Neogene amphibians and reptiles (Caudata, Anura, Gekkota, Lacertilia, and Testudines) from the south of Western Siberia, Russia, and Northeastern Kazakhstan.
The present-day amphibian and reptile fauna of Western Siberia are the least diverse of the Palaearctic Realm, as a consequence of the unfavourable climatic conditions that predominate in this region. The origin and emergence of these herpetofaunal groups are poorly understood. Aside from the better-explored European Neogene localities yielding amphibian and reptile fossil remains, the Neogene herpetofauna of Western Asia is understudied. The few available data need critical reviews and new interpretations, taking into account the more recent records of the European herpetofauna. The comparison of this previous data with that of European fossil records would provide data on palaeobiogeographic affiliations of the region as well as on the origin and emergence of the present-day fauna of Western Siberia. An overview of the earliest occurrences of certain amphibian lineages is still needed. In addition, studies that address such knowledge gaps can be useful for molecular biologists in their calibration of molecular clocks. In this study, we considered critically reviewed available data from amphibian and reptile fauna from over 40 Western Siberian, Russian and Northeastern Kazakhstan localities, ranging from the Middle Miocene to Early Pleistocene. Herein, we provided new interpretations that arose from our assessment of the previously published and new data. More than 50 amphibians and reptile taxa were identified belonging to families Hynobiidae, Cryptobranchidae, Salamandridae, Palaeobatrachidae, Bombinatoridae, Pelobatidae, Hylidae, Bufonidae, Ranidae, Gekkonidae, Lacertidae, and Emydidae. Palaeobiogeographic analyses were performed for these groups and palaeoprecipitation values were estimated for 12 localities, using the bioclimatic analysis of herpetofaunal assemblages. The Neogene assemblage of Western Siberia was found to be dominated by groups of European affinities, such as Palaeobatrachidae, Bombina, Hyla, Bufo bufo, and a small part of this assemblage included Eastern Palaearctic taxa (e.g. Salamandrella, Tylototriton, Bufotes viridis). For several taxa (e.g. Mioproteus, Hyla, Bombina, Rana temporaria), the Western Siberian occurrences represented their most eastern Eurasian records. The most diverse collection of fossil remains was found in the Middle Miocene. Less diversity has been registered towards the Early Pleistocene, potentially due to the progressive cooling of the climate in the Northern Hemisphere. The results of our study showed higher-amplitude changes of precipitation development in Western Siberia from the Early Miocene to the Pliocene, than previously assumed.


A rare and unexpected case of retained foetal bone after an unsafe abortion.
Unsafe abortion is one of the most neglected healthcare problems in developing countries. One of the rare complications of unsafe abortion is retained foetal bone. Prevalence of disease is around 0.15% among patients undergoing diagnostic hysteroscopy. Patients have no specific symptoms. Case reports have focused on subfertility, abnormal uterine bleeding, lower abdominal pain, abnormal vaginal discharge, dyspareunia, dysmenorrhoea and spontaneous passage of bony fragments. Retained foetal bone fragments may cause acute pelvic inflammatory disease in rare cases regardless of the time interval after abortion. This condition can also present as recurrent vagitinis or endometritis refractory to ampirical antimicrobial treatment. In such cases, foreign body in uterine cavity should be kept in mind. Such patients should primarily be evaluated by ultrasonography which has substantial clinical importance in differential diagnosis of these cases. We present a case of misdiagnosed retained foetal bone complicated with recurrent vaginal discharge and acute pelvic inflammatory disease.


Telomeric fingerprinting of the violet root rot fungus, Helicobasidium mompa: a useful tool for karyotype estimation.
We hybridized the telomere-associated DNA sequence pTel46 isolated from Coprinus cinereus with Helicobasidium mompa genomic DNA. The hybridized fragments were more sensitive to Bal31 nuclease than those that were not hybridized, suggesting that they were located at the ends of chromosomes in H. mompa. The hybridization profile can be used to estimate chromosome number, since the number of chromosomes in a single basidiospore isolate is about half that in putative parent strains. Thus, single basidiospore and field isolates might be homokaryons and heterokaryons respectively. We found telomere-linked restriction fragment length polymorphisms (RFLPs) in strains of H. mompa isolated from field and individual basidiosporcs. Thus, this marker appears to be an excellent tool with which to reveal the considerable polymorphism of H. mompa and to identify strains. The RFLP was not found among several strains of the same mycelial compatibility group (MCG) isolated from the same field, suggesting that strains belonging to an MCG group are identical.


Organic acids from leaves, fruits, and rinds of Garcinia cowa.
Organic acids in fresh leaves, fruits, and dried rinds of Garcinia cowa (G. cowa) were determined by high-performance liquid chromatography. Fresh leaves, fruits, and dried rinds were extracted with water at 120 degrees C for 20-30 min under 15 lbs/in(2) pressure. Also, dried rinds were extracted with solvents (acetone and methanol) using a Soxhlet extractor at 60 degrees C for 8 h each. The samples were injected to HPLC under gradient elution with 0.01 M phosphoric acid and methanol with a flow rate of 0.7 mL/min using UV detection at 210 nm. The major organic acid was found to be (-)-hydroxycitric acid present in leaves, fruits, and rinds to the extent of 1.7, 2.3, and 12.7%, respectively. (-)-Hydroxycitric acid lactone, and oxalic and citric acids are present in leaves, fruits, and rinds in minor quantities. This is the first report on the composition of organic acids from G. cowa.


[Intraoperative Neurological Monitoring from the Anesthesiologist's Point of View Preface and Comments].
Intraoperative neurophysiological monitoring has been increasingly utilized for many neurosurgical procedures as well as for spine and aortic surgery. The recent advances in monitoring devices and anesthesia techniques have improved the reliability and accuracy of intraoperative neurological monitoring. In this issue, we review the basic principle, methods, and clinical application of several modalities of neurological monitoring to detect neural tissue ischemia and the direct physical injury to the specific neural pathway during surgical procedures. These modalities include near-infrared spectroscopy, motor evoked potentials, somatosensory evoked potentials, auditory brainstem responses, and visual evoked potentials. Pitfalls and limitations of each modality are also discussed. Evidence for the efficacy of the monitoring varied with surgical procedures, but has been well validated in some procedures. Anesthesiologists can contribute to the reliability and efficacy of neurophysiological monitoring by maintaining good physiological homeostasis and stable levels of anesthesia during the surgical procedure. With appropriate knowledge and experience, the anesthesiologist should work together with the neuromonitoring staff and surgeon to ensure neurological safety for the patient during and after surgery.


Detection and Enrichment of Rare Antigen-specific B Cells for Analysis of Phenotype and Function.
B cells reactive with a specific antigen usually occur at a frequency of <0.05% of lymphocytes. For decades researchers have sought methods to isolate and enrich these rare cells for studies of their phenotype and biology. Approaches are inevitably based on the principle that B cells recognize native antigen by virtue of cell surface receptors that are representative in specificity of antibodies that will eventually be secreted by their differentiated daughters. Perhaps the most obvious approach to the problem involves use of fluorochrome-conjugated antigens in conjunction with fluorescence-activated cell sorting (FACS). However, the utility of these methods is limited by cell frequency and the achievable rate of analysis and isolation by electronic sorting. A novel method to enrich rare antigen-specific B cells using magnetic nanoparticles that results in high yield enrichment of antigen-reactive B cells from large starting cell populations is described. This method enables improved monitoring of the phenotype and biology of antigen reactive cells before and following in vivo antigen encounter, such as after immunization or during development of autoimmunity.


The St Jude Medical symmetry aortic connector system for proximal vein graft anastomoses in coronary artery bypass grafting.
A new device designed to create proximal vein graft anastomoses to the aorta in coronary artery bypass grafting was recently developed by the St Jude Medical Anastomotic Technology Group (Minneapolis, Minn). This new anastomosis system consists of a nickel-titanium (nitinol) connector, an aortic cutter, and a delivery device. The loading of the vein on the aortic connector and its delivery to the aorta are described. In 43 consecutive patients (mean age 68 +/- 10 years, age range 33-91 years), 65 proximal vein graft anastomoses were performed with the new system. Intraoperative flow rates were assessed for all grafts according to the transit time principle. All connector anastomoses were performed without the use of any aortic clamp. Times to complete these mechanical anastomoses were less than 10 seconds in all cases. Hemostasis was instantaneous in all cases, with only 3 system failures. These connectors were easily removed so that the anastomoses could be performed with standard suturing technique through the same aortotomy without complications. All vein grafts were patent at the end of the procedure, and there were no intraoperative or postoperative complications related to the device. The aortic connector system was easy to handle and allowed quick creation of reliable, reproducible, and uniform anastomoses. In addition, anastomoses could be done without any clamping of the aorta, which is especially attractive for off-pump procedures, because aortic manipulation and therefore the risks of embolism and aortic dissection would be further minimized. In on-pump cases this technique would facilitate the single-clamp technique, again minimizing aortic manipulation.


Intracardiac echo-facilitated 3D electroanatomical mapping of ventricular arrhythmias from the papillary muscles: assessing the 'fourth dimension' during ablation.
Ventricular arrhythmias (VA) originating from a papillary muscle (PM) have recently been described as a distinct clinical entity with peculiar features that make its treatment with catheter ablation challenging. Here, we report our experience using an intracardiac echo-facilitated 3D electroanatomical mapping approach in a case series of patients undergoing ablation for PM VA. Sixteen patients who underwent catheter ablation for ventricular tachycardia (VT) or symptomatic premature ventricular contractions originating from left ventricular PMs were included in the study. A total of 24 procedures (mean 1.5 per patient) were performed: 15 using a retrograde aortic approach and 9 using a transseptal approach. Integrated intracardiac ultrasound for 3D electroanatomical mapping was used in 15 of the 24 procedures. The posteromedial PM was the most frequent culprit for the clinical arrhythmia, and the body was the part of the PM most likely to be the successful site for ablation. The site of ablation was identified based on the best pace map matching the clinical arrhythmia and the site of earliest the activation. At a mean follow-up of 10.5 ± 7 months, only two patients had recurrent arrhythmias following a repeat ablation procedure. An echo-facilitated 3D electroanatomical mapping allows for real-time creation of precise geometries of cardiac chambers and endocavitary structures. This is useful during procedures such as catheter ablation of VAs originating from PMs, which require detailed representation of anatomical landmarks. Routine adoption of this technique should be considered to improve outcomes of PM VA ablation.


Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty.
Assembly of the spliceosome requires the participation of SR proteins, a family of splicing factors rich in arginine-serine dipeptide repeats. The repeat regions (RS domains) are polyphosphorylated by the SRPK and Clk/Sty families of kinases. The two families of kinases have distinct enzymatic properties, raising the question of how they may work to regulate the function of SR proteins in RNA metabolism in mammalian cells. Here we report the first mass spectral analysis of the RS domain of ASF/SF2, a prototypical SR protein. We found that SRPK1 was responsible for efficient phosphorylation of a short stretch of amino acids in the N-terminal portion of the RS domain of ASF/SF2 while Clk/Sty was able to transfer phosphate to all available serine residues in the RS domain, indicating that SR proteins may be phosphorylated by different kinases in a stepwise manner. Both kinases bind with high affinity and use fully processive catalytic mechanisms to achieve either restrictive or complete RS domain phosphorylation. These findings have important implications on the regulation of SR proteins in vivo by the SRPK and Clk/Sty families of kinases.


Inhibitory effect of 2-chlorodeoxyadenosine on granulocytic, erythroid, and T-lymphocytic colony growth.
Previous studies have shown that 2-chloro-2'-deoxyadenosine (CdA) is markedly toxic to normal and malignant human lymphocytes in vitro and in vivo. Recent clinical trials have shown that CdA is a very promising drug for the treatment of lymphoid malignancies. The present investigations were designed to test the effect of CdA on the in vitro clonal growth of both myeloid progenitors and T-lymphocyte colony-forming cells (CFU-TL) obtained from normal human bone marrow and peripheral blood. Cells were exposed to CdA in doses up to 1280 nmol/L. To reduce indirect effects of CdA mediated by accessory cells, monocyte- and T-lymphocyte-depleted bone marrow cells were used for our investigations. The results show a marked inhibition of myeloid progenitor and lymphocyte colony-forming cells in a dose-dependent manner, correlating with maturation stage in that the immature progenitor cells are more sensitive to this drug. Furthermore, our studies suggest that a sequence of metabolic events previously described for lymphocytes may be operative in myeloid progenitor cells because a minimal exposure time of 48 hours is required to obtain a marked inhibition. CdA toxicity was proposed to be linked with phosphorylation by deoxycytidine-kinase (E.C. 18.104.22.168), the levels of which have been found to be high in lymphocytes, but low in granulocytes. However, the marked inhibition of myeloid progenitor cells shown in these studies suggests that other factors such as modulation of the effect of CdA by the ambient levels of other deoxynucleosides might influence the apparent sensitivity of myeloid cells.


Understanding Factors Associated with Uptake of Lung Cancer Screening among Individuals at High Risk.
Early detection using low-dose computed tomography scanning reduces lung cancer-specific mortality by 20% among high-risk individuals. Despite its efficacy, the uptake of lung cancer screening (LCS) remains low. This study aimed to identify factors associated with the uptake of LCS in high-risk individuals. Data for this study were obtained from the Behavioral Risk Factor Surveillance System (n=11,297). Multivariable logistic regression models were used. Individuals with no health insurance (OR: 0.33, 95% CI: 0.19-0.58), no primary health care provider (OR: 0.40, 95% CI: 0.25-0.64), no chronic obstructive pulmonary disease (OR: 0.37, 95% CI: 0.28- 0.49), and racial/ethnic minorities other than Black and Hispanic (OR: 0.49, 95% CI: 0.31-0.78) were less likely to participate in annual LCS. Low-dose computed tomography uptake varied widely across the 24 U.S. states. The findings from this study have important implications for designing more effective interventions to target specific U.S. states and subgroups for the uptake of annual LCS.


Symptom clusters in advanced illness.
To review the four sets of symptom clusters commonly seen in patients with advanced illness, and their definitions, associated symptomatology, and management. Research and review articles and textbooks. Symptoms of patients with advanced illness tend to occur not isolation, but in symptom clusters. The ability to cluster symptoms in both assessment and management reduces the use of polypharmacy, systemic toxicities, and improves the patient's quality of life. It is important that the nurse providing symptom management for the oncology patient understand the importance of clustering certain symptoms together.


On the stereochemistry and biosynthesis of lipoxin B.
Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icosatetraenoi c acid. Two isomers of LXB were identified by using an improved isolation procedure. These compounds were shown to be (5S,14R,15S)-5,14,15-trihydroxy-6,8,10,12-trans-icosatetraenoic acid (8-trans-LXB) and (5S,14S,15S)-5,14,15-trihydroxy-6,8,10,12-trans-icosatetraenoic acid [(14S)-8-trans-LXB]. Experiments with 18O2 showed that formation of LXB and its two isomers occurred with incorporation of molecular oxygen at C-5 but not at C-14. These results together with the finding that (15S)-hydroxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HETE) is a precursor of LXB compounds in activated leukocytes suggest that 15-hydroxy-5,6-epoxy-7,9,13-trans-11-cis-icosatetraenoic acid or its equivalent is a common intermediate in the biosynthesis of LXB and its two isomers.


Computational tools help improve protein stability but with a solubility tradeoff.
Accurately predicting changes in protein stability upon amino acid substitution is a much sought after goal. Destabilizing mutations are often implicated in disease, whereas stabilizing mutations are of great value for industrial and therapeutic biotechnology. Increasing protein stability is an especially challenging task, with random substitution yielding stabilizing mutations in only ∼2% of cases. To overcome this bottleneck, computational tools that aim to predict the effect of mutations have been developed; however, achieving accuracy and consistency remains challenging. Here, we combined 11 freely available tools into a meta-predictor (meieringlab.uwaterloo.ca/stabilitypredict/). Validation against ∼600 experimental mutations indicated that our meta-predictor has improved performance over any of the individual tools. The meta-predictor was then used to recommend 10 mutations in a previously designed protein of moderate thermodynamic stability, ThreeFoil. Experimental characterization showed that four mutations increased protein stability and could be amplified through ThreeFoil's structural symmetry to yield several multiple mutants with >2-kcal/mol stabilization. By avoiding residues within functional ties, we could maintain ThreeFoil's glycan-binding capacity. Despite successfully achieving substantial stabilization, however, almost all mutations decreased protein solubility, the most common cause of protein design failure. Examination of the 600-mutation data set revealed that stabilizing mutations on the protein surface tend to increase hydrophobicity and that the individual tools favor this approach to gain stability. Thus, whereas currently available tools can increase protein stability and combining them into a meta-predictor yields enhanced reliability, improvements to the potentials/force fields underlying these tools are needed to avoid gaining protein stability at the cost of solubility.


Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.
Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery.


Stress abnormalities in individuals at risk for psychosis: a review of studies in subjects with familial risk or with "at risk" mental state.
Increased sensitivity to stress is known to play an important role in the transition to first episode psychosis (FEP). Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, and, in general, an increased sensitivity to stress, have been hypothesised to be components of the vulnerability to psychosis, but whether these abnormalities are already present before the onset of psychosis has not yet been systematically reviewed. Here we have reviewed all studies examining psychological and biological markers of the stress response in the relatives of psychotic patients and in individuals at Ultra High Risk (UHR) for psychosis. In relatives, there is evidence of increased sensitivity to stress, as shown by increased emotional reactivity to daily life stress, increased adrenocorticotropic hormone (ACTH) in response to stress, increased pituitary volume and reduced hippocampal volume. However, evidence of increased cortisol levels is less consistent. On the other hand, subjects who experience attenuated psychotic symptoms show increased cortisol levels as well as increased pituitary and reduced hippocampal volumes. Moreover, this HPA axis hyperactivity seems to be even greater among those individuals who subsequently develop frank psychosis. In summary, an enhanced HPA axis response to stress appears to be part of the biological vulnerability to psychosis which is present prior to the onset of psychosis. A further increase in cortisol levels during the transition to FEP suggests the presence of an additive factor, possibly environmental, at this stage of the illness. Possible causes and consequences of HPA axis impairment in risk for psychosis are discussed.


How I do it: managing radiation dose in CT.
Computed tomography (CT) is an imaging test that is widely used worldwide to establish medical diagnoses and perform image-guided interventions. More recently, concern has been raised about the risk of carcinogenesis from medical radiation, with a focus on CT. The purpose of this article is to (a) describe the importance of educating radiology personnel, patients, and referring clinicians about the concerns over CT radiation, (b) describe commonly used CT parameters and radiation units, (c) discuss the importance of establishing a dedicated radiology team to manage CT radiation, and (d) describe specific CT techniques to minimize radiation while providing diagnostic examinations.


Two new flavanones from Polytrichum commune Hedw.
Seven flavanones, including two new compounds coupled with styryl units, communins C (1) and D (2), as well as five known compounds, were isolated from Polytrichum commune Hedw. The planar structures of all compounds were determined using extensive spectroscopic analysis. The absolute configurations of two new compounds were assigned by comparing experimental ECD with calculated ECD. The cytotoxicity of all isolates against HCT-116, BGC803, MCF7 and PANC-1 cell lines was evaluated. Communin D exhibited significant cytotoxic activity on BGC803 cells with an IC50 value of 9.3 μM.


Deoxynucleoside salvage facilitates DNA repair during ribonucleotide reductase blockade in human cervical cancers.
Cells generate 2'-deoxyribonucleoside triphosphates (dNTPs) for both replication and repair of damaged DNA predominantly through de novo reduction of intracellular ribonucleotides by ribonucleotide reductase (RNR). Cells can also salvage deoxynucleosides by deoxycytidine kinase/thymidine kinase 1 in the cytosol or by deoxyguanosine kinase/thymidine kinase 2 in mitochondria. In this study we investigated whether the salvage dNTP supply pathway facilitates DNA damage repair, promoting cell survival, when pharmacological inhibition of RNR by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC no. 663249) impairs the de novo pathway. Human cervical cancer cells were subjected to radiation with or without 3-AP under medium deoxynucleoside concentrations of 0, 0.05, 0.5 and 5.0 µM. Efficacy of DNA damage repair was assessed by γ-H2AX flow cytometry and focus counts, by single cell electrophoresis (Comet assay), and by caspase 3 cleavage assay as a marker of treatment-induced apoptosis. Cell survival was assessed by colony formation. We found that deoxyribonucleotide salvage facilitates DNA repair during RNR inhibition by 3-AP and that salvage reduces the radiochemosensitivity of human cervical cancer cells.


On physical nanoscale aspects of compatibility of steels with hydrogen and natural gas.
The possibilities of effective solutions of relevant technological problems are considered based on the analysis of fundamental physical aspects, elucidation of the nano-structural mechanisms and interrelations of aging and hydrogen embrittlement of materials (steels) in the hydrogen industry and gas-main industries. The adverse effects which these mechanisms and processes have on the service properties and technological lifetime of materials are analyzed. The concomitant fundamental process of formation of carbohydride-like and other segregation nanostructures at dislocations (with the segregation capacity 1 to 1.5 orders of magnitude greater than in the widely used Cottrell 'atmosphere' model) and grain boundaries is discussed in the context of how these nanostructures affect technological processes (aging, hydrogen embrittlement, stress corrosion damage, and failure) and the physicomechanical properties of the metallic materials (including the technological lifetimes of pipeline steels).


Zero control reference materials for infant formula methods development.
A zero control reference material (ZRM) for milk and soy-based infant formula was manufactured and characterized. The ZRM was free of retinyl palmitate and all-rac-alpha-tocopheryl acetate. The composition was similar to commercially available infant formula. The ZRM provides a valuable tool to ascertain method performance.


[Parasite fauna and features of the parasite community structure in the minnow Phoxinus phoxinus (Linnaeus) from Yenisei and Kacha rivers].
Phoxinus phoxinus is a species widely distributed throughout Palaearctic and is a good model for investigation of parasite communities. Species composition and structure of parasite communities in the minnow from the streams if different types, namely Yenisei river near Krasnoyarsk City and its left affluent Kacha River, were examined. Indices of Shannon, Simpson, and Berger-Parker were used to describe the component parasite communities. Twenty five parasite species of seven classes were revealed, and ectoparasite were found to be dominating among them. The host-specific parasite species Paratrichodina phoxini (Infusoria), Dactylogyrus borealis (Monogenea), Parahemiurus merus and Diplostomum phoxini (Digenea) constitute the peculiarity of the parasite fauna in minnow. Parasite community of minnow in the Kacha river is the most various one. It is caused by the following factors--favorable temperature conditions, composition of ichthyofauna, and a high density of fish population in the Kacha river. Metacercaria of Diplostomum phoxini, the specific parasites of minnow's brain, are dominating in both streams.


Aminophylline injection and theophylline tablets: Acute response in partially reversible chronic airway obstruction.
Intravenous injections of aminophylline (250 mg) and tablets of theophylline (Neulin) (400 mg) were given, on separate occasions, to 10 patients with partially reversible severe airway obstruction. The dose of aminophylline was shown to be inadequate on the basis of the unsatisfactory plasma theophylline levels and a poor ventilatory response. Two hours after oral administration of theophylline, a mean plasma theophylline concentration in the optimal range (10 to 20 mug/ml) was reached, and a consistent improvement in the mean forced expiratory volume in one second (FEV1) occurred. A further large improvement in FEV1 after inhalation of salbutamol showed that the improvement in ventilation with the theophylline tablets, although consistent, was less than maximal.


A coevolutionary residue network at the site of a functionally important conformational change in a phosphohexomutase enzyme family.
Coevolution analyses identify residues that co-vary with each other during evolution, revealing sequence relationships unobservable from traditional multiple sequence alignments. Here we describe a coevolutionary analysis of phosphomannomutase/phosphoglucomutase (PMM/PGM), a widespread and diverse enzyme family involved in carbohydrate biosynthesis. Mutual information and graph theory were utilized to identify a network of highly connected residues with high significance. An examination of the most tightly connected regions of the coevolutionary network reveals that most of the involved residues are localized near an interdomain interface of this enzyme, known to be the site of a functionally important conformational change. The roles of four interface residues found in this network were examined via site-directed mutagenesis and kinetic characterization. For three of these residues, mutation to alanine reduces enzyme specificity to ~10% or less of wild-type, while the other has ~45% activity of wild-type enzyme. An additional mutant of an interface residue that is not densely connected in the coevolutionary network was also characterized, and shows no change in activity relative to wild-type enzyme. The results of these studies are interpreted in the context of structural and functional data on PMM/PGM. Together, they demonstrate that a network of coevolving residues links the highly conserved active site with the interdomain conformational change necessary for the multi-step catalytic reaction. This work adds to our understanding of the functional roles of coevolving residue networks, and has implications for the definition of catalytically important residues.


Expanding the 'aplysinospin cascade' through DNA-templated [2+2] photocycloaddition.
Inspired by the unique ability of nucleic acids to template chemical transformations that are otherwise impossible in solution, we embarked on the generalisation of our DNA-templated [2+2] photo-induced homo- and heterodimerization of aplysinopsins. Our process ensures a straightforward access to cyclobutane containing natural products and analogues thereof. Most importantly, this conceptual biomimetic achievement presents interesting arguments to build a biosynthetic scenario.


Pleiotrophin regulates bone morphogenetic protein (BMP)-induced ectopic osteogenesis.
We previously isolated pleiotrophin (PTN) from bovine bone as a protein and showed that it stimulated osteoblastic growth and differentiation. Further details of its function, however, have not been fully clarified. The aim of this paper was to elucidate the effects of PTN on bone morphogenetic protein (BMP)-induced ectopic osteogenesis. Recombinant human BMP (rhBMP)-2 (1.2 microg) was combined with a fibrous glass membrane, which had been established as an effective carrier. Various amounts of the purified bovine PTN (5, 10, 50, and 100 microg) or rhPTN (5 and 10 microg) were added to the rhBMP-2/carrier composites and implanted into rats subcutaneously as reported. It was found that the amount of bone induced in the system increased with the addition of 10 microg of either purified PTN or rhPTN. However, the amount of bone decreased with the addition of 50 or 100 microg of purified PTN dose-dependently, as judged by both alkaline phosphatase activity and calcium content in the retrieved implants. It was concluded that purified PTN or rhPTN, at ratios of concentration of 10-100 microg of PTN to 1.2 microg of rhBMP-2 in the carrier, regulated the ectopic bone-inducing activity of rhBMP-2.


Advice Giving: A Subtle Pathway to Power.
We propose that interpersonal behaviors can activate feelings of power, and we examine this idea in the context of advice giving. Specifically, we show (a) that advice giving is an interpersonal behavior that enhances individuals' sense of power and (b) that those who seek power are motivated to engage in advice giving. Four studies, including two experiments ( N = 290, N = 188), an organization-based field study ( N = 94), and a negotiation simulation ( N = 124), demonstrate that giving advice enhances the adviser's sense of power because it gives the adviser perceived influence over others' actions. Two of our studies further demonstrate that people with a high tendency to seek power are more likely to give advice than those with a low tendency. This research establishes advice giving as a subtle route to a sense of power, shows that the desire to feel powerful motivates advice giving, and highlights the dynamic interplay between power and advice.


3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina.
3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.


Paleopathology in osseous remains from the 16th century. A survey of rheumatic diseases.
To describe the rheumatic conditions found in skeletal remains of Amerindian ancestry disinterred from a 16th century Mexican cemetery. A physical anthropologist and 2 rheumatologists surveyed the recovered skeletal remains. We examined the skeletal remains of 443 subjects. We found 19 cases of Pott's disease, 17 of osteoarthrosis in various anatomical locations, 2 spondyloarthropathies, probably ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis, one probable septic arthritis in the stemoclavicular joint, and 2 compression fractures of the spine. We found no cases of gout or rheumatoid arthritis. This is the first report on the presence of rheumatic conditions in colonial Mexico. Studying the remains of these populations can provide useful information about the origin and evolution of different rheumatic conditions.


A prospective study of salvage high-intensity focused ultrasound for locally radiorecurrent prostate cancer: early results.
After radical external beam radiation therapy (EBRT), local recurrence may benefit from definitive local therapy. The objective of this study was to evaluate the safety and short-term biochemical results and morbidity after salvage high-intensity focused ultrasound (HIFU) treatment in patients with biopsy-proven local prostate cancer recurrence after EBRT. From October 2006 46 patients were treated with HIFU. Bone scan and abdominal CT/MRI scan were negative. Median follow-up was 9 months (range 3-24 months). The median prostate-specific antigen (PSA) nadir was 0.3 ng/ml (range 0-24 ng/ml). Eighteen patients (39.1%) were classified as failures. In addition, there were four patients (8.7%) with post-HIFU PSA nadir > 0.5 ng/ml. No patients died during follow-up. One patient developed urethrorectal fistulae and was successfully treated conservatively. Two patients developed urethrocutaneous fistulae. Seven patients (15.2%) and one patient (2.1%) developed grade 2 and grade 3 incontinence, respectively. Seven men (15.2%) had erectile function sufficient for intercourse pre-HIFU and only two men (4.3%) post-HIFU. Early results of salvage HIFU in patients with local recurrence of prostate cancer after radical EBRT indicate the procedure to be a reasonable treatment option, but better patient selection criteria are needed. The side-effects are not negligible.


Structural and dynamical properties of dilute gel networks in colloid-polymer mixtures.
The competition of short-ranged depletion attraction and long-ranged repulsion between colloidal particles in colloid-polymer mixtures leads to the formation of heterogeneous gel-like structures. Our special focus will be on the states where the colloids arrange in thin strands that span the whole system and that we will refer to as dilute gel networks. These states occur at low packing fractions for attractions that are stronger than those at both the binodal line of the equilibrium gas-liquid phase separation and the directed percolation transition line. By using Brownian dynamics simulations, we explore the formation, structure, and aging dynamics of dilute gel networks. The essential connections in a dilute gel network are determined by constructing reduced networks. We compare the observed properties to those of clumpy gels or cluster fluids. Our results demonstrate that both the structure and the (often slow) dynamics of the stable or meta-stable heterogeneous states in colloid-polymer mixtures possess distinct features on various length and time scales and thus are richly diverse.


Trophic ecomorphology of Siluriformes (Pisces, Osteichthyes) from a tropical stream.
The present study analysed the relationship between morphology and trophic structure of Siluriformes (Pisces, Osteichthyes) from the Caracu Stream (22º 45' S and 53º 15' W), a tributary of the Paraná River (Brazil). Sampling was carried out at three sites using electrofishing, and two species of Loricariidae and four of Heptapteridae were obtained. A cluster analysis revealed the presence of three trophic guilds (detritivores, insectivores and omnivores). Principal components analysis demonstrated the segregation of two ecomorphotypes: at one extreme there were the detritivores (Loricariidae) with morphological structures that are fundamental in allowing them to fix themselves to substrates characterised by rushing torrents, thus permitting them to graze on the detritus and organic materials encrusted on the substrate; at the other extreme of the gradient there were the insectivores and omnivores (Heptapteridae), with morphological characteristics that promote superior performance in the exploitation of structurally complex habitats with low current velocity, colonised by insects and plants. Canonical discriminant analysis revealed an ecomorphological divergence between insectivores, which have morphological structures that permit them to capture prey in small spaces among rocks, and omnivores, which have a more compressed body and tend to explore food items deposited in marginal backwater zones. Mantel tests showed that trophic structure was significantly related to the body shape of a species, independently of the phylogenetic history, indicating that, in this case, there was an ecomorphotype for each trophic guild. Therefore, the present study demonstrated that the Siluriformes of the Caracu Stream were ecomorphologically structured and that morphology can be applied as an additional tool in predicting the trophic structure of this group.


Using regulatory enforcement theory to explain compliance with quality and patient safety regulations: the case of internal audits.
Implementing an accredited quality and patient safety management system is inevitable for hospitals. Even in the case of an obligatory rule system, different approaches to implement such a system can be used: coercive (based on monitoring and threats of punishment) and catalytic (based on dialogue and suggestion). This study takes these different approaches as a starting point to explore whether and how implementation actions are linked to compliance. By doing so, this study aims to contribute to the knowledge on how to increase compliance with obligatory rules and regulations. The internal audit system (the 'tracer system') of a large Dutch academic hospital is used as a case to investigate different implementation approaches and their effect on compliance. This case allowed us to use a multi-actor and multi-method approach for data collection. Internal audits (N = 16) were observed, audit reports were analyzed, and semi-structured interviews were conducted with both the internal auditors (N = 23) and the ward leaders (N = 14) responsible for compliance. Framework analysis was used to analyze the data. Although all auditors use catalytic enforcement actions, these do not lead to (intended) compliance of all ward leaders. Rather, the catalytic actions contribute to (intended) compliance of ward leaders that are motivated, whereas they do not for the ward leaders that are not motivated. For the motivated ward leaders, catalytic enforcement actions contribute to (intended) compliance by increasing ward leaders' knowledge of the rules and how to comply with them. Our findings suggest that the effectiveness of implementation actions depends not only on the actions themselves, but also on the pre-existing motivation to comply. These findings imply that there is not one 'best' approach to the implementation of obligatory rules. Rather, the most effective approach depends on the willingness to comply with rules and regulations.


Genetically determined chromosome instability syndromes.
Spontaneously increased chromosomal instability is well documented in the three autosomal recessive diseases, Fanconi's anemia (FA), Bloom's syndrome (BS), and ataxia telangiectasia (AT). Other conditions have been reported to be associated with chromosomal breakage. Some are still single observations: in Werner's syndrome only fibroblasts are affected, and systemic sclerosis may not be an inherited disease. Various aspects of FA, BS, and AT are discussed which have emerged since recent reviews have been published. The differential diagnosis in FA has become more important than it was in the past. Proven heterogeneity in FA demands definition of what to name FA and FA variants. The analysis of cancer frequencies and types in FA and AT lacks important clues. This should stimulate all of us to mutual exchange of data and creation of registries not only of patients and follow-ups, but also of characterized cell strains. A synopsis of results from cell and cytogenetic studies demonstrates similarities and differences in detail of the general phenomenon of chromosomal instability which FA, BS, and AT share. Results from biochemical studies at the DNA level together with cytogenetic findings indicate different but still undefined failures in DNA metabolism or DNA repair mechanisms due to the different genes. A new approach to analyzing the impairment of DNA repair in FA is briefly described. DNA related enzymes are produced in the cytoplasm and have to be transported to the nucleus. The subcellular distribution of topoisomerase activity was found to be unusual in three placentas of FA patients. Other DNA enzymes were distributed normally. Thus, a specific mechanism for movement of the enzyme through the nuclear membrane seems to be defective.


Dynamic response of denitrifying poly-P accumulating organisms batch culture to increased nitrite concentration as electron acceptor.
Despite the fact that, in practice, enhanced biological phosphorus removal (EBPR) is often combined with biological nitrogen removal (BNR), the feasibility of nitrite (an intermediate in BNR) utilization, by denitrifying poly-P accumulating organisms (DPAO) is still unclear. In this study, the effect of nitrite on the EBPR was evaluated by investigating the dynamic response of DPAO to the gradual change of electron acceptor from nitrate to nitrite in an anaerobic/anoxic sequencing batch reactor (SBR). Under the nitrate condition, excellent EBPR was achieved, characterized by the DPAO biomass dominating in the sludge (51%-72% of VSS). Of the DPAO, 34% was the DPAOnitrate that could only use nitrate as electron acceptor, and 66% was the DPAOnitrite that could use nitrate/nitrite as electron acceptor. Nitrite in excess of 12 mg N/L had inhibition effect on the anoxic phosphorus uptake. As the electron acceptor changed, EBPR degraded slowly due to the gradual exclusion of the DPAOnitrate out of the reactor. The DPAOnitrite, therefore, became the single type of DPAO under the nitrite condition, and finally occupied only 33%-49% of the total sludge of VSS. Simultaneously, glycogen accumulating organisms (GAO), the competitor to the DPAO for substrate in the anaerobic phase, was significantly enhanced and grew to dominance in the reactor (46-62% of VSS). Also, the periodical exposure of sludge to the increased nitrite concentration elevated the inhibition level of nitrite for the anoxic phosphorus uptake (80 mg N/L). More attention should be paid to nitrite accumulation at full-scale wastewater treatment plants from the perspective of the stability of EBPR performance.


Urothelial carcinoma with villoglandular differentiation (UCVGD) with small cell neuroendocrine carcinoma of urinary bladder.
Urothelial carcinoma with villoglandular differentiation (UCVGD) is a rare aggressive variant of urothelial carcinoma. It is usually associated with high-grade urothelial carcinoma or rarely adenocarcinoma. There is only one other previous report of UCVGD associated with small cell neuroendocrine carcinoma of urinary bladder. We report the second case of UCVGD with small cell neuroendocrine carcinoma of urinary bladder in a 74-year-old non-smoker male patient. The mass was muscle invasive and also invaded the prostate. This entity needs to be confidently diagnosed due to its prognostic and therapeutic implications.


Comparative analytical study of the selected wine varieties grown in Montenegro.
Samples of the selected red wine varieties grown in Montenegro (Merlot, Cabernet Sauvignon and Vranac; vintages 2010-2012) were compared according to total phenolic content, anti-DPPH radical activity, phenolic profile and elemental composition. All the samples showed profound anti-DPPH radical activity, due to high content of total phenolic compounds (R = 0.92). The most abundant phenolics were catechin and gallic acid with the highest values recorded for Merlot 2012 (43.22 and 28.65 mg/L, respectively). In addition to this, the content of essential elements including the potentially toxic ones was within healthy (safe) level for all the samples analysed. This study has actually pointed out Merlot wine variety as the best quality one, though all three varieties may be used as safe and health-promoting nutritional products.


META. 3. A genetic algorithm for metabolic transform priorities optimization.
META is a knowledge-based expert system that simulates the biotransformation of xenobiotics. It operates with the help of a dictionary (knowledge base) to seek target fragments in a compound and transform them to products. Here, a genetic algorithm is introduced to help build the knowledge base and optimize the performance of the methodology.


COMPARISON OF THE LEVELS OF C-REACTIVE PROTEIN, GLP-1 AND GLP-2 AMONG INDIVIDUALS WITH DIABETES, MORBID OBESITY AND HEALTHY CONTROLS: AN EXPLORATORY STUDY.
The glucagon-like peptides 1 and 2 (GLP-1/GLP-2) are gut hormones that may directly affect the glucose homeostasis and their activity seems to be significantly affected by chronic inflammation. To evaluate the postprandial levels of glucagon-like peptides 1 and 2 (GLP-1/GLP-2), C-reactive protein (CRP), and the postprandial glucose and insulin levels among individuals with obesity, type 2 diabetes, and healthy controls. An exploratory cross-sectional study, which involved individuals awaiting for bariatric/metabolic surgery and healthy controls. Postprandial levels of GLP-1, GLP-2, glucose, and insulin were obtained after a standard meal tolerance test. Inflammation was assessed by means of CRP. There were 30 individuals enrolled in the study, divided into three groups: non-diabetic with morbid obesity (NDO; n=11 individuals), diabetic with mild obesity (T2D; n=12 individuals), and healthy controls (C; n=7 individuals). The mean CRP levels were significantly higher in the NDO group (6.6±4.7 mg/dL) than in the T2D (3.3±2.2 mg/dL) and C groups (2.5±3.2 mg/dL) (P=0.038). The GLP-1 levels following standard meal tolerance test and the area under the curve of GLP-1 did not differ among the three groups. The GLP-2 levels were significantly lower in the NDO and T2D than in the C group following standard meal tolerance test at all the times evaluated. The area under the curve of the GLP-2 was significantly lower in the NDO and T2D groups than in the C group (P=0.05 and P=0.01, respectively). GLP-2 levels were impaired in the individuals with obesity and diabetes. This mechanism seems to be enrolled in preventing the worsening of the glucose homeostasis in these individuals.


Fatty acid synthesis is a therapeutic target in human liposarcoma.
Liposarcomas (LS) are mesenchymal tumors that can recur after surgical resection and often do not respond to presently available medical therapies. This study demonstrates the dependence of LS on de novo long-chain fatty acid synthesis for growth. Lipogenesis can be impaired by inhibiting the activities of lipogenic enzymes, including acetyl CoA-carboxylase (ACC) and fatty acid synthase (FASN), or by suppressing the expression of key genes involved in the pathway and its regulation. The FASN inhibitors cerulenin and orlistat reduced the growth of two LS cell lines (LiSa2, SW872), as did inhibition of ACC with soraphen A. CDDO-Me, a synthetic triterpenoid, suppressed expression of Spot 14 and FASN genes and likewise inhibited LS cell growth. Importantly, the anti-proliferative effect of each agent was prevented by the co-administration of palmitate, the major product of cellular long-chain fatty acid synthesis. In stark contrast to LS cells, these compounds had no effect on the growth of fibroblasts. Four biochemically distinct agents that target critical points in the fatty acid synthetic pathway exert anti-proliferative effects on LS cells, and rescue of cell growth by palmitic acid suggests that reduced tumor cell lipogenesis mediates the growth inhibition. These findings warrant further studies aimed at the clinical exploitation of the dependence of LS cell growth on fatty acids.


A molecular phylogeny of the Sylvia cantillans complex: cryptic species within the Mediterranean basin.
The subalpine warbler Sylvia cantillans is formally considered a polytypic species, with four subspecies, European S. c. cantillans, albistriata, moltonii (recently resumed name: subalpina) and North African S. c.inornata. They are very similar in external morphology but clearly differ in their vocalizations. We evaluated their uncertain taxonomic status reconstructing the phylogenetic and phylogeographic relationships among populations sampled across major biogeographical areas in the European species' range, using nucleotide sequences of the mitochondrial cytochrome b gene (mtDNA cyt b). A variety of phylogenetic analyses concordantly led to identify four major groups, only partially corresponding to the three European nominal subspecies. Phylogenetic trees showed a monophyletic group including all moltonii individuals, well diverged from all other taxa. Populations taxonomically assigned to cantillans were polyphyletic being split into two distinct clades (western and southern cantillans), with monophyletic albistriata closely related to southern cantillans. Individuals of moltonii and southern cantillans sampled in sites of sympatry in central Italy were assigned to their respective groups, with perfect concordance between phenotypic and genetic identifications. All findings indicate that moltonii should be ranked as a distinct species. Former subspecies cantillans is polyphyletic, but additional data are needed to define the taxonomic status of its two clades. Albistriata is phylogenetically related to southern cantillans and should be provisionally kept as a subspecies of S. cantillans. The cantillans complex thus provides an interesting case-study illustrating geographical structuring across small geographical ranges, and it exemplifies speciation through differentiation in allopatry leading to reproductive isolation after a secondary contact.


The Association of TNF-Alpha Inhibitors and Development of IgA Nephropathy in Patients with Rheumatoid Arthritis and Diabetes.
IgA nephropathy (IgAN) is a rather uncommon complication of TNF-alpha inhibition with a range of findings such as asymptomatic microscopic/macroscopic hematuria or different degrees of proteinuria and could progress to end-stage renal disease. We are reporting three patients with longstanding rheumatoid arthritis (RA), which developed IgAN while receiving TNF-alpha inhibitors. All off our three patients had RA, which lasted 2-4 years, and none of them had a prior history of chronic kidney disease. Two patients were treated with adalimumab while one patient was treated with golimumab. Discontinuation of anti-TNF-alpha therapy and initiation of immunosuppressive therapy led to improvement in serologic abnormalities and renal function in two patients, while the third patient's 24-hour proteinuria was only partially reduced, which supports previous reports on TNF-alpha inhibitor induced autoimmunity. Two of our patients had previously been diagnosed with type 2 diabetes mellitus while the third patient developed diabetes years after the onset of IgAN. This is in line with the previously described association of IgAN and diabetes mellitus. To our best knowledge, this is the first report to analyze the development of IgAN as a potential consequence of anti-TNF-alpha therapy and its possible association with pretreatment or posttreatment diabetes.


Rare and common variants in ROM1 and PRPH2 genes trans-modify Stargardt/ABCA4 disease.
Over 1,500 variants in the ABCA4 locus cause phenotypes ranging from severe, early-onset retinal degeneration to very late-onset maculopathies. The resulting ABCA4/Stargardt disease is the most prevalent Mendelian eye disorder, although its underlying clinical heterogeneity, including penetrance of many alleles, are not well-understood. We hypothesized that a share of this complexity is explained by trans-modifiers, i.e., variants in unlinked loci, which are currently unknown. We sought to identify these by performing exome sequencing in a large cohort for a rare disease of 622 cases and compared variation in seven genes known to clinically phenocopy ABCA4 disease to cohorts of ethnically matched controls. We identified a significant enrichment of variants in 2 out of the 7 genes. Moderately rare, likely functional, variants, at the minor allele frequency (MAF) <0.005 and CADD>25, were enriched in ROM1, where 1.3% of 622 patients harbored a ROM1 variant compared to 0.3% of 10,865 controls (p = 2.41E04; OR 3.81 95% CI [1.77; 8.22]). More importantly, analysis of common variants (MAF>0.1) identified a frequent haplotype in PRPH2, tagged by the p.Asp338 variant with MAF = 0.21 in the matched general population that was significantly increased in the patient cohort, MAF 0.25, p = 0.0014. Significant differences were also observed between ABCA4 disease subgroups. In the late-onset subgroup, defined by the hypomorphic p.Asn1868Ile variant and including c.4253+43G>A, the allele frequency for the PRPH2 p.Asp338 variant was 0.15 vs 0.27 in the remaining cohort, p = 0.00057. Known functional data allowed suggesting a mechanism by which the PRPH2 haplotype influences the ABCA4 disease penetrance. These associations were replicated in an independent cohort of 408 patients. The association was highly statistically significant in the combined cohorts of 1,030 cases, p = 4.00E-05 for all patients and p = 0.00014 for the hypomorph subgroup, suggesting a substantial trans-modifying role in ABCA4 disease for both rare and common variants in two unlinked loci.


Colitis cystica profunda.
Colitis cystica profunda is a benign disease characterized by variably sized mucin-filled cysts beneath the muscularis mucosae. The clinocpathologic features of five patients are described. The accumulated evidence suggests that awareness of this entity both by clinicians and pathologists with help differentiate it from carcinoma and decrease the need for radical surgery.


Correlates of recent drug use among victimized women on probation and parole.
Guided by the Comprehensive Health Seeking and Coping Paradigm (CHSCP; Nyamathi, 1989), the present research sought to examine associations between victimization, psychological distress, lawbreaking and recent drug use (past 12 months) among 406 victimized women on probation and parole. Bivariate differences between women who reported recent drug use and those who did not report recent use were compared across the 4 domains of the CHSCP (sociodemographic characteristics, personal resources, lifetime victimization, dynamic crime and drug factors). Variables significantly related to recent drug use at the bivariate level were retained in the multivariate analysis. The final multivariate model, using stepwise logistic regression via backward elimination, retained five candidate variables indicating women who recently used drugs, were younger, were not sexually victimized as children, began using drugs before they were 13 years of age, were on probation, and had engaged in more recent lawbreaking. The final model accounted for approximately 30% of the variance in drug use over the past 12 months. Implications for intervention and future research are discussed.


Lyophilisation and sterilisation of liposomal vaccines to produce stable and sterile products.
The advantages of liposomes as delivery systems for peptide, protein and DNA vaccines is well-recognised, unfortunately their application has been stinted by their instability during storage and their limited shelf-life. Further, sterilisation of these systems has been problematic, with degradation of the liposomes being reported after sterilisation using the various techniques available. Work form our laboratory has investigated techniques that can be applied to particulate liposomal vaccines such that they can be prepared in a freeze-dried and sterile format. In this article, we describe techniques for the lyophilisation, cryoprotection and sterilisation of liposomal vaccines. Applying these methods allows for the retention of both the chemical integrity of the lipids and the key physico-chemical characteristics of the liposomes (e.g., particle size, zeta potential, and dynamic viscosity), thus supporting the enhanced transition of liposomal vaccines from the bench to the clinic.


Chromatin remodeling factor LSH affects fumarate hydratase as a cancer driver.
Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progression; however, the dynamic interplay between them remains poorly understood. As reported in the article entitled "Chromatin remodeling factor LSH drives cancer progression by suppressing the activity of fumarate hydratase," which was recently published in Cancer Research, our group examined the physiological role of lymphocyte-specific helicase (LSH) in nasopharyngeal carcinoma (NPC) by focusing on cancer progression and the tricarboxylic acid cycle. We found that LSH was overexpressed in NPC, and its expression associated with Epstein-Barr virus infection. We also found that LSH directly suppressed fumarate hydratase (FH), a key component of the tricarboxylic acid cycle, in combination with euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a. Depletion of FH promoted epithelial-mesenchymal transition (EMT). Moreover, LSH controlled expression of tricarboxylic acid cycle intermediates that promote cancer progression, including EMT, through activation by inhibitor of nuclear factor kappa-B kinase alpha (IKKα), a chromatin modifier and transcriptional activator. Our study showed that LSH plays a critical role in cancer progression, which has important implications for the development of novel strategies to treat NPC.


Species level mapping of a seagrass bed using an unmanned aerial vehicle and deep learning technique.
Seagrass beds are essential habitats in coastal ecosystems, providing valuable ecosystem services, but are threatened by various climate change and human activities. Seagrass monitoring by remote sensing have been conducted over past decades using satellite and aerial images, which have low resolution to analyze changes in the composition of different seagrass species in the meadows. Recently, unmanned aerial vehicles (UAVs) have allowed us to obtain much higher resolution images, which is promising in observing fine-scale changes in seagrass species composition. Furthermore, image processing techniques based on deep learning can be applied to the discrimination of seagrass species that were difficult based only on color variation. In this study, we conducted mapping of a multispecific seagrass bed in Saroma-ko Lagoon, Hokkaido, Japan, and compared the accuracy of the three discrimination methods of seagrass bed areas and species composition, i.e., pixel-based classification, object-based classification, and the application of deep neural network. We set five benthic classes, two seagrass species (Zostera marina and Z. japonica), brown and green macroalgae, and no vegetation for creating a benthic cover map. High-resolution images by UAV photography enabled us to produce a map at fine scales (<1 cm resolution). The application of a deep neural network successfully classified the two seagrass species. The accuracy of seagrass bed classification was the highest (82%) when the deep neural network was applied. Our results highlighted that a combination of UAV mapping and deep learning could help monitor the spatial extent of seagrass beds and classify their species composition at very fine scales.


Interoceptive ingredients of body ownership: Affective touch and cardiac awareness in the rubber hand illusion.
The sense of body ownership represents a fundamental aspect of bodily self-consciousness. Using multisensory integration paradigms, recent studies have shown that both exteroceptive and interoceptive information contribute to our sense of body ownership. Interoception refers to the physiological sense of the condition of the body, including afferent signals that originate inside the body and outside the body. However, it remains unclear whether individual sensitivity to interoceptive modalities is unitary or differs between modalities. It is also unclear whether the effect of interoceptive information on body ownership is caused by exteroceptive 'visual capture' of these modalities, or by bottom-up processing of interoceptive information. This study aimed to test these questions in two separate samples. In the first experiment (N = 76), we examined the relationship between two different interoceptive modalities, namely cardiac awareness based on a heartbeat counting task, and affective touch perception based on stimulation of a specialized C tactile (CT) afferent system. This is an interoceptive modality of affective and social significance. In a second experiment (N = 63), we explored whether 'off-line' trait interoceptive sensitivity based on a heartbeat counting task would modulate the extent to which CT affective touch influences the multisensory process during the rubber hand illusion (RHI). We found that affective touch enhanced the subjective experience of body ownership during the RHI. Nevertheless, interoceptive sensitivity, as measured by a heartbeat counting task, did not modulate this effect, nor did it relate to the perception of ownership or of CT-optimal affective touch more generally. By contrast, this trait measure of interoceptive sensitivity appeared most relevant when the multisensory context of interoception was ambiguous, suggesting that the perception of interoceptive signals and their effects on body ownership may depend on individual abilities to regulate the balance of interoception and exteroception in given contexts.


Size-dependent reversal of the elastic interaction energy between misfit nanostructures.
By exploiting a fully three-dimensional finite-element modeling of strain fields, we investigate the spatial dependence of the elastic interaction energy between misfitting nanostructures beyond the point-dipole approximation. When interacting islands are finite in size, the detailed shape of the elastic strain field around and under the islands may convert the repulsive interactions, usually experienced between equal-sized islands, into an attractive basin between a large island and a population of neighboring clusters smaller than a critical size. The results of the simulations applied to large Ge islands grown on a Si(111) substrate have significant implications for the understanding of the strain-mediated coarsening of quantum dots around the islands.


Primary allogeneic mitochondrial mix (PAMM) transfer/transplant by MitoCeption to address damage in PBMCs caused by ultraviolet radiation.
Artificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 °C and then co-incubated at 37 °C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival. Using a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage. Our results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol.


Variability in dentofacial phenotypes in four families with WNT10A mutations.
This article describes the inter- and intra-familial phenotypic variability in four families with WNT10A mutations. Clinical characteristics of the patients range from mild to severe isolated tooth agenesis, over mild symptoms of ectodermal dysplasia, to more severe syndromic forms like odonto-onycho-dermal dysplasia (OODD) and Schöpf-Schulz-Passarge syndrome (SSPS). Recurrent WNT10A mutations were identified in all affected family members and the associated symptoms are presented with emphasis on the dentofacial phenotypes obtained with inter alia three-dimensional facial stereophotogrammetry. A comprehensive overview of the literature regarding WNT10A mutations, associated conditions and developmental defects is presented. We conclude that OODD and SSPS should be considered as variable expressions of the same WNT10A genotype. In all affected individuals, a dished-in facial appearance was observed which might be helpful in the clinical setting as a clue to the underlying genetic etiology.


Papillary haemangioma: a case report of multiple facial location.
Papillary haemangiomas were recently defined as morphologically distinct and benign cutaneous haemangiomas showing a predominantly intravascular capillary proliferation within dilated thin-walled dermal blood vessels. We describe the case of a 45-year-old woman who presented with multiple eruptive red-bluish raised papules and nodules distributed over the skin of the chin that were related to a papillary haemangioma.


Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 4: how to assess coherence.
The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE working group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) relevance, (3) coherence and (4) adequacy of data. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual's coherence component. We developed the coherence component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual coherence component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. When applying CERQual, we define coherence as how clear and cogent the fit is between the data from the primary studies and a review finding that synthesises that data. In this paper, we describe the coherence component and its rationale and offer guidance on how to assess coherence in the context of a review finding as part of the CERQual approach. This guidance outlines the information required to assess coherence, the steps that need to be taken to assess coherence and examples of coherence assessments. This paper provides guidance for review authors and others on undertaking an assessment of coherence in the context of the CERQual approach. We suggest that threats to coherence may arise when the data supporting a review finding are contradictory, ambiguous or incomplete or where competing theories exist that could be used to synthesise the data. We expect the CERQual approach, and its individual components, to develop further as our experiences with the practical implementation of the approach increase.


The effect of maternal diet on maternal and fetal hepatic and brown adipose tissue lipogenesis and blood and tissue metabolites.
Both starvation of and feeding a high linoleic acid content diet to rats during late pregnancy resulted in (relative to stock diet fed controls) a decrease in maternal hepatic glycogen content and lipogenesis, reduced blood glucose levels and an increase in blood ketone levels whereas only fat feeding caused an increase in blood triglyceride levels and only starvation resulted in a decrease in the amount of brown adipose tissue. Maternal starvation resulted in decreased fetal body, liver and brown adipose tissue weights, diminished liver and brown adipose glycogen content and lipogenesis and lowered blood glucose levels. Both maternal fat feeding and starvation caused triglyceride accumulation in fetal liver, elevated blood ketone levels and an increased proportion of fetal liver and carcass fatty acids accounted for by linoleic acid.


Chest pain with minimal activities and flexion of trunk: a rare case of angina.
A 53-year-old woman presented with effort-induced chest pain during daily activities and similar symptoms with trunk flexion. A treadmill exercise test revealed a Mobitz II atrioventricular block. Coronarography and computed tomography confirmed the diagnosis of anomalous origin of the right coronary artery from the left coronary sinus, so surgical revascularization was indicated. We discuss the peculiarity of the clinical presentation and its possible pathogenic mechanism.


A case of concurrent uterine cervical adenocarcinoma and renal-cell carcinoma, and subsequent vaginal metastasis from the renal-cell carcinoma.
We report a case of concurrent uterine cervical adenocarcinoma and renal-cell carcinoma and a subsequent vaginal metastasis from the renal-cell carcinoma. The renal-cell carcinoma, which was located in the upper pole of the right kidney, was detected incidentally by preoperative CT scanning. We simultaneously performed in a timely manner radical hysterectomy, pelvic and paraaortic lymphadenectomies, and a right nephrectomy. Subsequently, however, the patient suffered from vaginal metastasis arising from the renal-cell carcinoma. As a result of this case, we emphasize the importance of making a thorough preoperative assessment prior to performance any definitive surgery for a gynecologic malignancy.


Performance analyses and improvements for the IEEE 802.15.4 CSMA/CA scheme with heterogeneous buffered conditions.
Studies of the IEEE 802.15.4 Carrier Sense Multiple Access with Collision Avoidance (CSMA/CA) scheme have been received considerable attention recently, with most of these studies focusing on homogeneous or saturated traffic. Two novel transmission schemes-OSTS/BSTS (One Service a Time Scheme/Bulk Service a Time Scheme)-are proposed in this paper to improve the behaviors of time-critical buffered networks with heterogeneous unsaturated traffic. First, we propose a model which contains two modified semi-Markov chains and a macro-Markov chain combined with the theory of M/G/1/K queues to evaluate the characteristics of these two improved CSMA/CA schemes, in which traffic arrivals and accessing packets are bestowed with non-preemptive priority over each other, instead of prioritization. Then, throughput, packet delay and energy consumption of unsaturated, unacknowledged IEEE 802.15.4 beacon-enabled networks are predicted based on the overall point of view which takes the dependent interactions of different types of nodes into account. Moreover, performance comparisons of these two schemes with other non-priority schemes are also proposed. Analysis and simulation results show that delay and fairness of our schemes are superior to those of other schemes, while throughput and energy efficiency are superior to others in more heterogeneous situations. Comprehensive simulations demonstrate that the analysis results of these models match well with the simulation results.


SF3B1 mutation and ATM deletion codrive leukemogenesis via centromeric R-loop dysregulation.
RNA splicing factor SF3B1 is recurrently mutated in various cancers, particularly in hematologic malignancies. We previously reported that coexpression of Sf3b1 mutation and Atm deletion in B cells, but not either lesion alone, leads to the onset of chronic lymphocytic leukemia (CLL) with CLL cells harboring chromosome amplification. However, the exact role of Sf3b1 mutation and Atm deletion in chromosomal instability (CIN) remains unclear. Here, we demonstrated that SF3B1 mutation promotes centromeric R-loop (cen-R-loop) accumulation, leading to increased chromosome oscillation, impaired chromosome segregation, altered spindle architecture, and aneuploidy, which could be alleviated by removal of cen-R-loop and exaggerated by deletion of ATM. Aberrant splicing of key genes involved in R-loop processing underlay augmentation of cen-R-loop, as overexpression of the normal isoform, but not the altered form, mitigated mitotic stress in SF3B1-mutant cells. Our study identifies a critical role of splice variants in linking RNA splicing dysregulation and CIN and highlights cen-R-loop augmentation as a key mechanism for leukemogenesis.


A localized double-quantum filter for the in vivo detection of brain glucose.
A double-quantum filter (DQF) sequence with PRESS localization was developed for in vivo detection of the glucose resonances in the 3.85-ppm region of the brain proton spectrum. The efficiency and spectral editing characteristics were studied in phantom and animal experiments. Approximately 45% detection efficiency was achieved at 4.7 T with TE = 68 ms. Since the efficiency of the DQF method is dependent on the relative phases of the RF pulses, a phase calibration procedure was used to correct for phase shifts induced by the spatial localization. In addition to detecting the 3.85-ppm glucose resonances with approximately 45% efficiency, the DQF sequence simultaneously detects 1.3-ppm lactate resonance with approximately 20% efficiency. The use of the DQF technique for simultaneously monitoring both the input and output of anaerobic glycolysis in the brain was demonstrated by detecting brain glucose and lactate in the same acquisition after iv injection of glucose followed by the induction of global ischemia.


Specific activation of the G protein-coupled receptor BNGR-A21 by the neuropeptide corazonin from the silkworm, Bombyx mori, dually couples to the G(q) and G(s) signaling cascades.
Corazonin, an undecapeptide neurohormone sharing a highly conserved amino acid sequence across Insecta, plays different physiological roles in the regulation of heart contraction rates, silk spinning rates, the induction of dark color and morphometric phase changes, and ecdysis. Corazonin receptors have been identified in Drosophila melanogaster, Manduca sexta, and Musca domestica. However, detailed information on the signaling and major physiological functions of corazonin and its receptor is largely unknown. In the current study, using both the mammalian cell line HEK293 and insect cell lines BmN and Sf21, we paired the Bombyx corazonin neuropeptide as a specific endogenous ligand for the Bombyx neuropeptide G protein-coupled receptor A21 (BNGR-A21), and we therefore designated this receptor as BmCrzR. Further characterization indicated that synthetic BmCrz demonstrated a high affinity for and activated BmCrzR, resulting in intracellular cAMP accumulation, Ca(2+) mobilization, and ERK1/2 phosphorylation via the Gq- and Gs-coupled signaling pathways. The direct interaction of BmCrzR with BmCrz was confirmed by a rhodamine-labeled BmCrz peptide. Moreover, experiments with double-stranded RNA and synthetic peptide injection suggested a possible role of BmCrz/BmCrzR in the regulation of larval growth and spinning rate. Our present results provide the first in-depth information on BmCrzR-mediated signaling for further elucidation of the BmCrz/BmCrzR system in the regulation of fundamental physiological processes.


The effect of pretreatment with adrenal-protecting compounds on the metabolism of 7,12-dimethylbenz[a]anthracene and related compounds by rat-liver homogenates.
1. 7,12-Dimethylbenz[a]anthracene is converted by rat-liver homogenates into products with the properties of the 7- and 12-hydroxymethyl derivatives, the 7,12-dihydroxymethyl derivative, the related carboxylic acids and ring-hydroxylated products such as the 8,9-dihydro-8,9-dihydroxy derivative and phenols. Ring-hydroxylated products and products arising from the further oxidation of the hydroxymethyl groups were formed when the hydroxymethyl derivatives were themselves incubated with rat-liver homogenates. 2. Pretreatment of the animal with 3-methylcholanthrene or with Sudan III, which can protect rat adrenal glands from damage by 7,12-dimethylbenz[a]anthracene or by its 7-hydroxymethyl derivative, led to an increased rate of metabolism of 7,12-dimethylbenz[a]anthracene and its hydroxymethyl derivatives. The metabolic routes mainly affected were those involving the formation of ring-hydroxylated products. 3. Pretreatment with phenobarbitone led to a small increase in the rate of metabolism of the hydrocarbon and of its hydroxymethyl derivatives, but the increase appeared mainly to involve increased metabolism of the methyl and hydroxymethyl groups. 4. Pretreatment with metyrapone increased the rate of metabolism of the hydrocarbon mainly by increasing the amounts of products resulting from hydroxylation of the methyl groups: small increases in the amounts of ring-hydroxylated products were also produced. 8. Of a number of hydrocarbons and of derivatives of 3-methylcholanthrene tested as enzyme inducers, 3-methylcholanthrene itself was the most effective.


Rabbit glomerular and tubular basement membranes: morphology and differential solubilization.
Rabbit glomeruli and tubules were obtained by retrograde perfusion of magnetite into the lower aorta as previously described for the isolation of rat glomeruli. In addition, an alternative method of separating rabbit glomerular and tubular basement membranes from a single renal cortex preparation was developed. These preparations, which represent the Triton X-100-insoluble material, were extracted in sequence with deoxycholate, dodecyl sulfate in the presence and absence of 2-mercaptoethanol at 8 degrees C and again in the latter at 100 degrees C. The polypeptides solubilized at each step of this sequence were characterized by electrophoresis. The final extract consisted almost exclusively of red-staining, presumably collagenous bands, while the earlier extracts consisted of blue-staining, presumably noncollagenous bands. No significant differences were found between the glomerular and tubular basement membrane extracts.


Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience.
To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada between 1995 and 2016. Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P = .02). Adolescents aged 11-17 years (OR, 0.53; P = .03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90 days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.


[The role of E. coli adhesins in the pathogenesis of urinary infection].
One thousand five hundred strains obtained from patients suffering from different clinical forms of urinary infections (UI) and dependent glands have been studied with the aim of establishing the pathogenic responsibility of E. coli adhesion protein (ADH) in urinary infections (UI). ADH were determined using agglutination techniques with guinea pig and human red cells, C. albicans and S. cerevisiae spores and GAL-GAL sensitized latex. In non complicated UI, the presence of ADH is the main invasion mechanism for E. coli. The frequency of adherent strains is very high (569/648) in acute cases (207/247 cystitis + 69/98 recurrent cystitis + 108/114 pyelonephritis + 140/154 prostatitis + 28/35 orchyepidimitis and scarce (14/184) in asymptomatic or chronic cases (6/107 bacteriurias + 7/67 prostatitis + 1/10 orchyepidimitis). A close relationship is established between the presence of ADH and clinical symptoms. The acute cases with general symptoms are caused in 85% of cases (188/216) by strains with ADH type MR specially subtype P. The acute cases with local symptoms (only urinary syndrome) are caused in 77% of cases (297/387) by strains with ADH type Ms. In complicated UI the expression of adhesion proteins does not constitute and essential requisite in order to invade the urinary tract. It is suggested that males are significantly more resistant the females to UI both parenchymal and urinary tract. It is deduced that underlying factors are more predisposing to UI the smaller the adherence rate of isolated strains is. Thus, reflux and neurogenic bladder probes are by far more aggressive alterations than prostatic adenoma, bladder tumor and lithiasis.


Modeling of single and competitive metal adsorption onto a natural polysaccharide.
Sugar beet pulp, a common agricultural waste, was studied in the removal of metal ions from aqueous solutions. Potentiometric titrations were used to characterize the surface acidity of the polysaccharide. The acid properties of the material can be described by invoking three distinct types of surface functional groups with the intrinsic acidity constants (pKa(int)) values 3.43+/-0.1, 6.05+/-0.05, and 7.89+/-0.1, respectively. The contents of each functional group (i.e., the carboxyl and phenol moieties) were also determined. Then, a simple surface complexation model with the diffuse layer model successfully described the sorption of several metal ions (Cu2+, Zn2+, Cd2+, and Ni2+) onto the polysaccharide under various experimental conditions: pH ranging from 2 to 5.5, ionic strength from 0.01 to 0.1 M, metal concentration between 10(-4) and 10(-3) M, for a constant sorbent concentration equal to 2.5 g x L(-1). It was observed experimentally that the affinity of the polysaccharide was in the sequence of Cu2+ > Zn2+ > Cd2+ > Ni2+. Predictions of sorption in binary-metal systems based on single-metal data fits represented competitive sorption data reasonably well.


Spontaneous osteochondroma resolution in a young female: imaging and histopathological findings.
To report the first operated and histopathologically studied case of spontaneously resolving solitary osteochondroma. An 18-year-old girl presented with leg pain of 2 months' duration. She had been diagnosed to have a proximal tibial osteochondroma since the age of 9 years. Excision biopsy of the tumor remnant and its surrounding tissue was done after CT and MRI imaging. The spontaneous resolution of this case could have been due to simultaneous interruption of blood supply to the tumor and its cartilaginous cap or hyperemia around the tumor.


Risk Factors and Predictive Model Development of Thirty-Day Post-Operative Surgical Site Infection in the Veterans Administration Surgical Population.
Surgical site infection (SSI) complicates approximately 2% of surgeries in the Veterans Affairs (VA) hospitals. Surgical site infections are responsible for increased morbidity, length of hospital stay, cost, and mortality. Surgical site infection can be minimized by modifying risk factors. In this study, we identified risk factors and developed accurate predictive surgical specialty-specific SSI risk prediction models for the Veterans Health Administration (VHA) surgery population. In a retrospective observation study, surgical patients who underwent surgery from October 2013 to September 2016 from 136 VA hospitals were included. The Veteran Affairs Surgical Quality Improvement Program (VASQIP) database was used for the pre-operative demographic and clinical characteristics, intra-operative characteristics, and 30-day post-operative outcomes. The study population represents 11 surgical specialties: neurosurgery, urology, podiatry, otolaryngology, general, orthopedic, plastic, thoracic, vascular, cardiac coronary artery bypass graft (CABG), and cardiac valve/other surgery. Multivariable logistic regression models were developed for the 30-day post-operative SSIs. Among 354,528 surgical procedures, 6,538 (1.8%) had SSIs within 30 days. Surgical site infection rates varied among surgical specialty (0.7%-3.0%). Surgical site infection rates were higher in emergency procedures, procedures with long operative duration, greater complexity, and higher relative value units. Other factors associated with increased SSI risk were high level of American Society of Anesthesiologists (ASA) classification (level 4 and 5), dyspnea, open wound/infection, wound classification, ascites, bleeding disorder, chemotherapy, smoking, history of severe chronic obstructive pulmonary disease (COPD), radiotherapy, steroid use for chronic conditions, and weight loss. Each surgical specialty had a distinct combination of risk factors. Accurate SSI risk-predictive surgery specialty-specific models were developed with number of variables ranging from 9 to 21 and the C-index ranging from 0.63 to 0.81, indicating acceptable discrimination. The decile plot of predicted versus observed SSI rates showed strong calibration. Surgery specialty-specific risk factors of 30-day post-operative SSI rates have been identified for a variety of surgery specialties. Accurate SSI risk-predictive surgery specialty-specific SSI predictive models have been developed and validated for the VHA surgery population. These models can be used to develop optimal preventive measures for high-risk patients, patient-centered care planning, and surgical quality improvement.


Evaluation of hearing in children with autism by using TEOAE and ABR.
Assessment of auditory abilities is important in the diagnosis and treatment of children with autism. The aim was to evaluate hearing objectively by using transient evoked otoacoustic emission (TEOAE) and auditory brainstem response (ABR). Tests were performed on 30 children with autism and 15 typically developing children, following otomicroscopy and tympanometry. The children with autism were sedated before the tests. Positive emissions and normal hearing level at ABR were obtained in both ears of all children in the control group and of 25 children with autism. TEOAE and ABR results varied in the remaining five children with autism. The mean III-V interpeak latencies (IPLs) in both ears of children with autism were longer than those in the control group. Hearing loss may be more common in children with autism than in typically developing children.


Distribution of ABO and Rh Blood Groups in Patients With Keratoconus: A Case-Control Study.
Association of keratoconus (KC) with genetic predisposition and environmental factors has been well documented. However, no single study has investigated the possible relationship between ABO and Rh blood groups and KC. A case-control study was designed in a university hospital enrolling 214 patients with KC in the case group and equal number of age- and sex-matched healthy subjects in the control group. Primary characteristics, ABO blood group, and Rh factors were compared between the two groups. Topographic findings of KC eyes and the severity of the diseases were investigated according to the distribution of the blood groups. Blood group O and Rh(+) phenotype were most frequent in both groups. There was no significant difference between the two groups in terms of ABO blood groups or Rh factors. Mean keratometery (K), central corneal thickness, thinnest corneal thickness, flat K, steep K, sphere and cylinder, spherical equivalent, and uncorrected visual acuity were all similar between ABO blood groups and Rh(+) and Rh(-) groups. However, the best spectacle-corrected visual acuity (BCVA) had the highest value in AB blood group (0.35 ± 0.22 logMAR, P=0.005). Moreover, the blood group AB revealed the highest frequency for grade 3 KC, followed by grades 1, 2, and 4 (P=0.003). We observed no significant excess of any particular blood group among KC cases compared with healthy subjects. Except BCVA, none of the keratometric or topographic findings was significantly different between blood groups.


3D Bioprinting of Highly Thixotropic Alginate/Methylcellulose Hydrogel with Strong Interface Bonding.
A robust alginate/methylcellulose (Alg/MC) blend hydrogel, with a strategy to improve adhesion between printed layers, has been fabricated for the first time for three-dimensional (3D) bioprinting. The optimized Alg/MC blend hydrogel exhibits a highly thixotropic property, great extrudability, and stackability. With treatment by a trisodium citrate (TSC) solution, the interfacial bonding between the printed layers is significantly improved. The TSC solution acts as a chelating agent to remove the superficial calcium ions at each layer. Post-cross-linking in a CaCl2 bath after 3D printing further enhances the adhesion strength between the layers. The key parameters affecting the interfacial strength of the Alg/MC hydrogel are found to be the concentration of TSC, the volume of TSC, and the concentration of CaCl2 in the bath. The Alg/MC hydrogel with the aid of TSC demonstrates superior printability, high stackability (150 layers can be printed), and high shape fidelity. A good cell viability of >95% is obtained for a freshly 3D-bioprinted Alg/MC construct. The novel Alg/MC hydrogel with the aid of TSC has been shown to have a great potential as an advanced 3D bioprinting material.


Potassium channel antagonists and vascular reactivity in stroke-prone spontaneously hypertensive rats.
The goal of this study was to characterize differences in contractile responsiveness to several potassium channel antagonists in vascular smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY). Helically-cut strips of carotid arteries (endothelium removed) from SHRSP and WKY were mounted in muscle baths for measurement of isometric force generation. Contractile responses to tetraethylammonium (10(-4) to 3 x 10(-2) mol/L) and barium (3 x 10(-5) mol/L), blockers of the voltage-dependent and large conductance, calcium activated potassium channels, were greater in carotid arteries from SHRSP than in those from WKY. In contrast, contractile responses to the voltage-dependent potassium channel blockers 3,4-diamino-pyridine (10(-6) to 3 x 10(-3) mol/L) and sparteine (10(-6) to 3 x 10(-2) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid arteries from SHRSP and WKY did not contract to apamin (10(-9) to 10(-6) mol/L), an antagonist of the small conductance, calcium activated potassium channel. Furthermore, relaxation responses to diazoxide (3 x 10(-4) mol/L), an activator of the ATP-sensitive potassium channel, and subsequent contractions to the ATP-sensitive potassium channel blocker glyburide (10(-8) to 3 x 10(-6) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid artery segments from SHRSP were more sensitive to the contractile effects of elevated potassium than those from WKY. We conclude that altered activity of the large conductance, calcium activated potassium channel may play a role in the increased responsiveness observed in arteries from SHRSP.


A Rat Model of Oral Mucositis Induced by Cancer Chemotherapy for Quantitative Experiments.
Oral mucositis, which occurs frequently in the treatment of cancer, is a major problem. In this study, we aimed to develop a rat model of oral mucositis induced by cancer chemotherapy for quantitative measurement. A model animal of oral mucositis was prepared by injecting an acetic acid aqueous solution into the buccal mucosa of rats to which a 5-FU solution had been previously administered. The doses of 5-FU and acetic acid were examined, and a treatment experiment using Kenalog® was performed. The optimal dose of the 5-FU solution and the optimal concentration of the acetic acid aqueous solution were 40 mg/kg and 25%, respectively. Treatment with Kenalog® confirmed that this model mimics immunocompromised oral mucositis. Compared with a mouse model, oral mucositis can be easily observed in this model and provides a large amount of oral mucosal tissue.