, 10 synthetic pyrethroids, and two herbicides) in nonalcoholic carbonated beverages (cola, orange, lemon-lime, and citra) using GC with tandem MS. The procedure mainly involved LLE by dichloromethane and dSPE cleanup in the presence of magnesium sulfate, primary secondary amine, and C18. The RSD of the developed method was found to be less than 14%. The LOD and LOQ values for all the analyzed pesticides were found in the ranges of 0.001-0.027 μg/L and 0.004-0.088 μg/L, respectively. The LOQ levels of the pesticides analyzed were found to be well below the recommended limit by the European Union (0.1 μg/L in water). The mean recoveries of pesticides in different nonalcoholic carbonated beverages (cola, orange, lemon-lime, and citra) were found to be in the range of 79-111%, with RSDs less than 11%. The validation data prove that the method can be acceptable to regulatory agencies for the routine analysis of MCMR pesticides in nonalcoholic carbonated beverages.


Genetic predisposition scores associate with muscular strength, size, and trainability.
The number of studies trying to identify genetic sequence variation related to muscular phenotypes has increased enormously. The aim of this study was to identify the role of a genetic predisposition score (GPS) based on earlier identified gene variants for different muscular endophenotypes to explain the individual differences in muscular fitness characteristics and the response to training in patients with coronary artery disease. Two hundred and sixty coronary artery disease patients followed a standard ambulatory, 3-month supervised training program for cardiac patients. Maximal knee extension strength (KES) and rectus femoris diameter were measured at baseline and after rehabilitation. Sixty-five single nucleotide polymorphisms (SNP) in 30 genes were selected based on genotype-phenotype association literature. Backward regression analysis revealed subsets of SNP associated with the different phenotypes. GPS were constructed for all sets of SNP by adding up the strength-increasing alleles. General linear models and multiple stepwise regression analysis were used to test the explained variance of the GPS in baseline and strength responses. Receiver operating characteristic curve analyses were performed to discriminate between high- and low-responder status. GPS were significantly associated with the rectus femoris diameter (P < 0.01) and its response (P < 0.0001), the isometric KES (P < 0.05) and its response (P < 0.01), the isokinetic KES at 60° · s (P < 0.05) and 180° · s (P < 0.001) and their responses to training (P < 0.0001), and the isokinetic KES endurance (P < 0.001) and its change after training (P < 0.0001). The GPS was shown as an independent determinant in baseline and response phenotypes with partial explained variance up to 23%. Receiver operating characteristic analysis showed a significant discriminating accuracy of the models, including the GPS for responses to training, with areas under the curve ranging from 0.62 to 0.85. GPS for muscular phenotypes showed to be associated with baseline KES, muscle diameter, and the response to training in cardiac rehabilitation patients.


ILI-related school dismissal monitoring system: an overview and assessment.
This report provides an overview and assessment of the School Dismissal Monitoring System (SDMS) that was developed by the Centers for Disease Control and Prevention (CDC) and the US Department of Education (ED) to monitor influenza-like illness (ILI)-related school dismissals during the 2009-2010 school year in the United States. SDMS was developed with considerable consultation with CDC's and ED's partners. Further, each state appointed a single school dismissal monitoring contact, even if that state also had its own school-dismissal monitoring system in place. The SDMS received data from three sources: (1) direct reports submitted through CDC's Web site, (2) state monitoring systems, and (3) media scans and online searches. All cases identified through any of the three data sources were verified. Between August 3, 2009, and December 18, 2009, a total of 812 dismissal events (ie, a single school dismissal or dismissal of all schools in a district) were reported in the United States. These dismissal events had an impact on 1947 schools, approximately 623 616 students, and 40 521 teachers. The SDMS yielded real-time, national summary data that were used widely throughout the US government for situational awareness to assess the impact of CDC guidance and community mitigation efforts and to inform the development of guidance, resources, and tools for schools.


Identifying potential drivers of distribution patterns of invasive Corbicula fluminea relative to native freshwater mussels (Unionidae) across spatial scales.
This study aimed to identify the importance of ecological factors to distribution patterns of the invasive Clam (Corbicula fluminea) relative to native mussels (family: Unionidae) across seven rivers within the Mobile and Tennessee basins, Southeast United States. We quantitatively surveyed dense, diverse native mussel aggregations across 20 river reaches and estimated mussel density, biomass, and species richness along with density of invasive C. fluminea (hereafter Corbicula). We measured substrate particle size, velocity, and depth in quadrats where animals were collected. Additionally, we characterized reach scale environmental parameters including seston quantity and quality (% Carbon, % Nitrogen, % Phosphorous), water chemistry (ammonium [ NH 4 + ], soluble reactive phosphorous [SRP]), and watershed area and land cover. Using model selection, logistic regression, and multivariate analysis, we characterized habitat features and their association to invasive Corbicula within mussel beds. We found that Corbicula were more likely to occur and more abundant in quadrats with greater mussel biomass, larger substrate size, faster water velocity, and shallower water depth. At the reach scale, Corbicula densities increased where particle sizes were larger. Mussel richness, density, and biomass increased with watershed area. Water column NH 4 + increased at reaches with more urban land cover. No land cover variables influenced Corbicula populations or mussel communities. The strong overlapping distribution of Corbicula and mussels support the hypothesis that Corbicula are not necessarily limited by habitat factors and may be passengers of change in rivers where mussels have declined due to habitat degradation. Whether Corbicula is facilitated by mussels or negatively interacts with mussels in these systems remains to be seen. Focused experiments that manipulate patch scale variables would improve our understanding of the role of species interactions (e.g., competition, predation, facilitation) or physical habitat factors in influencing spatial overlap between Corbicula and native mussels.


Acute ST-segment elevation myocardial infarction: a rare initial presentation of previously undiagnosed essential thrombocythemia.
Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by hemorrhagic and thrombotic complications. We describe a rare case of ST-segment elevation myocardial infarction (STEMI) in a patient with previously undiagnosed ET, confirmed by gene mutation. A 68-year-old man presented with severe acute chest pain and was diagnosed with STEMI. Primary coronary angiography showed severe stenosis with thrombus in the proximal left anterior descending coronary artery. Percutaneous aspiration thrombectomy was performed with no residual stenosis. The patient was discharged on antiplatelet agents, aspirin, and clopidogrel. Further investigations for intracoronary thrombus with no underlying atherosclerotic disease revealed positive Janus kinase 2 (JAK2) V617F gene mutation, and this was consistent with a diagnosis of ET with elevated platelet count. This case describes a rare initial presentation of previously undiagnosed ET with acute STEMI and highlights the potential importance of secondary workup for non-atherosclerotic causes of STEMI with isolated intracoronary thrombus otherwise normal coronary vasculature with no focal atherosclerosis.


Huge Aneurysm of the Proper Hepatic Artery.
Hepatic artery aneurysms are rarely diagnosed. It is mainly because of non specific symptoms. They are generally an incidental findings during imaging studies. They are usually detected in the sixth decade, predominantly in men. We report herein a case of an 80 year-old man with a huge hepatic artery aneurysm revealed by abdominal pain and chronic anemia. It was treated by embolisation. Hepatic artery aneurysms are second among visceral aneurysms. They may cause abdominal pain, jaundice and hemorrhagic events.


[Secondary prevention following cerebral ischemia: is monotherapy with acetylsalicylic acid still first choice?].
Acetylsalicylic acid (ASA) alone (at least 30 mg per day) in post-cerebral ischaemia patients reduces the relative risk of further vascular events by 13% compared with placebo. A meta-analysis of all studies shows that the combination of ASA with dipyridamole reduces the relative risk by 16% (95% confidence interval: 5-26%) compared with ASA alone, but confirmation by a major trial appears desirable, because of discrepant results of a recent trial and 4 previous ones. Clopidogrel might reduce the risk by 7% compared with ASA alone, but this drug is expected to be expensive. Anticoagulation therapy with an international normalized ratio (INR) of 2.0-4.0 is particularly efficacious for secondary prevention in patients with atrial fibrillation, but anticoagulation therapy with an INR of 3.0-4.5 is not safe in secondary prevention of cerebral ischaemia of presumed arterial origin. Finally, not all atherosclerotic vascular diseases are identical from the therapeutic point of view; the effect of treatment depends in part on the clinical manifestation form.


Unexpected synergistic and antagonistic antibiotic activity against Staphylococcus biofilms.
To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management of periprosthetic joint infections (PJIs). Using the dissolvable bead biofilm assay, the minimum biofilm eradication concentration (MBEC) was determined for the most commonly used antimicrobial agents and combination regimens against staphylococcal PJIs. The established fractional inhibitory concentration (FIC) index was modified to create the fractional biofilm eradication concentration (FBEC) index to evaluate synergism or antagonism between antibiotics. Only gentamicin (MBEC 64 mg/L) and daptomycin (MBEC 64 mg/L) were observed to be effective antistaphylococcal agents at clinically achievable concentrations. Supplementation of gentamicin with daptomycin, vancomycin or ciprofloxacin resulted in a similar or lower MBEC than gentamicin alone (FBEC index 0.25-2). Conversely, when rifampicin, clindamycin or linezolid was added to gentamicin, there was an increase in the MBEC of gentamicin relative to its use as a monotherapy (FBEC index 8-32). This study found that gentamicin and daptomycin were the only effective single-agent antibiotics against established Staphylococcus biofilms. Interestingly the addition of a bacteriostatic antibiotic was found to antagonize the ability of gentamicin to eradicate Staphylococcus biofilms.


Experimental Evidence for the Role of Intonation in Evidential Marking.
This paper investigates the role of intonation in the marking of directly-perceived information in Majorcan Catalan polar questions. We conducted a perception experiment in which a total of 72 participants were introduced to a set of twins who were exposed to different types of evidence for a given p(roposition). One twin inferred p based on direct sensory information (via one of the five senses), while the other had been told that p by a third party, that is, reported information. Participants listened to a set of discourse contexts that ended in critical stimuli with three attested combinations of particle/intonation in this variety of Catalan: (1) polar questions produced with a falling nuclear contour ¡H+L* L%; (2) polar questions headed with the particle que 'that' produced with ¡H+L* L%; and (3) polar questions headed with the particle que and produced with a rise-fall L+H* L%. After hearing the stimulus, participants had to decide which of the twins had uttered the question-the one who inferred a proposition ( p) based on direct sensory information or the one who had been told p by a third party. The results show that listeners very consistently associate the que + L+H* L% combination with inferences drawn from direct sensory evidence as opposed to reported evidence. This shows that particles may work in tandem with intonation to convey the information source. Importantly, we show that intonation is a part of grammar that may be recruited for evidential strategies.


Extra-articular step osteotomy of the olecranon: A biomechanical assessment.
Trans-olecranon chevron osteotomies (COs) remain the gold standard surgical approach to type C fractures of the distal humerus. This technique is associated with a high complication rate and development of an extra-articular olecranon osteotomy may be advantageous. The aim of this study was to compare the load to failure of COs with extra-articular oblique osteotomies (OOs) as well as modified, extra-articular step osteotomies (SOs). These three osteotomies and their subsequent fixation utilizing a standardized tension band wiring technique were tested in 42 composite analog ulnae models at 20° and 70° of flexion. Triceps loading was simulated with a servo hydraulic testing machine. All specimens were isometrically loaded until failure. Kinematic and force data, as well as interfragmentary motion were recorded. At 70°, CO failed at a mean load of 963 N (SD 104 N), the OO at 1512 N (SD 208 N) and the SO at 1484 N (SD 153 N), (P<0.001). At 20°, CO failed at a mean load of 707 N (SD 104 N) and OO at 1009 N (SD 85 N) (P=0.006). The highest load to failure was observed for the SO, which was 1277 N (SD 172 N). The load to failure of the SO was significantly higher than the CO as well as the OO. Extra-articular osteotomies showed a significantly higher load to failure in comparison to traditional CO. At near full extension (20° of flexion), this biomechanical advantage was further enhanced by a step-cut modification of the extra-articular oblique osteotomy.


Effect of recombinant adeno-associated virus expressing calcitonin gene-related peptide on chick embryo umbilical artery vasospasm model.
In the present study, a recombinant adeno-associated virus vector containing the calcitonin gene related peptide gene (rAAV-CGRP) was constructed and the therapeutic effect of rAAV-CGRP on a chick umbilical artery vasospasm model induced by chick embryo allantoic cavity hemorrhage was investigated. Fresh specific pathogen-free fertilized chicken eggs were randomly divided into a rAAV-CGRP group, an empty vector virus (AAV) group, and a control group, with 24 eggs in each group. An umbilical arterial vasospasm model was established using a needle puncture method on a vein in the chorioallantoic membrane to induce a hemorrhage in the allantoic cavity of 11-day-old chicken embryonated eggs. A total of 24 h after model establishment, 1 ml of rAAV-CGRP and empty vector virus solution of rAAV-CGRP and empty vector virus solution was, respectively, injected into the allantoic cavity in the rAAV-CGRP and AAV groups. Experimental results showed that after 72 h of model establishment, the mortality rates of the 3-, 5- and 7-day subgroups in the rAAV-CGRP group were lower than in the subgroups of the AAV injection group. After 3, 5 and 7 days of model establishment in the rAAV-CGRP group, the cross-sectional area of the inner diameter of the umbilical arteries was larger than that of the AAV group; the vessel wall thicknesses of the rAAV-CGRP group were thinner than in the AAV group. In addition, the concentration of CGRP in chick embryo allantoic fluid significantly increased and was several times higher than in the AAV group (P<0.05). In conclusion, administration of rAAV-CGRP through the allantoic cavity may increase the viability of a vasospasm model induced by chick allantoic cavity hemorrhage, significantly improve umbilical artery vasospasm, and increase CGRP expression in the chick embryo allantoic cavity. This approach also provides a novel experimental model for identifying other target genes for the gene therapy of vasospasm.


Knowledge of morphologically complex words: a developmental study of older children and young adolescents.
This study examined knowledge of derived nominals (e.g., measurement, prediction) and derived adjectives (e.g., algebraic, molecular) in older children and young adolescents. Little was known about students' comprehension of these morphologically complex words that occur in textbooks that are used in public schools to teach challenging subjects such as science, mathematics, social studies, health, and literature. The Word Knowledge Task (WKT), designed for the present study, was used to examine participants' comprehension of 15 derived nominals and 15 derived adjectives that were selected from state-adopted textbooks. This written, multiple-choice task was administered to 10-year-old children and 13-year-old adolescents (N = 94) who were attending public schools. All participants spoke English and were typical achievers. The findings indicated that the adolescents outperformed the children on both types of derived words; the derived nominals were more difficult than the derived adjectives for both groups; and comprehension was associated with frequency of occurrence in print, with easier words generally more common than more difficult ones. Knowledge of morphologically complex words such as derived nominals and derived adjectives is a late linguistic attainment. Given the importance of these words for academic success, instructional programs are needed to ensure that children and adolescents are able to learn their meanings using appropriate strategies.


Accuracy of CAD/CAM crown fit with infrared and LED cameras.
The intraoral recording of digital images is a critical component of fabricating accurate Cerec restorations. This study evaluated the marginal fit and internal adaptation of Cerec ceramic crowns fabricated using different cameras, alternative powdering materials, and multiple image capture sequences. A master epoxy resin model was fabricated using a polyvinylsiloxane (PVS) impression of a typodont with an all-ceramic crown preparation on tooth 14. A titanium dioxide powder/mechanical sprayer and an aerosol contrast spray were used to create a uniformly reflective surface. An infrared laser Cerec 3/RedCam unit and LED Cerec AC/BlueCam unit were used to record images for crown fabrication. Three different image capture sequences were performed to record the data. Crowns were made for each test group using a Cerec AC unit with V3.80 software. The crowns were milled from blocks of IPS EmpressCAD. Marginal fit and internal adaptation of the crowns to the master model of the preparation was assessed with a measuring microscope at 20X. The data was analyzed using a two-way ANOVA. No significant differences were found in the marginal fit, axial wall adaptation, or occlusal wall adaptation between any of the test groups (p < 0.05). Within the confines of this in vitro study, there were no significant differences between the marginal fit and internal adaptation of Cerec CAD/CAM ceramic crowns fabricated with: 1) the infrared laser camera (RedCam) and the LED camera (BlueCam), 2) titanium dioxide powder or aerosol contrast spray, or 3) multiple imaging sequences for recording the preparation and adjacent teeth.


A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.
Using accumulating SNP (Single-Nucleotide Polymorphism) data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS), a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6)-NPS) causing non-synonymous substitution on the 6(th) position (V to L) of the NPS mature peptide region. L(6)-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6)-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th) position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.


A case of hypersensitivity syndrome to both vancomycin and teicoplanin.
Drug hypersensitivity syndrome to both vancomycin and teicoplanin has not been previously reported. We describe here a 50-yr-old male patient with vertebral osteomyelitis and epidural abscess who developed hypersensitivity syndrome to both vancomycin and teicoplanin. Skin rash, fever, eosinophilia, interstitial pneumonitis, and interstitial nephritis developed following the administration of each drug, and resolved after withdrawing the drugs and treating with high dose corticosteroids. The vertebral osteomyelitis was successfully treated with 6-week course of linezolid without further complications. Skin patch tests for vancomycin and teicoplanin was done 2 months after the recovery; a weak positive result for vancomycin (10% aq.,+at D2 and +at D4 with erythema and vesicles; ICDRG scale), and a doubtful result for teicoplanin (4% aq.-at D2 and+/-at D4 with macular erythema; ICDRG scale). We present this case to alert clinicians to the hypersensitivity syndrome that can result from vancomycin and teicoplanin, with possible cross-reactivity, which could potentially be life-threatening.


Penile injuries: A 10-year experience.
We report our 10-year experience with penile injuries. We retrospectively reviewed the records of 156 cases of male external genitalia injuries between May 2002 and December 2012. Of these, only 26 patients presented without urethral injuries and were included in this study. Patients were divided into 4 groups: Group 1 (n = 12) with patients with penile fractures injuries; Group 2 (n = 5) with patients with penile amputation injuries; Group 3 (n = 2) with patients with penile penetrating injuries; and Group 4 (n = 7) with patients with penile soft tissue injuries. Grading of injury was done using the American Association for the Surgery of Trauma (AAST)-Organ injury scale of penile injury. Penile injuries without urethral injuries are urological emergencies which require immediate attention.


Staphylococcus aureus Nasal Colonization among Children with Sickle Cell Disease at the Children's Hospital, Accra: Prevalence, Risk Factors, and Antibiotic Resistance.
The aim of this study was to investigate S. aureus carriage among children with sickle cell disease (SCD), including the prevalence, risk factors, and antibiotic resistance. The study was cross-sectional, and involved 120 children with SCD recruited at the Princess Marie Louise Children's Hospital (PML) in Accra and 100 apparently healthy children from environs of the hospital. Nasal swab samples were collected from the study participants and cultured for bacteria. Confirmation of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) isolates were done using the tube coagulase test and mecA polymerase chain reaction, respectively. All the S. aureus isolates were tested against standard antimicrobial agents using the Kirby-Bauer method. A structured questionnaire was used to obtain the socio-demographic and clinical data of the study participants. Binary logistic regression was used to identify determinants of S. aureus and MRSA carriage among the study participants. The nasal carriage prevalence of S. aureus was 33.3% (n = 40) and 10% (n = 10) among the participants of the SCD and control groups, respectively. As regards MRSA nasal carriage prevalence, the respective values were 3.33% (n = 4) and 0.00% (n = 0). SCD was significantly associated with S. aureus colonization (p < 0.0001, OR = 4.045), but not MRSA colonization (p = 0.128). In the SCD group, the significant predictors of S. aureus carriage were increasing age (p = 0.003; OR = 1.275) and living in self-contained apartments (p = 0.033; OR = 3.632), whereas male gender (p = 0.018; OR = 0.344) and the practice of self-medication (p = 0.039; OR = 0.233) were protective of S. aureus carriage. In the control group, a history of hospitalization in the past year was a risk factor for the carriage of S. aureus (p = 0.048; OR = 14.333). Among the participants of the SCD and control groups, respectively, the resistance prevalence recorded by S. aureus against the various antibiotics investigated were penicillin (100% each), cotrimoxazole (27.5% vs. 20%), tetracycline (25% vs. 50%), rifampicin (82.5% vs. 50%), erythromycin (30% vs. 20%), clindamycin (32.5% vs. 50%), gentamicin (7.5% vs. 20%), cefoxitin (27.5% vs. 20%), linezolid (30% vs. 40%), and fusidic acid (95% vs. 80%). The proportion of S. aureus isolates that were multidrug resistant (MDR) was 92.5% (37/40) in the SCD group and 100% (10/10) in the control group.


Design and research of piezoelectric energy harvesting device applicable to wireless mouse.
This paper presents a piezoelectric energy harvesting device applicable to wireless mouse (WM-PEH). Adding magnetic force to the excitation piezoelectric generating unit makes the impact better and more pronounced. The polygonal roller can increase the excitation frequency of the piezoelectric generating unit and broaden the energy collection range and capability of the WM-PEH. The theoretical and simulation analysis of WM-PEH was carried out in this paper. The effects of the length ratio of the exciter rod to the support frame and the circular impact area on the output characteristics of the prototype were discussed in the experiment. When the length ratio of the exciter rod and the support rod is 3:1, the activity increment of the exciter rod is the largest, and the maximum output voltage can reach 42 V and the maximum output power is 22.43 mW when it acts on a circular generator set with a radius of 1.5 mm. The design of the device is highly integrated with the wireless mouse that is widely used, and the piezoelectric energy harvesting mechanism and the wireless mouse are perfectly combined, which provides a scientific basis for the subsequent development of a self-powered wireless mouse.


Historical Review of Acute Pancreatitis Research Over the Last 80 Years.
Research on acute pancreatitis (AP) has been ongoing for a long time. It is necessary to summarize and investigate the history of AP research. Publications related to AP research were retrieved from PubMed. Medical Subject Headings (MeSH) terms, countries, journals, and publication dates were analyzed. Co-occurrence analysis was conducted to illustrate the holistic trend in AP research. A dynamic bar graph, heat maps, and line charts were created to illustrate change trends of MeSH terms. In total, 28,222 publications with 8558 MeSH terms were retrieved from 1941 to 2020. Among these, 16,575 publications with 7228 MeSH terms were from 2001 to 2020. The top 10 MeSH terms showed a considerable change from 1941 to 1970 but remained stable since the 1970s. Four clusters obtained from the co-occurrence analysis were "experiments on animals," "diagnosis and treatment," "prognosis and expectation," and "protein and enzyme." From 1941 to 2020, 33 MeSH terms with increasing trends (MH-I) and 15 MeSH terms with decreasing trends (MH-D) were selected to create a heat map (every decade). Meanwhile, 16 MH-I and 41 MH-D were selected to create the heat map from 2001 to 2020 (every 2 years). Over the past 80 years, the pathogenesis, treatment, risk management, and experimental model were the main research highlights. Optimal supportive management, minimally invasive treatment, and prediction of prognosis are subjects of interest for clinical practitioners; signal transduction to identify a target for precise treatment is the focus of experimental research in AP.


What grid cells convey about rat location.
We characterize the relationship between the simultaneously recorded quantities of rodent grid cell firing and the position of the rat. The formalization reveals various properties of grid cell activity when considered as a neural code for representing and updating estimates of the rat's location. We show that, although the spatially periodic response of grid cells appears wasteful, the code is fully combinatorial in capacity. The resulting range for unambiguous position representation is vastly greater than the approximately 1-10 m periods of individual lattices, allowing for unique high-resolution position specification over the behavioral foraging ranges of rats, with excess capacity that could be used for error correction. Next, we show that the merits of the grid cell code for position representation extend well beyond capacity and include arithmetic properties that facilitate position updating. We conclude by considering the numerous implications, for downstream readouts and experimental tests, of the properties of the grid cell code.


Severe ketoacidosis as the first manifestation of diabetes mellitus after age fifty.
Two women over the age of 50 years presented with ketoacidosis as the first manifestation of diabetes mellitus. The first patient failed to respond to a regimen of hourly intramuscular injections of regular insulin. She only improved when a continuous intravenous infusion of regular insulin was utilized. The second patient was treated with a continuous infusion of insulin for a prolonged period. Her course was uneventful. It is recommended that a regimen of continuous infusion of regular insulin be the treatment of choice in the management of older patients presenting with ketoacidosis at the time of diagnosis of diabetes mellitus.


The Coadministration of Unoxidized and Oxidized Desi Ghee Ameliorates the Toxic Effects of Thermally Oxidized Ghee in Rabbits.
Desi Ghee was thermally oxidized at 160°C for 9 h and characterized for peroxide value (PV), free fatty acid (FFA), thiobarbituric acid reactive substances (TBARS), radical scavenging activity (RSA), and fatty acid and cholesterol composition using GC-MS. Oxidized (OG) and normal ghee (NG) were fed to rabbits in different doses. Blood was collected for hematology and biochemical analyses after 7 and 14 days. The oxidation of desi ghee increased the PV, FFA, and TBARS values and showed a decline in the RSA values. GC-MS revealed that desi ghee was rich in saturated fatty acids (55.9 g/100 g) and significant amounts of oleic acid (26.2 g/100 g). The OG significantly decreased the body weight, which was normalized by the coadministration of NG. Serum lipid profile showed a dose dependent increase in total cholesterol, triglycerides, and low density lipoproteins (LDL) and decrease in RBCs count, hematocrit, glucose, and hemoglobin concentration with OG feeding. These parameters were normalized by coadministration of NG. Liver histopathology of OG fed groups showed bile duct dilation and necrotic changes, while normal architecture showed in NG groups, compared to control. These results indicate that NG has no significant effect on rabbits comparing with OG and that it was beneficial when coadministered with oxidized ghee.


Efficacy of Nivolumab Plus Ipilimumab in a Patient With Renal Cell Carcinoma Concomitant With Cardiac Metastasis: A Case Report.
Patients with metastatic renal cell carcinoma (RCC) with cardiac metastasis have had poor outcomes in the era of molecular targeted therapy. There are few reported outcomes for patients with cardiac metastasis of RCC treated with immune checkpoint inhibitors (ICIs). A 32-year-old female presented with metastatic RCC (unclassified type) with contralateral renal and cardiac metastases, as well as renal hilar lymph node metastases (cT4N2M1). An 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) computed tomographic (CT) scan was useful in diagnosing cardiac metastasis. Nivolumab plus ipilimumab achieved prominent shrinkage of almost all tumors except for one cardiac tumor. FDG-PET/CT scan also revealed the marked attenuation of FDG uptake in each tumor. In addition, a needle biopsy of the remaining primary renal tumor was pathologically observed to have no viable cancer cells. This successful case suggests that ICIs might provide a better outcome even for patients with cardiac metastasis of RCC, and that FDG-PET/CT scan might be useful for therapeutic assessment, as well as diagnosis.


Anatomic Reconstruction of the Proximal Tibiofibular Joint.
Proximal tibiofibular joint (PTFJ) instability can be easily missed or confused for other, more common lateral knee pathologies such as meniscal tears, fibular collateral ligament injury, biceps femoris pathology, or iliotibial band syndrome. Because of this confusion, some authors believe that PTFJ instability is more common than initially appreciated. Patients with PTFJ subluxation may have no history of inciting trauma or injury, and it is not uncommon for these patients to have bilateral symptoms and generalized ligamentous laxity. Currently, the optimal surgical treatment for patients with chronic PTFJ instability is unknown. Historically, a variety of surgical treatments have been reported. Initially, joint arthrodesis and fibular head resection were recommended. More recently, temporary screw fixation, nonanatomic reconstruction with strips of the biceps femoris tendon or iliotibial band, and reconstruction with free hamstring autograft have been described. The purpose of this report is to present our surgical technique for treatment of chronic PTFJ instability using an anatomic reconstruction of the posterior ligamentous structures of the PTFJ with a semitendinosus autograft.


The zebrafish ventricle: A hub of cardiac endothelial cells for in vitro cell behavior studies.
Despite our increasing understanding of zebrafish heart development and regeneration, there is limited information about the distribution of endothelial cells (ECs) in the adult zebrafish heart. Here, we investigate and compare the distribution of cardiac ECs (cECs) in adult mouse and zebrafish ventricles. Surprisingly, we find that (i) active coronary vessel growth is present in adult zebrafish, (ii) ~37 and ~39% of cells in the zebrafish heart are ECs and cardiomyocytes, respectively, a composition similar to that seen in mouse. However, we find that in zebrafish, ~36% of the ventricular tissue is covered with ECs, i.e., a substantially larger proportion than in mouse. Capitalising on the high abundance of cECs in zebrafish, we established a protocol to isolate them with high purity using fluorescent transgenic lines. Our approach eliminates side-effects due to antibody utilisation. Moreover, the isolated cECs maintained a high proliferation index even after three passages and were amenable to pharmacological treatments to study cEC migration in vitro. Such primary cultures will be a useful tool for supplementary in vitro studies on the accumulating zebrafish mutant lines as well as the screening of small molecule libraries on cardiac specific endothelial cells.


A Novel Iterative CT Reconstruction Approach Based on FBP Algorithm.
The Filtered Back-Projection (FBP) algorithm and its modified versions are the most important techniques for CT (Computerized tomography) reconstruction, however, it may produce aliasing degradation in the reconstructed images due to projection discretization. The general iterative reconstruction (IR) algorithms suffer from their heavy calculation burden and other drawbacks. In this paper, an iterative FBP approach is proposed to reduce the aliasing degradation. In the approach, the image reconstructed by FBP algorithm is treated as the intermediate image and projected along the original projection directions to produce the reprojection data. The difference between the original and reprojection data is filtered by a special digital filter, and then is reconstructed by FBP to produce a correction term. The correction term is added to the intermediate image to update it. This procedure can be performed iteratively to improve the reconstruction performance gradually until certain stopping criterion is satisfied. Some simulations and tests on real data show the proposed approach is better than FBP algorithm or some IR algorithms in term of some general image criteria. The calculation burden is several times that of FBP, which is much less than that of general IR algorithms and acceptable in the most situations. Therefore, the proposed algorithm has the potential applications in practical CT systems.


Global diversity of earthworms and enchytraeids (Clitellata): papers in honor of András Zicsi (1928-2015). Editorial.
This Special Volume of Zootaxa unites forty papers written in honor of the late András Zicsi (1928-2015), the eminent earthworm taxonomist. They deal with the taxonomy, systematics and distribution of earthworms and enchytraeids, the two major groups of soil-dwelling Oligochaeta. Altogether, 71 new species-group taxa are described, 60 species and subspecies of earthworms and 11 species of enchytraeids. They are from 15 countries all around the globe: Spain, Italy, Hungary, Turkey, Botswana, Mexico, Colombia, Brazil, China, Japan, Korea, Taiwan, Laos, Malaysia, Thailand, and Vietnam.


Strategies for the determination of pharmacophoric 3D database queries.
Strategies are described for constructing pharmacophoric 3D database queries, based on a series of active and inactive analogs. The results are highly selective database queries, which are consistent with the generally accepted pharmacophore for a number of systems. The foundation of these strategies is the method of Mayer, Naylor, Motoc and Marshall [J. Comput.-Aided Mol. Design, 1 (1987) 3] for inferring a unique binding geometry for angiotensin-converting enzyme (ACE) inhibitors. The strategies described here generalize their approach to cases where the chemical features responsible for binding are not a priori apparent, and to cases where the binding geometry deduced by that method is not unique. The key new insight, the selectivity principle, is to rank the multiple solutions produced by the method of Mayer et al. by their selectivity, a value that is related to the proportion of a database that is returned as a database hit list. Retrospective analyses are described for D2-antagonists, ACE inhibitors, fibrinogen antagonists, and beta 2-antagonists.


Psychiatric correlates of MR deep white matter lesions in probable Alzheimer's disease.
The authors examined the relationship between psychiatric symptoms and the presence of of MR deep white matter lesions (DWMLs) in 28 probable Alzheimer's disease (AD) patients with mild to moderate dementia. The difference in frequency of psychiatric symptoms between patients with and without DWMLs was not statistically significant. However, MR global scores of severity correlated with the presence of ideational disturbances (such as low self-esteem and suicidal ideation). Analysis of specific cerebral regions indicated that the highest correlation occurred in the frontal white matter. Thus, DWMLs are correlated with specific symptoms of depression in AD. Whether DWMLs are etiologically related to these symptoms remains to be determined.


Canis familiaris allergen Can f 7: Expression, purification and analysis of B cell epitopes in Chinese children with dog allergies.
Dogs are a major source of indoor allergens. However, the prevalence of dog allergies in China remains unclear, especially in children. In the present study, Can f 7, a canine allergen belonging to the Niemann pick type C2 protein family, was selected to study its sensitization rate in Chinese children with dog allergies. The Can f 7 gene was subcloned into a pET‑28a vector and expressed in Escherichia coli BL21 (DE3) cells. Recombinant Can f 7 was purified by nickel affinity chromatography, identified by SDS‑PAGE electrophoresis, and had its allergenicity assessed by western blot, ELISA and basophil activation tests. Through a series of bioinformatical approaches, B‑cell epitopes, secondary structures, and 3 dimensional (3D) homology modeling of Can f 7 were predicted. The activity of the B cell epitopes was verified by ELISA. The recombinant Can f 7 showed a distinct band with a molecular weight of 14 kDa. Six of 20 sera from dog‑allergic children reacted positively to the Can f 7. Can f 7 induced an ~4.0‑fold increase in cluster of differentiation 63 and C‑C motif chemokine receptor R3 expression in basophils sensitized with the serum of dog‑allergic children compared with those of non‑allergic controls. The secondary structure analysis showed that Can f 7 contains 6 β‑sheets. Five B cell epitopes of Can f 7 were predicted, and two of these were confirmed by ELISA. These results indicate that Can f 7 is an important canine allergen in Chinese children and provide novel data for further research concerning the use of Can f 7 in the diagnosis and treatment of Chinese children with canine allergy symptoms.


Dietary Habits and Eating Practices and Their Association with Overweight and Obesity in Rural and Urban Black South African Adolescents.
The aim of this study was to investigate differences/similarities in dietary habits and eating practices between younger and older, rural and urban South African adolescents in specific environments (home, community and school) and their associations with overweight and obesity. Dietary habits, eating practices, and anthropometric measurements were performed on rural (n = 392, mean age = 13 years) and urban (n = 3098, mean age = 14 years) adolescents. Logistic regression analysis was used to examine the associations between dietary habits and eating practices, with overweight and obesity risk. Differences in dietary habits and eating practices by gender and by site within the three environments were identified. After adjusting for gender, site, dietary habits, and eating practices within the home, community and school environment, eating the main meal with family some days (OR = 1.78, 95% CI = 1.114-2.835; p ≤ 0.02), eating the main meal with family almost every day (OR = 1.61, 95% CI = 1.106-2.343; p ≤ 0.01), and irregular frequency of consuming breakfast on weekdays (OR = 1.38, 95% CI = 1.007-1.896; p ≤ 0.05) were all associated with increased risk of overweight and obesity. For "Year 15" adolescents, irregular frequency of consuming breakfast on weekends within the home environment (OR = 1.53, 95% CI = 1.099-2.129, p ≤ 0.01), was associated with increased risk of overweight and obesity. For both early- and mid-adolescents, being male (OR = 0.401, 95% CI = 0.299-0.537; p ≤ 0.00; OR = 0.29, 95% CI = 0.218-0.397; p ≤ 0.00) was associated with reduced risk of overweight and obesity, while residing in a rural setting (OR = 0.55, 95% CI = 0.324-0.924; p ≤ 0.02) was associated with reduced risk of overweight and obesity only among early-adolescents. Only dietary habits and eating practices within the home environment were associated with increased risk of overweight and obesity.


Sex-Based Differences in Asthma among Preschool and School-Aged Children in Korea.
The purpose of this study was to explore risk factors related to asthma prevalence among preschool and school-aged children using a representative national dataset from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2009-2011. We evaluated the demographic information, health status, household environment, socioeconomic status, and parents' health status of 3,542 children aged 4-12 years. A sex-stratified multivariate logistic regression was used to obtain adjusted prevalence odds ratios (ORs) and 95% confidence intervals after accounting for primary sample units, stratification, and sample weights. The sex-specific asthma prevalence in the 4- to 12-year-old children was 7.39% in boys and 6.27% in girls. Boys and girls with comorbid atopic dermatitis were more likely to have asthma than those without atopic dermatitis (boys: OR = 2.20, p = 0.0071; girls: OR = 2.33, p = 0.0031). Boys and girls with ≥1 asthmatic parent were more likely to have asthma than those without asthmatic parents (boys: OR = 3.90, p = 0.0006; girls: OR = 3.65, p = 0.0138). As girls got older, the prevalence of asthma decreased (OR = 0.90, p = 0.0408). Girls residing in rural areas were 60% less likely to have asthma than those residing in urban areas (p = 0.0309). Boys with ≥5 family members were more likely to have asthma than those with ≤3 family members (OR = 2.45, p = 0.0323). The factors related to asthma prevalence may differ depending on sex in preschool and school-aged children. By understanding the characteristics of sex-based differences in asthma, individualized asthma management plans may be established clinically.


Body Caudal Undulation Measured by Soft Sensors and Emulated by Soft Artificial Muscles.
We propose the use of bio-inspired robotics equipped with soft sensor technologies to gain a better understanding of the mechanics and control of animal movement. Soft robotic systems can be used to generate new hypotheses and uncover fundamental principles underlying animal locomotion and sensory capabilities, which could subsequently be validated using living organisms. Physical models increasingly include lateral body movements, notably back and tail bending, which are necessary for horizontal plane undulation in model systems ranging from fish to amphibians and reptiles. We present a comparative study of the use of physical modeling in conjunction with soft robotics and integrated soft and hyperelastic sensors to monitor local pressures, enabling local feedback control, and discuss issues related to understanding the mechanics and control of undulatory locomotion. A parallel approach combining live animal data with biorobotic physical modeling promises to be beneficial for gaining a better understanding of systems in motion.


The effect of radiotherapy on fat content and fatty acids in myxoid liposarcomas quantified by MRI.
Myxoid liposarcomas are highly radiosensitive. Consequently radiotherapy is often used pre-operatively to reduce tumor volume and lessen the post-operative deficit. In soft-tissue sarcomas therapy response is mainly evaluated using magnetic resonance imaging (MRI) and the fundamental criterion for a positive response is decreased tumor size. In myxoid liposarcomas an increased fat content is also known to occur as a response to radiotherapy. To highlight the difficulties of MRI for therapy response evaluation in irradiated myxoid liposarcomas, by using MRI Dixon techniques enabling objective quantification of proton density fat fraction (%) and the number of double bonds (ndb; unsaturation degree) of fatty acids. Secondly, to compare quantitative fat fraction measurements versus visual grading of fat content on T1-weighted images. Prior to surgery, two patients with myxoid liposarcoma were treated with 50Gy. Following radiotherapy, both tumors on MRI showed reduced size, elevated fat fraction and transformed fat fraction histograms with diverse changes of ndb, while histopathological specimens showed discordant treatment effects; one case having good response and the other having poor response. A decrease in tumor size and increase in fat content on MRI cannot be interpreted as positive therapy response in radiotherapy of myxoid liposarcomas. Our data also give further supporting evidence that differentiation and maturation of tumor cells is the cause for the lipoma-like areas seen after radiotherapy. Finally, quantitative MRI Dixon techniques are preferable to visual grading for estimating the fat content in lipomatous tumors.


Neutrophilic noncoding RNAs predict outcomes of acute ischemic stroke patients treated with recombinant tissue plasminogen activator.
There's no evidence demonstrating the association between noncoding RNAs levels before IV recombinant tissue plasminogen activator (rtPA) administration and the outcomes of acute ischemic stroke (AIS). 145 AIS patients received rtPA treatment were recruited at the stroke center from 2018 to 2019, and 103 patients were included in this study. A panel of noncoding RNAs (miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and lncRNA H19) were measured in the circulating neutrophils of AIS patients before rtPA treatment. Endpoints included excellent outcome (modified Rankin Scale score [mRS] 0-1) or poor outcome (mRS > 1) at 3 months and symptomatic intracerebral hemorrhage (sICH) after rtPA treatment. Among the eight noncoding RNAs detected in circulating neutrophils of the 103 participants, miRNA-23a levels were associated with the stroke severity on admission and symptom progression at 24 h after rtPA treatment. A noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 was screened to predict the functional outcome at 3 months and the incidence of sICH after rtPA treatment. In the logistic regression analysis, the noncoding RNA score ≥ -0.336 (OR = 2.862 [1.029-7.958], p = 0.044) was an independent predictor of the poor outcome at 3 months after adjustment of clinical variables, the addition of the noncoding RNA score to the clinical model improved the discrimination (IDI% = 4.68 [0.65-8.71], p = 0.020), as well as the net reclassification (NRI% = 33.04 [0.54-71.49], p = 0.016). The noncoding RNA score ≥ -0.336 (OR = 5.250 [1.096-25.135], p = 0.038) was also independently predicted the sICH, the addition of the noncoding RNA score to the clinical variables improved discrimination and reclassification as well. The noncoding RNA score was also associated with the infarct volume and symptom improvement at 7 days after rtPA treatment. In conclusion, a higher neutrophilic noncoding RNA score provides predictive value to identify AIS patients with worse outcomes after rtPA treatment. miRNA-23a, miRNA-99a, and lncRNA H19 are worth further investigation for their effects in thrombolysis after AIS.


[Long-Term Care Preferences Among Individuals of Advanced Age in Germany: Results of a Population-Based Study].
The need for long-term care is expected to increase markedly in the next decades as a result of demographic ageing. Consequently, it is important to know the long-term care preferences. This study investigated the long-term care preferences among older individuals in Germany. Based on a systematic review and expert interviews, a questionnaire was designed to assess long-term care preferences. Data were gathered from a representative telephone survey of the German population (n=1,006; 65 years and above) in 2015. The mean age was 75.2 years (±6.6 years, ranging from 65 to 96 years). While nearly 90% of the individuals preferred home care, other care settings such as nursing care abroad were mostly undesired. In case of home care, most of the individuals preferred care provided by friends/family or formal caregivers, whereas the idea of all-day care services (such as employed private caregivers) was less popular. With respect to home care, additional services such as household assistance, transportation services, and emergency call systems were highly valued by the study participants, whereas continual supervision throughout the day was seen as less important. In case of inpatient care, more than 90% of the individuals preferred a private room, with the inpatient facility located near home or close to relatives' homes. A wide range of activities was appreciated. Given these preferences, it is assumed that there is a gap between expectations (preferences) and reality (utilization) regarding long-term care in Germany. Interventions aimed at minimizing this gap are urgently needed. For example, strategies to raise the awareness of private long-term care provision might be fruitful.


Small bots, big impact: solving the conundrum of cooperation in optional Prisoner's Dilemma game through simple strategies.
Cooperation plays a crucial role in both nature and human society, and the conundrum of cooperation attracts the attention from interdisciplinary research. In this study, we investigated the evolution of cooperation in optional Prisoner's Dilemma games by introducing simple bots. We focused on one-shot and anonymous games, where the bots could be programmed to always cooperate, always defect, never participate or choose each action with equal probability. Our results show that cooperative bots facilitate the emergence of cooperation among ordinary players in both well-mixed populations and a regular lattice under weak imitation scenarios. Introducing loner bots has no impact on the emergence of cooperation in well-mixed populations, but it facilitates the dominance of cooperation in regular lattices under strong imitation scenarios. However, too many loner bots on a regular lattice inhibit the spread of cooperation and can eventually result in a breakdown of cooperation. Our findings emphasize the significance of bot design in promoting cooperation and offer useful insights for encouraging cooperation in real-world scenarios.


The biochemistry of vitamin B6 is basic to the cause of the Chinese restaurant syndrome.
The concept of this basic research was that monosodium L-glutamate could reveal a deficiency of vitamin B6 by the neurological reactions known as the Chinese Restaurant Syndrome. An other amino acid, tryptophan, administered to subjects, is known to reveal a deficiency of vitamin B6 by the excretory xanthurenic acid, etc. The presence and degree of a deficiency of vitamin B6 in 155 students on no supplemental B6 was determined by the differential assay of aspartate transaminase of erythrocytes which also allows each subject to be a control. Twenty-seven of 155 students had extraordinarily low basal specific activities of the transaminase, less than 0.26 mumol pyruvate/(h X 10(8) erythrocytes). These 27 were challenged with glutamate and a placebo. Twelve of 27 revealed the Chinese Restaurant Syndrome, and 15 did not. By double blind trials, the 12 "responders" were treated with pyridoxine and a placebo for twelve weeks, and then were rechallenged with glutamate and a placebo. Decoding showed 3 of 12 received placebo to pyridoxine and then revealed the symptoms of the syndrome again to glutamate; 9 of 12 received pyridoxine and then 8 of 9 failed to respond to glutamate. These results show, p less than 0.01, that the symptoms of the Chinese Restaurant Syndrome to oral glutamate fail to reoccur after treatment which pyridoxine, and that the biochemistry of vitamin B6 is basic to the cause of the Chinese Restaurant Syndrome.


Odorranalectin is a small peptide lectin with potential for drug delivery and targeting.
Lectins are sugar-binding proteins that specifically recognize sugar complexes. Based on the specificity of protein-sugar interactions, different lectins could be used as carrier molecules to target drugs specifically to different cells which express different glycan arrays. In spite of lectin's interesting biological potential for drug targeting and delivery, a potential disadvantage of natural lectins may be large size molecules that results in immunogenicity and toxicity. Smaller peptides which can mimic the function of lectins are promising candidates for drug targeting. Small peptide with lectin-like behavior was screened from amphibian skin secretions and its structure and function were studied by NMR, NMR-titration, SPR and mutant analysis. A lectin-like peptide named odorranalectin was identified from skin secretions of Odorrana grahami. It was composed of 17 aa with a sequence of YASPKCFRYPNGVLACT. L-fucose could specifically inhibit the haemagglutination induced by odorranalectin. (125)I-odorranalectin was stable in mice plasma. In experimental mouse models, odorranalectin was proved to mainly conjugate to liver, spleen and lung after i.v. administration. Odorranalectin showed extremely low toxicity and immunogenicity in mice. The small size and single disulfide bridge of odorranalectin make it easy to manipulate for developing as a drug targeting system. The cyclic peptide of odorranalectin disclosed by solution NMR study adopts a beta-turn conformation stabilized by one intramolecular disulfide bond between Cys6-Cys16 and three hydrogen bonds between Phe7-Ala15, Tyr9-Val13, Tyr9-Gly12. Residues K5, C6, F7, C16 and T17 consist of the binding site of L-fucose on odorranalectin determined by NMR titration and mutant analysis. The structure of odorranalectin in bound form is more stable than in free form. These findings identify the smallest lectin so far, and show the application potential of odorranalectin for drug delivery and targeting. It also disclosed a new strategy of amphibian anti-infection.


Lactational efficiency complex of rats: provisional model for interpretation of energy balance data.
In experiments to determine maintenance requirements and partial efficiencies of conversion of diet and body tissue to milk, correlations between independent variables interfered with multiple regression procedures usually used in analyzing nutritional energetic data. Therefore, an alternative of a largely deterministic model of energy transformations in lactating rats was developed. Food intake, initial and final body weights, and diet composition were inputs to the model. These inputs were partitioned among the several metabolic functions of lactating rats within the model, and estimates of milk energy, heat increment of production, energy used for maintenance, and heat increment of maintenance were computed. The model was validated with rats and diets not used in model development. Inferences were: (a) average efficiency of body energy conversion to milk is 83%; (b) average gross and net efficiencies of milk production on balanced rations are 57 and 80%; and, (c) maintenance requirements vary as a function of food intake. A logistic function relating maintenance to food intake was developed based on the postulate that changes in intake of food cause changes in weights of several vital organs changing the maintenance requirement. This postulate explains, in part, changes in maintenance requirements during long food restriction and during gestation and lactation.


Mitral valve repair: past, present, and future.
Mitral valve repair is the operation of choice for mitral valve regurgitation, with appropriate selection. Studies have shown that mitral repair is associated with a decrease in both long-term thromboembolic complications and mortality. Since its initial description, various selection criteria and techniques of mitral valve repair have been discussed in the literature. This review serves as a synopsis of the previous achievements, present status, and possible future directions of mitral valve repair, specifically from an Asian perspective. Vast experience has been amassed in understanding mitral valve pathophysiology, and excellent surgical treatments for mitral regurgitation have been developed. With the efforts of pioneers in the field of mitral valve repair, standard surgical treatment strategies have been proven to restore the life-expectancy of patients with degenerative mitral regurgitation to that of the age-adjusted population. Minimally invasive techniques of mitral valve repair further reduce access trauma, and could potentially benefit patients previously excluded from conventional surgery.


Seroprevalence of Baylisascaris procyonis Infection among Humans, Santa Barbara County, California, USA, 2014-2016.
Baylisascaris procyonis (raccoon roundworm) infection is common in raccoons and can cause devastating pathology in other animals, including humans. Limited information is available on the frequency of asymptomatic human infection. We tested 150 adults from California, USA, for B. procyonis antibodies; 11 were seropositive, suggesting that subclinical infection does occur.


Tuberculosis remains a major burden in systemic lupus erythematosus patients in Durban, South Africa.
Infections are common in systemic lupus erythematosus (SLE), with tuberculosis (TB) being important in an endemic environment. We studied the prevalence and spectrum of TB in SLE in Durban, South Africa. A medical records review of SLE patients seen over 13-year period, and the demographic data, clinical manifestations, laboratory findings, treatment and outcome were noted. There were 512 SLE patients and 72 (14.1%) had TB. Thirty (41.7%) had pulmonary TB (PTB) and 42 (58.3%) had extra-pulmonary TB (EPTB). The prevalence of TB among the different ethnic groups was 36/282 (12.8%) for Indian people, 29/184 (15.8%) Black African people, 7/26 (26.9%) admixed African people and none among the 18 White people. Comparison of the 72 SLE-TB patients with 72 SLE controls showed no difference in gender, age at SLE diagnosis and disease duration. The SLE-TB patients had a significant increase in the clinical and laboratory features of disease activity (arthritis, mucocutaneous lesions, renal involvement, vasculitis, low complement, raised ds-DNA antibodies), and cumulative prednisone use over the preceding 3 months.Compared to PTB, the EPTB patients were significantly younger, developed TB earlier after SLE diagnosis, and had higher disease activity. The EPTB patients also had increase in features of disease activity (renal, thrombocytopenia, ds-DNA antibodies), and increase in ever use of intravenous methylprednisolone (IV-MP) and mycophenolate mofetil (MMF). On multivariate analysis, the independent risk factors for EPTB were ever use of MMF (p = 0.003) and IV-MP (p = 0.027). Analysis of the cumulative SLE criteria showed renal involvement was an independent risk factor for EPTB. The outcome was similar in both groups. We show an increased prevalence of TB (14.1%) and EPTB (58.3%) in SLE in an endemic area and confirm that features of disease activity and use of immunosuppressive therapy are the major risk factors. Renal involvement (as a cumulative criterion) is an independent risk factor for EPTB.


Health hazard labeling for hazard communication in the pharmaceutical industry.
Company health and safety professionals must advise workers of the potential hazards of workplace chemicals. Yet it is difficult to develop one, consistent corporate labeling strategy for worldwide use. This chapter describes one company's approach to devising a corporate policy satisfying all criteria.


[Principles and methods of good practice for the translation process for instruments of nursing research and nursing practice].
Cross-cultural, valid and reliable instruments are increasingly used in nursing, yet their attainment is labour-intensive. The translation of valid instruments into another language and cultural context is the most common method used for generating cross-cultural instruments. This approach is challenging since the development of culturally equivalent translated instruments demands familiarity with basic requirements of linguistic adaptation, cultural concepts and psychometric changes inherent in the translation process. However, the quality of data derived from translated instruments relies on the accuracy of the translation process applied. The aim of this article is to illustrate the different methods for translation, as well as to present an example and principles of good practice regarding this subject.


Synergistic cytotoxicity against human tumor cell lines by oncolytic adenovirus dl1520 (ONYX-015) and melphalan.
In light of the need for more selective anticancer therapy, much work has been directed at developing compounds or biological agents that target functions specific to cancer cells. To this end, numerous viruses have been engineered to exploit the dependence of cancer cells on particular anomalies that contribute to their rogue proliferative activity, such as dysfunctional p53, overactive mitogenic signaling, or a defective interferon response. The oncolytic human adenovirus dl1520 (ONYX-015) was engineered to propagate specifically in p53-deficient tumors, which comprise over half of all tumors. Based on successes in clinical trials, the full potential of dl1520 and other oncolytic viruses may be even better realized by using them in combination with conventional chemotherapy drugs. As a model system in which to test this potential, representative cell lines from 2 common cancer types, oral squamous cell carcinoma (HN-5a) and colon adenocarcinoma (HT-29), were chosen, as well as platinum-drug-resistant variants of each. Following preliminary screening of virus and drug combinations, dl1520 and melphalan were found to synergistically inhibit proliferation of all the cancer cell lines. Melphalan pretreatment or cotreatment with dl1520 enhanced inhibition of proliferation by dl1520 by up to 60% and increased apoptosis by up to 25%. The tight-junction protein CAR (coxsackie and adenovirus receptor), via which adenovirus enters cells, was not upregulated by treatment with melphalan, suggesting that other mechanisms contribute to synergy. The synergy between melphalan and dl1520 suggests that tumor-selective cell killing by oncolytic viruses may be augmented by combining with cytotoxic drugs.


IgA Nephropathy - Beyond the Renal Cortex.
Immunoglobulin A (IgA) nephropathy is the most common glomerular disease worldwide. It usually presents as a nephritic syndrome with macroscopic hematuria, oliguria, and proteinuria with or without azotemia. Rapidly progressive glomerulonephritis with crescents is being described in about 30% of cases and is mostly associated with nephrotic-range proteinuria, accelerated hypertension, and accelerated decline toward end-stage renal disease. Medullary angiitis is a rare finding in renal biopsy and is usually associated with pauci-immune glomerulonephritis. We describe a rare association of medullary angiitis in IgA nephropathy, probably the first reported case in the country.


A novel peptide from human apolipoprotein(a) inhibits angiogenesis and tumor growth by targeting c-Src phosphorylation in VEGF-induced human umbilical endothelial cells.
Many angiogenesis inhibitors are derived from large plasma proteins. Previous studies showed that the Kringle5-like domain (termed KV) in human apolipoprotein (a) is a potential antiangiogenic factor. However, its active region and the underling molecular mechanism remain elusive. Here, we identified an 11-amino acid peptide (named KV11) as the key region for the antiangiogenic function of the KV domain of apolipoprotein (a). We demonstrate that KV11 inhibits angiogenesis in vitro by suppressing human umbilical vein endothelial cell migration and microtubule formation. KV11 inhibits angiogenesis in chicken chorioallantoic membrane assays and mouse corneal micropocket angiogenesis assays in vivo. KV11 peptide shows no effect on tumor cell growth or proliferation, but significantly inhibits tumor growth in SCID mouse xenograft tumor model (p < 0.01) by preventing tumor angiogenesis. We elucidate that KV11 peptide suppresses angiogenesis and tumor progression by targeting the c-Src/ERK signaling pathways. Together, these studies provide the first evidence that KV11 from apolipoprotein KV domain has anti-angiogenesis functions and may be an anti-tumor drug candidate.


Sodium hyperosmolarity of intestinal lymph causes arteriolar vasodilation in part mediated by EDRF.
This study evaluated 1) the effect of increased submucosal lymph osmolarity on the regulation of first-order (1A) and second-order (2A) intestinal arterioles and 2) the role of endothelium-derived relaxing factor (EDRF) in hypertonic-induced vasodilation. Increasing the submucosal lymph osmolarity from 280 to 400 mosM, in increments of 30 mosM, resulted in a dose-dependent dilation of 1A and 2A. A submucosal lymph tonicity of 340 mosM, as occurs during glucose and oleic acid absorption, caused dilation of 1A (118%) and 2A (124%) equivalent to that during absorptive hyperemia. The dilation caused by 400 mosM mannitol (137%) was similar to that with 340 mosM NaCl (131%) and approximately 70% of that with 400 mosM NaCl (152%). After EDRF blockade, the responses to sodium hypertonicity decreased by about one-half; blockade reduced mannitol-induced dilation by 22%. These results indicate that sodium hypertonicity, as occurs during absorption, can play a major role in absorptive hyperemia, and about one-half of the dilation is related to a sodium-coupled release of EDRF.


Integration of signaling pathways regulating chondrocyte differentiation during endochondral bone formation.
During endochondral bone formation, chondrocytes undergo a process of terminal differentiation or maturation, during which the rate of proliferation decreases, cells become hypertrophic, and the extracellular matrix is altered by production of a unique protein, collagen X, as well as proteins that promote mineralization. The matrix surrounding the hypertrophic chondrocytes eventually becomes mineralized, and the mineralized matrix serves as a template for bone deposition. This process is responsible for most longitudinal bone growth, both during embryonic development and in the postnatal long bone growth plates. Chondrocyte maturation must be precisely controlled, balancing proliferation with terminal differentiation; changes in the rate of either proliferation or differentiation result in shortened bones. Numerous signaling molecules have been implicated in regulation of this process. These include the negative regulators Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP; Pthlh, PTH-like hormone), as well as a number of positive regulators. This review will focus on several positive regulators which exert profound effects on chondrocyte maturation: the thyroid hormones T3 and T4, retinoic acid (the major active metabolite of vitamin A) and bone morphogenetic proteins (BMPs), as well as the transcription factor Runx2. Each of these molecules is essential for endochondral bone formation and cannot compensate for the others; abrogation of any one of them prevents differentiation. The important features of each of these signaling pathways will be discussed as they relate to chondrocyte maturation, and a model will be proposed suggesting how these pathways may converge to regulate this process.


Datamining approaches for examining the low prevalence of N-acetylglutamate synthase deficiency and understanding transcriptional regulation of urea cycle genes.
Ammonia, which is toxic to the brain, is converted into non-toxic urea, through a pathway of six enzymatically catalyzed steps known as the urea cycle. In this pathway, N-acetylglutamate synthase (NAGS, EC 126.96.36.199) catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl coenzyme A. NAGS deficiency (NAGSD) is the rarest of the urea cycle disorders, yet is unique in that ureagenesis can be restored with the drug N-carbamylglutamate (NCG). We investigated whether the rarity of NAGSD could be due to low sequence variation in the NAGS genomic region, high NAGS tolerance for amino acid replacements, and alternative sources of NAG and NCG in the body. We also evaluated whether the small genomic footprint of the NAGS catalytic domain might play a role. The small number of patients diagnosed with NAGSD could result from the absence of specific disease biomarkers and/or short NAGS catalytic domain. We screened for sequence variants in NAGS regulatory regions in patients suspected of having NAGSD and found a novel NAGS regulatory element in the first intron of the NAGS gene. We applied the same datamining approach to identify regulatory elements in the remaining urea cycle genes. In addition to the known promoters and enhancers of each gene, we identified several novel regulatory elements in their upstream regions and first introns. The identification of cis-regulatory elements of urea cycle genes and their associated transcription factors holds promise for uncovering shared mechanisms governing urea cycle gene expression and potentially leading to new treatments for urea cycle disorders.


Tomographic Evaluation of the Upper Cervical Spine in Patients with Cleft lip and Palate and Class III Malocclusion.
To perform a morphometric analysis of the upper cervical spine (UCS) by means of cone-beam computed tomography (CBCT) for the diagnosis of malformations or craniocervical instabilities in patients with cleft lip and palate (CLP) and class III malocclusion. A total of 72 CBCTs from adult patients (48 male and 24 female) with Angle Class III malocclusion were divided into three groups: 1) Unilateral cleft lip and palate (UCLP) (n = 29; male = 65.5%; age = 24, 2 ± 4.2 years); 2) Bilateral cleft lip and palate (BCLP) (n = 18; male = 83.3%; age = 26.4 ± 6.0 years); 3) Control group (CON) (n = 25; male = 56.0%; age = 27.8 ± 9.3 years). The version 11.7 of the Dolphin® software (Chatsworth, California, USA) was used to evaluate the morphometric measurements and anomalies of the UCS. Data were analyzed by descriptive and inferential statistics (p ≤ 0.05). For the UCLP, BCLP and CON groups, respectively, the measures were: atlantodental interval (2.1 ± 0.5; 2.1 ± 0.4; 2.0 ± 0.3 mm), basion-opisthion (35.9 ± 3.2; 36.4 ± 3.0; 34.7 ± 1.9 mm), hyoid-C3 (34.5 ± 3.7; 34.5 ± 5.2; 35.3 ± 4.5 mm), and hyoid-sella (108.1 ± 9.8; 111.3 ± 9.2; 109.7 ± 10 mm); clivus-canal angle (152.3 ± 13; 150.3 ± 10; 150.7 ± 10°) and Torg-Pavlov index (1.0 ± 0.2; 1.0 ± 0.1; 1.1 ± 0.2). Potentially unstable anomalies and malformations were more prevalent in the UCLP group (34,4%). Subjects with UCLP presented compressive or unstable anomalies on upper cervical spine, more frequently than controls and BCLP, despite the lack of statistically significant differences among groups. Future studies could increase the safety of patients and healthcare professionals specialized in craniofacial anomalies.


Hepatosplenic T-cell lymphoma: treatment challenges.
Hepatosplenic lymphoma (HSTCL) is a rare T-cell malignancy occurring in young males, associated with immune deficiency in 20% of the cases which, despite aggressive treatments, has a poor survival. Specific recommendations for first-line treatment remain debatable. Published data covering case reports or series of HSTCL concur that allogeneic stem cell transplant should be proposed as a consolidation after response to chemotherapy in all patients eligible for transplant. In the light of two recent clinical examples, we also confirm that specific chemotherapy and a first-line consolidation with allogeneic transplantation when a donor is available to represent a treatment of choice these rare and distinctive lymphomas. Recent molecular studies are summarized in this review and suggest potential targets for new therapeutic strategies. Major progresses have been achieved in improving the outcome of HSTCL l patients using intensive chemotherapy and allogeneic transplantation.


S-adenosylmethionine treatment of depression: a controlled clinical trial.
The antidepressant properties of S-adenosylmethionine, an endogenous methyl donor, were studied in inpatients who met the DSM-III criteria for major depression. Nine patients given intravenous S-adenosylmethionine and nine given low oral doses of imipramine were compared in a double-blind design for 14 days. The S-adenosylmethionine produced superior results by the end of the first week of treatment. By the end of the second week, 66% of the S-adenosylmethionine patients had a clinically significant improvement in depressive symptoms, compared to 22% of the imipramine patients. Side effects appeared to be fewer with S-adenosylmethionine than with imipramine during the last 5 days of the study.


Naringin Mitigates Cardiac Hypertrophy by Reducing Oxidative Stress and Inactivating c-Jun Nuclear Kinase-1 Protein in Type I Diabetes.
Cardiac hypertrophy (CH) in type 1 diabetes mellitus is attributed to increased oxidative stress-associated activation of c-Jun Nuclear Kinase (JNK). We investigated the effects of naringin on hyperglycemia-associated oxidative stress, activation of JNK-1, and CH. Male Sprague-Dawley rats (225-250 g) (n = 7) were divided into 6 groups. Groups I and II were orally treated with distilled water [3.0 mL/kg body weight/day (BW)] and naringin (50 mg/kg BW), respectively. Groups III-VI were rendered diabetic by a single intraperitoneal injection of 65 mg/kg BW of streptozotocin. Groups III, IV, and V were further treated with insulin (4.0 I.U, s.c, twice daily), naringin (50 mg/kg BW), and ramipril (3.0 mg/kg BW), respectively. After 56 days, the animals were sacrificed and then plasma and cardiac tissues obtained for further analysis. Naringin treatment of diabetic rats significantly reversed oxidative stress, lipid peroxidation, proteins oxidation, CH indices, and JNK protein activation compared with untreated diabetic animals. Our results do suggest that naringin mitigates CH by inhibiting oxidative stress leading to inactivation of JNK-1. Naringin supplements could therefore ameliorate CH in diabetic patients.