The survey of Seira Lubbock, 1870 (Collembola, Entomobryidae, Seirinae) from Iberian Peninsula and Canary Islands, including three new species.
Here we present a survey of Seira fauna from Iberian Peninsula and Canary Islands, including the description of three new species from Spain: Seira barrai sp. nov., Seira betica sp. nov. and Seira burgersi sp. nov., the latter with unprece-dented antennal morphology for Seira. Five species from Western Europe are redescribed and their dorsal detailed chaetotaxy is revealed for the first time: S. domestica (Nicolet), S. dinizi Gama, S. ferrarii Parona, S. mantis Zeppelini Bellini and S. pini Jordana Arbea, the first two from type locality, and the latter two based on analysis of the type material. A note on chaetal interpretation of the first abdominal segment for Seira is presented. An identification key to 31 species with known dorsal chaetotaxy from Western Palearctic region is also provided, including a discussion on dense macrochaetotaxy present in Palearctic and Oriental species and its reduction in species from others biogeographic regions.


HEALTH SELECTION THEORY: AN EXPLANATION FOR THE PARADOX BETWEEN PERCEIVED MALE WELL-BEING AND MORTALITY.
Paradoxically, men report better health and quality of life than women, but men experience higher mortality rates than women at most ages. One conclusion from these findings is that men have been selected to disregard signs of ill health, or even to deceive themselves about their health, to their detriment because presenting themselves as healthy has fitness benefits. We hypothesize that men have been sexually selected to present themselves to women as healthy but that the cost of not attending to their minor health problems results in earlier mortality than women. We present a review of the human and primate literature that supports health selection theory, the hypothesis that females have preferentially selected males who present themselves as healthy.


Comparison of the ACC/AHA and Framingham algorithms to assess cardiovascular risk in HIV-infected patients.
The aim of this study was to compare the predictions of Framingham cardiovascular (CV) risk score (FRS) and the American College of Cardiology/American Heart Association (ACC/AHA) risk score in an HIV outpatient clinic in the city of Vitoria, Espirito Santo, Brazil. In a cross-sectional study 341 HIV infected patients over 40 years old consecutively recruited were interviewed. Cohen's kappa coefficient was used to assess agreement between the two algorithms. 61.3% were stratified as low risk by Framingham score, compared with 54% by ACC/AHA score (Spearman correlation 0.845; p<0.000). Only 26.1% were classified as cardiovascular high risk by Framingham compared to 46% by ACC/AHA score (Kappa=0.745; p<0.039). Only one out of eight patients had cardiovascular high risk by Framingham at the time of a myocardial infarction event registered up to five years before the study period. Both cardiovascular risk scores but especially Framingham underestimated high-risk patients in this HIV-infected population.


Preliminary impacts of PACS technology on radiology department operations.
The potential benefits of digital imaging to clinical operations focuses on both quantitative and qualitative improvements. In the future it is postulated that it will totally replace analog imaging, creating the 'filmless' Radiology department. Although this could result in dramatic savings in film costs, realization of this scenario will require continued improvements in the performance and cost of component technologies, acceptance by the medical and legal communities of the reliability of the medium, and changes in the practice and process of radiology. Baltimore VAMC has recently become one of the truly 'filmless' radiology departments through use of a leading commercial Picture Archiving and Communications System (PACS) and DHCP's Digital Imaging System. This document outlines the results of a preliminary assessment of PACS technology as it is installed at Baltimore, and its impact on operations.


Benchmarking B-cell epitope prediction for the design of peptide-based vaccines: problems and prospects.
To better support the design of peptide-based vaccines, refinement of methods to predict B-cell epitopes necessitates meaningful benchmarking against empirical data on the cross-reactivity of polyclonal antipeptide antibodies with proteins, such that the positive data reflect functionally relevant cross-reactivity (which is consistent with antibody-mediated change in protein function) and the negative data reflect genuine absence of cross-reactivity (rather than apparent absence of cross-reactivity due to artifactual masking of B-cell epitopes in immunoassays). These data are heterogeneous in view of multiple factors that complicate B-cell epitope prediction, notably physicochemical factors that define key structural differences between immunizing peptides and their cognate proteins (e.g., unmatched electrical charges along the peptide-protein sequence alignments). If the data are partitioned with respect to these factors, iterative parallel benchmarking against the resulting subsets of data provides a basis for systematically identifying and addressing the limitations of methods for B-cell epitope prediction as applied to vaccine design.


The Small Protein YmoA Controls the Csr System and Adjusts Expression of Virulence-Relevant Traits of Yersinia pseudotuberculosis.
Virulence gene expression of Yersinia pseudotuberculosis changes during the different stages of infection and this is tightly controlled by environmental cues. In this study, we show that the small protein YmoA, a member of the Hha family, is part of this process. It controls temperature- and nutrient-dependent early and later stage virulence genes in an opposing manner and co-regulates bacterial stress responses and metabolic functions. Our analysis further revealed that YmoA exerts this function by modulating the global post-transcriptional regulatory Csr system. YmoA pre-dominantly enhances the stability of the regulatory RNA CsrC. This involves a stabilizing stem-loop structure within the 5'-region of CsrC. YmoA-mediated CsrC stabilization depends on H-NS, but not on the RNA chaperone Hfq. YmoA-promoted reprogramming of the Csr system has severe consequences for the cell: we found that a mutant deficient of ymoA is strongly reduced in its ability to enter host cells and to disseminate to the Peyer's patches, mesenteric lymph nodes, liver and spleen in mice. We propose a model in which YmoA controls transition from the initial colonization phase in the intestine toward the host defense phase important for the long-term establishment of the infection in underlying tissues.


Is distance to chemotherapy an obstacle to adjuvant care among the N.C. Medicaid-enrolled colon cancer patients?
Adjuvant chemotherapy for colon cancer has been linked to patient and provider characteristics but little is known about whether distance to chemotherapy providers constitutes an obstacle to chemotherapy. A total of 1,184 Medicaid patients diagnosed with colon cancer in North Carolina in 1999-2002 comprised the sample. Data from the N.C. Central Cancer Registry, N.C. Medicaid Claims, American Hospital Directory and US Census were merged. Logistic regression models were used to estimate the association between chemotherapy receipt and the distance to nearest chemotherapy provider. Compared to the referent group of SEER-staged II (local) cancer patients living less than 2 miles from the nearest chemotherapy provider, the odds of receiving chemotherapy fell as the distance to the nearest provider increased. The odds ratio (OR) for those living ≥5 to <15 miles away was 0.13 [95% confidence intervals (CI), 0.04-0.39], and OR for those living ≥15 miles away was 0.06 (95% CI, 0.01-0.52). Patients diagnosed with regional, SEER-staged III (regional) cancer were less likely to receive chemotherapy if they lived in rural areas more than 20 miles away from the nearest provider (OR =0.08; 95% CI, 0.01-0.72). However, we found no evidence of association between chemotherapy receipt and distance to the nearest provider for regional cancer patients living in urban areas and those living in rural areas within 20 miles from the nearest chemotherapy provider. Distance to provider may be an obstacle to chemotherapy for some groups of low-income colon cancer patients. Relieving travel burdens of rural patients living far from providers may help Medicaid increase guideline-consistent adjuvant care for regional cancer patients.


Corpus callosotomy: clinical and electroencephalographic effects.
Six persons (five male, one female), 15-41 years of age (mean, 23 years), with medically intractable epilepsy for 7-35 years (mean, 15 years) underwent total corpus callosum section (anterior commissure to posterior commissure) for treatment of seizures resulting in falls and injuries. Preoperative EEGs demonstrated two or more morphologically distinct interictal discharges, at least one of which was generalized. Generalized ictal EEG discharges were documented in all cases to account for the clinical seizures resulting in injury. A comparison of generalized epileptiform discharges in comparable states of arousal pre- and postoperatively demonstrated a statistically significant (p less than 0.05) reduction of generalized discharges after surgery. Postoperative observation periods have ranged from 10 to 30 months (mean, 17.6 months) and have documented a statistically significant (p less than 0.05) decrease in the number of falling seizures (means: preoperative, 23.2 seizures/month; postoperative, 0.7 seizures/month). A statistically significant difference in pre- and postoperative total (generalized and focal) interictal discharges was not demonstrated. Long-term, clinically apparent complications of surgery did not occur in our patients. Thus, sectioning of the corpus callosum interrupts generalized epileptiform discharges (as documented by the postoperative EEG) and usually results in a significant decrease in generalized seizures.


Food-Induced Increase of Acetylcholine in Mouse Hypothalamus.
Using microdialysis in C57Bl6 mice, we monitored cholinergic activity in the hypothalamus. Food intake after an overnight fast caused a 3-fold increase of extracellular acetylcholine (ACh) concentrations in the hypothalamus. The effect lasted for about 30 min. Food containing no calories (kaolin pellets), or food that was presented but not accessible, also increased ACh release. In contrast, injections of glucose or β-hydroxybutyrate did not change extracellular ACh. Mice deficient in muscarinic M3 receptors had the same cholinergic response as wild-type mice. We conclude that the increase of ACh in the hypothalamus was not caused by local detection of nutrients but by anticipation of food intake. This suggests the involvement of motivational circuits in the basal forebrain which is reinforced by the fact that we found slight increases of ACh in the nucleus accumbens during feeding.


Involvement of DNA in Gel Formation of Scallop (Patinopecten yessoensis) Male Gonad Hydrolysates and Corresponding Hybrid Gel with κ-Carrageenan.
Involvement of DNA in gelation and microstructural properties of scallop (Patinopecten yessoensis) male gonad hydrolysates (SMGHs) and corresponding hybrid gel with κ-carrageenan (SMGHs/κ-C) was studied using DNase pretreatment. Although DNase pretreatment significantly transformed SMGHs from weak gels to liquid, it made SMGHs have a superior synergistic effect on gel formation with κ-C by evidence of 2.7-fold G' and 1.1-fold melting temperature. However, the relaxation time (T21 and T23), functional groups, and flocculation behavior were comparable between SMGHs/κ-C and SMGHs/DNase/κ-C. Moreover, SMGHs/DNase/κ-C exhibited a denser network with more numerous patches and larger void spaces. These results suggest that DNA contributes to the gel formation of SMGHs whereas restricts more cationic peptides in SMGHs to bind sulfate groups in κ-C during gel formation.


Design and psychometric evaluation of the Psychological Adaptation to Genetic Information Scale.
To develop and psychometrically evaluate the Psychological Adaptation to Genetic Information Scale (PAGIS). A cross-sectional, Web-based survey of participants (n=323) recruited via Internet electronic mailing lists or Websites for people affected by genetic diseases. Item analysis, confirmatory principal components analysis, and internal consistency reliability using Cronbach's alpha were used to construct the 26-item PAGIS. Five factors (nonintrusiveness, support, self-worth, certainty, and self-efficacy) explained 57.7% of the variance in psychological adaptation to genetic information. The internal consistency reliability of the total PAGIS was .90, and the subscale reliabilities ranged from .77 to .87. Psychological adaptation to genetic information is a multidimensional phenomenon comprised of nonintrusiveness, support, self-worth, certainty, and self-efficacy. The PAGIS has initial reliability and validity for use in future research.


Khat chewing among students of higher education in Jazan region, Saudi Arabia: prevalence, pattern, and related factors.
(1) To estimate the prevalence and behavioral patterns of Khat chewing and (2) to investigate factors that influenced the pattern of Khat use among undergraduate students in different higher education institutions in Jazan region, Saudi Arabia. A cross-sectional study using a pretested structured self-administered quantitative questionnaire was used to collect data. SPSS version 17 software program was used for data analysis. The overall current Khat chewing prevalence among higher education students was found to be 23.1%, significantly higher among males at 38.5% than among females at 2.1% (P < 0.001). Lifetime Khat chewer students were 24.8% for males at 40.5%, significantly higher compared with females at 3.7% (P < 0.001). Univariate analysis revealed that the gender of student, smoking status of student, a friend's smoking, and Khat chewing were associated with a significant high risk of Khat chewing (P < 0.001 for all). The use of Khat trend is increasing among higher education students in Jazan region. A multilevel, value based, comprehensive, and strategic long-term intervention plan is needed. The comprehensive plan may include social interventions geared by creating recreations alternatives and opportunities for youth and a critical review for current authorities' interventions and services.


Mitochondrial genome of Protobothrops mucrosquamatus (Squamata: Viperidae: Crotalinae).
Protobothrops mucrosquamatus is the endangered snake that is distributed in southwestern China and other adjacent countries of Asia. We determined the complete mitochondrial genome of P. mucrosquamatus. The circle genome with the total length of 17,233 bp contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 control regions. Overall base composition of the complete mtDNA was 32.98% A, 25.17% T, 29.19% C and 12.67% G. All the genes in P. mucrosquamatus were distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes that were encoded on the L-strand.


Highly Conductive Polyoxanorbornene-Based Polymer Electrolyte for Lithium-Metal Batteries.
This present study illustrates the synthesis and preparation of polyoxanorbornene-based bottlebrush polymers with poly(ethylene oxide) (PEO) side chains by ring-opening metathesis polymerization for solid polymer electrolytes (SPE). In addition to the conductive PEO side chains, the polyoxanorbornene backbones may act as another ion conductor to further promote Li-ion movement within the SPE matrix. These results suggest that these bottlebrush polymer electrolytes provide impressively high ionic conductivity of 7.12 × 10-4 S cm-1 at room temperature and excellent electrochemical performance, including high-rate capabilities and cycling stability when paired with a Li metal anode and a LiFePO4 cathode. The new design paradigm, which has dual ionic conductive pathways, provides an unexplored avenue for inventing new SPEs and emphasizes the importance of molecular engineering to develop highly stable and conductive polymer electrolytes for lithium-metal batteries (LMB).


Pure ion current collection in ion sensitive probe measurement with a metal mesh guard electrode for evaluation of ion temperature in magnetized plasma.
This paper presents a new design of ion sensitive probe (ISP) that enables collection of pure ion current for accurate measurement of the perpendicular ion temperature in magnetized plasmas. The new type of ISP resolves a longstanding issue widely observed in ISP type measurements, namely, that the current-voltage characteristic is smeared by an unexpected electron current in the standard ISP model. The new ISP is equipped with a fine scale metal mesh on the sensor entrance to prevent electrons from flowing to the sensor, a phenomenon considered to be caused by the space-charge effect. The new ISP successfully measured the ion temperature of electron cyclotron resonance plasmas.


Activation of phosphatidylinositol 3-kinase by membrane localization of p110alpha predisposes mammary glands to neoplastic transformation.
Phosphatidylinositol 3-kinases (PI3K) constitute important regulators of various signaling pathways with relevance in cancer. Enhanced activation of p110alpha, the catalytic subunit of PI3K, was found in a high proportion of many human tumor types. We generated a mouse model in which PI3K is activated by forced recruitment of p110alpha to the membrane. Different transgenic lines expressing myristoylated p110alpha protein under the control of the epithelial-specific mouse mammary tumor virus promoter were selected according to different levels of PI3K activity and characterized. Delayed mammary gland involution and morphologic changes of the mammary ducts could be detected in young transgenic female mice. These changes were more pronounced in old animals, especially in mutiparous females, in which we observed increased ductal branching, alveolar hyperplasia, and intraductal neoplasia. We also observed a small percentage of mammary tumors. Crosses of myrp110alpha transgenic mice with heterozygous p53(+/-) knockout mice resulted in neither enhanced tumorigenesis nor in a stronger mammary gland phenotype. However, the CDK4 activating mutation (R24C) lead to increased tumorigenesis in transgenic myrp110alpha mice, emphasizing the postulated perturbation of the interaction of the CDK4/Rb/E2F cascade and the PI3K signaling in many human cancers. Interestingly, in tumors of myrp110alpha transgenic mice, we observed an increased phosphorylation of the estrogen receptor-alpha, a typical feature of human breast cancer. The model presented here will help to discover additional factors which influence the progression of preneoplastic lesions to tumors in the mammary gland and to explore antitumor therapies based on PI3K or estrogen receptor-alpha pathway inhibition.


Levels of glucose-regulatory hormones in patients with non-islet cell tumor hypoglycemia: including a review of the literature.
Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II. The hormone profile data of 15 patients with NICTH from published case reports were reviewed and included in the analyses. Mean plasma glucose levels (36 vs. 29 mg/dL), serum IRI (0.53 vs. 0.37 μIU/mL), CPR (0.15 vs. 0.20 ng/mL), IGF-I SDS (-3.55 vs. -3.18 SD) and ACTH levels (27.3 vs. 33.8 pg/mL) were not significantly different between the big and normal IGF-II groups. However, mean serum GH (0.85 vs. 9.62 ng/mL) and plasma cortisol levels (16.2 vs. 34.5 μg/dL) were significantly lower in the big IGF-II group than in the normal IGF-II group (both p<0.05). In conclusion, although the magnitude of the decrease in insulin and IGF-I levels did not differ between spontaneous hypoglycemic patients caused by other etiologies, patients with NICTH tended to have low basal GH levels during hypoglycemic episodes. These differences in hormone profile may be helpful for selecting patients who require analysis of IGF-II.


Rat liver thiol proteinases: cathepsin B, cathepsin H and cathepsin L.
Data on following points of lysosomal thiol proteinases (cathepsins B, H and L) from rat liver are described in this paper: Partial amino acid sequence of cathepsin B, substrate specificity of cathepsin L, immunological studies of cathepsin B and H and effectiveness of E-64, specific thiol proteinase inhibitor in vivo.


Thermosalient effect of a naphthalene diimide and tetrachlorocobaltate hybrid and changes of color and magnetic properties by ammonia vapor.
An organic-inorganic hybrid metal halide (OIMH), namely the electron-deficient naphthalene diimide (NDI) and [CoCl4]2- hybrid (1), showed potential as a sensor for ammonia and amines, in addition to magnetic changes upon vapochromism. Crystal 1 exhibited thermosalient behavior such as leaping and movement, at around 130 °C, which could be explained to be associated with the removal of water molecules from the crystal lattice as shown by TGA and DSC. Compound 1 changed from green to black within 5 minutes when exposed to ammonia vapor, which was attributed to the radical formation in the NDI moiety as evidenced by ESR, and this phenomenon was preserved even when other mono- and di-alkylamines were applied. The exposure of 1 to ammonia resulted in a subsequent color alteration, progressing from black to a gradually dark orange after one day (1_NH3_1 day). This transformation was concomitant with the formation of [Co(NH3)6]3+ from [CoCl4]2-, leading to a modification of the magnetic properties from paramagnetic Co(II) (S = 3/2) to diamagnetic Co(III) (S = 0). Based on these findings, compound 1 represents the first example of an OIMH that exhibits thermosalient behaviour, color change, and magnetic conversion upon exposure to ammonia.


Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat.
A novel peptide called ghrelin or motilin-related-peptide (MTLRP) was found in the stomach of various mammals. We studied its effect on the motor function of the rat gastrointestinal tract. In normal, conscious unoperated animals, ghrelin/MTLRP (5 or 20 microg/kg iv) significantly accelerated the gastric emptying of a methylcellulose liquid solution (gastric residue after 15 min: 57 +/- 7, 42 +/- 11, 17 +/- 4, and 9 +/- 3% of the ingested meal with doses of 0, 1, 5, and 20 microg/kg iv, respectively) Transit of the methylcellulose liquid solution was also accelerated by ghrelin/MTLRP in the small intestine but not in the colon. Des-[Gln(14)]ghrelin, also found in the mammalian stomach, was as potent as ghrelin in emptying the stomach (gastric residue after 15 min: 12 +/- 3% at a dose of 20 microg/kg iv). In rats in which postoperative gastrointestinal ileus had been experimentally induced, ghrelin/MTLRP (20 microg/kg iv) reversed the delayed gastric evacuation (gastric residue after 15 min: 28 +/- 7% of the ingested meal vs. 82 +/- 9% with saline). In comparison, the gastric ileus was not modified by high doses of motilin (77 +/- 7%) or erythromycin (82 +/- 6%) and was only partially improved by calcitonin gene-related peptide (CGRP) 8-37 antagonist (59 +/- 7%). Ghrelin/MTLRP, therefore, accelerates the gastric emptying and small intestinal transit of a liquid meal and is a strong prokinetic agent capable of reversing the postoperative gastric ileus in rat.


Challenges to the development of the trauma system in Egypt.
Trauma is a hidden disease in Egypt, and its significance on public health has been underestimated for decades. Road traffic accidents are the leading cause of injuries presented to hospitals in Egypt. Trauma systems in developed countries effectively reduced the morbidity and mortality associated with injuries in crowded cities. Developing a trauma system in Egypt is mandatory with the exploding population growth, increasing incidence of injuries, and the vast expansion of the infrastructures in the road network. However, the implementation of the trauma system in Egypt will not be devoid of challenges, including a lack of mandatory healthcare infrastructures such as adequate pre-hospital care, poor quality of data, and a shortage of adequately trained emergency physicians across the country.


Cardiac function during vagus escape.
It is generally believed that the stimulation of vagus nerve has no direct effect on ventricular myocardium. But recent work has demonstrated clear-cut negative inotropic effect of vagal stimulation on ventricles. In an attempt to study further the effect of vagal stimulation on heart, 15 dogs were studied hemodynamically under nembutal anaesthesia. Bilateral vagotomy caused 9% elevation of heart rate whereas arterial pressure and cardiac output increased by 5% and 3% respectively. Stroke volume output decreased by 8%. Stimulation of the cut peripheral end of vagus caused cardiac standstill followed by vagus escape. During the steady state of vagus escape there was marked reduction in arterial pressure, heart rate and cardiac output, but the stroke volume was significantly elevated above the mean control. These findings suggest that when heart rate decreases, the stroke volume increases in order to restore the decreased cardiac output and that this happens inspite of the negative inotropic effect of vagal stimulation. Thus the Frank-Starling mechanism has a very significant role in an intact organism with normal hemodynamics.


Regulation of the proliferation of spermatogonial stem cells.
The proliferating cells in the seminiferous epithelium can be subdivided into the (morphologically) undifferentiated and the differentiating spermatogonia. In turn the undifferentiated spermatogonia can be subdivided according to their topographical arrangement into clones consisting of one cell, the A-single (As) spermatogonia, two cells, the A-paired (Apr) spermatogonia or groups of 4, 8 or 16 cells, the A-aligned (Aal) spermatogonia. Most likely the As spermatogonia are the stem cells of spermatogesis. When these cells divide their daughter cells can either migrate away from each other and become two new stem cells or stay together as Apr spermatogonia. The Apr spermatogonia can divide further to form Aal spermatogonia. Although suggestions have been made for the existence of a class of long-cycling stem cells with a higher probability for self-renewal, all cell kinetic data are still compatible with a homogeneous population of stem cells, the proliferative activity of which varies during the cycle of the seminiferous epithelium. Radiobiological studies have revealed that the radiosensitivity of the stem cells varies with their proliferative activity and that there is no particular class of radioresistant stem cells. In both rat and Chinese hamster the cell cycle time of the undifferentiated spermatogonia appeared to be much longer than that of the differentiating spermatogonia. All types of undifferentiated spermatogonia have the same minimum cell cycle time. However, the As spermatogonia, the stem cells, generally divide after longer intervals. The proliferative activity of the undifferentiated spermatogonia varies during the cycle of the seminiferous epithelium. At a certain moment during the epithelial cycle the undifferentiated spermatogonia, including the stem cells, are stimulated to proliferate. After a period of active proliferation the Apr and Aal spermatogonia are arrested in G1 phase possibly by the production of a chalone by the differentiating spermatogonia. In both rat and Chinese hamster the As spermatogonia are less sensitive towards this inhibition and continue to proliferate for some time longer. In the normal epithelium the probability of self-renewal of the stem cells varies with their proliferative activity in such a way that is low during active proliferation. In the normal epithelium there appeared to be no regulatory mechanism to ensure an even density of the stem cells. A large variation in stem cell density was found between areas. However, after heavy cell loss, for example after irradiation, the probability of self-renewal was found to be close to 100%. In primates the undifferentiated spermatogonia are composed of the so-called Ap and Ad spermatogonia.(ABSTRACT TRUNCATED AT 400 WORDS)


The immunocompetence of Schwann cells.
Schwann cells are the myelinating glial cells of the peripheral nervous system that support and ensheath axons with myelin to enable rapid saltatory signal propagation in the axon. Immunocompetence, however, has only recently been recognized as an important feature of Schwann cells. An autoimmune response against components of the peripheral nervous system triggers disabling inflammatory neuropathies in patients and corresponding animal models. The immune system participates in nerve damage and disease manifestation even in non-inflammatory hereditary neuropathies. A growing body of evidence suggests that Schwann cells may modulate local immune responses by recognizing and presenting antigens and may also influence and terminate nerve inflammation by secreting cytokines. This review summarizes current knowledge on the interaction of Schwann cells with the immune system, which is involved in diseases of the peripheral nervous system.


Control of Recombination Directionality by the Listeria Phage A118 Protein Gp44 and the Coiled-Coil Motif of Its Serine Integrase.
The serine integrase of phage A118 catalyzes integrative recombination between attP on the phage and a specific attB locus on the chromosome of Listeria monocytogenes, but it is unable to promote excisive recombination between the hybrid attL and attR sites found on the integrated prophage without assistance by a recombination directionality factor (RDF). We have identified and characterized the phage-encoded RDF Gp44, which activates the A118 integrase for excision and inhibits integration. Gp44 binds to the C-terminal DNA binding domain of integrase, and we have localized the primary binding site to be within the mobile coiled-coil (CC) motif but distinct from the distal tip of the CC that is required for recombination. This interaction is sufficient to inhibit integration, but a second interaction involving the N-terminal end of Gp44 is also required to activate excision. We provide evidence that these two contacts modulate the trajectory of the CC motifs as they extend out from the integrase core in a manner dependent upon the identities of the four att sites. Our results support a model whereby Gp44 shapes the Int-bound complexes to control which att sites can synapse and recombine.IMPORTANCE Serine integrases mediate directional recombination between bacteriophage and bacterial chromosomes. These highly regulated site-specific recombination reactions are integral to the life cycle of temperate phage and, in the case of Listeria monocytogenes lysogenized by A118 family phage, are an essential virulence determinant. Serine integrases are also utilized as tools for genetic engineering and synthetic biology because of their exquisite unidirectional control of the DNA exchange reaction. Here, we identify and characterize the recombination directionality factor (RDF) that activates excision and inhibits integration reactions by the phage A118 integrase. We provide evidence that the A118 RDF binds to and modulates the trajectory of the long coiled-coil motif that extends from the large carboxyl-terminal DNA binding domain and is postulated to control the early steps of recombination site synapsis.


The role of experiential avoidance in the early stages of an online mindfulness-based intervention: Two mediation studies.
Objectives There is evidence to suggest that only 2-4 weeks of mindfulness-based interventions (MBIs) can already alleviate emotional stress. The current studies sought to examine whether experiential avoidance mediated the effects of MBIs on emotional distress during an early stage of the intervention. Methods: Chinese participants with high emotional distress were recruited. Study 1 included 324 participants, randomly assigned to an online MBI (N = 171) or a control group (N = 153). Experiential avoidance and general emotional distress were measured at baseline and after the 3rd week of the intervention. Study 2 included 158 participants, randomly assigned to an online MBI (N = 79) or a control group (N = 79). Experiential avoidance and emotional distress were measured at baseline and weekly in the first three weeks. Results: Compared to the control group, experiential avoidance and emotional distress were significantly improved in the MBI group during the first three weeks of the intervention (Cohen's d = 0.22-0.63). Moreover, changes in experiential avoidance mediated the effects of MBI on emotional distress in the early stage in both contemporary and lagged mediation models. Discussion: Experiential avoidance is an important mediator during the early-stage of MBIs for alleviating emotional distress.


Making the clock tick: the transcriptional landscape of the plant circadian clock.
Circadian clocks are molecular timekeepers that synchronise internal physiological processes with the external environment by integrating light and temperature stimuli. As in other eukaryotic organisms, circadian rhythms in plants are largely generated by an array of nuclear transcriptional regulators and associated co-regulators that are arranged into a series of interconnected molecular loops. These transcriptional regulators recruit chromatin-modifying enzymes that adjust the structure of the nucleosome to promote or inhibit DNA accessibility and thus guide transcription rates. In this review, we discuss the recent advances made in understanding the architecture of the Arabidopsis oscillator and the chromatin dynamics that regulate the generation of rhythmic patterns of gene expression within the circadian clock.


Seronegative Sjögren Syndrome: A Forgotten Entity?
As a highly varied disease, Sjögren syndrome (SS; also termed Sjögren disease) is estimated to affect 0.01% to 0.72% of the population, with an overwhelming bias toward the female gender.1 SS causes a significant burden to the quality of life of patients and inhibits their function.


Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis.
Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphologically benign appearance. In the previous study, we reported LAM-associated lymphangiogenesis and implicated its role in the progression of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lymphatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retroperitoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical [1 of 5] and axillary [0 of 5]). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.


[Principles of the hygienic standardization of extraneous substances (food additives and admixtures) in food products].
At the root of hygienic standardization of extraneous substances on the ground toxicological experimentation there lies the notion of the noxious action threshold and of the maximum permissible concentration of the substance (MPC). The influence of diverse environmental factors of low intensity on man should not bring forth even temporary disturbances of the homeostasis, including the reproductive function, as well as the strain on defensive and adaptive compensatory mechanisms during the whole of the life span. There arises the need for elaborating indicators that might characterize the "viability" of the organism, or, in other words, the possibility of its performing all the functions that are inherent in a given species. In setting up a biological experiment the maximum attention should be concentrated on integral tests and behavioral reactions that reflect general processes proceeding in the organism, as well as on utilization of "functional loads" that reveal the physiological reliability, on a study of late after-effects at all stages marking the development of the species, but, especially, on bearing in mind the possibility of emerging teratogenic properties. Much study still requires the problem of "indirect" toxic effect of extraneous substances and also of a stringent recording of the food ration for the test animals, which plays an important part in the protection, or, conversely, the debiliation of the organism.


Twelve tips for delivering successful interprofessional case conferences.
Interprofessional case conferences (ICCs) offer an interactive, practical way to engage members of two or more health professions in discussions that involve learning and working together to improve patient care. Well-orchestrated ICCs provide opportunities to integrate interprofessional (IP) education into routine clinical practice. The authors provide 12 tips to support the conceptualization, planning, implementation, facilitation, evaluation, and sustainability of ICCs. They draw from extensive experience as IP educators and facilitators of ICCs and from literature on IP education, case-based learning, small-group facilitation, peer-assisted learning, and learner engagement - all of which offer insights into ICCs but have not been integrated and applied to this context.


[Acute hemolysis with subsequent life-threatening pancreatitis in hemodialysis. A complication which is not preventable with current dialysis equipment].
A retrospective study was undertaken of 14 patients (eleven men, three women; mean age 52 [33-68] years in whom haemolysis had occurred during chronic haemodialysis (n = 12) or haemofiltration (n = 2). The haemolysis was of mechanical cause in eight patients, by an osmotic mechanism in one, and of unknown cause in five. Cardinal symptoms were nausea in 14 patients, abdominal pain in nine, vomiting in eight and raised blood pressure in ten. The plasma was discoloured in all patients and there was also an increase in free haemoglobin (110-2400 mg/dl) and (or) lactate dehydrogenase (311-7403 U/l). In all of eleven patients in whom it was measured the activity of serum amylase and (or) lipase was more than doubled (to 73-2400 U/l and 473-16,740 U/l, respectively). All patients were treated symptomatically, three had a blood exchange, two others plasma separation. Eight patients recovered within a few days, but necrotizing pancreatitis developed in six, three of whom died while two had permanent sequelae. This series shows that dialysis-induced acute haemolysis can cause life-threatening pancreatitis. Narrowings within the extracorporeal circuit, not always recognized in current dialysis equipment, are the most frequent cause of the mechanical haemolysis.


The Marmara earthquake: admission laboratory features of patients with nephrological problems.
Earthquakes are major causes of morbidity and mortality. North-western Turkey was struck by a devastating earthquake in August 1999, which caused several thousand deaths. Among the most important morbid events in survivors were acute nephrological problems. Within the first week of the disaster, specific questionnaires asking about 63 clinical and laboratory parameters were sent to 35 reference hospitals that were treating the victims. Of the registered 639 victims, 423 were admitted within the first 3 days of the disaster; the admission laboratory data of these 423 patients are the subject of this analysis. In the 423 patients (233 males, mean age 31.3+/-14.4 years), time under the rubble was 10.7+/-10.4 h. Mean values at admission were as follows: serum potassium 5.4+/-1.3 mEq/l, creatine phosphokinase 58205+/-77889 IU/l, albumin 2.6+/-0.7 g/dl, phosphorus 5.2+/-1.8 mg/dl, haematocrit 35.0+/-9.3%, leukocyte count 14945+/-6614/mm(3), platelet count 183975+/-134012/mm(3), blood urea nitrogen 55.1+/-28.9 mg/dl, and creatinine 3.9+/-2.3 mg/dl. Serum potassium above 6.5 mEq/l was noted in 91 patients (22.7%), an alarming finding for risk of fatal arrhythmias. Non-survivors were characterized by higher figures of serum potassium (P=0.001), as well as lower haematocrit (P=0.028), platelets (P<0.001), and serum albumin (P=0.003). In a multivariate analysis model of admission laboratory parameters, serum creatinine (P<0.001, o.r.=2.19), potassium (P=0.001, o.r.=3.64), and phosphorus (P=0.004, o.r.=1.78) predicted dialysis needs, whereas serum albumin (P=0.028, o.r.=0.23) and creatinine (P=0.039, o.r.=0.60) were related to mortality. Admission laboratory data may be useful for predicting dialysis needs and survival chance of disaster victims. High incidences of some life-threatening abnormalities dictate the need for empirical therapy even in the field.


Preserved cognitive skills in dementia of the Alzheimer type.
To describe preserved cognitive skills in patients with dementia. Case series. Community clinic. Five patients who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and were claimed to retain a cognitive skill. None. Standard neuropsychological tests and individualized measures of patient's skilled behaviors. For patients who remained skilled at games, performance was compared with that of normal controls in direct competition. For the patient-trombonist, raters compared premorbid and postmorbid recordings of his play. One patient continued to play the trombone in a Dixieland band, although he could not name well-known numbers that he played. Another continued to solve adult jigsaw puzzles. A third patient retained skill at canasta, the fourth at dominoes. The fifth patient remained a skillful contract bridge player, although he could not name the suits or articulate simple bidding rules. Four patients had impaired performance on standard anterograde and remote memory and naming tests but performed normally on pursuit rotor and letter fluency tests. Mini-Mental State Examination scores for these patients ranged from 10 to 22. One patient refused neuropsychological testing but displayed his skill. Together with previous studies of preserved piano playing or painting skills, our findings indicate that a broad range of complex cognitive abilities may be preserved in patients with dementia of the Alzheimer type who cannot perform simpler actions.


One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus and canine kobuvirus.
To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 102.1 TCID50 for CDV, 101.9 TCID50 for CPV and 103 copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.


[The Study of Surgical Outcome for Robotic-Assisted Laparoscopic Radical Prostatectomy : Experience of a Single Surgeon with 70 Initial Cases].
We investigated the surgical outcome for robotic-assisted laparoscopic radical prostatectomy (RALP) withinitial 70 prostate cancer cases performed by a single surgeon between June 2014 and May 2016. The surgeon had a previous experience of more than 400 cases of laparoscopic radical prostatectomy (LRP). Comparative study of the surgical outcome was made between the first 35 patients (group 1) and the second 35 patients (group 2). The console time without lymph node dissection significantly decreased from group 1 to 2 (193 min vs 158 min, p=0.002). Among specific 3 parts of the console operation (part 1 : until the bladder neck transection, part 2 : until the prostate removal and part 3 : urethrovesical anastomosis), duration of parts 1 and 2 similarly decreased witha significant difference of 0. 001 and 0. 002, respectively. Continence recovery rates 1 month after RALP were significantly higher in group 2 than in group 1 (group1 : 48.5% vs group 2 : 74.2%, p=0.02). Between groups 1 and 2, the positive surgical margin rates of both pT2 and pT3 were similar (group 1 : 20. 8 and 50. 0%, group 2 : 17. 2 and 50. 0%, respectively). The perioperative 8 complications (11.4%) were classified into Clavien-Dindo grades 1 and 2. Our surgical outcome of initial 70 RALP cases was considered as comparable to that reported from the high volume centers.


Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable - epidemiology, diagnostics and treatment.
This review presents an overview of the most important rodent-borne hemorrhagic fever pathogens directly transmitted from rodents to humans, namely Leptospira and hantaviruses, together with the New- and Old-World arenaviruses. These zoonotic diseases frequently share clinical symptoms, transmission routes and other epidemiological features and often have an emerging pattern. Differential diagnostics could benefit from a syndrome-based approach grouping these pathogens. In this review extensive descriptions of the epidemiology, clinical symptoms, diagnostics and treatment are provided including a practical overview, listing clinical features, diagnostics and risk factors for each selected rodent-borne hemorrhagic fever pathogen.


Population history of north Africa: evidence from classical genetic markers.
After an intensive bibliographic search, we compiled all the available data on allele frequencies for classical genetic polymorphisms referring to North African populations and synthesized the data in an attempt to reconstruct the populations' demographic history using two complementary methods: (1) principal components analysis and (2) genetic distances represented by neighbor-joining trees. In both analyses the main feature of the genetic landscape in northern Africa is an east-west pattern of variation pointing to the differentiation between the Berber and Arab population groups of the northwest and the populations of Libya and Egypt. Moreover, Libya and Egypt show the smallest genetic distances with the European populations, including the Iberian Peninsula. The most plausible interpretation of these results is that, although demic diffusion during the Neolithic could explain the genetic similarity between northeast Africa and Europe by a parallel process of gene flow from the Near East, a Mesolithic (or older) differentiation of the populations in the northwestern regions with later limited gene flow is needed to understand the genetic picture. The most isolated groups (Mauritanians, Tuaregs, and south Algerian Berbers) were the most differentiated and, although no clear structure can be discerned among the different Arab- and Berber-speaking groups, Arab speakers as a whole are closer to Egyptians and Libyans. By contrast, the genetic contribution of sub-Saharan Africa appears to be small.


A New Chinese Medicine Intestine Formula Greatly Improves the Effect of Aminosalicylate on Ulcerative Colitis.
Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon. Current medical treatment of UC relies predominantly on the use of traditional drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which failed to effectively control this disease's progression and produced various side effects. Here, we report a new Chinese medicine intestine formula (CIF) which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In the present study, 60 patients with chronic UC were treated with oral mesalazine alone or in combination with CIF enema. The combination of mesalazine and CIF greatly and significantly improved the clinical symptoms and colon mucosal condition and improved the Mayo Clinic Disease Activity Index and health-related quality of life, when compared to mesalazine alone. In particular, the addition of CIF further decreased serum levels of tumor necrosis factor-alpha and hypersensitivity C-reactive protein but in contrast increased interleukin-4. Thus, the results demonstrate the beneficial role of CIF in UC treatment, which may be mediated by the regulation of inflammation.


Randomized Phase 3 Trial of Ombitasvir/Paritaprevir/Ritonavir and Ribavirin for Hepatitis C Virus Genotype 2-Infected Japanese Patients.
In Japan, hepatitis C virus (HCV) genotype (GT) 2 accounts for approximately 32% of HCV infections. Limited treatment options exist in Japan for HCV GT2-infected patients. GIFT-II was a phase 3, randomized, open-label study evaluating the efficacy and safety of 16- and 12-week regimens of co-formulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus ribavirin (RBV) in Japanese adults with HCV GT2 infection. Patients were randomized in a 1:1 ratio to once-daily, co-formulated OBV/PTV/r (25/150/100 mg) with weight-based RBV for 16 or 12 weeks. The primary efficacy endpoint was the sustained virologic response at 12 weeks post-treatment (SVR12) rate in the primary efficacy population of non-cirrhotic treatment-naive patients. A total of 171 patients were randomized to OBV/PTV/r + RBV. In the primary efficacy population, SVR12 rates were 91.5% (43/47; 95% confidence interval 83.5-99.5%) and 75.0% (36/48; 95% confidence interval 62.8-87.2%) in the 16-week arm and 12-week arm, respectively. No patient in the 16-week arm relapsed by post-treatment week 12. Among non-cirrhotic treatment-experienced patients, the overall SVR rate in the 16-week arm was 75.8% (25/33) and was highest [93.8% (15/16)] among those who had relapsed after previous interferon-based therapy. SVR12 rates were consistently higher in patients with HCV GT2a infection versus HCV GT2b infection [16-week treatment arm: 93.9% (31/33) versus 85.7% (12/14) and 93.8% (15/16) versus 56.3% (9/16) among non-cirrhotic treatment-naive and treatment-experienced patients, respectively]. No patient discontinued treatment because of an adverse event. The most common adverse events were anemia, increased blood bilirubin, and nasopharyngitis. OBV/PTV/r + RBV for 16 weeks resulted in high SVR12 rates in non-cirrhotic Japanese patients infected with HCV GT2 who were treatment-naive or who had relapsed after an interferon-based therapy. Higher SVR12 rates were observed among patients with HCV GT2a infection versus those with GT2b infection. This regimen demonstrated a favorable safety profile. ClinicalTrials.gov identifier, NCT02023112. AbbVie.


Ethnic variations regarding clinical profiles and symptom representation in prisoners with psychotic disorders.
Black and minority ethnic (BME) groups are known to have higher prevalences of psychotic disorders and are over-represented in western penitentiaries and forensic psychiatric institutions. Research from regular mental healthcare settings suggests that they could show different and more severe psychotic symptoms. Aims To explore ethnic variations in severity of symptomatology of BME and non-BME detainees with psychotic disorders. In this study, 824 patients with psychotic disorders from seven different ethnic groups, imprisoned in a penitentiary psychiatric centre in the Netherlands, were compared on symptom severity and symptom representation using the BPRS-E clinical interview. Data were analysed by means of a multilevel analysis. BME patients with psychotic disorders are over-represented in forensic psychiatry, and symptom profiles of prisoners with psychotic disorders vary by ethnicity. Additionally, severity levels of overall psychopathology differ between ethnic groups: patients with an ethnic majority status show more severe levels of psychopathology compared with BME patients. There are differences in symptom severity and symptom profiles between BME patients and non-BME patients. Disregarding these differences could have an adverse effect on the outcome of the treatment. Possible explanations and clinical impact are discussed. Declaration of interest None.


A twisted hand: bHLH protein phosphorylation and dimerization regulate limb development.
Saethre-Chotzen syndrome (SCS), a human autosomal dominant condition with limb defects and craniosynostosis, is caused by haploinsufficiency of TWIST1, a basic helix-loop-helix (bHLH) transcription factor. Until recently, the molecular pathogenesis of the limb defects in SCS has not been well understood. Now, Firulli et al.1 show in mouse and chick that ectopic expression of a related bHLH protein, Hand2, results in phenocopies of the limb defects caused by Twist1 loss-of-function mutations. These two proteins interact in a dosage-dependent antagonistic manner, and both can be regulated through phosphorylation at conserved helix I amino acid residues. These findings provide an important link between the misregulation of Twist1 dimerization and the limb phenotypes observed in SCS.


[Determination of ciprofloxacin in human serum by high-performance liquid chromatography].
A high-performance liquid chromatography method was developed for the rapid determination of ciprofloxacin in human serum. After protein precipitation, chromatographic separation of ciprofloxacin in plasma was achieved with an octyl column and 20 mmol/L phosphate buffer, methanol and acetonitrile 76/12/12 (v/v/v), pH 4, as mobile phase. Quantitative determination was monitored on a fluorescence detector using an excitation and emission wavelength of 278 and 450 nm, respectively. Enrofloxacin was used as internal standard. Calibration curve is linear over the range 0,12 to 20 microg/mL (r=0,9992). Limit of detection and limit of quantification are 0,04 and 0,12 microg/mL, respectively. Within-day coefficient of variation (2,0 to 3,1 %) and day-to-day coefficient of variation (4,3 to 5,5 %) at three different concentrations are sufficient. Relative recovery ranged from 91,1 to 94,0 % at three different concentrations. Each analysis requires no longer than 7 min.


Rank-dependent deactivation in network evolution.
A rank-dependent deactivation mechanism is introduced to network evolution. The growth dynamics of the network is based on a finite memory of individuals, which is implemented by deactivating one site at each time step. The model shows striking features of a wide range of real-world networks: power-law degree distribution, high clustering coefficient, and disassortative degree correlation.


Aminothienopyridazines as imaging probes of tau pathology: a patent evaluation of WO2013090497.
Small-molecule ligands, amenable to positron emission tomography (PET) imaging of different types of neurodegenerative disease-associated amyloid deposits in the CNS of living patients, hold considerable promise for diagnostic purposes, as well as for monitoring disease progression and the effectiveness of treatments. The patent entitled 'Heterocyclic Compounds as Imaging Probes of Tau Pathology' (WO2013090497) discloses the identification of a novel class of tau imaging agents, the aminothienopyridazines. Selected compounds from this class are described that can stain selectively tau pathology in brain tissue sections. Moreover, examples of this class of compounds exhibit absorption, distribution, metabolism, excretion and pharmacokinetics (ADME-PK) properties that are appropriate for CNS PET ligands.


Solitary Fibrous Tumor of the Vagina with Potentially Malignant Features: A Case Report and Review of the Literature.
Extrapleural solitary fibrous tumors are being increasingly reported. The retroperitoneum, deep soft tissues of the proximal extremities, abdominal cavity, trunk, head and neck are among the most common extraserosal locations reported. A recurrent solitary fibrous tumor involving the vagina of a 25-year-old woman is reported. Microscopically, the tumor was hypercellular and composed of mitotically active spindle cells. Immunohistochemically, the tumor cells were positive for vimentin, CD34, and bcl-2. Four cases of solitary fibrous tumors involving the vagina have been reported previously. To the best of our knowledge, this is the first case with clinical and histological features suggestive of a malignant behavior.


JAK kinase targeting in hematologic malignancies: a sinuous pathway from identification of genetic alterations towards clinical indications.
Constitutive JAK-STAT pathway activation occurs in most myeloproliferative neoplasms as well as in a significant proportion of other hematologic malignancies, and is frequently a marker of poor prognosis. The underlying molecular alterations are heterogeneous as they include activating mutations in distinct components (cytokine receptor, JAK, STAT), overexpression (cytokine receptor, JAK) or rare JAK2 fusion proteins. In some cases, concomitant loss of negative regulators contributes to pathogenesis by further boosting the activation of the cascade. Exploiting the signaling bottleneck provided by the limited number of JAK kinases is an attractive therapeutic strategy for hematologic neoplasms driven by constitutive JAK-STAT pathway activation. However, given the conserved nature of the kinase domain among family members and the interrelated roles of JAK kinases in many physiological processes, including hematopoiesis and immunity, broad usage of JAK inhibitors in hematology is challenged by their narrow therapeutic window. Novel therapies are, therefore, needed. The development of more selective inhibitors is a questionable strategy as such inhibitors might abrogate the beneficial contribution of alleviating the cancer-related pro-inflammatory microenvironment and raise selective pressure to a threshold that allows the emergence of malignant subclones harboring drug-resistant mutations. In contrast, synergistic combinations of JAK inhibitors with drugs targeting cascades that work in concert with JAK-STAT pathway appear to be promising therapeutic alternatives to JAK inhibitors as monotherapies.


Simultaneous bilateral total hip arthroplasties do not lead to higher complication or allogeneic transfusion rates compared to unilateral procedures.
About 20 % of patients undergoing a primary total hip arthroplasty could undergo a second contralateral procedure within five years. The possibility to perform simultaneous bilateral hip replacements instead of two-stage surgery could reduce hospitalisation time and patient management costs, but concerns exist because of risks related to massive blood loss and possible increase in complication rates. The purpose of this study is to assess the veracity of these concerns. Parameters like blood loss, transfused blood units, total hospital length of stay (surgical and rehabilitation) and presence of in-hospital complications were collected from surgery reports of two different groups of patients. The first group comprised patients undergoing simultaneous bilateral total hip arthroplasty (n = 63), while the second group consisted of patients undergoing unilateral surgery (n = 97). Occurrence of complications within six post-operative months was assessed by phone interview. No differences were observed in complication, revision and mortality rates between the study groups. On the contrary, blood loss was significantly higher in the bilateral group, but the application of appropriate transfusion protocols reduced the use of allogeneic blood transfusion to the levels recorded for unilateral patients. Moreover, the difference in length of hospital stay (about two days) between the two groups was not clinically relevant. Our data show that simultaneous bilateral procedures do not lead to higher complication or allogeneic transfusion rates in comparison to unilateral hip replacement, and that, in cases of bilateral disease, they could significantly reduce the total length of hospital stay and, therefore, patient management costs.


A comparative study of releasing and nonreleasing human basophils: nonreleasing basophils lack an early component of the signal transduction pathway that follows IgE cross-linking.
Basophils from approximately one fifth of the population were found to be unresponsive (nonreleasers), in terms of both histamine and leukotriene release, to an IgE cross-linking stimulus, such as anti-IgE antibody. Although unresponsive to any IgE-mediated stimulation, these basophils responded to non-IgE-mediated stimuli, such as the phorbol ester, 12-o-tetradecanoyl phorbol-13 acetate, the calcium ionophore, A23187, and to formyl-methionyl-leucyl-phenylalanine peptide. These stimuli produced equal dose-response curves in both releaser (basophils able to respond with greater than 5% histamine release to anti-IgE antibody) and nonreleaser basophils. Nonreleaser basophils possessed statistically similar densities of cell-surface IgE antibody (287,000 versus 400,000 IgE molecules per basophil for releaser and nonreleaser basophils, respectively), and with 12-o-tetradecanoyl phorbol-13 acetate as a probe of anti-IgE-induced cross-linking, the IgE on nonreleaser basophils was found to be cross-linked by the polyclonal anti-IgE antibody used for these studies. Interleukin-3 (IL-3) has previously been demonstrated to enhance markedly both histamine and leukotriene release in human basophils. However, IL-3 was unable to convert nonreleasing basophils into releasing basophils, as measured by anti-IgE antibody. IL-3 equivalently enhanced formyl methionine peptide-induced release in both releaser and nonreleaser basophils, suggesting that the lack of an effect on anti-IgE-induced release was not due to a lack of IL-3 receptors. Although there are several possible interpretations of these data, these results and results of our previous studies of protein kinase C activation and cytosolic Ca++ elevations in human basophils suggest that nonreleasing basophils have a defect in early signal transduction, possibly involving the influx of Ca++.


Mixing of the immiscible: hydrocarbons in water-ice near the ice crystallization temperature.
Structural changes in hydrocarbon-doped water-ice during amorphous to crystalline phase conversion are investigated using polycyclic aromatic hydrocarbons (PAHs) as probes. We show that aggregation of impurity molecules occurs due to the amorphous-crystalline transition in ice, especially when they are hydrophobic molecules such as PAHs. Using ultraviolet-visible (UV-vis), Fourier-transform Infrared (FTIR), and laser-induced-fluorescence (LIF) spectroscopic techniques, we show that, although ice infrared absorption features change from a broad structureless band corresponding to amorphous ice to a sharp structured crystalline ice bands, simultaneously, sharper isolated PAH UV absorption features measured in the amorphous ice host turn broad upon ice crystallization. A simultaneous decrease in the monomer fluorescence and increase in the excimer emission band is observed, a clear indication for the formation of PAH molecular aggregates when amorphous ice is converted to crystalline ice at higher temperatures. Similar to the irreversible amorphous-crystalline phase transitions, the UV, fluorescence, and excimer emissions indicate that PAHs undergo irreversible aggregation. Our studies suggest that organic impurities exist as aggregates rather than monomers trapped in crystalline water-ice when cycled through temperatures that convert amorphous ice to crystalline ice, rendering a better insight into phenomena such as the formation of cometary crust. This aggregate formation also may significantly change the secondary reaction pathways and rates in impurity-doped ices in the lab, on Earth, in the solar system, and in the interstellar medium.


Capturing the semantic relationship between clinical terms with current MeSH bibliographic coding.
This paper compares bibliographic retrieval using current MeSH (Medical Subject Headings) to bibliographic retrieval using explicitly coded semantic relationships between index terms. In a previous study, ten lists of abstracts, each list containing 20-40 papers discussing a specific pair of terms, were analyzed to identify the specific relationship(s) between those terms discussed in each paper. In the present study, we analyze how well current MeSH coding using topical subheadings and check tags, can selectively retrieve those papers discussing each semantic relationship.


Automated retinal imaging and trend analysis - a tool for health monitoring.
Most current diagnostic devices are expensive, require trained specialists to operate and gather static images with sparse data points. This leads to preventable diseases going undetected until late stage, resulting in greatly narrowed treatment options. This is especially true for retinal imaging. Future solutions are low cost, portable, self-administered by the patient, and capable of providing multiple data points, population analysis, and trending. This enables preventative interventions through mass accessibility, constant monitoring, and predictive modeling.


Osteogenic differentiation of bone marrow mesenchymal stem cells on the collagen/silk fibroin bi-template-induced biomimetic bone substitutes.
Biomimetic bone substitutes of collagen-silk fibroin/hydroxyapatite (COL-SF/HA) were synthesized via a bi-template-induced coassembly strategy. Collagen-hydroxyapatite (COL-HA) and silk fibroin-hydroxyapatite (SF-HA) served as controls were prepared with similar method. The osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) seeded onto the resulting materials was evaluated both in vitro and in vivo. The results suggested that the bi-template-induced biomimetic substitutes were able to support the growth and proliferation of BMSCs. We further demonstrated that BMSCs were stimulated to differentiate into the osteoblast cell lineage by evaluating several specific osteogenic markers including staining of alkaline phosphate (ALP) and calcium nodular and expression of osteogenic genes of osteocalcin (OCN) and osteonectin (ONN). The rat femoral defect model was used to assess the aforementioned biomimetic bone substitutes combined with BMSCs in vivo. Histological analysis indicated that the bi-template material exhibited good biocompatibility and strong ability of the new bone formation in comparison with the control of single-template material in vivo.


A comparison between "Cronholm-Ottosson depression rating scale" and variables concerned with depressive symptomatology in "the comprehensive psychopathological rating scale--CPRS".
In a study concerning 40 patients with depressive disorders the Cronholm-Ottosson depression rating scale and items concerning symptomatology from the Comprehensive Psychopathological Rating Scale--CPRS were compared. The total scores scales showed a rather satisfactory correlation (rs - 0,77). When patients were divided into two groups with depressive syndromes of a psychotic and non-psychotic dimension respectively the total scores of the items from CPRS from CPRS differed significantly for the groups while the total scores for the Cronholm-Ottosson depression rating scale showed a less pronounced, statistically non-significant difference between the groups, probably reflecting a reduced validity for the latter scale.


Pharmacological targeting of the integrated protein kinase B, phosphatase and tensin homolog deleted on chromosome 10, and transforming growth factor-beta pathways in prostate cancer.
Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is much desired. Central to this goal is the development of novel targeted pharmacological interventions. To develop these treatment strategies, an understanding of the integration of cellular pathways involved in both tumorigenesis and tumor suppression is crucial. Of further interest are the events elicited by drug treatments that exploit the underlying molecular pathology in cancer. This review briefly describes the evidence that suggests integration of three established pathways: the tumorigenic phosphoinositide 3-kinase/protein kinase B (AKT) pathway, the tumor suppressive phosphatase and tensin homolog deleted on chromosome 10 pathway, and the tumor suppressive transforming growth factor-beta pathway. More importantly, we discuss novel pharmaceutical agents that target key points of integration in these three pathways. These new therapeutic strategies include the use of agents that target iron to inhibit proliferation via multiple mechanisms and suppression of AKT by cytosolic phospholipase A(2)-alpha inhibitors.


Calcium kinetics in male white-tailed deer.
Calcium kinetic analysis was combined with calcium balance data on two 2-year-old and two 4-year-old male white-tailed deer. There were three 10-day trials. Trial 1, February 3-13, was conducted after velvet shedding. Trial 2, May 26-June 5, was conducted after about a month of slow antler growth. Trial 3, August 18-28, was conducted shortly before velvet shedding, after the peak of antler growth. Significant differences (P less than 0.05) between trials 1 and 2 included increased calcium absorption and fractional calcium absorption from the intestine. Skeletal resorption decreased, resulting in an increased calcium balance. Significant differences (P less than 0.05) between trials 1 and 3 included increased skeletal accretion and total calcium flow into the pool. Nonsignificant differences (P greater than 0.05) between trials 2 and 3 included decreased average intestinal calcium absorption and increased skeletal resorption resulting in a decreased calcium balance. The younger deer had nonsignificantly lower (P greater than 0.1) endogenous fecal and significantly lower (P less than 0.1) urinary calcium excretions. The younger deer also maintained higher fractional absorption rates from the intestine than the older deer. The percent decrease in skeletal resorption and increase in calcium balance was greater in the younger deer between trials 1 and 2 and between trials 1 and 3.


Biomaterials used for tissue engineering of barrier-forming cell monolayers in the eye.
Cell monolayers that form a barrier between two structures play an important role for the maintenance of tissue functionality. In the anterior portion of the eye, the corneal endothelium forms a barrier that controls fluid exchange between the aqueous humor of the anterior chamber and the corneal stroma. This monolayer is central in the pathogenesis of Fuchs endothelial corneal dystrophy (FECD). FECD is a common corneal disease, in which corneal endothelial cells deposit extracellular matrix that increases the thickness of its basal membrane (Descemet's membrane), and forms excrescences (guttae). With time, there is a decrease in endothelial cell density that generates vision loss. Transplantation of a monolayer of healthy corneal endothelial cells on a Descemet membrane substitute could become an interesting alternative for the treatment of this pathology. In the back of the eye, the retinal pigment epithelium (RPE) forms the blood-retinal barrier, controlling fluid exchange between the choriocapillaris and the photoreceptors of the outer retina. In the retinal disease dry age-related macular degeneration (dry AMD), deposits (drusen) form between the RPE and its basal membrane (Bruch's membrane). These deposits hinder fluid exchange, resulting in progressive RPE cell death, which in turn generates photoreceptor cell death, and vision loss. Transplantation of a RPE monolayer on a Bruch's membrane/choroidal stromal substitute to replace the RPE before photoreceptor cell death could become a treatment alternative for this eye disease. This review will present the different biomaterials that are proposed for the engineering of a monolayer of corneal endothelium for the treatment of FECD, and a RPE monolayer for the treatment of dry AMD.


Diel shifts in carboxylation pathway and metabolite dynamics in the CAM bromeliad Aechmea 'Maya' in response to elevated CO2.
The deployment of temporally separated carboxylation pathways for net CO(2) uptake in CAM plants provides plasticity and thus uncertainty on how species with this photosynthetic pathway will respond to life in a higher-CO(2) world. The present study examined how long-term exposure to elevated CO(2) influences the relative contributions that C(3) and C(4) carboxylation make to net carbon gain and to establish how this impacts on the availability of carbohydrates for export and growth and on water use efficiency over the day/night cycle. Integrated measurements of leaf gas exchange and diel metabolite dynamics (e.g. malate, soluble sugars, starch) were made in leaves of the CAM bromeliad Aechmea 'Maya' after exposure to 700 micromol mol(-1) CO(2) for 5 months. There was a 60 % increase in 24-h carbon gain under elevated CO(2) due to a stimulation of daytime C(3) and C(4) carboxylation in phases II and IV where water use efficiency was comparable with that measured at night. The extra CO(2) taken up under elevated CO(2) was largely accumulated as hexose sugars during phase IV and net daytime export of carbohydrate was abolished. Under elevated CO(2) there was no stimulation of dark carboxylation and nocturnal export and respiration appeared to be the stronger sinks for carbohydrate. Despite the increased size of the soluble sugar storage pool under elevated CO(2), there was no change in the net allocation of carbohydrates between provision of substrates for CAM and export/respiration in A. 'Maya'. The data imply the existence of discrete pools of carbohydrate that provide substrate for CAM or sugars for export/respiration. The 2-fold increase in water-use efficiency could be a major physiological advantage to growth under elevated CO(2) in this CAM bromeliad.


Providers of antenatal care services in Ghana: evidence from Ghana demographic and health surveys 1988-2014.
Antenatal care is one of the three most essential care - antenatal, delivery and post-natal, given to women during pregnancy and has the potential to contribute towards the achievement of the Sustainable Development Goal (SDG) target 3.1- reducing the global maternal mortality ratio to less than 70 per 100,000 and target 3.8 - achieve universal health coverage. The main objective is to examine the contribution of the various providers of antenatal care services in Ghana from 1988 to 2014. The study uses data from all the six rounds of the Ghana Demographic and Health Survey (GDHS). Binary logistic regression models were applied to examine the association between background characteristics of respondents and providers of antenatal care services. The results show that majority of antenatal care services were provided by nurses over the period under review. The proportion of women who received antenatal care services from nurses improved over the period from 55% in 1988 to 89.5% in 2014. Moreover, there was a decline in antenatal care services provided by traditional birth attendants and women who did not receive antenatal care services from any service provider over the years under review. It was observed that women from rural areas were more likely to utilise antenatal care services provided by traditional birth attendants, whilst those from urban areas were more likely to utilise antenatal care from doctors and nurses. To further improve access to and utilisation of antenatal care services provided by nurses and doctors it is recommended that the Ghana Health Service and the Ministry of Health should put in place systems aimed at improving on the quality of care given such as regular training workshops for health personnel and assessment of patient's satisfaction with services provided. Also, they should encourage women in rural areas especially those from the savannah zone to utilise antenatal care services from skilled providers through social and behaviour change communication campaigns.


[Epidemiological utilization of hospital data. Incidence of tumors of the bladder in the Province of Vercelli in the decade 1972-1981].
A descriptive epidemiology study carried out with the purpose of assessing the incidence of malignant bladder cancer in the province of Vercelli is reported. 833 hospitalised cases were observed in the period 1972-1981. Incidence rates were calculated on the resident population at the date of the last two national censuses. Sex, patient age and distribution in the three areas into which the province is subdivided are illustrated and discussed and trend in incidence rates in the two five-year periods 1972-1976 and 1977-1981 reported. The standardised rates are compared with those of the provinces of Turin and Varese.


Using choice to increase on-task behavior in individuals with traumatic brain injury.
An ABA'B design was used to evaluate the effects of choice on task engagement for 3 adults who had been diagnosed with traumatic brain injury. A yoked-control condition, in which tasks that were selected by each participant were assigned subsequently to that participant by a trainer, was implemented to help distinguish between the effects of task preference and choice. The results for all 3 participants indicated that permitting individuals to choose from a list of tasks increased on-task behavior.


Paracetamol allergy in clinical practice.
Paracetamol is a widely used analgesic to which hypersensitivity reactions are rare. Reactions to paracetamol may be due to the pharmacological effects of cyclooxygenase-1 inhibition or, more rarely, due to a selective allergy against paracetamol. This article aims to review the current literature in the context of two cases seen in the authors' allergy practice. Paracetamol allergy is uncommon and, as a result, may be overlooked as a cause for immediate hypersensitivity, which can lead to a significant delay in diagnosis. Currently, specialist referral for a supervised oral challenge is required for formal diagnosis.


Photo-Electro-Thermal Model and Fuzzy Adaptive PID Control for UV LEDs in Charge Management.
Inertial sensors can serve as inertial references for space missions and require charge management systems to maintain their on-orbit performance. To achieve non-contact charge management through UV discharge, effective control strategies are necessary to improve the optical power output performances of UV light sources while accurately modeling their operating characteristics. This paper proposes a low-power photo-electro-thermal model for widely used AlGaN-based UV LEDs, which comprehensively considers the interaction of optical, electrical, and thermal characteristics of UV LEDs during low-power operations. Based on this model, an optical power control system utilizing a fuzzy adaptive PID controller is constructed, in which a switch is introduced to coordinate the working state of the controller. Thus, the steady-state performance is effectively improved while ensuring dynamic performance. The results show that the proposed model has an average prediction error of 5.8 nW during steady-state operations, and the fuzzy adaptive PID controller with a switch can reduce the fluctuation of light output to 0.67 nW during a single discharge task, meeting the charge management requirements of high-precision inertial sensors.


Detection of leptospires in tissue using an immunoperoxidase staining procedure.
An immunoperoxidase technique for the localisation of leptospires in sections of formalin fixed paraffin embedded kidney tissue is described. The procedure utilises a two-layered antibody sandwich with rabbit anti-leptospiral immunoglobin. Using antiserum to specific leptospiral serovars the presence and distribution of specific serovar in the tissue could be determined. The technique was also used to detect leptospires of given serovars in smears made from infected tissues and fluids. There was good correlation between culture results and results of the immunoperoxidase staining method on kidneys infected with leptospires. The diagnostic possibilities of the technique on formalin fixed tissue specimens are discussed.


Thoracic and lumbar spine trauma.
The thoracic and lumbar regions of the spine have unique anatomic and biomechanical features that result in different characteristic patterns of injury. This article reviews common injuries to the thoracic and lumbar spine and emphasizes the relationship between anatomic features and characteristic patterns of injury. An approach to imaging of the trauma patient is presented, focusing on detection and classification of spinal injuries.


The human genes for complement components 6 (C6) and 9 (C9) are closely linked on chromosome 5.
We have used a cDNA probe for human complement component 9 (C9), which detects three DNA polymorphisms, to analyse the inheritance of C9 in families informative for C6 protein variants. We found that these genes are closely linked with a lod score of 9.28 at recombination fraction 0.00. There is not indication of allelic association.


Quest for quality prize.
Abington (Pa.) Memorial Hospital won this year's American Hospital Quest for Quality Prize for its patient safety program, which aims to head off harm when errors occur.


[Modern fertility technologies: challenges for psychosomatic anthropology].
In the present paper the topic is considered on the basis of homologous in-vitro fertilization, taking homologous test-tube fertilization as representative of other fertilization methods. The first part of the article considers a number of obvious forms of damage and symptoms, the second the simplified anthropology on which medical fertilization methods are based and the challenge--arising from this--to develop a new psychosomatic anthropology, crystallized in the paradigm of the advent of a child.


Waking electroencephalogram activity as a consequence of sleep and total sleep deprivation in the rat.
Effects of 6 hours of total sleep deprivation (TSD) by gentle handling and 6 hours of sleep on the waking electroencephalogram (EEG) activity of 14 Wistar rats were studied during the lights-on portion of the light-dark cycle under two TSD schedules: a) TSD 0800-1400 hours and sleep 1400-2000 hours, and b) sleep 0800-1400 hours and TSD 1400-2000 hours. EEG was recorded monopolarly from left and right parietals referred to ipsilateral reference electrodes. Spectral analysis was performed on samples of waking EEG during TSD (each 30 minutes) and during sleep (each 60 minutes after enforced awakening). The following significant changes were observed: TSD induced a linear increase in the absolute power of delta (1.46-3.42 Hz) and the full band (1.6-24.9 Hz) and produced a decrease in the interparietal correlation of theta. Sleep induced the opposite results. Theta relative power (power in a band expressed as a percentage of total power between 1.46 and 24.9 Hz) showed a circadian effect. It was higher at 1400 hours than at 0800 and 2000 hours after both sleep and TSD conditions. Six hours of TSD were enough to induce significant changes in the waking EEG regardless of position of TSD in the lights-on period of the light-dark cycle.


[The heart and doping].
Doping is becoming an everyday problem in sports medicine. Its main feature is its universality: it concerns all sports, even the most unexpected, from cycling to billiards; all countries are affected with certain continental preferences with regards to the substances used; it is seen in all levels of competition, both in amateurs and professionals. Doping is observed early on, even in childhood. Many substances are used and they are increasingly available: all bodily functions are targeted: cerebral, metabolic, cardiovascular, respiratory, haematological and, in the near future, genetic. Detection of doping is difficult and unpredictable in a legislative environment which is gradually improving. The different modes of action of the doping substances often target the cardiovascular system, especially with regards to their potential complications: hypertension, arrhythmias, thrombosis, coronary artery and peripheral artery diseases and also cardiomyopathies. Every cardiologist should therefore be aware of the problem, even outside the context of sport, as it may impact on daily cardiological practice.


[New opportunities, MRI biomarkers in the evaluation of head and neck cancer].
Magnetic resonance imaging (MRI) has developed rapidly during the past few years and, according to the needs of therapy, has opened new perspectives in oncologic imaging with better and better realization of the latest technological advances. After the introduction of "organ preservation" protocols the role of imaging has become more important. New therapeutic methods (improvement in radiation therapy and chemotherapy) need better tumor characterization and prognostic information along with the most accurate anatomical information. Multiparametric anatomical and functional MR imaging (MM-MRI) using high magnetic field strength (3 Tesla) are useful in determining tumor-specific MRI biomarkers and in evaluating the changes in these parameters during therapy to provide early assessment of the therapeutic response. Diffusion-weighted MRI (DW-MRI) provides information at the cellular level about cell density and the integrity of the plasma membrane. DW-MRI shows potential in improving the detection of cancer due to its high specificity and high negative predictive value. Quantification is performed using an apparent diffusion coefficient (ADC), the values are independent of the magnetic field strength. In the latest publications the accuracy of DW-MRI has been reported around 90% for the differentiation between malignant versus benign tumor using an ADC cut-off mean value of 0.700-1.200 10(-3) mm(2)/s units, but no common threshold ADC value exists in clinical routine for the differentiation of malignant and benign tissues. Dynamic contrast-enhanced MRI (DCE-MRI), as a marker of angiogenesis, provides information about vascularization at the tissue level. Angiogenetic alterations cause changes in the parameters of vascular physiology (perfusion, blood volume, capillary permeability) and thus alter the contrast enhancement observed on contrast MRI. High-grade and/or advanced stage tumors are associated with increased blood volume, increased permeability and increased perfusion; the data can be evaluated using semiquantitative or quantitative methods. Magnetic resonance spectroscopic imaging (MRSI) provides biochemical analysis at the molecular level. The results are promising, although further studies are required to determine whether MRSI can be used to identify or exclude cancer within regions where the cancer is not evident on conventional MRI or with the other functional imaging methods. Some of the studies demonstrated the usefulness of these functional MRI methods also in the head and neck region to differentiate benign from malignant tumors, to quantify the response to radiation therapy and chemotherapy, to identify residual or recurrent tumor and to correlate the perfusion or diffusion data with prognosis. There are still some overlaps between benign and malignant changes, and the use of these functional MR measurements in routine diagnostics are still not fully validated today. Functional MR measurements are useful parts of the high quality multiparametric MRI, they offer important supportive biological and molecular information with the aid of high resolution morphological imaging.


[Study of bone mesenchymal stem cells tropism for hepatic tumors and effect on the form of tumor stromal].
To investigate the tropism capacity of the rat bone mesenchymal stem cells (BMSC) for hepatic tumors microenvironment and the effect on the form of tumor stromal. Rat BMSC were isolated, cultured and expanded, then incubated with superparamagnetic iron oxide (SPIO) nanoparticles. Prussian blue stain was performed for showing intracellular irons. Walker-256 cells were injected into the rat livers directly to establish hepatic tumor models. The experiment was divided into two experimental groups (the group venous injected with BMSC after tumors becoming mass: tail venous injected with BMSC after MR showed the presence of tumors at 6-8 days after operation and the group venous injected with BMSC before tumors becoming mass: tail venous injected with BMSC when MR showed no presence of tumors at 3 days after operation) and one control group. To the experimental groups animals, MRI was made before venous injection of BMSC and at 5, 10, 15 days after BMSC transplantation. The rats were killed at corresponding period. The pathologic examinations were analyzed, including HE, Prussian blue stain. The expression of vascular endothelial growth factor (VEGF), CD31, von Willebrand factor (vWF) in the specimens harvested at 10 days after BMSC transplantation were detected immunohistochemically. Prussian blue staining of SPIO labeled BMSC demonstrated cells could be effectively labeled and the labeling efficiency was almost 90%. After BMSC transplantation, two experimental groups were showed tuberculous signal intensity loss at the margin of tumors on T(2) weighted MR images at 5, 10 days after transplantation and the signal intensity loss was not visualized at 15 days after transplantation. The control group was not observed signal intensity decrease. Prussian blue staining of histological analysis showed blue-stained iron particles distributed at the margin of tumor at 5, 10, 15 days after transplantation. Immunohistochemical examination showed that the expression of VEGF, CD31, vWF in two experimental groups at 10 days after transplantation were higher than that in the control group (F = 34.03, P < 0.01; F = 84.24, P < 0.01; F = 7.08, P < 0.05). Rat BMSC have the ability to migrate towards hepatic tumors in vivo and promote to form vascular endothelium.


Baseline susceptibility of Mediterranean strains of Trialeurodes vaporariorum (Westwood) to cyantraniliprole.
Cyantraniliprole is a novel anthranilic diamide insecticide that acts on a broad spectrum of insect pests, exclusively by activating their ryanodine receptors. Cyantraniliprole is very effective against whitefly and it presents a favorable ecotoxicological profile. In this study, the baseline susceptibility to cyantraniliprole of Trialeurodes vaporariorum populations from the Mediterranean area was established in nymphal systemic uptake bioassays. The bioassay data showed that the susceptibility to cyantraniliprole varied among the strains collected across the Mediterranean basin. The 50% lethal concentration (LC50 ) range of cyantraniliprole for 16 field populations was from 0.017 to 0.194 mg L-1 , a 11.4-fold natural variability between the least and most sensitive populations. These LC50 values are similar to those reported in a previous study of the use of cyantraniliprol against another species of whitefly, Bemisia tabaci [LC50 = 0.048 (0.034-0.063) mg L-1 ]. The current study confirmed the effectiveness of cyantraniliprole against T. vaporarioum strains, adding to the evidence that cyantraniliprole is a promising tool for use in integrated pest management programs. Future shifts in the susceptibility of whitefly field populations to cyantraniliprole may be documented according to the baseline susceptibility range of the populations tested in this research. © 2018 Society of Chemical Industry.


[Cost-effectiveness and budget impact of ivabradine in heart failure therapy].
Cost-effectiveness of ivabradine was assessed by the National Institute for Health and Clinical Excellence (NICE) in 2012, based on the data derived from the SHIFT trial: NICE considered ivabradine cost-effective for treating chronic heart failure, supporting drug reimbursement by the national healthcare system (NHS). The aim of this study was to assess the cost-effectiveness of ivabradine on top of standard care in heart failure therapy, by adapting a Markovian model to the Italian population and organization, previously developed for submission to national regulatory bodies. The demographic and clinical characteristics of the Italian population were derived from both the SHIFT trial and the IN-HF Outcome registry (Italian real practice data). Costs were drawn from the Italian NHS information system. All analyses adopted the Italian NHS perspective. In a lifetime horizon, in the base case, our assessment confirms that adoption of ivabradine seems socially acceptable with a cost per quality-adjusted life year (QALY) of €17,434.86 (incremental cost of €2,952.85 and QALYs gained 0.21). The incremental cost/life-year gained (LYG) is €15,557.24 (LYG gained 0.24) and hospitalization costs avoided are €3,420.77 (avoided hospitalizations 0.76). A probabilistic sensitivity analysis showed that ivabradine on top of standard treatment is cost-effective in more than 87% of cases accepting a threshold of €30,000, and in more than 93% of cases with a threshold of €40,000. The results obtained for the Italian population and in the organizational context of the Italian NHS show social acceptability (cost per QALY) of ivabradine therapy in the treatment of heart failure.


Histopathological examination of spine tumors after treatment with radiosurgery.
OBJECTIVE Increased survival time after diagnosis of neoplastic disease has resulted in a gradual increase in spine tumor incidence. Radiosurgery is frequently a viable alternative to operative management in a population with severe medical comorbidities. The authors sought to assess the histopathological consequences of radiosurgery in the subset of patients progressing to operative intervention. METHODS Eighteen patients who underwent radiosurgery for spine tumors between 2008 and 2014 subsequently progressed to surgical treatment. A histopathological examination of these cases was performed. Indications for surgery included symptomatic compression fractures, radiographic instability, and symptoms of cord or cauda equina compression. Biopsy samples were obtained from the tumor within the radiosurgical zone in all cases and were permanently fixated. Viable tumor samples were stained for Ki 67. RESULTS Fifteen patients had metastatic lesions and 3 patients had neurofibromas. The mean patient age was 57 years. The operative indication was symptomatic compression in 10 cases (67%). The most frequent metastatic lesions were breast cancer (4 cases), renal cell carcinoma (3), prostate cancer (2), and endometrial cancer (2). In 9 (60%) of the 15 metastatic cases, histological examination of the lesions showed minimal evidence of inflammation. Viable tumor at the margins of the radiosurgery was seen in 9 (60%) of the metastatic cases. Necrosis in the tumor bed was frequent, as was fibrotic bone marrow. Vascular ectasia was seen in 2 of 15 metastatic cases, but sclerosis with ectasia was frequent. No evidence of malignant conversion was seen in the periphery of the lesions in the 3 neurofibroma cases. In 1 case of neurofibroma, the lesion demonstrated some small areas of remnant tumor in the radiosurgical target zone. CONCLUSIONS This case series demonstrates important histopathological characteristics of spinal lesions treated by SRS. Regions with the highest exposure to radiation appear to be densely necrotic and show little evidence of tumor growth, whereas peripheral regions distant from the radiation dosage are more likely to demonstrate viable tumor in malignant and benign neoplasms. Physiological tissue appears to be similarly affected. With additional investigation, a more homogenized field of hypofractionated radiation exposure may allow for tumor obliteration with relative preservation of critical anatomical structures.


Diuretic effect of intraventricular and intravenous infusions of noradrenaline in conscious sheep.
Infusion of noradrenaline at rates between 32-160 nmol.min-1 for 30 min into one lateral cerebral ventricle of conscious sheep caused a diuresis which was accompanied by negative solute-free water reabsorption and which lasted for 90-120 min. The range of noradrenaline infusion rates used reflects differences between individual animals in the rate of infusion necessry to cause diuresis. Intracerebroventricular (ICV) infusion of noradrenaline at half the diuretic rate caused no significant changes in urine flow. The diuresis induced by ICV noradrenaline infusion was prevented by concurrent ICV administration of the alpha-adrenergic antagonist, phentolamine, but was not prevented by concurrent ICV administration of the beta antagonist, propranolol, or by concurrent intravenous infusion of phentolamine. Intravenous infusion of noradrenaline at rates that were diuretic by ICV infusion caused a diuresis of approximately 30 min duration which coincided with the period of intravenous noradrenaline infusion. This diuresis was prevented by concurrent intravenous infusion of phentolamine. These results were interpreted as indicating that the higher rates of ICV infusion of noradrenaline caused the prolonged water diuresis by acting at a site in the brain and, thereby, inhibiting the release of endogenous vasopressin. ICV infusion of noradrenaline at all rates was followed by a reduction in mean arterial blood pressure and pulse pressure with variable changes in heart rate and by depression of the rates of renal clearance of PAH, potassium and total solute.