Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes.
Human recombinant interleukins 1 alpha and 1 beta (rIL-1 alpha and -1 beta) both induced monophasic peripheral neutrophilia and lymphopenia in Lewis rats 1.5 hr after i.v. injection. The kinetics of rIL-1 alpha- and -1 beta-induced neutrophilia were similar to those induced by human monocyte-derived IL-1, IL-1 alpha, and IL-1 beta, and the peripheral neutrophilia was accompanied by a marked decrease in marrow neutrophils. Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia. Acetylsalicylic acid, a cyclooxygenase inhibitor, did not inhibit IL-1-induced neutrophilia, suggesting that products of the lipoxygenase rather than the cyclooxygenase pathway of arachidonate metabolism may contribute to the neutrophilia. Human recombinant tumor necrosis factor-alpha (rTNF) administered i.v. to Lewis rats induced peripheral neutropenia, two peaks of neutrophilia, and lymphopenia. A wide range of doses of rTNF resulted in an initial neutropenia at 0.5 hr after injection followed by a first peak of neutrophilia at 1.5 hr and a second peak of neutrophilia at 6 hr. The initial neutropenia and the first peak of neutrophilia were not inhibited by pretreatment of rats with dexamethasone, indomethacin, or aspirin. The second peak of neutrophilia was inhibited by both dexamethasone and indomethacin, but was not at all inhibited by aspirin, suggesting that the second peak of neutrophilia is mediated by the release of endogenous cytokines, especially by IL-1, since exogenous IL-1-induced neutrophilia is also completely inhibited by dexamethasone and indomethacin but not by aspirin. The TNF-induced peripheral neutrophilia is also accompanied by a significant depletion of bone marrow neutrophils, indicating that the source of increased circulating neutrophils is, at least in part, via recruitment of marrow neutrophils. Systemic blood pressure was not affected by IL-1 or rTNF at the dosages employed, showing that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic change-related release of adrenal hormones. Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)


Synthesis and characterizations of pyridazine-based iron chelators.
In an attempt to design ligands which require both a high iron(III) affinity and a low iron(II) affinity, the 3-hydroxypyridin-4-one structure has been modified to introduce an additional nitrogen atom in the pyridine ring to form a pyridazine. The target molecules were synthesized from a chlorine-substituted pyridazine using step-by-step methoxylations. A total of six 3- and 5-hydroxypyridazin-4(1H)-ones have been synthesized, with a methyl, ethyl or n-propyl group on the N1 of the pyridazine ring. In the reaction of the pyridazines with alkyl iodide, the presence of acetone drives the reaction to afford pyridazinones rather than the desired pyridaziniums. The pK(a) values of the free ligands, the stability constants of their iron(III) complexes and corresponding pFe(III) values demonstrate that this type of ligand has lower values when compared with those of deferiprone. The reduction potential values of the iron complexes obtained from cyclic voltammetry measurements, are used to determine the corresponding pFe(II) values. Although two compounds of the 20 series have marginally higher log β3(Fe(III))/log β3(Fe(II)) ratios than those of deferiprone, they possess pFe(III) values <20, indicating that this type of chelator is unlikely to be optimized into a useful therapeutic agent.


Evidence for normal cell-mediated immunity in scrapie-infected mice.
Comparisons between mixed lymphocyte cultures of splenocytes from scrapie-infected and normal mouse brain-inoculated control mice did not reveal any evidence of an impaired cell-mediated immune response in scrapie-infected mice. Likewise, mixed lymphocyte cultures of splenocytes from scrapie-infected and normal mice demonstrated that infected spleen cells had no scrapie-specific antigens on their surfaces. These data suggested that the absence of a detectable scrapie-specific immune response in infected mice was the result of an absence of an exposed scrapie-specific antigen and not due to any direct effect on the immune system.


Cloning of the genome of equine herpesvirus 4 strain TH20p as an infectious bacterial artificial chromosome.
Equine herpesvirus 4 (EHV-4) is a major cause of respiratory tract disease in horses worldwide. The generation of recombinant viruses, which would lead to understanding of viral gene functions, has been hindered by the absence of suitable cell lines and small-animal models of the infection. In the present study, the genome of EHV-4 strain TH20p was cloned as a stable and infectious BAC without any deletions of the viral genes. Mini F plasmid sequences flanked by loxP sites were inserted into the intergenic region between genes 58 and 59. Coinfection of the recombinant virus with a recombinant adenovirus expressing Cre recombinase resulted in the excision of the BAC sequences. Importantly, the resulting recombinant EHV-4 replicated comparably to the wild-type virus in fetal horse kidney cells. The recombinant EHV-4 will facilitate EHV-4 research and provide the opportunity to exploit the power of BAC technology for production of recombinant viral vaccines.


Analysis of response patterns on the MMPI-2 in psychiatric prison inmates.
In order to assess mental health status, and the classification of both the overreporting and underreporting scales and indexes, 102 psychiatric prison inmates deemed mentally incompetent to stand trial completed the Spanish adaptation of the MMPI-2 under standard instructions (honest responding). The results showed patterns of consistent, non-random, nor extremely acquiescent responses. Moreover, no-outlier responses were detected. In line with the psychiatric diagnosis, all the psychiatric prison inmates were classified by the basic clinical scales as clinical cases of the psychotic dyad i.e., schizophrenia and paranoid ideation. The overreporting scales and indexes (i.e., F, K, Fb, F-K, Fp, Ds and FBS) classified the participants as malingerers, whereas the L, Wsd, and Od underreporting scales as good feigners. These scales assessing impression management i.e., consciously faking good biased responses, did not classify overreporters. Thus, they are robust indicators of honest responding among psychiatric prison inmates. The implications of these results for the practice of forensic psychology are discussed.


Using phosphoproteomics and next generation sequencing to discover novel therapeutic targets in patient antibodies.
Introduction: The goal of this review is to survey proteomics and next generation sequencing (NGS) approaches to discover phosphopeptide neoantigens that can be used as targets for individualized cancer therapy and diagnostics. Neoantigens are peptides or proteins that can be derived from tumor-specific or viral alterations containing mutated sequences including different post-translational modifications that will not be found in normal human cells. These neoantigens can be highly specific for the individual affected tissue. Mass spectrometry combined with NGS allow identifying autoantibodies specific for neoantigens, including neoantigens that contain phosphorylated moieties. Areas covered: We discuss recognition of neoantigens through the application of phosphoproteomics. We focus on phosphoprotein modifications that can be accurately identified with mass spectrometry and can serve as rarely described targets for immunotherapy and diagnosis in cancer and autoimmune diseases. Identification of these phospho-moiety containing neoantigens gives the possibility to search for corresponding autoantibodies, especially if NGS and mass spectrometry are combined. Expert commentary: Identification of post-translational modifications with mass spectrometry gives possibilities to define modifications that are specific for cancer and autoimmune diseases. This technology develops rapidly, and gives opportunities to select neoantigens that are highly specific for cancer and immune diseases and to sequence autoantibodies involved.


Health care spending and use of information technology in OECD countries.
In 2003, the United States had fewer practicing physicians, practicing nurses, and acute care bed days per capita than the median country in the Organization for Economic Cooperation and Development (OECD). Nevertheless, U.S. health spending per capita was almost two and a half times the per capita health spending of the median OECD country. One proposal for both lowering health spending and improving quality is the adoption of health information technology (HIT). The United States lags as much as a dozen years behind other industrialized countries in HIT adoption--countries where national governments have played major roles in establishing the rule, and health insurers have paid most of the costs.


Endoscopic removal of a bullet from the parapharyngeal space just anterior-lateral to the first vertebral body: case report.
In all head and neck bullet injuries, treatment has to be individualized, as there is no universal protocol for all cases. Five important steps of management should be taken: securing airways, hemorrhage control, recognizing other injuries, foreign body removal when necessary, and repair of facial wounds. In this report, the case of a 28-year-old male patient will be presented and discussed. The patient was referred from a surgery clinic to an ear, nose and throat (ENT) outpatient clinic complaining of right neck pain, throat pain, and foreign body sensation in the throat for 2 months following a firearm injury to his face. The entry wound was observed on the left alar cartilage of his nose, which was almost healed and had left a scar. A sinus computed tomography scan showed a bullet in the right parapharyngeal space about 3 mm in front of the first vertebral body. The bullet was successfully removed using a trans-nasal endoscopic approach with the support of an image-guided navigational system and frequent fluoroscopy. These 2 methods help to replace the old traditional open approaches.


Peer relationships of deaf children with cochlear implants: predictors of peer entry and peer interaction success.
This study investigated factors that affect the development of positive peer relationships among deaf children with cochlear implants. Ten 5- to 6-year-old deaf children with implants were observed under conditions varying peer context difficulty in a Peer Entry task. Results revealed better outcomes for deaf children interacting in one-on-one situations compared to interactions including two other hearing children and better performance among girls than boys. In addition, longer duration of implant use and higher self-esteem were associated with better performance on the Peer Task, which was in turn related to parental reports of children's social functioning outside the experimental situation. These findings contribute to the growing literature describing the benefits of cochlear implantation in the areas of communication and socialization, while pointing to interventions that may enhance deaf children's social competence.


Mechanisms navigating the TGF-β pathway in prostate cancer.
Few pharmacotherapies are currently available to treat castration resistant prostate cancer (CRPC), with low impact on patient survival. Transforming growth factor-β (TGF-β) is a multi-functional peptide with opposite roles in prostate tumorigenesis as an inhibitor in normal growth and early stage disease and a promoter in advanced prostate cancer. Dysregulated TGF-β signaling leads to a cascade of events contributing to oncogenesis, including up-regulated proliferation, decreased apoptosis, epithelial-to-mesenchymal transition (EMT) and evasion of immune surveillance. TGF-β signaling pathway presents an appropriate venue for establishing a therapeutic targeting platform in CRPC. Exploitation of TGF-β effectors and their cross talk with the androgen axis pathway will provide new insights into mechanisms of resistance of the current antiandrogen therapeutic strategies and lead to generation of new effective treatment modalities for CRPC. Points of functional convergence of TGF-β with key oncogenic pathways, including mitogen-activated protein kinase (MAPK) and androgen receptor (AR), are discussed as navigated within the EMT landscape in the tumor microenvironment. In this context the emerging anti-TGF-β pharmacotherapies for prostate cancer treatment are considered. Targeting the functional cross-talk between the TGF-β signaling effectors with the androgen axis supports the development of novel therapeutic strategies for treating CRPC with high specificity and efficacy in a personalized-medicine approach.


Thermoperiodism in cocklebur seed germination.
Germination potential in nondormant, upper cocklebur (Xanthium pensylvanicum Wallr.) seeds, which were incapable of germinating under constant temperatures below 25 C in air, was increased by exposure to diurnally alternating temperatures. The cocklebur seeds failed to respond to the temperature fluctuations in the beginning of water imbibition, and their responsiveness appeared only after aerobic presoaking for a limited period or after anaerobic pretreatment for 1 to 3 days.Maximal germination was obtained after exposure to a thermoperiodic regime of 8 hours at 23 C and 16 hours at 8 C. A process occurring during the high temperature phase was aerobic and had to precede the inductive low temperature phase, its effect increasing with temperature. Critical minimum length of the inductive low temperature phase changed with the duration of a preceding anaerobiosis, for instance about 4 hours after 1 day anaerobiosis, but about 2 hours after 2 days. Percentage of subsequent germination was in proportion to the number of thermoperiodic cycles. A process of the inductive low temperature phase was not perturbed by inserting a brief higher temperature period into its phase; indeed, such insertion rather increased germination potential when performed in the earlier parts of the inductive low temperature phase. The effect of the low temperature survived for 13 to 17 hours during the higher temperature period.


Cost analysis and clinical applicability of the Resonance metallic ureteral stent.
The Resonance metallic stent is a new wire-based ureteral stent that was initially developed for patients with malignant ureteral obstruction. Potential advantages over traditional stents include resistance to encrustation and to external compression, allowing for increased dwell times and the maintenance of upper tract drainage when traditional polymer stents have failed. We present a comparative cost analysis of Resonance metallic and standard polymer stent use in patients with benign urinary obstruction and review the literature regarding the Resonance stent.


Effect of the environmental pollutant hexachlorobenzene (HCB) on the neuronal differentiation of mouse embryonic stem cells.
Exposure to persistent environmental pollutants may constitute an important factor on the onset of a number of neurological disorders such as autism, Parkinson's disease, and Attention Deficit Disorder (ADD), which have also been linked to reduced GABAergic neuronal function. GABAergic neurons produce γ-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the brain. However, the lack of appropriate models has hindered the study of suspected environmental pollutants on GABAergic function. In this work, we have examined the effect of hexachlorobenzene (HCB), a persistent and bioaccumulative environmental pollutant, on the function and morphology of GABAergic neurons generated in vitro from mouse embryonic stem (ES) cells. We observed that: (1) treatment with 0.5 nM HCB did not affect cell viability, but affected the neuronal differentiation of ES cells; (2) HCB induced the production of reactive oxygen species (ROS); and (3) HCB repressed neurite outgrowth in GABAergic neurons, but this effect was reversed by the ROS scavenger N-acetylcysteine (NAC). Our study also revealed that HCB did not significantly interfere with the function of K+ ion channels in the neuronal soma, which indicates that this pollutant does not affect the maturation of the GABAergic neuronal soma. Our results suggest a mechanism by which environmental pollutants interfere with normal GABAergic neuronal function and may promote the onset of a number of neurological disorders such as autism and ADD.


Monitoring mis-acylated tRNA suppression efficiency in mammalian cells via EGFP fluorescence recovery.
A reporter assay was developed to detect and quantify nonsense codon suppression by chemically aminoacylated tRNAs in mammalian cells. It is based on the cellular expression of the enhanced green fluorescent protein (EGFP) as a reporter for the site-specific amino acid incorporation in its sequence using an orthogonal suppressor tRNA derived from Escherichia coli. Suppression of an engineered amber codon at position 64 in the EGFP run-off transcript could be achieved by the incorporation of a leucine via an in vitro aminoacylated suppressor tRNA. Microinjection of defined amounts of mutagenized EGFP mRNA and suppressor tRNA into individual cells allowed us to accurately determine suppression efficiencies by measuring the EGFP fluorescence intensity in individual cells using laser-scanning confocal microscopy. Control experiments showed the absence of natural suppression or aminoacylation of the synthetic tRNA by endogenous aminoacyl-tRNA synthetases. This reporter assay opens the way for the optimization of essential experimental parameters for expanding the scope of the suppressor tRNA technology to different cell types.


Two-lung and one-lung ventilation in patients with chronic obstructive pulmonary disease: the effects of position and F(IO)2.
We compared the effects of position and fraction of inspired oxygen (F(IO)2) on oxygenation during thoracic surgery in 24 consenting patients randomly assigned to receive an F(IO)2 of 0.4 (eight patients, Group 0.4), 0.6 (eight patients, Group 0.6), or 1.0 (eight patients, Group 1.0) during the periods of two-lung (TLV) and one-lung ventilation (OLV) in the supine and lateral positions. TLV and OLV were maintained while the patients were first in the supine and then in the lateral position for 15 min each. Thereafter, respiratory mechanical data were obtained, and arterial blood gas samples were drawn. Pao2 decreased during OLV compared with TLV in both the supine and lateral positions. In all three groups, Pao2 was significantly higher during OLV in the lateral than in the supine position: 101 (72-201) vs 63 (57-144) mm Hg in Group 0.4; 268 (162-311) vs 155 (114-235) mm Hg in Group 0.6; and 486 (288-563) vs 301 (216-422) mm Hg in Group 1.0, respectively (P < 0.02, Wilcoxon's signed rank test). We conclude that, compared with the supine position, gravity augments the redistribution of perfusion as a result of hypoxic pulmonary vasoconstriction, when patients are in the lateral position, which explains the higher Pao2 during OLV. This study compares oxygenation during thoracic surgery during periods of two-lung and one-lung ventilation with patients in the supine and lateral positions when using three different fraction of inspired oxygen values. Arterial oxygen tension was decreased in all three groups during one-lung ventilation in comparison with the two-lung ventilation values, but the decrease was significantly less in the lateral, compared with the supine position.


UK patients with primary Sjögren's syndrome are at increased risk from clinical depression.
This study was undertaken to assess the presence and degree of anxiety and depression in a group of UK patients with primary Sjögren's syndrome (1 degrees SS). Cross-sectional. Department of Oral Medicine, Liverpool University Dental Hospital. Eighty adult patients; 40 diagnosed with 1 degrees SS according to the revised European Criteria and 40 age/gender-matched controls with no history of chronic illness. Hospital Anxiety and Depression Scale (HADS), a self-administered questionnaire designed to evaluate the presence and degree of anxiety and depression in a clinical setting. Age, gender, Hospital Anxiety and Depression Scale (HADS). Forty patients with 1degrees SS and 40/age/gender-matched controls completed the HADS. Scores for anxiety in both the 1 degrees SS and control groups showed no statistically significant difference. Patients with 1 degrees SS had statistically significant higher, mean HADS scores for depression than the controls. There was an increased prevalence of 'definite' clinical depression in the 1 degrees SS group. Patients with 1 degrees SS appear to be at increased risk from clinical depression. Early recognition and appropriate intervention is therefore essential to reduce the negative impact of depression on the patient's quality of life and outcome of their disease.


The formation of different types of the artifacts in the amplification reaction with using different classes of the molecular-genetic markers (Indel and SSR) was studied. It was shown that DNA heteroduplexes formed during amplification of heterozygous samples, as fragments of target genes and microsatellite loci. During the electrophoresis in native polyacrylamide gel of the amplification products of homozygous samples for microsatellite loci it was revealed specific additional fragments that do not belong to the class of heteroduplex DNA. It was supposed, that the additional fragments belong to a special type of homoduplex DNA – non-linear homoduplexes. The analysis revealed that the formation of a non-linear homoduplex DNA takes place on the 20–25 cycle of the PCR, both at the amplification of the individual samples, and individual DNA fragments that was cut out from the gel.


Prospective evaluation of transnasal esophagogastroduodenoscopy: feasibility and study on performance and tolerance.
With a pediatric endoscope, esophagogastroduodenoscopy (EGD) can be performed via a nasal route in adults. To evaluate this new procedure, we conducted a randomized comparative study of the feasibility of diagnostic transnasal EGD and assessed the factors influencing its quality and tolerance (endoscope diameter or route). Transnasal EGD was attempted in 100 patients to assess its feasibility. For the analysis of quality and tolerance, 150 patients were randomized as follows into 3 groups according to the route of examinations: (1) oral route with 9.8 mm diameter standard videoendoscope; (2) oral route with 6.0 mm diameter pediatric videoendoscope; (3) transnasal route with 6.0 mm diameter pediatric videoendoscope. The operator assessed the quality of examination by standard scores. Patients quantified pain intensity, nausea, and choking sensation. Transnasal EGD was feasible in 82% of patients. The quality of the examination was significantly lower with pediatric endoscope. No difference was noted concerning pain intensity, but nausea and choking sensation were significantly reduced when the nasal route was used. Transnasal EGD is feasible in the routine practice of diagnostic EGD. The nasal route, and not endoscope diameter (6.0 mm vs 9.8 mm diameter), is the determining factor that explains increased patient tolerance during transnasal EGD. Technical improvements in pediatric videoendoscopes are required.


The analysis of 1-propanol and 2-propanol in humid air samples using selected ion flow tube mass spectrometry.
Following the observation that propanol is present in the breath samples of cystic fibrosis (CF) patients infected by Pseudomonas aeruginosa (PA), a study of the reactions of H(3)O(+), NO(+) and O(2) (+.) with 1-propanol and 2-propanol has been conducted using selected ion flow tube mass spectrometry (SIFT-MS). In this study the number and the distribution of the product ions from NO(+) reactions with the two propanol isomers under humid air conditions were able to differentiate between the two isomers. The reaction mechanisms and the structures of the product ions for these reactions, especially those with H(3)O(+) and NO(+), have been proposed. As an example, 2-propanol was shown to be present in a breath sample from one CF patient infected with PA, and also in a PA isolate from another CF patient grown on Pseudomonas-selective media. The results of this study allow an analytical procedure to be advanced for the analysis of the two propanol isomers, which can also be utilised in other applications.


Distribution of cells binding anti-IgE in the trachea and in the thoracic lymph nodes of ovalbumin-sensitized rats.
We investigated in the present study the distribution of anti-IgE binding cells in the trachea and in the thoracic lymph nodes of ovalbumin (OA)-sensitized rats. Sensitization of the airways was induced through a single intratracheal injection of the antigen, and was controlled by recording in vitro the antigen-induced contraction of the tracheal muscle: 12 of 15 (80%) OA-injected rats had a demonstrable status of tracheal sensitization. An immunohistochemical method was used for the localization of the anti-IgE binding cells in cryostat and in Carnoy fixed tissue sections. Virtually no cell was found to bind anti-IgE in the tracheas or in the thoracic lymph nodes from control animals. Conversely, we found in OA-sensitized rats that: 1) numerous IgE plasma cells appeared in the medullary cords of the lymph nodes (not in the trachea); 2) in tracheal sections, IgE concentrated in the cytoplasm of subepithelial mast cells and of nonciliated rounded epithelial cells (possibly the so-called globule leukocytes), but few if any mast cells of the connective tissue bound the anti-IgE conjugates.


Tc-99m red blood cell bleeding scan in a pregnant woman presenting with hematemesis: a brief review of indications and guidelines for radionuclide scans during pregnancy.
A 6-month pregnant 35-year-old woman with hematemesis and dark blood in her stool was evaluated for location of an active gastrointestinal bleeding site. The findings from 2 esophagogastroduodenoscopies and a colonoscopy were negative. The patient was referred for a Tc-99m red blood cell scintigraphy, for location of an active bleeding site. As the patient was 6 months pregnant, the necessity of the case was discussed with the patient's referring physician and after determining that this study was necessary, the risk of radiation exposure to the fetus was discussed with the radiation safety officer and the patient. The procedure was performed after the patient signed informed consent regarding the considerations of radiation safety to the fetus. The Tc-99m red blood cell bleeding scan clearly shows activity in the fetus in addition to a large arteriovenous malformation in the patient. The visualized fetus prompted this report to discuss radiation risks concerns and a brief review of indications and guidelines for performing nuclear medicine procedures in pregnant patients.


[Development and application of cDNA microarray of tumor metastasis-associated genes].
To study the method of preparing cDNA microarray of tumor metastasis-associated genes and its application in the investigation of gene expression profile. After amplification and purification by PCR, 400 tumor metastasis-associated gene clones were obtained and dotted onto the slides coated by poly-lysine. Total RNA from specimens of human colorectal carcinoma, lung carcinoma, and normal tissue samples were extracted and labeled by fluorescent staining. The labeled probes were then hybridized with the cDNA microarray. Uniform background and clear signal of the microarray were demonstrated by ScanArrayTM 4000. Specific mRNA expression profiles in association with colorectal cancer and lung cancer were subsequently obtained, showing that 30 genes were consistently up-regulated or down-regulated in the tissue samples examined, including motility factors, adhesion molecules, extracellular matrix-degrading enzymes, oncogenes, tumor-suppressor genes, apoptosis and anti-apoptosis genes, tumor angiogenesis factors and signal transduction factors, etc. The optimized method is highly sensitive and applicable in examining gene expression profile. The two cancers investigated in this study do not obviously differ in light of tumor metastasis-associated gene expression profiles, indicating similar molecular mechanism accounting for the infiltration and metastatic behavior of different types of cancers.


Incomplete Information, Inferences, and Individual Differences: The Case of Environmental Judgments.
A model for inference of missing information is explicated and tested in two studies (Ns = 74, 76) of judgments about two environmental issues (endangered species reintroduction and the siting of a waste processing facility). Participants made judgments of scenarios in which information relevant to the judgment was varied orthogonally and, in some cases, relevant information was missing. The results showed individual differences-as well as intraindividual differences-in the assumptions participants made about missing information and in the tendency to infer missing cues. Reported assumptions about missing information predicted some aspects of the judgments. The data for only a small minority (15%) of the participants were consistent with the inferred values model. Participants may use different methods for dealing with missing information at different times or may not generally follow either an inference or averaging model in such contexts. Less favorable judgments were given for scenarios with incomplete information (the "penalty" effect), and this effect showed individual and intraindividual variation that was related to reported assumptions about missing information. We discuss the implications of these results for societal conflicts over controversial issues and for understanding the sources of individual differences in judgments. Copyright 2000 Academic Press.


Pediatric seizures.
On the basis of strong evidence, treatment is highly dependent on the seizure semiology results, electroencephalography (EEG) findings, and origin. • On the basis of moderate evidence and consensus, vigorous use of video EEG recordings and home video cameras should be used to delineate the epileptic syndromes. • On the basis of strong evidence, pediatric epilepsy syndromes have common comorbidities. As a consensus, some pediatric epilepsy centers consider referral to a neuropsychologist to be first-line care in these patients. • On the basis of strong evidence and consensus, antiepileptic drug therapy has its own complications and should be discontinued after an appropriate treatment course. • On the basis of moderate evidence and consensus, uncontrolled seizures put patients at risk for significant morbidity and mortality.


Role of TGF‑β in the motility of ShcD‑overexpressing 293 cells.
The newly identified Src homology and collagen (Shc) family member ShcD was observed to be upregulated in 50% of vertical growth phase and metastatic melanomas. The aim of the present study was to investigate the mechanism by which ShcD mediates cell motility. 293 cell lines were altered to stably express GFP (GF) or GFP‑ShcD (G5). Treatment of the cells with transforming growth factor (TGF)β2 promoted extracellular signal‑regulated kinase (ERK) phosphorylation and, to a lesser extent, Smad2 phosphorylation in GFP‑ShcD‑expressing cells but not in GFP‑overexpressing cells. GFP‑ShcD‑expressing cells exhibited upregulated expression of certain epithelial‑mesenchymal transition‑related genes, such as snail family transcriptional repressor 1 and SLUG, than GFP‑expressing cells. Higher levels of ERK were found in the nuclear fraction of GFP‑ShcD‑expressing cells than that of GFP‑expressing cells. Overall, GFP‑ShcD‑expressing cells demonstrated enhanced migration compared with GFP‑expressing cells. A slight increase in cell migration was observed in both cell lines (GF and G5) when the cells were allowed to migrate towards conditioned medium derived from TGFβ2‑treated GFP‑ShcD expressing cells. Collectively, ShcD upregulation was proposed to induce cell migration by affecting the expression of certain epithelial‑mesenchymal transition‑related genes. Thus, our findings may improve understanding of the role of ShcD in cell migration.


Production at the Curie level of no-carrier-added 6-18F-fluoro-L-dopa.
6-(18)F-fluoro-L-dopa ((18)F-FDOPA) has proven to be a useful radiopharmaceutical for the evaluation of presynaptic dopaminergic function using PET. In comparison to electrophilic synthesis, the no-carrier-added (NCA) nucleophilic method has several advantages. These include much higher available activity and specific activity. Recently, we have described an NCA enantioselective synthesis using a chiral phase-transfer catalyst. However, some chemicals were difficult to implement into a commercially available synthesizer, restricting access to this radiopharmaceutical to only a few PET centers. In this paper, 2 important chemical improvements are proposed to simplify production of (18)F-FDOPA, resulting in straightforward automation of the synthesis in a commercially available module. First, a fast, simple, and reliable synthesis of 2-(18)F-fluoro-4,5-dimethoxybenzyl iodide on a solid-phase support was developed. Second, a phase-transfer catalyst alkylation of a glycine derivative at room temperature was used to enable enantioselective carbon-carbon bond formation. After hydrolysis and high-performance liquid chromatography purification, a high enantiomeric excess of (18)F-FDOPA (≈ 97%) was obtained using a chiral catalyst available from a biphenyl 3 substrate. The total synthesis time was 63 min, and the decay-corrected radiochemical yield was 36% ± 3% (n = 8). By exploiting the advantages of this NCA approach, using a starting activity of 185 GBq of NCA (18)F-fluoride, high activities of (18)F-FDOPA (>45 GBq) with high specific activity (≥ 753 GBq/μmol) are now available at the end of synthesis for use in clinical investigations.


Auditory brainstem evoked potentials in early-treated congenital hypothyroidism.
To evaluate the effect of early treatment of congenital hypothyroidism on central nervous system development, auditory brainstem evoked potentials were determined in 32 patients with hyperthyrotropinemia diagnosed during neonatal screening. The patients included 27 with congenital hypothyroidism and 5 with transient hypothyroidism. Abnormal auditory brainstem evoked potential tracings were found in 8 patients (congenital hypothyroidism in 7 and transient hypothyroidism in 1). Four of these patients had increased peripheral conduction time (wave I prolongation), and the other 4 had increased central conduction time (wave III or V prolongation). The patients with abnormal auditory brainstem evoked potentials did not show increased initial manifestations, yet 6 of them had lower initial thyroxine levels. Specific auditory brainstem evoked potential abnormalities were found in 25% of early-treated patients with congenital hypothyroidism. The possible causal relationship between deviant auditory brainstem evoked potential patterns and later neurodevelopment demands further clarification. This study suggests the usefulness of auditory brainstem evoked potential assessment to provide information about electrophysiologic deviation of the auditory pathway in patients with early-treated congenital hypothyroidism.


Coexistence of morphea and systemic sclerosis.
While the association of morphea and systemic sclerosis (SSc) is considered to be a rare condition, we observed well-demarcated sclerotic skin changes indistinguishable from morphea in 9 of 135 SSc patients who visited our clinic during the last decade. We consider this rate of incidence (6.7%) to be high enough to consider morphea to be one of the skin involvements of SSc. There was a significantly (p < 0.01) higher incidence of morphea in males (3 of 5) than in females (6 of 130). Only 3 of 111 SSc patients positive for antinuclear antibody (ANA) also showed morphea, whereas 6 of 9 patients negative for ANA showed morphea (p < 0.01). Although the mechanism underlying the development of morphea in SSc patients remains unknown, our observations suggest a heterogeneous pathogenesis related to SSc gender and ANA type.


Effect of particle size on composition, physicochemical, functional, and structural properties of insoluble dietary fiber concentrate from citrus peel.
To investigate the composition, physicochemical, functional, and structural properties of citrus insoluble dietary fiber concentrate from citrus peel affected by different particle sizes, citrus insoluble dietary fiber concentrate was modified by coarse crush and superfine grinding treatments. The results showed that the contents of hemicellulose and lignin significantly decrease and a significant increase in cellulose and insoluble dietary fiber contents with the reduction in particle size. In addition, the markedly decreased particle size and obviously microstructural changes of citrus insoluble dietary fiber concentrate powder were observed. The color value of citrus insoluble dietary fiber concentrate was observably improved, crystallinity and thermal stability of modified fiber slightly increase with the decrease in particle size, which is due to the partial elimination of hemicellulose and lignin after the treatments. However, water holding capacity, water swelling capacity, and oil holding capacity were found to be lower with the reduction in particle size, which might be attributed to the fact that superfine grinding treatment destroyed the structure integrity, thus causing some soluble components to break away from the cellulose backbone, or due to aggregation of smaller granules. The present study suggested that decreasing the particle size could effectively change some properties of citrus insoluble dietary fiber concentrate, which will provide new perspectives for the application of citrus insoluble dietary fiber concentrate in food products.


The primary care physician and Alzheimer's disease: an international position paper.
This paper aims to define the role of the primary care physician (PCP) in the management of Alzheimer's disease (AD) and to propose a model for a work plan. The proposals in this position paper stem from a collaborative work of experts involved in the care of AD patients. It combines evidence from a literature review and expert's opinions who met in Paris, France, on July 2009 during the International Association of Geriatrics and Gerontology (IAGG) World Congress. The PCP's intervention appears essential at many levels: detection of the onset of dementia, diagnostic management, treatment and follow-up. The key role of the PCP in the management of AD, as care providers and care planners, is consolidated by the family caregiver's confidence in their skills. In primary care practice the first step is to identify dementia. The group proposes a "case finding" strategy, in target situations in which dementia should be detected to allow, secondarily, a diagnosis of AD, in certain cases. We propose that the PCP identifies 'typical' cases. In typical cases, among older subjects, the diagnosis of "probable AD" can be done by the PCP and then confirm by the specialist. While under-diagnosis of AD exists, so does under-disclosure. Disclosure to patient and family should be done by both specialist and PCP. Then, the PCP has a central role in management of the disease with the general objectives to detect, prevent and treat, when possible, the complications of the disease (falls, malnutrition, behavioural and psychological symptoms of dementia). The PCP needs to give basic information to the caregiver on respite care and home support services in order to prevent crisis situations such as unplanned institutionalisation and "emergency" hospital admission. Finally, therapeutic research must be integrated in the daily practice of PCP. It is a matter of patients' right to benefit from access to innovation and clinical research whatever his age or diseases, while of course fully respecting the rules and protective measures that are in force.


Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.
To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.


[Dental status as a predictive factor in the development of squamous cell carcinoma of the oral mucosa].
The aim of this work was to study the influence of components of dental status on the local immunity of the oral cavity; we compared the results of the study of patients with squamous cell carcinoma (SCC) of the oral mucosa and patients without neoplasm. The study involved 136 patients with squamous cell carcinoma of the oral mucosa and 57 patients without neoplasms. In the role of the constituent characteristics of dental status were examined: the use of removable and fixed dentures, dental caries, dental plaque, sharp edges of fullings. Matrix metalloproteinases (MMPs) 2, 8 and 9, as well as their tissue inhibitors 1 and 2 were assessed in oral fluid. The results suggest the influence of all factors on local immune status of the oral cavity as proved by the significant changes in MMPs level. The use of removable dentures resulted in the pronounced decrease of MMPs and should be considered in oral SSC screening and non-invasive diagnostics.


A Two-Wired Ultra-High Input Impedance Active Electrode.
This paper presents a novel two-wired active electrode that achieves ultrahigh input impedance using power supply bootstrapping. The proposed circuit reduces the input capacitance of a buffer amplifier while enabling measurements using leads with only two wires, providing a low-complexity and low-cost solution for interference rejection and artifact reduction in dc-coupled dry-contact biopotential measurements. An implemented prototype shows that, even using standard operational amplifiers, an input capacitance as low as 71 fF can be obtained, maintaining a high impedance in a 0-1 kHz bandwidth, sufficient for ECG, EEG, and EMG measurements. The circuit has a simple and easily replicable implementation that requires no individual adjustment. A common mode rejection ratio (CMRR) above 103 dB at 50 Hz was achieved and the increased rejection to interference due to the potential divider effect was experimentally tested maintaining a 92-dB CMRR at 50 Hz with a 1.2-M source impedance unbalance. ECG measurements were conducted to validate the active electrode against a traditional alternative, and a test with dry-contact EEG electrodes was successfully conducted. Although the proposed circuit is intended to acquire superficial electrophysiological signals using dry electrodes, it can be used for measurement from other high-impedance sources, such as micropipette electrodes.


[Indoor pollution from airborne glass fibers in biomedical research laboratories].
It is known that the presence of fibers in indoor environment is able to lead to irritative symptoms of skin and mucous membranes. Such troubles have been repeatedly claimed by workers in biomedical research laboratories of our University. For this reason, an investigation for the evaluation of the risk and for propose preventional solutions has been performed (also for absolve fully to D.Lgs. 626/94). On account of the environmental investigations has been revealed the presence of rock wool fibers-included in a water lime matrix-sprayed in big quantity on the ceilings. Therefore, the phases and the methods followed for the analysis of the risks are showed together with evaluations in order to the preventional interventions, also on the basis of what has been established by the lawgiver.


Antibacterial activity and mechanism of berberine against Streptococcus agalactiae.
The antibacterial activity and mechanism of berberine against Streptococcus agalactiae were investigated in this study by analyzing the growth, morphology and protein of the S. agalactiae cells treated with berberine. The antibacterial susceptibility test result indicated minimum inhibition concentration (MIC) of berberine against Streptococcus agalactiae was 78 μg/mL and the time-kill curves showed the correlation of concentration-time. After the bacteria was exposed to 78 μg/mL berberine, the fragmentary cell membrane and cells unequal division were observed by the transmission electron microscopy (TEM), indicating the bacterial cells were severely damaged. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) study demonstrated that berberine could damage bacterial cells through destroying cellular proteins. Meanwhile, Fluorescence microscope revealed that berberine could affect the synthesis of DNA. In conclusion, these results strongly suggested that berberine may damage the structure of bacterial cell membrane and inhibit synthesis of protein and DNA, which cause Streptococcus agalactiae bacteria to die eventually.


Adaptation by normal listeners to upward spectral shifts of speech: implications for cochlear implants.
Multi-channel cochlear implants typically present spectral information to the wrong "place" in the auditory nerve array, because electrodes can only be inserted partway into the cochlea. Although such spectral shifts are known to cause large immediate decrements in performance in simulations, the extent to which listeners can adapt to such shifts has yet to be investigated. Here, the effects of a four-channel implant in normal listeners have been simulated, and performance tested with unshifted spectral information and with the equivalent of a 6.5-mm basalward shift on the basilar membrane (1.3-2.9 octaves, depending on frequency). As expected, the unshifted simulation led to relatively high levels of mean performance (e.g., 64% of words in sentences correctly identified) whereas the shifted simulation led to very poor results (e.g., 1% of words). However, after just nine 20-min sessions of connected discourse tracking with the shifted simulation, performance improved significantly for the identification of intervocalic consonants, medial vowels in monosyllables, and words in sentences (30% of words). Also, listeners were able to track connected discourse of shifted signals without lipreading at rates up to 40 words per minute. Although we do not know if complete adaptation to the shifted signals is possible, it is clear that short-term experiments seriously exaggerate the long-term consequences of such spectral shifts.


Sterigmatocystin: occurrence in foodstuffs and analytical methods--an overview.
Sterigmatocystin (STC) is a mycotoxin produced by fungi of many different Aspergillus species. Other species such as Bipolaris, Chaetomium, Emiricella are also able to produce STC. STC producing fungi were frequently isolated from different foodstuffs, while STC was regularly detected in grains, corn, bread, cheese, spices, coffee beans, soybeans, pistachio nuts, animal feed and silage. STC shows different toxicological, mutagenic and carcinogenic effects in animals and has been recognized as a 2B carcinogen (possible human carcinogen) by International Agency for Research on Cancer. There are more than 775 publications available in Scopus (and more than 505 in PubMed) mentioning STC, but there is no summary information available about STC occurrence and analysis in food. This review presents an overview of the worldwide information on the occurrence of STC in different foodstuffs during the last 40 years, and describes the progress made in analytical methodology for the determination of STC in food.


Spectral characteristics of carbonyl substituted 2,2'-bithiophenes in polymer matrices and low polar solvents.
The spectral characteristics of monosubstituted derivatives of 2,2'-bithiophene (1-BT) with simple carbonyl substituents, including -COCF3 (trifluoroacetyl, 2-BTCF), -COCH2CN (oxopropanenitrile, 3-BTCN) and -COCH3 (acetyl, 4-BTCE), and the more complex 5'-((9H-fluoren-9-ylidene)methyl)-3-methyl, 5-methyl carboxylate (5-BTFL) were investigated. Absorption and fluorescence spectra and fluorescence lifetimes were measured in solvents with various polarities and compared with those in polymer matrices (polystyrene, PS; polymethyl methacrylate, PMMA; and polyvinyl chloride, PVC). Although the parent, 1-BT, absorbed near 300 nm and exhibited no or weak fluorescence, the substitution of 1-BTwith simple substituents at position 5 resulted in a bathochromic shift of approximately 50 nm or more in absorption and distinct fluorescence above 400 nm. The largest shift in absorption and fluorescence was observed for the complex 5-BTFL with fluorene as a substituent for 1-BT. The most intense fluorescence was observed for the derivative 2-BTCF with trifluoroacetyl as a substituent in the polar PVC matrix. The lifetimes of fluorescence of all substituted 2,2'-bithiophenes were in the range from 0.3 to 3 ns. The polymer matrices increased the intensity of fluorescence to some extent and prolonged the lifetime of the 2,2'-bithiophene derivatives. The reasons for the variation in the fluorescence intensity resulting from the substitution of the parent dimer are discussed.


Lexical or orthographic agraphia.
A case of agraphia was studied in the framework of the information-processing approach and in relation to comparable studies on alexia. Three dissociations are of interest in this patient's picture: (a) in language production: impairment of writing without impairment of speech; (b) in writing: impairment of spelling without impairment of phoneme-grapheme conversion; (c) in visible language: impairment of writing without equivalent impairment of reading. The implications of these dissociations for any model of linguistic processes are discussed.


Case Report: Combined Ischemic Optic Neuropathy and Central Retinal Artery Occlusion after Starting Hemodialysis.
This case highlights ocular ischemia after hemodialysis resulting in permanent vision loss. Fifteen percent of the U.S. population suffers from chronic kidney disease. Eye care providers should recommend risk factor modifications to their patients with end-stage renal disease before hemodialysis is started to prevent loss of vision. The purpose of this study was to demonstrate a case of concurrent nonarteritic anterior ischemic optic neuropathy and central retinal artery occlusion in the setting of hemodialysis initiation. A 68-year-old Irish man with end-stage renal disease undergoing dialysis presented, complaining of 3 weeks of progressive vision loss in his left eye. His medical history is complex and includes extensive cardiac disease, bilateral carotid stenosis, and peripheral vascular disease. His surgical history includes a right carotid endarterectomy, bilateral lower extremity amputations, and an aortic valve replacement. Clinical examination revealed light perception vision with an afferent pupillary defect in the left eye and count finger peripheral vision only in the superior temporal quadrant of his vision. The dilated fundus examination showed significant pallid disc edema and focal areas of retina whitening with attenuated peripapillary vasculature in the left eye. This edema was confirmed by optical coherence tomography and supported optic nerve and retinal infarction. A temporal artery biopsy confirmed no evidence of arteritis. Hemodynamic disruption during dialysis in patients with end-stage renal disease and overlying anemia can result in optic nerve and retinal infarction. Patients who are predisposed to nonarteritic anterior ischemic optic neuropathy or central retinal artery occlusion should be educated on this before starting dialysis to ensure careful blood pressure monitoring.


Glutathione peroxidase knockout mice are susceptible to myocardial ischemia reperfusion injury.
To test our hypothesis that intracellular antioxidant enzymes constitute a cellular defense against acute stress, we studied myocardial ischemia reperfusion injury in the setting of reduced level of glutathione peroxidase using GSHPx-1 gene knockout mice. Knockout mice were developed by disrupting the coding sequence of GSHPx-1 gene after inserting a neomycin resistance gene derived from pMCIpol A into the EcoRI site located in exon 2. Isolated perfused hearts were prepared from two groups of mice-knockout and nontransgenic controls. A 4-0 silk was attached to the apex of the heart which in turn was attached to a force transducer. Hearts were perfused by the Langendorff mode, and after 20 minutes of stabilization subjected to 30 minutes of ischemia followed by 2 hours of reperfusion. The force developed by the heart (DF) and the first derivative of DF (dF/dt) were recorded. Creatine kinase (CK) release was measured in the perfusate and the infarct size was measured at the end of each experiment. For both GSHPx-1 knockout and nontransgenic control groups, DF and dF/dt were significantly lower during early postischemic reperfusion compared with baseline, but these values were significantly higher for the control group than the knockout mice throughout most of the reperfusion period. CK release from the heart increased during reperfusion for both groups, but this increase was significantly lower for the control group. The infarct size was also smaller for the control mice as compared with knockouts. The results indicate that the knockout mice are more susceptible to ischemia reperfusion injury, suggesting the importance of GSHPx-1 gene in myocardial protection from ischemic reperfusion injury.


Pedicle screw placement in the thoracic spine: a randomized comparison study of computer-assisted navigation and conventional techniques.
To evaluate the accuracy of computer-assisted pedicle screw installation and its clinical benefit as compared with conventional pedicle screw installation techniques. Total 176 thoracic pedicle screws placed in 42 thoracic fracture patients were involved in the study randomly, 20 patients under conventional fluoroscopic control (84 screws) and 22 patients had screw insertion under three dimensional (3D) computer-assisted navigation (92 screws). The 2 groups were compared for accuracy of screw placement, time for screw insertion by postoperative thin-cut CT scans and statistical analysis by X(2) test. The cortical perforations were then graded by 2-mm increments: Grade I (good, no cortical perforation), Grade II (screw outside the pedicle less than 2 mm), Grade III (screw outside the pedicle larger than 2 mm). In computer assisted group, 88 (95.65%) were Grade I (good), 4 (4.35%) were Grade II (less than 2mm), no Grade III (larger than 2 mm) violations. In conventional group, there were 14 cortical violations (16.67%), 70 (83.33%) were Grade I (good), 11 (13.1%) were Grade II (less than 2 mm), and 3 (3.57%) were Grade III (larger than 2 mm) violations (P less than 0.001). The number (19.57%) of upper thoracic pedicle screws ( T(1)-T(4) ) inserted under 3D computer-assisted navigation was significantly higher than that (3.57%) by conventional fluoroscopic control (P less than 0.001). Average screw insertion time in conventional group was (4.56+/-1.03) min and (2.54+/-0.63) min in computer assisted group (P less than 0.001). In the conventional group, one patient had pleura injury and one had a minor dura violation. This study provides further evidence that 3D computer-assisted navigation placement of pedicle screws can increase accuracy, reduce surgical time, and be performed safely and effectively at all levels of the thoracic spine, particularly upper thoracic spine.


Expression of Saccharomyces cerevisiae MATa and MAT alpha enhances the HO endonuclease-stimulation of chromosomal rearrangements directed by his3 recombinational substrates.
Radiation resistance in Saccharomyces cerevisiae is greater in a/alpha diploids than in aa or alpha alpha diploids, and higher levels of radiation resistance correlates with more mitotic recombination. Specifically, we investigated whether the stimulation of directed translocations, inversions, and unequal sister chromatid exchanges (SCEs) by HO endonuclease-induced double-strand breaks (DSBs) is enhanced in a/alpha cells. These rearrangements result from mitotic recombination between two truncated his3 genes, his3-delta 5' and his3-delta 3'::HOcs, positioned on non-homologous chromosomes or positioned in juxtaposition on the same chromosome in inverted or direct orientation. Mitotic recombination was initiated by HO endonuclease-induced DSBs at the HO cut site (HOcs) located at his3-delta 3'::HOcs, and His+ recombinants were selected. In MATa-inc haploid strains, which do not switch mating-type, the DSB reduced viability, relative to undamaged cells, and increases the frequency of His+ recombinants containing translocations to 2.4 x 10(-4) (seven-fold), SCEs to 5.4 x 10(-4) (five-fold), and inversions to 1.8 x 10(-3) (six-fold). Compared to a haploids, DSB-stimulated frequencies in a/alpha haploids were three-fold higher for translocations, two-fold higher for SCEs, and ten-fold higher for inversions; however DSB-induced lethality was greater in a/alpha haploids. Compared to aa diploids, DSB-stimulated frequencies of translocations and viability after chromosome cleavage were greater in a/alpha diploids. We suggest that heterozygosity at MAT may elevate the frequency of DSB-initiated reciprocal exchange events in both haploid and diploid cells, but may only increase viability after chromosome cleavage in diploid cells.


Natural versus artificial creation of base pairs in DNA: origin of nucleobases from the perspectives of unnatural base pair studies.
Since life began on Earth, the four types of bases (A, G, C, and T(U)) that form two sets of base pairs have remained unchanged as the components of nucleic acids that replicate and transfer genetic information. Throughout evolution, except for the U to T modification, the four base structures have not changed. This constancy within the genetic code raises the question of how these complicated nucleotides were generated from the molecules in a primordial soup on the early Earth. At some prebiotic stage, the complementarity of base pairs might have accelerated the generation and accumulation of nucleotides or oligonucleotides. We have no clues whether one pair of nucleobases initially appeared on the early Earth during this process or a set of two base pairs appeared simultaneously. Recently, researchers have developed new artificial pairs of nucleobases (unnatural base pairs) that function alongside the natural base pairs. Some unnatural base pairs in duplex DNA can be efficiently and faithfully amplified in a polymerase chain reaction (PCR) using thermostable DNA polymerases. The addition of unnatural base pair systems could expand the genetic alphabet of DNA, thus providing a new mechanism for the generation novel biopolymers by the site-specific incorporation of functional components into nucleic acids and proteins. Furthermore, the process of unnatural base pair development might provide clues to the origin of the natural base pairs in a primordial soup on the early Earth. In this Account, we describe the development of three representative types of unnatural base pairs that function as a third pair of nucleobases in PCR and reconsider the origin of the natural nucleic acids. As researchers developing unnatural base pairs, they use repeated "proof of concept" experiments. As researchers design new base pairs, they improve the structures that function in PCR and eliminate those that do not. We expect that this process is similar to the one functioning in the chemical evolution and selection of the natural nucleobases. Interestingly, the initial structures designed by each research group were quite similar to those of the latest successful unnatural base pairs. In this regard, it is tempting to form a hypothesis that the base pairs on the primordial Earth, in which the natural purine bases, A and G, and pyrimidine bases, C and T(U), originated from structurally similar compounds, such as hypoxanthine for a purine base predecessor. Subsequently, the initial base pair evolved to the present two sets of base pairs via a keto-enol tautomerization of the initial compounds.


Association Analysis of IL10, TNF-α, and IL23R-IL12RB2 SNPs with Behçet's Disease Risk in Western Algeria.
We have conducted the first study of the association of interleukin (IL)-10, tumor necrosis factor alpha (TNF-α), and IL23R-IL12RB2 region single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) in Western Algeria. A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPs from the IL10 promoter [c.-819T > C (rs1800871), c.-592A > C (rs1800872)], 6 SNPs from the TNF-α promoter [c.-1211T > C (rs1799964), c.-1043C > A (rs1800630), c.-1037C > T (rs1799724), c.-556G > A (rs1800750), c.-488G > A (rs1800629), and c.-418G > A (rs361525)], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A > C (rs12119179), g.67740092G > A (rs11209032), and g.67760140T > C (rs924080)]. The minor alleles c.-819T and c.-592A were significantly associated with BD [odds ratio (OR) = 2.18; 95% confidence interval (CI) 1.28-3.73, p = 0.003]; whereas, there was weaker association between TNF-α promoter SNPs or IL23R-IL12RB2 region and disease risk. Unlike the TNF-α and the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria.


The number of segregating sites in expanding human populations, with implications for estimates of demographic parameters.
The frequency distribution of pairwise differences between sequences of mtDNA has recently been used to estimate the size of human populations before and after a hypothetical episode of rapid population growth and the time at which the population grew. To test the internal consistency of this method, we used three different sets of human mtDNA data and the corresponding demographic parameters estimated from the distribution of pairwise differences to determine by simulation the expected number of segregating sites, S, and its empirical distribution. The results indicate that the observed values of S are significantly lower than expected in two of three cases under the assumption of the infinite-sites model. Further simulations in which mutations were allowed to occur more than once at the same site and in which there was variation in mutation rate among sites show that the expected number of segregating sites can be much lower than under the infinite-site assumption. Nevertheless, the observed value of S is still significantly different from the value expected under the expansion hypothesis in two of three cases.


[Copia-like retrotransposon in Amaranthus].
This study analyzed the characteristics of reverse transcriptase sequences of copia-like retrotransposons in Amaranthus via PCR amplification and sequence approaches. The results are as follows: (1) The reverse transcriptase sequences of copia-like retrotransposons were detected in all 30 Amaranthus accessions studied, indicating that this class of retrotransposons is ubiquitous in Amaranthus; (2) Twenty-eight reverse transcriptases in A. quitensis were cloned and sequenced, showing extensive heterogeneity in base deletion mutation and stop codon mutation; (3) Cluster and alignment analyses of the 28 sequences and other published sequences of the reverse transcriptase from other species (such as rice, tomato and Drosophila) showed that the copia-like retrotransposons in A. quitensis have a close relationship with those in dicot and monocot plants. The evolution of copia-like retrotransposons in A. tricolor, which might be of the same origin as the copia and 1731 in Drosophila, was discussed.


Colostrum-Induced Temporary Changes in the Expression of Proteins Regulating the Epithelial Barrier Function in the Intestine.
The intestinal wall and epithelial cells are interconnected by numerous intercellular junctions. Colostrum (Col), in its natural form, is a secretion of the mammary gland of mammals at the end of pregnancy and up to 72 h after birth. Recently, it has been used as a biologically active dietary supplement with a high content of lactoferrin (Lf). Lf, a glycoprotein with a broad spectrum of activity, is becoming more popular in health-promoting supplements. This study aims to investigate whether Col supplementation can affect small and large intestine morphology by modulating the expression of selected proteins involved in tissue integrity. We examined the thickness of the epithelium, and the length of the microvilli, and assessed the expression of CDH1, CDH2, CTNNB, CX43, VCL, OCLN, HP, MYH9, and ACTG2 gene levels using qRT-PCR and at the protein level using IHC. Additionally, to evaluate whether the effect of Col supplementation is temporary or persistent, we performed all analyses on tissues collected from animals receiving Col for 1, 3, or 6 months. We noticed a decrease in CDH1 and CDH2 expression, especially after 3 months of supplementation in the large intestine and in CTNNB in the small intestine as well as increased levels of CX43 and CTNNB1 in the small intestine. The present data indicate that Col can temporarily alter some components of the cell adhesion molecules involved in the formation of the cellular barrier.


Noninvasive evaluation of lower urinary tract function in children with cerebral palsy.
The aim of this study was noninvasive evaluation of voiding function in children with cerebral palsy. Sixty children with cerebral palsy were enrolled in the study. Urinary system symptoms were recorded. Uroflowmetric tests were carried out, and postvoid residual volume was measured immediately after voiding by using a portable ultrasonic device developed for children. The expected age-related bladder capacity was calculated and compared with the observed bladder capacity. Uroflowmetric curves were evaluated and classified as normal (bell-shaped) and abnormal. Thirty-three of the children (55%) were symptomatic. In 17 (28.3%) of the children, postvoid residual urine was observed. There was a statistically significant difference between the expected bladder capacity (271.6 +/- 38.3 ml) and the observed bladder capacity (154.5 +/- 111.8 ml) (P < 0.001). Observed bladder capacity was lower than the expected bladder capacity in 56 (93.3%) of the children. In the evaluation of the uroflowmetric charts, 22 (36.7%) children had abnormal curves. Bladder capacity is decreased in most children with cerebral palsy, and postvoid residue is present in an important proportion. Uroflowmetry and portable ultrasonic device combination is a noninvasive, well-tolerated, and efficient method in the first line evaluation of lower urinary tract function in children with cerebral palsy.


Molecular MRI of Atherosclerotic Plaque With Targeted Contrast Agents.
Molecular MRI of atherosclerosis involves the use of novel contrast agents to image cellular and molecular processes within atherosclerotic plaque. Agents to image plaque lipid content, inflammation, angiogenesis, and thrombosis have been developed and studied extensively in animal models of atherosclerosis and vascular injury. Selected agents have also been studied in humans, with highly promising initial results. In this brief review, recent advances as well as opportunities and challenges in the field are discussed.


[Reparative bone regeneration after aseptic necrosis of the femoral head as influenced by 1-chloromethylsilatrane treatment].
The aim of this work was to study the effect of 1-chloromethyisilatranum on the processes of reparative bone regeneration in experimentally induced aseptic femoral head necrosis. Aseptic femoral head necrosis was modeled in 4 Chinchilla rabbits by destruction of spongy substance of femoral neck and cutting of ligamentum teres of its head. Rabbits of the experimental group were injected with 0.4 ml of 1% solution of 1-chloromethylsilatranum on postoperational days 5, 10, 15 and 20 into the damaged femoral head and close to the damaged joint. Animal were sacrificed by air embolism 5 weeks from the start of an experiment. Necrotic and repair processes in hip joints from damaged and intact sides were assessed radiologically and histologically prior to sacrifice. In rabbits of both control and experimental groups extensive aseptic necrosis of hip joints was found. The osseous tissue of damaged hip joints of experimental animals contained the chains of osteoblasts actively producing new bone matrix. Foci of bone regeneration were found both in the deep and peripheral regions of the epiphysis, which is indicative of active processes of bone repair. The results obtained suggest that administration of organic-silicon drug 1-chloromethylsilatranum stimulates (optimizes) the processes of repair osteogenesis following aseptic femoral head necrosis in experimental animals. Application of this preparation appears to be very promising.


Towards a more inclusive vision of the medical sciences.
Progress in the medical sciences is largely determined by two things: (i) the questions we ask, and (ii) how rigorously and vigorously we attempt to answer them. How do we know which questions are the right questions to ask, and thus the correct questions to spend our time and energies trying to answer? Such evaluative concerns bring into sharper focus the question--'What is medicine for?' The international study of rosuvastatin is important not simply because of the health benefits it may confer, but because it inspires a more robust and inclusive vision of the medical sciences. A vision which recognizes that the primary goal of medicine is to promote health, and that includes the health of 'normal' people as well as those with illness and disease. This inclusive vision of the medical sciences is a transformative one, it departs from the 'disease-model' approach which has dominated distinct areas of medical research for decades.


Characterization of a cycling murine pluripotent stem cell population.
In the present report we describe the properties of pluripotent stem cells isolated with elutriation and Percoll density gradient centrifugation techniques from spleens of recovering thiamphenicol pretreated anemic mice. Cells with a diameter between 7.2 and 8.4 microns and sedimenting at a density of 1.065 g/ml had a high capacity to repopulate lethally irradiated mice with all the hemopoietic precursor cells. The spleen colonies formed on day 8 and day 12 after inoculation in irradiated recipients showed no morphological differences in mixed and lineage-specific composition. Day 12 colonies were much larger than day 8 colonies. Pluripotent stem cells isolated from regenerating spleens were very susceptible to 3'-thymidine; 65% of the cells were killed. Only 2% kill was found in stem cells present in vivo 4 days earlier in the bone marrow. The purified stem cells were probably all in cycle and possibly partly synchronized.


Myxofibrosarcoma presenting as an exophytic, multi-lobed nodule on the leg.
Myxofibrosarcoma may present as a dermal or subcutaneous nodule, often on the extremity of an elderly patient. We present a case of myxofibrosarcoma on the lower leg of a 77-year-old man, which illustrates the deeply infiltrative growth pattern of these tumors, as well as the potential for superficial biopsies to show lower grade histopathologic features than subsequent excision specimens.


Optical modeling of changeable laser image functionality with analysis of the viewing performance.
Changeable laser image is a security feature commonly used on personalized documents. To understand and to predict the influence of different design parameters, a holistic optical modeling approach is essential. In this work a two-stage modeling process is performed using geometric ray tracing methods. The first stage, based on a basic optical model, allows us to identify the influencing parameters and to determine optimum solutions. The second stage, based on an advanced model, allows us to evaluate the optimum performance quantitatively in terms of the viewing angles and the contrast between two images. Simulation results are verified by experiments.


Anaplastic lymphoma kinase (ALK)-induced malignancies: novel mechanisms of cell transformation and potential therapeutic approaches.
Among the many oncogenic variants of the anaplastic lymphoma kinase (ALK), nucleophosmin 1 (NPM)/ALK fusion protein expressed in the subset of T-cell lymphoma (ALK(+)TCL) is currently the best characterized. NPM/ALK activates several signal transduction pathways, including PI3K/AKT, MEK/ERK, mTORC1, STAT3, and STAT5b. In turn, the pathways modulate expression and function of many genes and proteins involved in the key cellular functions such as proliferation, growth, survival, metabolism, and angiogenesis. Recent data indicate that NPM/ALK also promotes immune evasion of the ALK(+)TCL by inducing through STAT3 activation the expression of immunosuppressive cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGFss) and cell surface protein CD274 (PD-L1, B7-H1). In addition, NPM/ALK protects its own expression by mediating via STAT3 and at least one member of the DNA methyltransferase family DNMT1 epigenetic silencing of the SHP-1 and STAT5a genes. In ALK+TCL cells, SHP-1 and STAT5a proteins act as potent tumor suppressors by promoting degradation of the NPM/ALK protein and inhibiting expression of the NPM/ALK gene, respectively. These findings provide further rationale to therapeutically target ALK and its effector proteins, foremost STAT3. They also suggest that immunotherapeutic approaches to ALK(+)TCL and, possibly, other ALK-driven malignancies may require inhibition of ALK and STAT3 to achieve the optimal clinical efficacy.


Wrapping of intracranial aneurysms with gauze sponge.
A gauze sponge wrapping method to prevent recurrent subarachnoid hemorrhage (SAH) after incomplete obliteration of intracranial aneurysm or a residual neck after clipping was developed and tested. The authors performed the gauze wrapping for aneurysms with incomplete obliteration by clipping alone, abnormal changes of the parent artery wall which had the possibility of regrowth or rerupture, and surgical difficulties. The residual neck of the aneurysm or the abnormal arterial wall was tightly and completely wrapped, including the parent artery, and cemented with plastic adhesive. Seventy-eight (22.3%) of 349 surgically treated aneurysms were treated by gauze wrapping (26 wrapping only, 52 clipping and wrapping). The incidence of complications such as infection, angiospasm, and normal pressure hydrocephalus, and the clinical outcome were not significantly different for the wrapping and non-wrapping groups. No recurrent SAH was observed in the wrapping group during 3 months to 8.5 years follow-up. These results suggest that wrapping with gauze sponge is useful in the treatment for ruptured aneurysms which cannot be totally obliterated.


Fc Fragment of IgE Receptor Ig (FCER1G) acts as a key gene involved in cancer immune infiltration and tumour microenvironment.
Although recent studies have revealed the relationship between Fc Fragment of IgE Receptor Ig (FCER1G) and human tumours, there is still a lack of a more comprehensive pan-cancer analysis of FCER1G as an immune-related gene. In this study, we investigated the expression pattern and prognostic value of FCER1G based on multiple databases. Subsequently, we further explored the role of FCER1G in tumour proliferation and metastasis, as well as its genomic alterations and DNA methylation levels, we next assessed the association between FCER1G and the immune infiltrating cells of the tumour microenvironment in different cancers and verified it by immunohistochemical staining. The correlation between FCER1G and immune checkpoint genes expression and its predictive power in the immune checkpoint blockade treatment cohorts were used to evaluate the importance of FCER1G in immunotherapy. Enrichment analysis of FCER1G-associated partners was also performed. In addition, we substantiated the expression of FCER1G in specific cell types of different tumours using single-cell RNA sequencing data from different databases. Our research results showed that FCER1G is up-regulated in most tumour. Positive associations were found between FCER1G expression and tumour prognosis, proliferation, and metastasis, we also found that FCER1G is closely related to the tumour microenvironment and tumour immunity. Moreover, FCER1G-associated partners were enriched in pathways associated with neutrophils activation. Finally, we confirmed that FCER1G was mainly expressed in monocyte/macrophages of the tumour microenvironment. In conclusion, our findings provided a comprehensive understanding of FCER1G in oncogenesis and tumour immunology among various tumours and demonstrated its potential value in prognosis prediction and tumour immunotherapy.


Diffuse uterine adenomyosis: morphologic criteria and diagnostic accuracy of endovaginal sonography.
To determine the accuracy of endovaginal ultrasound (US) in the diagnosis of uterine adenomyosis and to evaluate the frequency of observed sonographic criteria. Endovaginal US was performed in 100 consecutive women undergoing hysterectomy for a variety of benign and malignant conditions. Adenomyosis was diagnosed when a poorly defined area of abnormal echotexture (decreased or increased echogenicity, heterogeneous echotexture, myometrial cysts) was present in the myometrium. All endovaginal US findings were correlated with those from histologic examination. Endovaginal US depicted 25 of 29 pathologically proved cases of adenomyosis. Adenomyosis was correctly ruled out in 61 of 71 patients. Endovaginal US had a sensitivity of 86%, a specificity of 86%, and a positive and negative predictive value of 71% and 94%, respectively. Of the 25 patients with true-positive findings at US, the myometrium demonstrated heterogeneous and hypoechoic areas with or without the presence of cysts in 21 (84%) patients, hypoechoic areas with cysts in three (12%) patients, and heterogeneous areas within the myometrium in one (4%) patient. Adenomyosis of the uterus can be accurately diagnosed with endovaginal US with use of specific sonographic criteria.


A new approach towards defibrillation electrodes: highly conductive isotropic carbon fibers.
A new carbon fiber material was studied for its potential benefit in defibrillation electrodes. Miniaturization of the fiber production can result in small strands with extremely large surface areas. Two carbon fiber patches and a single carbon fiber bundle were used for the purposes of this study, and the results were compared to those obtained with conventional titanium/mesh patch electrodes. Tests performed in a saline filled tank revealed considerably lower resistances through the carbon material when compared to standard mesh electrodes. There was also a higher peak current flow with lower voltage. The carbon fibers exhibited lower impedance for defibrillation and this may be related to low polarization known to occur with carbon materials. This new carbon material may prove to be useful and further research is required.


The modified AFP score: an attempt to make the results of anti-reflux surgery comparable.
Comparison of different strategies in anti-reflux therapy is complicated by wide variations in patient selection and in the criteria employed to assess outcome. A modification of the classification system originally developed by Bancewicz et al. was used to grade a series of 57 patients before and after fundoplication (primary reflux group). An additional group of 39 patients with an unsatisfactory result after previous Nissen fundoplication (failed Nissen group) were assessed before and after reoperation. The classification system used comprises three elements: the A element depicts gastro-oesophageal anatomy based on the findings at endoscopy: the F element codes the amount of acid reflux by means of 24-h intra-oesophageal pH monitoring; and the P element describes mucosal abnormalities. The overall severity was quantified by means of a score on a scale from 0 to 10. The mean preoperative score in the primary reflux group was 5.45 and in the failed Nissen group 7.3. After fundoplication, this was reduced to 1.07 and 1.30, respectively. In general, there was good correlation between the results of the three elements under consideration, pointing to a potential pathophysiological inter-relationship. Marked individual variation did occasionally occur. The AFP system enabled a detailed description of the preoperative and postoperative condition of the patient, and proved easy to use in clinical practice. Its employment is recommended as an objective means of comparing the value of different treatment strategies.


Interferon-induced sarcoidosis with uveitis as the initial symptom: a case report and review of the literature.
In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature. This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018. Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.


Blockchain in Health Care Innovation: Literature Review and Case Study From a Business Ecosystem Perspective.
Blockchain technology is leveraging its innovative potential in various sectors and its transformation of business-related processes has drawn much attention. Topics of research interest have focused on medical and health care applications, while research implications have generally concluded in system design, literature reviews, and case studies. However, a general overview and knowledge about the impact on the health care ecosystem is limited. This paper explores a potential paradigm shift and ecosystem evolution in health care utilizing blockchain technology. A literature review with a case study on a pioneering initiative was conducted. With a systematic life cycle analysis, this study sheds light on the evolutionary development of blockchain in health care scenarios and its interactive relationship among stakeholders. Four stages-birth, expansion, leadership, and self-renewal or death-in the life cycle of the business ecosystem were explored to elucidate the evolving trajectories of blockchain-based health care implementation. Focused impacts on the traditional health care industry are highlighted within each stage to further support the potential health care paradigm shift in the future. This paper enriches the existing body of literature in this field by illustrating the potential of blockchain in fulfilling stakeholders' needs and elucidating the phenomenon of coevolution within the health care ecosystem. Blockchain not only catalyzes the interactions among players but also facilitates the formation of the ecosystem life cycle. The collaborative network linked by blockchain may play a critical role on value creation, transfer, and sharing among the health care community. Future efforts may focus on empirical or case studies to validate the proposed evolution of the health care ecosystem.


Polyphenol uses in biomaterials engineering.
Polyphenols are micronutrients obtained from diet that have been suggested to play an important role in health. The health benefits of polyphenols and their protective effects in food systems as antioxidant compounds are well known and have been extensively investigated. However, their functional roles as a "processing cofactor" in tissue engineering applications are less widely known. This review focuses on the functionality of polyphenols and their application in biomaterials. Polyphenols have been used to stabilize collagen and to improve its resistance to degradation in biological systems. Therefore, they have been proposed to improve the performance of biomedical devices used in cardiovascular systems by improving the mechanical properties of grafted heart valves, enhancing microcirculation through the relaxation of the arterial walls and improving the capillary blood flow and pressure resistance. Polyphenols have been found to stimulate bone formation, mineralization, as well as the proliferation, differentiation, and the survival of osteoblasts. These effects are brought about by the stimulatory effect of polyphenols on osteoblast cells and their protective effect against oxidative stress and inflammatory cytokines. In addition, polyphenols inhibit the differentiation of the osteoclast cells. Collectively, these actions lead to promote bone formation and to reduce bone resorption, respectively. Moreover, polyphenols can increase the cross-linking of dentine and hence its mechanical stability. Overall, polyphenols provide interesting properties that will stimulate further research in the bioengineering field.


[Ovarian stimulation: is exogenous LH necessary in all patients?].
FSH and LH play an essential but different role in the growth of ovarian follicles during the cycle. In stimulation protocols, good follicular development is obtained in most patients treated with FSH alone whereas the role of LH is more complex and controversial. Clinical and pre-clinical studies have shown that optimal follicular development is obtain if (i) exposure to endogenous and/or exogenous LH is sufficient ("threshold" concept) and (ii) exposure to LH is not excessive ("ceiling" concept). The recombinant luteinizing hormone (r-hLH, Luveris) is the only available stand-alone preparation of LH. Its characteristics are a high specific activity, the absence of undesirable proteins and an excellent batch to batch consistency. Luveris is indicated in association with FSH for stimulating follicular development in LH and FSH deficient women (defined by an endogenous LH level < 1.2 UI/l). In this subgroup of patients, the therapeutic benefit of exogenous LH at a daily dose of 75 IU is only observed when endogenous serum LH is below than 1.2 IU/l: LH threshold concept. In ART, the combination of exogenous LH at a daily dose from 75 to 150 IU and recombinant FSH improved the ovarian stimulation results only in a minority of patients (5 to 17%). On the opposite, studies conducted in OMS I and II patients showed that high doses of exogenous LH lead to atresia of secondary follicles. So, a daily dose of exogenous LH greater than 225 IU had a deleterious effect on follicular growth: LH ceiling concept.


[Successful surgical management of spontaneous multiple free ileum perforation caused by regional enteritis (Crohn disease)].
Spontaneous free perforation of the small intestine is a rare early (first) complication of the Crohn's disease. Case reports have not exceeded the hundred. The authors report the case history of a 40 years old male patient who was successfully operated on double, multiple free perforation of ileum as first sign of the Crohn's disease. First the suture of the perforated small bowel and second the resection of reperforated ileum was carried out. The base on the macroscopic and microscopic appearance of the resected bowel, the diagnosis was supposed by pathologists too. Presented paper based on the very rare clinical finding.


Human umbilical cord-derived scaffolds for cartilage tissue engineering.
Since articular cartilage is an avascular tissue, it has limited self-regeneration capacity after damage. Current methods for human bone marrow-derived mesenchymal stem cell (hBM-MSC) differentiation into cartilage result in tissues with a lower quality as compared to native articular cartilage. Decellularized biological scaffolds have the potential to provide appropriate signals, in order to support cellular retention, migration, proliferation, and differentiation. Given the high amount of collagen, hyaluronic acid (HA), and glycosaminoglycan (GAG) in umbilical cord, this tissue can be considered as an abundant natural biomaterial for tissue engineering applications. Human umbilical cord-derived scaffolds were prepared, and the chondrogenic induction of hBM-MSCs loaded onto the scaffolds was investigated. Gelatin-based scaffolds as a commercial material was used as a control. The results show that hBM-MSCs in tissue-derived scaffolds have an increased expression of chondrogenic markers compared with gelatin, whereas there are no significant differences between the expression of hypertrophic and osteogenic markers between tissue and gelatin scaffolds. In conclusion, it is confirmed that umbilical cord-derived scaffolds are able to provide a native environment for the cells and can promote cartilage differentiation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1793-1802, 2019.


Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009-2010.
A multicentre resistance surveillance study [Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of 2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12 antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints for oral penicillin V recommended by the Clinical and Laboratory Standards Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP) ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable resistance rates of 0-88% against S. pneumoniae, 0-57% against MSSA and 0-76.5% against Streptococcus spp. isolates. The prevalence of extended-spectrum β-lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. β-Lactamase production rates amongst H. influenzae isolates ranged from 15% to 46.6% and amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%, respectively, were found, mainly in Mainland China. Levofloxacin resistance rates of 0-3.9% with a MIC(90) (minimum inhibitory concentration causing inhibition of 90% of isolates) of 1-2mg/L and moxifloxacin resistance rates of 0-1.7% with a MIC(90) of 0.125-0.5mg/L were found amongst PNSSP isolates. Moxifloxacin was very active against Streptococcus spp., H. influenzae and M. catarrhalis isolates, with MIC(90) values of 0.125-0.25, 0.032-0.5 and 0.064-0.125mg/L, respectively. These results from the CARTIPS study have confirmed some significant regional differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K. pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of antimicrobial surveillance programmes for guiding empirical therapy and for focusing interventional control of antimicrobial resistance in distinct geographic areas.


Motion microscopy for visualizing and quantifying small motions.
Although the human visual system is remarkable at perceiving and interpreting motions, it has limited sensitivity, and we cannot see motions that are smaller than some threshold. Although difficult to visualize, tiny motions below this threshold are important and can reveal physical mechanisms, or be precursors to large motions in the case of mechanical failure. Here, we present a "motion microscope," a computational tool that quantifies tiny motions in videos and then visualizes them by producing a new video in which the motions are made large enough to see. Three scientific visualizations are shown, spanning macroscopic to nanoscopic length scales. They are the resonant vibrations of a bridge demonstrating simultaneous spatial and temporal modal analysis, micrometer vibrations of a metamaterial demonstrating wave propagation through an elastic matrix with embedded resonating units, and nanometer motions of an extracellular tissue found in the inner ear demonstrating a mechanism of frequency separation in hearing. In these instances, the motion microscope uncovers hidden dynamics over a variety of length scales, leading to the discovery of previously unknown phenomena.


Superhydrophobic aluminum alloy surfaces by a novel one-step process.
A simple one-step process has been developed to render aluminum alloy surfaces superhydrophobic by immersing the aluminum alloy substrates in a solution containing NaOH and fluoroalkyl-silane (FAS-17) molecules. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements have been performed to characterize the morphological features, chemical composition and superhydrophobicity of the surfaces. The resulting surfaces provided a water contact angle as high as ∼162° and a contact angle hysteresis as low as ∼4°. The study indicates that it is possible to fabricate superhydrophobic aluminum surfaces easily and effectively without involving the traditional two-step processes.


Controlled fabrication of fluorescent barcode nanorods.
We report a novel technique for generating polymer fluorescent barcode nanorods by reactive ion etching of polymer multilayer films using nonclose-packed (ncp) colloidal microsphere arrays as masks. The fluorescent polymer multilayer films were spin-coated on a substrate, and ncp microsphere arrays were transferred onto these films. The exposed polymers were then etched away selectively, leaving color-encoded nanorods with well-preserved fluorescent properties. By modifying the spin-coating procedure, the amount of polymer in each layer could be tuned freely, which determined the relative fluorescence intensity of the barcode nanorods. These nanorod arrays can be detached from the substrate to form dispersions of coding materials. Moreover, the shape of the nanorods is controllable according to the different etching speeds of various materials, which also endows the nanorods with shape-encoded characters. This method offers opportunities for the fabrication of novel fluorescent barcodes which can be used for detecting and tracking applications.


Iron Deficiency Anemia in Inflammatory Bowel Disease: What Do We Know?
One of the most common extraintestinal manifestations of inflammatory bowel disease is iron deficiency anemia. It is often an untreated condition that significantly impairs patients' quality of life and elevates mortality and morbidity. Although it is often accompanied by mild symptoms (e.g., fatigue, lethargy), it can provoke severe health conditions, such as dyspnea, palpitation, angina, and mental disorders, and increases hospitalization and mortality rate as well. As anemia develops through several pathomechanisms, such as occult bleeding, chronic inflammation, and medicines (e.g., methotrexate), treating anemia effectively requires to manage the underlying pathological changes as well. Based on international publications and data, it is a frequent condition and more frequent in pediatrics. According to Goodhand et al., iron deficiency is present in more than 60% of children, whereas only 14% of them received oral iron therapy. Compared to adult patients, 22% have iron deficiency, and 48% of them received oral and 41% intravenous iron therapy. Miller et al. also highlighted that among young patients iron deficiency anemia is a frequent condition, as almost 50% of the patients were anemic in their cohort. European Crohn's and Colitis Organisation's statements are clear regarding the diagnosis of iron deficiency anemia, and the iron supplementation as well. Third-generation parenteral iron supplementations seem to be safer and more effective than oral iron pills. Oral iron in many cases cannot replace the iron homeostasis as well; furthermore, it can provoke dysbiosis, which can potentially lead to relapse. As a result, we claim that both oral and parenteral should be used more frequently; furthermore, intravenous iron could replace oral medicines as well in certain cases. Despite the fact that iron deficiency anemia is examined by many aspects, further questions can be raised. Can it imply underlying pathological lesions? Are both oral and intravenous iron therapy safe and effective? When and how are they used? We demand that more studies should be conducted regarding these issues.