What Radiologist Should Know about MRI Translational Forces and Hazard: An Ex-Vivo Simulation of Retained Metallic Shrapnel.
In a country immersed in endless rounds of wars, retained metallic foreign bodies remain a significant dilemma in the daily practice of every Lebanese radiologist. When a shrapnel's hazard is of concern, the decision between performing or refusing a justified MRI exam is not always straightforward. In this small trial, we aimed to better understand the shrapnel's MRI safety by mimicking our daily practice. Five shrapnel with an incremental increase in their long axis were put in an animal flesh and then introduced into a 3 T magnetic field. The behavior of each shrapnel was concretely assessed by performing before and after magnetic field exposure CT acquisitions. Translation along the z-axis ranged from 0.9 mm to 2.8 mm. Torque angle ranged between 2.8 and 54 degrees with an average of 15.62 degrees. Shrapnel's movements in the magnetic field are not negligible during the acute phase of injury where there is no reinforcing fibroblastic reaction and invite us to reconsider the MRI safety of these metallic foreign bodies. Standard radiographs may be sufficient, but a targeted CT scan may be of better value for a confident decision for assessment of shrapnel position near viscera and major vessels.


Methods for the study of lung metabolism.
The recognition of the non-respiratory functions of the lung has led to an increased interest in pulmonary metabolism. The practical methods used to study metabolism in other tissues have all been applied to the investigation of lung metabolism. Methods fall into two groups: those used in vivo and those used in vitro after disrupting the organ or isolating it from other tissues and perfusing its circulation. Some of the methods used in vitro disturb the tissue environment in such a way as to introduce experimental artifacts which make the interpretation of results difficult. There are advantages to the use of the isolated perfused organ technique which, although it has been established for many years, has recently been improved. This method lends itself particularly well to studies of the intermediary metabolism and uptake of drugs by lung tissue. These improvements are described and the application to pulmonary drug uptake is illustrated by reference to the drug mexiletine. The relative advantages of the various methods and their applications are discussed.


Integrating a Nurse-Midwife-Led Oral Health Intervention Into CenteringPregnancy Prenatal Care: Results of a Pilot Study.
National and professional organizations recommend oral health promotion in prenatal care to improve women's oral health. However, few prenatal programs include education about oral health promotion. The objective of this study was to determine if women receiving a brief, low-cost, and sustainable educational intervention entitled CenteringPregnancy Oral Health Promotion had clinically improved oral health compared to women receiving standard CenteringPregnancy care. Women attending CenteringPregnancy, a group prenatal care model, at 4 health centers in the San Francisco Bay Area, participated in this nonrandomized controlled pilot study in 2010 to 2011. The intervention arm received the CenteringPregnancy Oral Health Promotion intervention consisting of two 15-minute skills-based educational modules addressing maternal and infant oral health, each module presented in a separate CenteringPregnancy prenatal care session. The present analysis focused on the maternal module that included facilitated discussions and skills-building activities including proper tooth brushing. The control arm received standard CenteringPregnancy prenatal care. Dental examinations and questionnaires were administered prior to and approximately 9 weeks postintervention. Primary outcomes included the Plaque Index, percent bleeding on probing, and percent of gingival pocket depths 4 mm or greater. Secondary outcomes were self-reported oral health knowledge, attitudes (importance and self-efficacy), and behaviors (tooth brushing and flossing). Regression models tested whether pre to post changes in outcomes differed between the intervention versus the control arms. One hundred and one women participated in the study; 49 were in the intervention arm, and 52 were in the control arm. The control and intervention arms did not vary significantly at baseline. Significant pre to post differences were noted between the arms with significant improvements in the intervention arm for the Plaque Index, bleeding on probing, and pocket depths 4 mm or greater. Providing brief oral health education and skills-building activities within prenatal care may be effective in improving women's oral health during pregnancy. These findings provide support for developing a full-scale randomized clinical trial of the CenteringPregnancy Oral Health Promotion intervention.


Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can occur secondary to various infectious, malignant, and autoimmune triggers in patients without a known genetic predisposition. Clinical hallmarks are prolonged fever, cytopenias, hepatosplenomegaly, and neurological symptoms, but atypical variants presenting with signs of chronic immunodeficiency are increasingly recognized. Impaired secretion of perforin is a key feature in several genetic forms of the disease, but not required for disease pathogenesis. Despite progress in diagnostics and therapy, mortality of patients with severe HLH is still above 40%. Reference treatment is an etoposide-based protocol, but new approaches are currently explored. Key for a favorable prognosis is the rapid identification of an underlying genetic cause, which has been facilitated by recent immunological and genetic advances. In patients with predisposing genetic disease, hematopoietic stem cell transplantation is performed increasingly with reduced intensity conditioning regimes. Current research aims at a better understanding of disease pathogenesis and evaluation of more targeted approaches to therapy, including anti-cytokine antibodies and gene therapy.


Comment on "Outburst flood at 1920 BCE supports historicity of China's Great Flood and the Xia dynasty".
Wu et al (Reports, 5 August 2016, p. 579) reported an enormous flood in the upper Yellow River that destroyed the Lajia Ruins. However, published research shows that the Ruins were destroyed at 3950 years before the present (B.P.) by earthquakes accompanied with mudflows, whereas the landslide-dammed lake terminated about 5650 years B.P. Various kinds of sediments with different ages were taken as evidence to verify an outburst flood.


Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy.
Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs) of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH) and lower adenosine triphosphate (ATP) levels compared to the control. Furthermore, AgNP-treated bacteria showed downregulated expression of glutathione (GSH), upregulation of glutathione S-transferase (GST), and downregulation of both superoxide dismutase (SOD) and catalase (CAT). These physiological and biochemical measurements were consistently observed in AgNP-treated bacteria, thereby suggesting that AgNPs can induce bacterial cell death. Thus, the above results represent conclusive findings on the mechanism of action of AgNPs against different types of bacteria. This study also demonstrates the promising use of nanoparticles as antibacterial agents for use in the biotechnology and biomedical industry. Furthermore, this study is the first to propose the mode of action of AgNPs against MDR pathogens isolated from goats infected with subclinical mastitis.


Superior mesenteric blood flow in man following injection of bradykinin and vasopressin into the superior mesenteric artery.
The superior mesenteric blood flow was studied with a dye-dilution technique after catheterization of the superior mesenteric artery and vein. The investigation was performed in connection with portography in 22 patients with apparently normal small bowel function. Intra-arterial injection of 5, 10 or 20 mug bradykinin was followed within one minute by an increase, on the average, of 114, 176 and 223% respectively, in the superior mesenteric blood flow. The blood flow was dose-dependent in this range. The estimated vascular resistance decreased by 52, 61 and 67%, respectively. The portal venous pressure was increased slightly after intra-arterial injection, but the pressure was unchanged after intra-portal injection. Intra-arterial injection of bradykinin causes a highly improved venous phase at superior mesenteric angiography. This may be due not only to the increased flow but to some extent also to increased capillary permeability produced by bradykinin. Intra-arterial injection of 0.125 and 0.250 IU of vasopressin decreased the superior mesenteric blood flow by 53 and 54%, respectively, within 3 minutes of the injection. The dye-dilution method used was not applicable to blood flow below a level of about 200 ml/min. Continuous infusion of 0.05 IU/min decreased the superior mesenteric blood flow by, on an average, 58%. The portal venous pressure was decreased by 25% after the intra-arterial injection, but no change in pressure was recorded after intra-portal administration. The clinical use of intra-arterial infusion of vasopressin during gastrointenstinal bleeding is discussed.


Regulation of rat liver phenylalanine hydroxylase. II. Substrate binding and the role of activation in the control of enzymatic activity.
Activation by phenylalanine and reduction by the co-factor (6R)-tetrahydrobiopterin (BH4) are required for formation of active liver phenylalanine hydroxylase. This work describes effects of the activation and redox state on substrate and effector recognition of this enzyme, it establishes relationships among the pterin and phenylalanine binding sites on the different forms of the enzyme, and it provides a quantitative description of the enzyme's presumptive regulatory and catalytic sites. BH4, 7,8-dihydrobiopterin (BH2), 6-methyltetrahydropterin, and 5-deaza-6-methyltetrahydropterin were found to bind to unactivated phenylalanine hydroxylase with a stoichiometry of 1/enzyme subunit and with hyperbolic kinetics; all appear to compete for the same binding site on the enzyme, and all appear to bind in the proximity of, but not to, the enzyme's non-heme iron. In the transition from unactivated to activated enzyme, phenylalanine and pterin binding is modified, a new site for phenylalanine is formed, and the pterin site is replaced by a site of greatly decreased affinity for BH4 and BH2, one which does not appear to recognize the dihydroxypropyl side chain of BH4 and BH2. The pterin- and phenylalanine-binding sites on activated phenylalanine hydroxylase appear to be part of the enzyme's active site. Despite large effects on substrate binding, neither chelator binding ability nor solvent accessibility of the iron are affected by activation; activation appears to affect the nearby environment of the enzyme's iron but not the iron itself. Studies of oxidized and reduced phenylalanine hydroxylase indicate that the redox state is not a major determinant of pterin and phenylalanine association with enzyme.


Atmospheric mercury in the Canadian Arctic. Part I: a review of recent field measurements.
Long-range atmospheric transport and deposition are important sources of mercury (Hg) to Arctic aquatic and terrestrial ecosystems. We review here recent progress made in the study of the transport, transformation, deposition and reemission of atmospheric Hg in the Canadian Arctic, focusing on field measurements (see Dastoor et al., this issue for a review of modeling studies on the same topics). Redox processes control the speciation of atmospheric Hg, and thus impart an important influence on Hg deposition, particularly during atmospheric mercury depletion events (AMDEs). Bromine radicals were identified as the primary oxidant of atmospheric Hg during AMDEs. Since the start of monitoring at Alert (NU) in 1995, the timing of peak AMDE occurrence has shifted to earlier times in the spring (from May to April) in recent years, and while AMDE frequency and GEM concentrations are correlated with local meteorological conditions, the reasons for this timing-shift are not understood. Mercury is subject to various post-depositional processes in snowpacks and a large portion of deposited oxidized Hg can be reemitted following photoreduction; how much Hg is deposited and reemitted depends on geographical location, meteorological, vegetative and sea-ice conditions, as well as snow chemistry. Halide anions in the snow can stabilize Hg, therefore it is expected that a smaller fraction of deposited Hg will be reemitted from coastal snowpacks. Atmospheric gaseous Hg concentrations have decreased in some parts of the Arctic (e.g., Alert) from 2000 to 2009 but at a rate that was less than that at lower latitudes. Despite numerous recent advances, a number of knowledge gaps remain, including uncertainties in the identification of oxidized Hg species in the air (and how this relates to dry vs. wet deposition), physical-chemical processes in air, snow and water-especially over sea ice-and the relationship between these processes and climate change.


Medium-term monitoring reveals effects of El Niño Southern Oscillation climate variability on local salinity and faunal dynamics on a restored oyster reef.
Human activities and regional-scale climate variability drive changes in the ecology of coastal and marine ecosystems. Ecological restoration has emerged as a best-management practice to combat habitat degradation and restore lost ecological functions. However, relatively short project monitoring timeframes have limited our understanding of the effects of interannual climate cycles on water quality and restoration dynamics. We collected measurements on a 23-ha oyster reef constructed in the Gulf of Mexico to determine the relationship between El Niño Southern Oscillation (ENSO)-driven climate variability and local salinity patterns, and to evaluate the effects of this climate variability and salinity on oyster population dynamics and faunal community composition over a medium-term (five-year) timeframe. The role of ENSO-driven climate variability on local salinity patterns (primarily from changes in precipitation and evaporation) and faunal dynamics was investigated using the Oceanic Niño Index (ONI). Salinity was negatively correlated with ONI with an approximately 4-month lag. Higher ONI values (El Niño periods) were followed by reductions in salinity, increases in oyster recruitment and density, and reductions in resident motile fauna density and species richness. Lower ONI values (La Niña periods) had higher and less variable salinities, and higher areal coverage of restoration substrates by large oysters. ENSO-driven salinity reductions in the second year after reef construction coincided with a shift in resident motile faunal community composition that was maintained despite a second strong salinity reduction in year 5. Our results indicate that it is important to expand the typical monitoring timeframes to at least five years so that resource managers and restoration practitioners can better understand how both short-term environmental variability and longer-term climate cycles can affect the outcomes of restoration actions.


Peripheral-acting benzodiazepines inhibit the growth of human melanoma cells and potentiate the antiproliferative activity of recombinant human interferons.
In this study, we evaluated the effect of a series of peripheral-acting benzodiazepines (BZDs), alone and in combination with recombinant human leukocyte (IFN-alpha A), fibroblast (IFN-beta), or immune (IFN-gamma) interferon (IFN), on the growth of human melanoma cells. Specific peripheral-acting BZDs caused a marked suppression in the proliferation of human melanoma cells. The effect on melanoma cell growth required 72 h exposure to the peripheral-acting BZDs and was not observed if the compounds were removed by 48 h. The relative potency of antiproliferative activity of a series of peripheral-acting BZDs on human melanoma cell growth did not correlate with the reported ability of these agents to bind to peripheral sites on the cell membrane of Friend erythroleukemia cells (FELC), nor did they correlate with the ability of these agents to inhibit [3H]thymidine incorporation in FELC, induce differentiation in FELC, or inhibit neurite outgrowth in nerve growth factor-treated rat pheochromocytoma (PC12) cells. The growth of human melanoma cells was also inhibited by various recombinant human IFNs, with IFN-beta displaying greater antiproliferative activity than IFN-alpha A or IFN-gamma. When the peripheral-acting BZD Ro7-3351, which displays growth inhibitory properties when used alone, was combined with IFN, the antiproliferative activity of the combination was greater than either individual compound exerted independently. The combination of IFN-beta plus Ro7-3351 was more active in suppressing HO-1 melanoma cell growth than other IFN preparations in combination with this peripheral-type BZD. Even when combined with a peripheral-acting BZD, such as Ro5-4608, which displayed only marginal antiproliferative activity against human melanoma cells when applied alone, growth suppression of the combination of this peripheral-type BZD with all three types of IFNs was more than additive. These studies suggest that specific peripheral-acting BZDs, both alone and in combination with recombinant IFNs, display novel antiproliferative activity toward human melanoma cells which may involve a different genetic locus than previously observed in other model cell culture systems.


[Improved sternotomy closure with polyester tapes and conventional wires].
In the purpose of reducing the occurrence of postoperative sternal dehiscence, improved technique of closure with supplemental use of polyester tapes was performed. To add to the conventional closure with wires, two polyester tapes were used around the body of sternum through the intercostal spaces just before approximation of sternum. The sternum was firmly fixed at the body and the tapes will prevent cut sternum by the wires and disruption of the wires themselves. In our series of recent 155 cases with this technique of closure, no sternal dehiscence occurred.


Serum IL-13 levels at diagnosis and remission in children with malignant lymphoma.
Interleukin (IL)-13 has been reported to have a role in the pathogenesis of lymphoma through recent molecular studies predominantly in adult patients. As malignant lymphomas in children differ from adult counterparts in terms of histology and response to treatment, we aimed to determine the serum IL-13 levels of patients with lymphoma; its relation with clinical-laboratory parameters and to look for any correlation of serum IL-13 levels with different prognostic factors in children. Twenty-eight patients with malignant lymphoma and 20 age-matched healthy controls were included in the study. The median serum IL-13 level at diagnosis (range 0.59-68 pg/ml, median 3.40 pg/ml) was higher than that in remission (range 0.14-12.2 pg/ml, median 1.60 pg/ml) in the HL group (p < 0.05). Remarkably, median serum IL-13 level of patients with nodular sclerosis at diagnosis was higher than those with mixed-cellularity (p < 0.05) and declined to normal limits during remission (p < 0.05). In Burkitt's lymphoma (BL) subgroup, the median (range 2.94-154 pg/ml, median 4.5 pg/ml) was high and declined to normal levels during remission (range 0.55-11.30 pg/ml, median 1.57 pg/ml) and the difference was significant (p < 0.05). In terms of prognostic factors, serum IL-13 levels were found to be associated with white blood cells counts only in HL group. Although the number of patients is limited in our study, we found that the serum IL-13 levels exhibit variances in different histopathologic groups. IL-13 might have a role in histopathogenesis of lymphoma, but seems to have no prognostic significance. Nevertheless, more molecular studies are needed to evaluate the pathogenesis of HL.


The Marchetti-Vincenzi universal bundle nail for the treatment of tibial nonunion.
The authors report the results obtained in the treatment of 9 cases of uninfected hypertrophic or atrophic nonunion of the tibial diaphysis, using the Marchetti-Vicenzi Universal Bundle Nai. Lesions consisted in the sequelae of different types of diaphyseal fractures treated by means of several surgical procedures. Former fixation material was removed in all of the cases, the tibial medullary canal was reamed, and the Marchetti-Vicenzi Universal Bundle Nail was used for internal fixation. In some cases, additional procedures were used such as Osteomuscular Decortication (DOM) according to Judet, autologous bone grafting. All of the cases healed after a mean time of 22 weeks. The authors suggest that intramedullary nailing using the universal bundle nail is a reliable and safe procedure for the treatment of uninfected tibial nonunion.


Preparation of European Public Health Professionals in the Twenty-first Century.
The public health profession in Europe has a leadership role for ensuring European's health in the twenty-first century and therefore must assume responsibility for advancing education for research and practice. Three fundamental questions are explored: (1) What are the main public health problems facing public health professionals; (2) What are their existing competencies after training; and (3) What competencies do European employers expect? The European Schools of Public Health assessed their best success to be in the field of health promotion, followed by disease prevention including identification of priority health problems, and elimination of health hazards in the community. Conversely, they see the least success in dealing with preparedness and planning for public health emergencies. From an employer's perspective, significant gaps between current and desired levels of performance at the job exist for all Essential Public Health Operations of World Health Organization. Based on prior research and recent European surveys of Schools and Departments of Public Health, the following recommendations are made, which emphasize the leadership role of the European public health community: (1) the preparation of public health professionals requires an interface between public health functions, competencies, and performance; (2) competence-based education is important and allows debates on the scope of the required education; (3) governments have to realize that the present lack of infrastructure and capacity is detrimental to the people's health; (4) as public health challenges are increasingly global, educational institutions have to look beyond the national boundaries and participate in European and global networks for education, research, and practice.


Epidemiological aspects of head lice in children attending day care centres, urban and rural schools in Uberlândia, central Brazil.
From November 1996 to March 2000, a total of 884 children between 0 and 15 years, from 11 institutions including day care centres, public urban and public rural schools in Uberlândia, State of Minas Gerais, central Brazil, were examined for head louse infestation. Children's sex, race, age and some hairs characteristics were shown to be associated to parasite infestation. A prevalence rate of 35% was found and the highest rates were observed in black, female children, with long, dark, wavy hairs. Hairs density and thickness did not seem to influence significantly the distribution of this pediculosis in Uberlândia's schoolchildren. Differences observed between the prevalence rates of head lice in children from the urban institutions suggest there is a greater epidemiological heterogeneity in this group when compared to the rural schoolchildren.


Maternal gestational diabetes mellitus and the childhood asthma in offspring: a meta-analysis.
Maternal diabetes might be related to a high risk of allergic disease in offspring. However, it remains unknown if maternal gestational diabetes mellitus (GDM) is also associated with a high incidence of childhood asthma in offspring. A systematic review and meta-analysis was performed to investigate the above association. Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library, and Web of Science. A randomized-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. The Newcastle-Ottawa Scale was used for study quality evaluation. Subgroup analyses were performed to evaluate the potential influences of study characteristics on the outcome. Ten datasets from seven moderate to high quality cohort studies, involving 523,047 mother-child pairs were included in the meta-analysis. Overall, maternal GDM was associated with a higher risk of childhood asthma in offspring (risk ratio [RR]: 1.22, 95% confidence interval [CI]: 1.07 to 1.39, p = 0.003; I2 = 30%). Subgroup analyses showed that the association was not significantly affected by study design, validation methods for GDM, or diagnostic strategy for asthma (p for subgroup analyses all > 0.05). The association between maternal GDM and asthma in offspring was more remarkable after adjusting maternal body mass index in early pregnancy (RR: 1.50 versus 1.06, p < 0.001), but significantly weakened after adjusting hypertensive disorders during pregnancy (RR: 1.08 versus 1.50, p = 0.001). Maternal GDM may be associated with an increased incidence of childhood asthma in offspring.


Xenobiotics shape the physiology and gene expression of the active human gut microbiome.
The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider interindividual variations in the active human gut microbiome.


Validation of a capillary electrophoresis method for analysis of rabeprazole sodium in a pharmaceutical dosage form.
Rabeprazole sodium is an antisecretory agent that inhibits the enzyme H+/K+ ATPase present in the stomach parietal cells. There are few data about its quantitative determinations in laboratorial routines. Capillary electrophoresis is a method being used increasingly for analysis of pharmaceutical compounds, the main advantages of which are the simplicity of instrumentation, low consumption of sample and reagents, and fast analysis. The aim of this study was to develop and validate a capillary electrophoresis method for determination of rabeprazole sodium in coated tablets. The conditions used were a bare fused silica capillary with 48.0 cm length (39.5 cm effective) and 75 microm id; a 10mM, pH 9.0, sodium tetraborate run buffer; a diode array detector set at 291 nm; hydrodynamic injection (50 mbar/5 s); and a voltage of 20 kV. HP Chemstation CE rev. A.06.03 software was used for system control, data acquisition, and analysis. The method was demonstrated to be linear in the concentration range of 5.0-40.0 microg/mL (r = 0.9993), precise (interday relative standard deviation = 0.49), accurate (mean recovery = 103.1%), and specific. The limits of detection and quantitation were 1.29 and 3.91 microg/mL, respectively.


Novel permethylated beta-cyclodextrin derivatives appended with chromophores as efficient fluorescent sensors for the molecular recognition of bile salts.
Two novel permethylated beta-cyclodextrin (PM-beta-CD) derivatives, i.e., 6I-O-(1-naphtholxy)-2I,31-di-O-methylhexakis(2II-VII,3II-VII,6II-VII-tri-O-methyl)-beta-cyclodextrin (1) and 6I-O-(8-hydroxyquinoline)-2I,31-di-O-methylhexakis(2II-VII,3II-VII,6II-VII- tri-O-methyl)-beta-cyclodextrin (2), were synthesized in satisfactory yields, and their inclusion modes, complex-induced fluorescent behaviors, binding ability, and selectivity for bile salts of biological relevance (cholic acid sodium salt, CA; deoxycholic acid sodium salt, DCA; glycochoic acid sodium salt, GCA; taurocholic acid sodium salt, TCA) were investigated by the circular dichroism, 2D NMR, steady-state, and time-resolved fluorescent spectra. The results obtained from induced circular dichroism and ROESY spectra show that the chromophore groups of 1 and 2 reside in the central cavity of PM-beta-CD, and are expelled to the region of narrow torus rim upon complexation with bile guests, which presents the binding mode of cooperative inclusion. The transfer of the chromophore groups from the central cavity to the more hydrophobic torus rim leads to the remarkable increase of fluorescent intensities and longer fluorescent lifetimes of hosts 1 and 2 upon gradual addition of bile salts, which is importantly distinct from the molecular recognition of the chromophore-modified beta-CD species with bile salts. Interestingly, hosts 1 and 2 present much stronger binding ability for bile guests than PM-beta-CD. Differing from native beta-CD, all the PM-beta-CDs are more prone to include bile salts with longer tails, such as GCA and TCA. Their corresponding binding ability and molecular selectivity are closely discussed from the viewpoints of difference of cavity size/shape between beta-CD and PM-beta-CD, effect of substituent groups, and structures of bile guests, respectively.


Activation of ADP-ribosylation factor regulates biogenesis of the ATP7A-containing trans-Golgi network compartment and its Cu-induced trafficking.
ATP7A (MNK) regulates copper homeostasis by translocating from a compartment localized within the trans-Golgi network to the plasma membrane (PM) in response to increased copper load. The mechanisms that regulate the biogenesis of the MNK compartment and the trafficking of MNK are unclear. Here we show that the architecture of the MNK compartment is linked to the structure of the Golgi ribbon. Depletion of p115 tethering factor, which causes fragmentation of the Golgi ribbon, also disrupts the MNK compartment. In p115-depleted cells, MNK localizes to punctate structures that pattern on Golgi ministacks dispersed throughout the cell. Despite altered localization MNK trafficking still occurs, and MNK relocates from and returns to the fragmented compartment in response to copper. We further show that the biogenesis of the MNK compartment requires activation of ADP-ribosylation factor (Arf)1 GTPase, shown previously to facilitate the biogenesis of the Golgi ribbon. Activation of cellular Arf1 is prevented by 1) expressing an inactive "empty" form of Arf (Arf1/N126I), 2) expressing an inactive form of GBF1 (GBF1/E794K), guanine nucleotide exchange factor for Arf1, or 3) treating cells with brefeldin A, an inhibitor of GBF1 that disrupts MNK into a diffuse pattern. Importantly, preventing Arf activation inhibits copper-responsive trafficking of MNK to the PM. Our findings support a model in which active Arf is essential for the generation of the MNK compartment and for copper-responsive trafficking of MNK from there to the PM. Our findings provide an exciting foundation for identifying Arf1 effectors that facilitate the biogenesis of the MNK compartment and MNK traffic.


Prevalence of chromosomal aberrations in Argentinean agricultural workers.
Little is known about biosecurity measures and toxic effects during pesticide application in the province of Jujuy, Argentina, particularly concerning the protective measures and mixture of pesticides used by rural workers. We carried out an observational study of agricultural workers from Jujuy (76 exposed subjects and 53 controls) to investigate the prevalence of chromosomal aberrations (CAs) in human lymphocytes as well as the activity level of acetylcholinesterase (AChE) in red blood cell erythrocytes. Whole blood samples (5 mL) were collected in heparinized Vacutainer tubes for cytogenetic analysis and erythrocyte cholinesterase activity determination according to Ellman's method. Cytogenetic results showed a significant CA increase in pesticide-exposed individuals as compared with controls (4.20 ± 0.15 vs. 1.00 ± 0.05, respectively; p < 0.001), suggesting that pesticides are clastogenic agents causing DNA damage. Erythrocyte cholinesterase activity was significantly lower in exposed individuals, evidencing the possible occurrence of perturbations in blood as well as neurotoxicity in pesticide sprayers. These results suggest the need for periodic biomonitoring of these biomarkers together with education and training of occupational workers for the safe application of potentially harmful pesticides.


Recent studies of 5-fluorouracil resistance in pancreatic cancer.
Resistance to 5-fluorouracil (5-FU), an important anticancer drug, is a serious challenge in the treatment of pancreatic cancer. Equilibrative nucleoside transporter 1 and multidrug-resistance protein (MRP) 5 and MRP8, rather than P-glycoprotein, play important roles in 5-FU transport. Thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidine phosphorylase are four key enzymes involved in 5-FU metabolism. Other metabolic enzymes, including uridine monophosphate synthetase, also contribute to chemoresistance. Intracellular signaling pathways are an integrated network, and nuclear factor kappa-light-chain-enhancer of activated B cells, AKT and extracellular signal-regulated kinases are signaling pathways that are particularly relevant to 5-FU resistance. In addition, recent reports indicate that STAT-3 is a crucial survival protein. Proteomic assays provide a powerful tool for identifying target proteins and understanding the role of microRNAs and stromal factors to facilitate the development of strategies to combat 5-FU resistance.


Does an in-house internist at a GP practice result in reduced referrals to hospital-based specialist care?
Consistent evidence on the effects of specialist services in the primary care setting is lacking. Therefore, this study evaluated the effects of an in-house internist at a GP practice on the number of referrals to specialist care in the hospital setting. Additionally, the involved GPs and internist were asked to share their experiences with the intervention. A retrospective interrupted times series study. Two multidisciplinary general practitioner (GP) practices. An internist provided in-house patient consultations in two GP practices and participated in the multidisciplinary meetings. The referral data extracted from the electronic medical record system of the GP practices, including all referral letters from the GPs to specialist care in the hospital setting. The number of referrals to internal medicine in the hospital setting. This study used an autoregressive integrated moving average model to estimate the effect of the intervention taking account of a time trend and autocorrelation among the observations, comparing the pre-intervention period with the intervention period. It was found that the referrals to internal medicine did not statistically significant decrease during the intervention period. This small explorative study did not find any clues to support that an in-house internist at a primary care setting results in a decrease of referrals to internal medicine in the hospital setting. Key Points An in-house internist at a primary care setting did not result in a significant decrease of referrals to specialist care in the hospital setting. The GPs and internist experience a learning-effect, i.e. an increase of knowledge about internal medicine issues.


Pardon the Interruption(s)-Enabling a Safer Emergency Department Sign Out.
Patient "handoffs" or "sign outs" in medicine are widely recognized as highly vulnerable times for medical errors to occur. The Emergency Department (ED) has been identified as an environment where these transitions of care at shift changes are particularly high-risk due to a variety of factors, including frequent interruptions, which can further lead to errors in transfer of information. Our primary objective was to evaluate whether simple interventions could minimize interruptions during the sign out period in an attempt to improve patient safety. Multiple low-cost interventions were implemented, including an overhead chime, clerical staff diversion of phone calls and electrocardiograms, and prominent positioning of a movable pedestal sign. Utilizing a before-and-after study design, we directly observed team sign outs at various shift changes throughout the day over 2-month periods before and after implementation. Our primary outcome measure was the number of interruptions that occurred during designated sign out times. We also assessed total time spent in sign out, and a survey was sent to clinicians to assess their perception of sign out safety. Total sign out interruptions were significantly decreased as a result of the above-noted interventions (average 6.1 vs 1.1; P < 0.01). Total time spent during sign out was reduced (14.1 vs 11.4 minutes; P < 0.04), and clinicians' perception of safety improved significantly, with Likert scores of 4 or 5 on a 5 point scale increasing from 47.4% before to 91.7% after implementation. Patient sign out at shift change is a vulnerable time for patient safety and transition of care with interruptions further compromising the safe transfer of information. Simple interventions significantly decreased interruptions and were associated with shorter sign out periods and improved provider perception of sign out safety.


Inhibition of Trypanosoma cruzi egress from infected fibroblasts is mediated by CD4+ and mu+ immune cells.
Trypanosoma cruzi, the causative agent of Chagas disease, is able to reproduce intracellularly in many host cell types while in the mammalian host. Although cellular immunity is known to be important in resistance to infection, the ability of immune cells to interfere with the completion of the intracellular growth cycle of T. cruzi has not been described. Using a tissue culture system to study the parasite growth cycle, we have found that spleen cells from infected mice are able to decrease the number of parasites released from infected fibroblasts. Spleen cells from mice infected for as few as 14 days and as long as 300 days display this inhibitory ability. Parasite egress from infected cells is inhibited by factor(s) released by immune cells during coculture with infected fibroblasts. Immune cell depletion studies indicate that the inhibitory activity requires the presence of both CD4+ T cells and mu+ B cells. These results suggest a direct ability of immune cells to somehow interfere with the completion of the intracellular cycle, and this ability may play a role in control of this parasite.


Effects of biotic and abiotic constraints on the symbiosis between rhizobia and the tropical leguminous trees Acacia and Prosopis.
N2-fixing, drought tolerant and multipurpose Acacia and Prosopis species are appropriate trees for reforestation of degraded areas in arid and semiarid regions of the tropics and subtropics. Acacia and Prosopis trees form N2-fixing nodules with a wide range of rhizobia, for example African acacias mainly with Sinorhizobium sp. and Mesorhizobium sp., and Australian acacias with Bradyrhizobium sp. Although dry and hot seasons restrict formation of N2-fixing nodules on Acacia and Prosopis spp., fully grown trees and their symbiotic partners are well adapted to survive in harsh growth conditions. This review on one hand deals with major constraints of arid and semiarid soils, i.e. drought, salinity and high soil temperature, which affect growth of trees and rhizobia, and on the other hand with adaptation mechanisms by which both organisms survive through unfavourable periods. In addition, defects in infection and nodulation processes due to various abiotic and biotic constraints are reviewed. This knowledge is important when Acacia and Prosopis seedlings are used for forestation of degraded areas in arid and semiarid tropics.


Metastatic patterns in osteosarcoma.
The clinical courses of 193 patients with high-grade, non-metastatic osteosarcoma were reviewed to ascertain the evolution of the natural history of the disease. All patients had the primary lesion in the extremities and were treated at the Rizzoli Orthopaedic Institute between 1976 and 1982 with surgery alone (30 cases) or surgery plus adjuvant chemotherapy (163 cases). All patients were regularly followed at our Institute. One hundred and fourteen patients, of which 27 were treated with surgery alone and 87 treated with adjuvant chemotherapy, developed overt metastatic disease. No differences were found concerning the sites of the first relapse which, for approximately 90% of cases, were lungs in both groups. However, in the group of patients treated with adjuvant chemotherapy the development of overt metastatic disease, as compared to non-adjuvant patients, was delayed with time (13 vs 8 months) and the number of metastatic nodules in the lung at first relapse was reduced. This alteration in metastatic pattern due to adjuvant chemotherapy is important because it allows surgical resection of pulmonary metastases in a larger number of patients (51% vs 29%).


[CpNi(dithiolene)] (and diselenolene) neutral radical complexes.
Various preparations of the neutral radical [CpNi(dddt)] complex (dddt = 5,6-dihydro-1,4-dithiin-2,3-dithiolate) were investigated with CpNi sources, [Cp2Ni], [Cp2Ni](BF4), [CpNi(CO)]2, and [CpNi(cod)](BF4), and dithiolene transfer sources, O=C(dddt), the naked dithiolate (dddt(2-)), the monoanion of square-planar Ni dithiolene complex (NBu4)[Ni(dddt)2], and the neutral complex [Ni(dddt)2]. The reaction of [CpNi(cod)](BF4) with (NBu4)[Ni(dddt)2] gave the highest yield for the preparation of [CpNi(dddt)] (86%). [CpNi(ddds)] (ddds = 5,6-dihydro-1,4-dithiin-2,3-diselenolate), [CpNi(dsdt)] (dsdt = 5,6-dihydro-1,4-diselenin-2,3-dithiolate), [CpNi(bdt)] (bdt = 1,2-benzenedithiolate), and [CpNi(bds)] (bds = 1,2-benzenediselenolate) were synthesized by the reactions of [Cp2Ni] with the corresponding neutral Ni dithiolene complexes [Ni(ddds)2]2, [Ni(dsdt)2], [Ni(bdt)2], and [Ni(bds)2], respectively. The five, formally Ni(III), radical complexes oxidize and reduce reversibly. They exhibit, in the neutral state, a strong absorption in the NIR region, from 1000 nm in the dddt/ddds/dsdt series to 720 nm in the bdt/bds series with epsilon values between 2500 and 5000 M(-1) cm(-1). The molecular and solid state structures of the five complexes were determined by X-ray structure analyses. [CpNi(dddt)] and [CpNi(ddds)] are isostructural, while [CpNi(dsdt)] exhibits a closely related structure. Similarly, [CpNi(bdt)] and [CpNi(bds)] are also isostructural. Correlations between structural data and magnetic measurements show the presence of alternated spin chains in [CpNi(dddt)], [CpNi(ddds)], and [CpNi(dsdt)], while a remarkably strong antiferromagnetic interaction in [CpNi(bdt)] and [CpNi(bds)] is attributed to a Cp...Cp face-to-face sigma overlap, an original feature in organometallic radical complexes.


The Role of Periplaneta americana (Blattodea: Blattidae) in Modern Versus Traditional Chinese Medicine.
The purpose of this review is to elaborate the role of Periplaneta (P.) americana L. in modern and traditional Chinese medicine (TCM) and compare the use of the species in these two forms of medical treatments. From searches on Google Scholar, PubMed, and Web of Science databases, studies were identified involving TCMs with P. americana, which have a history of use over several thousand years, and demonstrate how extracts from this insect play a role in the treatment of diseases through antibacterial, antiviral, antitumor activity, and enhancement of immune function. Extracts from P. americana have not been fully developed for clinical use because the active components have not been completely purified or their molecular mechanisms thoroughly understood. The development of extraction technology in modern Chinese medicine has revealed that many extracts from P. americana are able to play an important role in the control of diseases such as cancer. Drugs such as 'Kangfuxin Solution' and 'Xinmailong Injection' are now widely used for gastrointestinal ulcers and chronic heart failure, having achieved beneficial curative effects in clinical studies. Based on this, the information from studies of P. americana in TCM and modern medicine should be combined and their respective advantages applied. This review provides an overview of the role of P. americana in modern and TCM and thus contributes to identification of further applications and area requiring drug development.


Antecedent control of oral reading errors and self-corrections by mentally retarded children.
Academic behaviors can be enhanced through the manipulation of either consequent or antecedent stimuli. In this study, we evaluated the effects of manipulating two antecedent stimulus events with respect to oral reading errors and self-corrections of four mentally retarded children. Using an alternating treatments design, the effects of previewing the target text and previewing an unrelated test were evaluated against no- previewing . In the first previewing condition, the teacher discussed the target text with the children before they were required to read it orally. The same procedure was used in the other previewing condition but with the provision that an unrelated text was previewed . Oral reading errors decreased and self-corrections increased when the children previewed the target text with their teacher before reading it orally. No changes were observed as a result of implementing the other two procedures, previewing an unrelated text and no- previewing . The results, which were consistent across all four children, showed that reading proficiency can be increased by manipulating antecedent stimulus events prior to oral reading.


[The recurrence of bladder cancer in the glans and fossa navicularis of urethra following cystectomy].
A 42-year-old male was admitted to our Hospital. Diagnosis of invasive bladder cancer was made and a total cystectomy was carried out on September 14, 1982. Histological examination showed transitional cell carcinoma, grade II-III, pT2N0M0. After cystectomy, the patient was treated with a combination chemotherapy of cis-platinum, cyclophosphamide, adriamycin and 5-fluorouracil. After 3 years, he noticed an area of reddish and painless rashes around the urethral meatus. A biopsy of the skin lesion showed a nest formation of transitional cell carcinoma with lymphocyte infiltration under the squamous epithelium. A urethrectomy was carried out on January, 28, 1986. A histologic study established the diagnosis of recurrent transitional cell carcinoma. The pathological process seemed to be a result of hematogenous metastasis rather than multicentricity or implantation.


The association between childhood environmental exposures and the subsequent development of Crohn's disease in the Western Cape, South Africa.
Environmental factors during childhood are thought to play a role in the aetiolgy of Crohn's Disease (CD). However the association between age at time of exposure and the subsequent development of CD in South Africa is unknown. A case control study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous environmental exposures during 3 age intervals; 0-5, 6-10 and 11-18 years were extracted using an investigator administered questionnaire. An agreement analysis was performed to determine the reliability of questionnaire data for all the relevant variables. This study included 194 CD patients and 213 controls. On multiple logistic regression analysis, a number of childhood environmental exposures during the 3 age interval were significantly associated with the risk of developing CD. During the age interval 6-10 years, never having had consumed unpasteurized milk (OR = 5.84; 95% CI, 2.73-13.53) and never having a donkey, horse, sheep or cow on the property (OR = 2.48; 95% CI, 1.09-5.98) significantly increased the risk of developing future CD. During the age interval 11-18 years, an independent risk-association was identified for; never having consumed unpasteurized milk (OR = 2.60; 95% CI, 1.17-6.10) and second-hand cigarette smoke exposure (OR = 1.93; 95% CI, 1.13-3.35). This study demonstrates that both limited microbial exposures and exposure to second-hand cigarette smoke during childhood is associated with future development of CD.


One-Pot Synthesis of Cu-Nanocluster-Decorated Brookite TiO2 Quasi-Nanocubes for Enhanced Activity and Selectivity of CO2 Photoreduction to CH4.
A new kind of metallic Cu-loaded brookite TiO2 composite, in which Cu nanoclusters with a small size of 1-3 nm are decorated on brookite TiO2 quasi nanocube (BTN) surfaces (hereafter referred to as Cu-BTN), is synthesized via a one-pot hydrothermal process and then used as photocatalyst for CO2 reduction. It was found that the decoration of Cu nanoclusters on BTN surfaces can improve the activity and selectivity of CO2 photoreduction to CH4 , and 1.5 % Cu-BTN gives a maximum overall photocatalytic activity (150.9 μmol g-1 h-1 ) for CO/CH4 production, which is ≈11.4 and ≈3.3 times higher than those of pristine BTN (13.2 μmol g-1 h-1 ) and Ag-BTN (45.2 μmol g-1 h-1 ). Moreover, the resultant Cu-BTN products can promote the selective generation of CH4 as compared to CO due to the number of surface oxygen vacancies and the CO2 /H2 O adsorption behavior, which differs from that of the pristine BTN. The present results demonstrate that brookite TiO2 would be a potential effective photocatalyst for CO2 photoreduction, and that Cu nanoclusters can act as an inexpensive and efficient co-catalyst alternative to the commonly used noble metals to improve the photoactivity and selectivity for CO2 reduction to CH4 .


Use of traps to capture black and gold howlers (Alouatta caraya) on the Islands of the upper Paraná River, Southern Brazil.
Howlers (genus Alouatta) are widely captured with the use of anesthetic projectiles; however, no capture protocol involving the use of traps has been described to date. In the present study we describe the first efficient capture program for black and gold howlers (Alouatta caraya) using traps, which was implemented on the islands of the upper Paraná River in southern Brazil. We constructed two trap models with either manual or automatic activation (trap A with two entrances and guillotine-type doors; trap B with one entrance and a guillotine-type door). The traps were suspended in the canopy by means of vertical climbing techniques, and were baited regularly and abundantly with bananas and mangoes. We captured 70 howlers (86% using manual activation and 14% using automatic activation) on four different islands. We restrained 41 of these animals and measured their body mass, which averaged 5.30 kg+/-1.79. Given our results, we suggest that the system described in the present study represents an alternative capture program for howlers in areas that have low food diversity and no other mammal species that will compete for the bait, as has been observed in riparian environments, islands, and forest fragments.


Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs.
A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t1/2β), Tmax, and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different (p < 0.05) to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive control group (tiamulin). In conclusion, 10% enrofloxacin enteric-coated granules had significant potential for treating APP and MS, and it provided an alternative enrofloxacin palatability formulation.


Evaluation and Comparison of Clonidine and Dexmedetomidine for Attenuation of Hemodynamic Response to Laryngoscopy and Intubation: A Randomized Controlled Study.
Laryngoscopy and tracheal intubation are noxious stimuli which evoke a transient but marked sympathetic response. Alpha-2 adrenoceptor agonists attenuate the sympathoadrenal responses by inhibiting noradrenaline release. This study aims to evaluate and compare the effect of intravenous dexmedetomidine and clonidine on cardiovascular response resulting from laryngoscopy and endotracheal intubation. This was a prospective randomized controlled study carried out in the operating room. Ninety American Society of Anesthesiologists Physical Status I and II patients were randomly allocated into three groups, that is, Group C (clonidine 2 μg/kg), Group D (dexmedetomidine 1 μg/kg), and Group S (normal saline) infused over 10 min. Blood pressures - systolic (SBP) and diastolic (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded after drug administration and intubation at subsequent intervals. Quantitative data were analyzed using ANOVA test (with post hoc Bonferroni correction for intragroup comparison). Qualitative data were analyzed using Chi-square test. P < 0.05 was considered statistically significant. HR, SBP, DBP, and MAP were lower in Group C and D compared to Group S at all times measured. HR was significantly lower in Group D compared to Group C after drug infusion. At 1 min after intubation, SBP and MAP were lower in Group D compared to Group C. At 3, 5, and 10 min after intubation, SBP, DBP, and MAP were lower in Group D compared to Group C. There was significant reduction in hemodynamic response by dexmedetomidine and clonidine as compared to controls. Furthermore, attenuation of the pressor response to intubation was better following premedication with dexmedetomidine than with clonidine.


The 2.7 A structure of AChBP, homologue of the ligand-binding domain of the nicotinic acetylcholine receptor.
Acetylcholine binding protein (AChBP) is a novel protein with high similarity to the extracellular domain of the nicotinic acetylcholine receptor. It is secreted from glia cells in the freshwater snail, Lymnaea stagnalis, where it modulates neuronal transmission. AChBP forms homopentamers with pharmacology that resembles the alpha7 nicotinic receptors. In the crystal structure of AChBP at 2.7 A, each protomer has a modified immunoglobulin fold. Almost all residues shown to be involved in ligand binding in the nicotinic receptor are found in a pocket at the subunit interface. This pocket is lined with aromatic residues, and filled with a HEPES buffer molecule. The AChBP crystal structure explains many of the biochemical studies on the nicotinic acetylcholine receptors. Surprisingly the interface between protomers is relatively weakly conserved between family members in the superfamily of pentameric ligand-gated ion channels. The lack of conservation has implications for the mechanism of gating of the ion channels.


Outcomes of Anatomic Reconstruction of Gunshot-Inflicted Lower Face Defects by Free Osteoseptocutaneous Fibula Flap and Expanded or Nonexpanded Temporal Scalp Flap Combination in Males.
Reconstruction of gunshot-inflicted composite lower face defects is a challenge for plastic surgeons. Functional and aesthetic repair of such defects mostly requires free or pedicled flap applications or combinations of both.In this study, the authors evaluated 7 males with gunshot-inflicted composite mandibular defects. All patients underwent reconstruction with a free osteoseptocutaneous fibula flap (FOCF) for the composite mandibular defect and a pre or nonexpanded temporal artery-based scalp flap for beardless facial skin. All patients were evaluated aesthetically and functionally with a postoperative evaluation scale. Average patient follow-up time was 3.5 years.All FOCFs survived completely. Expander exposition was observed in 2 preexpanded temporal scalp flaps. The problem was solved by rapid expansion and early flap application. All patients had acceptable functional and aesthetic results.In conclusion, the scalp flap should be considered in male beardless skin reconstruction due to its ease of application, reliability, and proximity to the defect. Preexpansion of this flap can decrease donor area morbidities. Moreover, the FOCF and scalp flap combination is a convenient procedure for gunshot-inflicted lower face defects, and such procedures produce good aesthetic and functional long-term outcomes.


Predictors of Positive Margins After Definitive Resection for Gastric Adenocarcinoma and Impact of Adjuvant Therapies.
Positive margins after definitive resection in gastric adenocarcinoma are associated with inferior outcomes. There are few randomized data to guide optimal adjuvant therapy after positive margins. Using the National Cancer Database, we identified 24,619 nonmetastatic gastric adenocarcinoma patients who received diagnoses from 2004 to 2013 and underwent definitive resection to analyze for predictors of positive surgical margins. Of these patients, 2754 had positive margins (11.2%). Multivariate prevalence ratios were used to determine predictors. Survival analyses were performed with a Cox proportional hazards model by use of several methods of propensity score analysis. Increasing T and/or N category, high grade, and lymphovascular invasion predicted higher rates of positive margins. Asian race, treatment at an academic center, and robotic surgery predicted lower rates of positive margins. Among positive-margin patients with adjuvant treatment (n=1021), with a median follow-up period of 55 months, age, comorbidity score, nodal disease, and T4 disease predicted for worse overall survival (OS). Treatment at an academic center was associated with improved OS. Use of adjuvant concurrent chemoradiation therapy (CCRT) was associated with higher OS compared with chemotherapy alone after positive margins (hazard ratio, 0.72; 95% confidence interval, 0.58-0.91; P=.005) after propensity matching adjusting for predictors of OS. The 2-year and 3-year OS for positive-margin patients with chemotherapy alone was 43% and 29%, respectively, compared with 53% and 38%, respectively, with adjuvant CCRT. The log-rank P value for survival was .0015. Stage, race, treatment center, and surgery approach predict for margin status after resection. Adjuvant CCRT after positive margins is associated with improved OS after accounting for available clinical variables.


[Lymphatic system in central nervous system].
The considerable metabolic activity of the central nervous system (CNS) requires an efficient system of tissue drainage and detoxification. The CNS is however devoid of lymphatic vessels, a vasculature ensuring interstitial fluid drainage and immune survey in other organs. A unique system of drainage has recently been identified between the cerebrospinal fluid (CSF), brain interstitial fluids and meningeal lymphatic vessels. This system is coupling a cerebral "glymphatic" flow with a meningeal lymphatic vasculature. The "glymphatic" system includes perivascular spaces and astrocytes, and drains interstitial fluids, from and towards the CSF. Meningeal lymphatic vessels are functionally linked to the cerebral "glymphatic" efflux by clearing intracerebral macromolecules and antigens towards the peripheral lymphatic system. The "glymphatic"-"meningeal lymphatics" system is potentially offering new therapeutic targets to improve cerebral drainage and immune survey in human CNS diseases.


Molecularly imprinted silica-silver nanowires for tryptophan recognition.
We report on silver nanowires (AgNWs) coated with molecularly imprinted silica (MIP SiO2) for recognition of tryptophan (Trp). The use of AgNWs as a template confers an imprinted material with adequate mechanical strength and with a capability of recognizing Trp due to its nanomorphology when compared to spherical microparticles with a similar surface-to-volume ratio. Studies on adsorption isotherms showed the MIP-SiO2-AgNWs to exhibit homogeneous affinity sites with narrow affinity distribution. This suggests that the synthesized material behaves as a 1D nanomaterial with a large area and small thickness with very similar affinity sites. Trp release from MIP-SiO2-AgNWs was demonstrated to be dominated by the diffusion rate of Trp as controlled by the specific interactions with the imprinted silica shell. Considering these results and the lack of toxicity of silica sol-gel materials, the material offers potential in the field of drug or pharmaceutical controlled delivery, but also in optoelectronic devices, electrodes and sensors.


[Serum proteins levels of school children in areas with variable air pollution, especially by carbon disulfide (CS2)].
Within an epidemiological transversal study concerning the effect of CS2 immissions on the health state of school children during 1987/1988, 340 9 to 10 years old children (198 exposed, 142 non-exposed) have been investigated. From a venous blood sample 12 serum proteins have been determined, among other determinations. From these 12 immunological parameters, relating the mean concentrations of them in connection to the two different areas 7 were significantly different, 2 probably different, and 3 had no differences (T-test). These results are discussed in connection with other data from the literature.


Phenotype and Genotype Study of Chinese POMT2-Related α-Dystroglycanopathy.
Alpha-dystroglycanopathy (α-DGP) is a subtype of muscular dystrophy caused by defects in the posttranslational glycosylation of α-dystroglycan (α-DG). Our study aimed to summarize the clinical and genetic features of POMT2-related α-DGP in a cohort of patients in China. Pedigrees, clinical data, and laboratory tests of patients diagnosed with POMT2-related α-DGP were analyzed retrospectively. The pathogenicity of variants in POMT2 were predicted by bioinformatics software. The variants with uncertain significance were verified by further analysis. The 11 patients, comprising eight males and three females, were from nine non-consanguineous families. They exhibited different degrees of muscle weakness, ambulation, and intellectual impairment. Among them, three had a muscle-eye-brain disease (MEB)-like phenotype, five presented congenital muscular dystrophy with intellectual disability (CMD-ID), and three presented limb-girdle muscular dystrophy (LGMD). Overall, nine novel variants of POMT2, including two non-sense, one frameshift and six missense variants, were identified. The pathogenicity of two missense variants, c.1891G > C and c.874G > C, was uncertain based on bioinformatics software prediction. In vitro minigene analysis showed that c.1891G > C affects the splicing of POMT2. Immunofluorescence staining with the IIH6C4 antibody of muscle biopsy from the patient carrying the c.874G > C variant showed an apparent lack of expression. This study summarizes the clinical and genetic characteristics of a cohort of POMT2-related α-DGP patients in China for the first time, expanding the mutational spectrum of the disease. Further study of the pathogenicity of some missense variants based on enzyme activity detection is needed.


The Production of Polyclonal Antibodies in Laboratory Animals. The Report and Recommendations of ECVAM Workshop 35.
This is the report of the thirty-fifth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (1). This joint ECVAM/FELASA (Federation of European Laboratory Animal Science Associations) workshop on The Immunisation of Laboratory Animals for the Production of Polyclonal Antibodies was held in Utrecht (The Netherlands), on 20-22 March 1998, under the co-chairmanship of Coenraad Hendriksen (RIVM, Bilthoven, The Netherlands) and Wim de Leeuw (Inspectorate for Health Protection, The Netherlands). The participants, all experts in the fields of immunology, laboratory animal science, or regulation, came from universities, industry and regulatory bodies. The aims of the workshop were: a) to discuss and evaluate current immunisation procedures for the production of polyclonal antibodies (including route of injection, animal species and adjuvant ); and b) to draft recommendations and guidelines to improve the immunisation procedures, with regard both to animal welfare and to the optimisation of immunisation protocols. This report summarises the outcome of the discussions and includes a number of recommendations and a set of draft guidelines (included in Appendix 1).


The anti-VEGF antibody bevacizumab potently reduces the growth rate of high-risk neuroblastoma xenografts.
Neuroblastoma (NB) is a rapidly growing, well-vascularized childhood cancer that often presents with metastases. The overall five-year survival in NB is approximately 45% despite multimodality treatment, and therefore there is a clinical need for new therapeutic strategies. NB frequently overexpresses the angiogenic factor VEGF (vascular endothelial growth factor). The aim of this study was to investigate the effect of bevacizumab (Avastin, Genentech/Roche), a humanized anti-VEGF-A antibody, on NB growth in three different xenograft models, chosen to resemble high-risk NB. The human NB cell lines SK-N-AS, IMR-32 and SH-SY5Y, which are poorly differentiated and overexpress VEGF-A, were injected s.c. in immunodeficient mice. Bevacizumab was given intraperitoneally twice weekly at 5 mg/kg body weight, starting at a tumor volume of 0.3 mL. Bevacizumab significantly (p < 0.01-0.05) reduced NB growth in vivo without toxicity by causing a 30-63% reduction of angiogenesis, but had no effect on NB cell survival in vitro. Serum concentrations of VEGF-A increased two- to six-fold during bevacizumab therapy which did not result in faster tumor growth compared with control animals. Based on our experimental data we suggest consideration of bevacizumab in treatment of high-risk NB that does not respond to conventional therapy and that overexpresses VEGF.


A new iron calcium phosphate material to improve the osteoconductive properties of a biodegradable ceramic: a study in rabbit calvaria.
β-tricalcium phosphate (β-TCP) is an osteoconductive and biodegradable material used in bone regeneration procedures, while iron has been suggested as a tool to improve the biological performance of calcium phosphate-based materials. However, the mechanisms of interaction between these materials and human cells are not fully understood. In order to clarify this relationship, we have studied the iron role in β-TCP ceramics. Iron-containing β-TCPs were prepared by replacing CaCO3 with C6H5FeO7 at different molar ratios. X-ray diffraction analysis indicated the occurrence of β-TCP as the sole phase in the pure β-TCP and iron-containing ceramics. The incorporation of iron ions in the β-TCP lattice decreased the specific surface area as the pore size was shifted toward meso- and/or macropores. Furthermore, the human osteoblastlike cell line MG-63 was cultured onto the ceramics to determine cell proliferation and viability, and it was observed that the iron-β-TCP ceramics have better cytocompatibility than pure β-TCP. Finally, in vivo assays were performed using rabbit calvaria as a bone model. The scaffolds were implanted for 8 and 12 weeks in the defects created in the skullcap with pure β-TCP as the control. The in vivo behavior, in terms of new bone formed, degradation, and residual graft material were investigated using sequential histological evaluations and histomorphometric analysis. The in vivo implantation of the ceramics showed enhanced bone tissue formation and scaffold degradation for iron-β-TCPs. Thus, iron appears to be a useful tool to enhance the osteoconductive properties of calcium phosphate ceramics.


Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.
Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.


Establishment of topographic circuit zones in the cerebellum of scrambler mutant mice.
The cerebellum is organized into zonal circuits that are thought to regulate ongoing motor behavior. Recent studies suggest that neuronal birthdates, gene expression patterning, and apoptosis control zone formation. Importantly, developing Purkinje cell zones are thought to provide the framework upon which afferent circuitry is organized. Yet, it is not clear whether altering the final placement of Purkinje cells affects the assembly of circuits into topographic zones. To gain insight into this problem, we examined zonal connectivity in scrambler mice; spontaneous mutants that have severe Purkinje cell ectopia due to the loss of reelin-disabled1 signaling. We used immunohistochemistry and neural tracing to determine whether displacement of Purkinje cell zones into ectopic positions triggers defects in zonal connectivity within sensory-motor circuits. Despite the abnormal placement of more than 95% of Purkinje cells in scrambler mice, the complementary relationship between molecularly distinct Purkinje cell zones is maintained, and consequently, afferents are targeted into topographic circuits. These data suggest that although loss of disabled1 distorts the Purkinje cell map, its absence does not obstruct the formation of zonal circuits. These findings support the hypothesis that Purkinje cell zones play an essential role in establishing afferent topography.


A unified connectomic target for deep brain stimulation in obsessive-compulsive disorder.
Multiple surgical targets for treating obsessive-compulsive disorder with deep brain stimulation (DBS) have been proposed. However, different targets may modulate the same neural network responsible for clinical improvement. We analyzed data from four cohorts of patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens or the subthalamic nucleus (STN). The same fiber bundle was associated with optimal clinical response in cohorts targeting either structure. This bundle connected frontal regions to the STN. When informing the tract target based on the first cohort, clinical improvements in the second could be significantly predicted, and vice versa. To further confirm results, clinical improvements in eight patients from a third center and six patients from a fourth center were significantly predicted based on their stimulation overlap with this tract. Our results show that connectivity-derived models may inform clinical improvements across DBS targets, surgeons and centers. The identified tract target is openly available in atlas form.


Local exponents of nonlinear compression in periodically driven noisy oscillators.
Nonlinear compression of periodic signals is a key feature of the active amplifier in inner ear organs of all vertebrates. Different exponents alpha(0) in [-0.88,-0.5] of the sensitivity vs forcing amplitude |chi| approximately f(alpha(0)) have been observed. Here we calculate analytically the local exponent for a generic oscillator, the normal form of a Hopf bifurcation driven by noise and a periodic signal. For weak noise and sufficient distance from the bifurcation on the unstable side, the exponent may be close to -1 for moderate forcing amplitudes beyond linear response. Such strong compression is also found in a model of hair bundle motility.


Clinical outcome of cardiac surgery in octogenarians.
The purpose of this study was to investigate the operative results and the clinical outcomes for octogenarians who underwent cardiac surgery. Twenty consecutive octogenarians who had cardiac operations at Samsung Medical Center from October 1994 through December 2004 were included in the study. The medical records were retrospectively reviewed and the follow-up results were obtained by the interview. The patients were 15 men and 5 women, and their mean age was 83.1 yr (range: 80-89 yr). The surgical priority was urgent for 5 patients and it was elective for 15 patients. Coronary artery bypass grafting (CABG) was performed in 14 patients, valve surgery was performed in 4 patients and CABG plus valve surgery was performed in 2 patients. There was one hospital death on day one after urgent CABG in an 80-yr-old man who had left main coronary artery occlusion. There were three deaths during the follow-up. Sudden death occurred in one patient at 2 months after valve surgery, and there were two non-cardiac deaths at 12 and 14 months, respectively, after CABG. Non-fatal postoperative complications occurred in 2 of 5 urgent patients and in 3 of 15 electives. The survival rate for the 19 hospital survivors at 24 months after surgery was 80% and the mean follow-up period was 22.5 months (range: 1-58 months). In conclusion, cardiac surgery could be performed within acceptable limits of the risk and its long-term results could be expected to be favorable for the octogenarians.


Small bowel intussussception due to metastatic melanoma of unknown primary site. Case report.
Malignant melanoma is characterized by metastases also to the gastrointestinal tract, especially in the small bowel. The diagnosis is often delayed because unspecific clinical presentation (frequently as chronic iron deficiency anemia, rectal bleeding or intestinal obstruction). We present a case of melanoma of unknown primary site, with clinical presentation of intestinal obstruction. A segmental resection of the ileum was performed including mesentery with lymph nodes. Histology revealed metastatic melanoma from unknown primary. PET and MRI confirmed disseminated disease without brain metastasis.


Combining radiotherapy with immunotherapy: the past, the present and the future.
The advent of immunotherapy is currently revolutionizing the field of oncology, where different drugs are used to stimulate different steps in a failing cancer immune response chain. This review gives a basic overview of the immune response against cancer, as well as the historical and current evidence on the interaction of radiotherapy with the immune system and the different forms of immunotherapy. Furthermore the review elaborates on the many open questions on how to exploit this interaction to the full extent in clinical practice.


Neisseria models of infection and persistence in the upper respiratory tract.
The Gram-negative bacteria genus Neisseria includes both pathogenic and commensal species that are found primarily in the upper respiratory tract of humans and animals. The development of animal models to study neisserial pathogenesis has focused almost exclusively on two species that cause disease in humans. These include Neisseria meningitidis, an obligate commensal that can cause invasive disease, and N. gonorrhoeae, the causative agent of gonorrhea. Both pathogens can persist in the upper respiratory tract. This article will give a brief overview of the genus Neisseria. The anatomy of the upper respiratory tract and its use as a niche for bacteria will be discussed. Next, studies that provide insight about the first stage of upper respiratory tract infection, namely colonization, will be reviewed. Most studies of upper respiratory tract infection have focused on N. meningitidis infections of laboratory mice. This review will also discuss models of respiratory tract persistence by Neisseria species, including commensals, in mice, non-human primates and human volunteers. The article includes a section that discusses the future utility of upper respiratory tract models in informing the development of effective antimicrobial therapies. Such knowledge is needed to minimize the dissemination of antimicrobial resistance from respiratory reservoirs.


Association between glutathione S-transferase T1, M1, and P1 genotypes and the risk of colorectal cancer.
Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.


A new PEG-lipid conjugate micelle for encapsulation of CdSe/ZnS quantum dots.
A new polymer conjugate of poly(ethylene glycol) (PEG) and 10,12-pentacosadiynoic acid (PCDA), PEG-PCDA conjugate, was synthesized by coupling reaction between carboxyl group of PCDA and hydroxyl group of PEG. Luminescent CdSe/ZnS QDs were encapsulated in the polymer micelles of mixtures of PEG-PCDA and PCDA using solid dispersion method to prepare water-soluble and biocompatible QD micelles. Upon UV-irradiation, the core of QD micelles was further stabilized by intramicellar crosslinking between neighboring PCDA moieties. The polymer conjugate was characterized by 1H-NMR, FT-IR, and GPC measurements, and thereof QD micelles observed using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The QD micelles were spherical with diameters in the range of 30-190 nm. The encapsulated QDs in polymer micelles are water-soluble and have the high potential for applications in biomedical imaging and detection due to their good colloidal stability and biocompatible surface.


[Functional consequences of cutaneous lipid perturbation].
Epidermal lipids constitute an ultimate frontier between the organism and its environment. Their essential role consists of providing a barrier limiting both transepidermal water loss and penetration of external factors, such as irritants. Efficacy of the barrier depends on the physicochemical properties of the substance applied to the skin surface and the increase in transepidermal water loss, which may be quantified, is proportional to the provoked perturbation in the barrier function. In atopic dermatitis epidermis, a significant decrease in the ceramide content and abnormally low levels of omega-6 fatty acids correlate with an increased rate of water loss at the skin surface--a sign of an impaired barrier. However, similar signs are observed in the atrophic epidermis provoked by long term local corticotherapy. Epidermal lipid profiles are also seriously modified in various ichthyoses, and are partially responsible for the hyperkeratosis observed clinically, e.g.: the recessive X-linked form is provoked by a mutation of the steroid sulphatase gene and the resulting accumulation of unconverted precursor of cholesterol. Modification of the lipid composition in acne contributes to comedo formation, whereas UV improves barrier function (and may provoke hyperkeratosis) through an increase in the stratum corneum lipid content. Another source of lipids at the epidermal surface is sebaceous glands. Waxes present in the sebum increase friction coefficient of the skin surface. Sebum also influences (decreases) the rate of penetration of lipophilic substances applied on the skin. Its role in the skin biology appears to be less vital than that of the lipids constituting the permeability barrier of the stratum corneum.


Noninvasive mechanical ventilation via face mask in patients with acute respiratory failure who refused endotracheal intubation.
To evaluate the response to noninvasive ventilation in a group of terminally ill patients with acute respiratory failure who refused endotracheal intubation. Case series. Medical intensive care units (ICUs) in a university health science center. Eleven patients, nine with hypercapnic and two with hypoxemic acute respiratory failure. Mean age of patients was 64 yrs. Mechanical ventilation was delivered via a face mask. The initial ventilatory setting was continuous positive airway pressure mode, with pressure-support ventilation of 10 to 20 cm H2O, titrated to achieve a respiratory rate of < 25 breaths/min and a tidal volume of 5 to 7 mL/kg. Ventilatory settings were adjusted based on results of arterial blood gases. Mean duration of mechanical ventilation was 44 hrs. Mechanical ventilation via face mask was effective in correcting gas exchange abnormalities in seven of 11 patients, all of whom survived and were discharged from the ICU. Four patients with hypercapnic acute respiratory failure died. Mechanical ventilation via face mask was effective in improving respiratory acidosis in three patients and had no effect in one patient. Two of the four patients could not be weaned from mechanical ventilation and opted for discontinuation of this method. Removal of the ventilator while retaining the mask for oxygen supplementation was a nontraumatic experience to the patient and family. Even when respiratory failure did not resolve, mechanical ventilation via face mask was effective in lessening dyspnea and allowed the patient to maintain autonomy and continuous verbal communication. We conclude that mechanical ventilation via face mask offers an effective, comfortable, and dignified method of supporting patients with end-stage disease and acute respiratory failure.


[Medical ethics in the 19th century literature].
Since the last century, humanity has been besieged by violence, crisis of the state of law and impunity, everything extended to crisis of medical ethics-moral. In addition to clinic cases and ethics and moral dilemmas in the nineteenth century, to investigate for testimonies of the history of medicine and medical ethics, moral, etiquette and education in the nineteenth century literature, considering this a trustworthy archive of them. Analytic-historical proceeding: Cases of autonomy, beneficence, justice, nonmaleficence and solidarity in 122 nineteenth century literary masterpieces (84 authors, 20 countries), selected--according to prestigious scholars--because they show coincidence and transcendence of real life objects with literary represented objects, taking for this article just Axel Munthe's Story of San Michele. FINDS: Grouped in statistical-analytic tables literary paragraphs about technical-scientific matters, professional exercise, medical-patient relation, clinic cases, moral-ethics dilemmas and medical etiquette and education were identified corroborating that the more worthy medical dimension has humanistic roots. Innovating contribution: focused through the lens of the medicine history and bioethics, literary masterpieces might be the reflexive-analytical way for the twenty-first century physician/reader, to recover the real objects represented, to choose his excelling path and to increase his ethos and contribution to the common welfare.


ST-Elevation Myocardial Infarction With Occluded Culprit Coronary Artery in a Young Patient Recovered From Mild COVID-19: A Case Report.
ST-elevation myocardial infarction (STEMI) is a cardiovascular emergency that requires an early reperfusion strategy to reduce mortality and hemodynamic, mechanical, and electrical complications. STEMI is more frequent in men older than 40 years with well-known cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking. The coronavirus disease 2019 (COVID-19) changed this reality worldwide due to the fact that STEMI cases associated with severe forms of COVID-19 began to be reported, which generally affected the older adult population; in contrast, there is still limited data on young healthy patients recovering from mild COVID-19. The exact mechanism behind the association remains unclear. We present a case of a healthy 29-year-old man with a history of mild COVID-19, diagnosed by reverse-transcription polymerase chain reaction 20 days before his admission with inferior STEMI. Coronary angiography revealed an occluded mid-right coronary artery, and he was successfully treated with a drug-eluting stent. The patient evolved favorably and was discharged on the fifth day of hospitalization.


Ileal Perforation with Norovirus Gastroenteritis in a 3-Month-Old Infant.
Noroviruses have been recognized as the leading cause of epidemic and sporadic gastroenteritis since the advent of molecular diagnostic technique. They have been documented in 5-31% of pediatric patients hospitalized with gastroenteritis. Although norovirus gastroenteritis is typically mild and self-limited, it causes severe, but sometimes fatal, conditions in the vulnerable population such as immunocompromised patients, young children, and the elderly. Bowel perforation due to norovirus infection is rare. We report a case of small bowel perforation with norovirus gastroenteritis in the infant with Down syndrome during the hospitalization with pneumonia. Severe dehydration may cause bowel ischemia and could have triggered bowel perforation in this case. Physicians should be alert to the potential surgical complications followed by severe acute diarrhea, especially in high risk groups.


[Establishment of HSP90 overexpressing cell line and effects on cell proliferation].
To establish a HSP90 highly expressing cell line and study the effect of high level of HSP90 on cell stress response. The recombined plasmid pSmycHSP, which contained the full length DNA coding for human HSP90 B, was introduced into mouse fibroblast cell line NIH-3T3 by electroporation after being subcloned, purified and identified by limited enzyme digestion. After screened by G418, the positive clones were selected and identified by immunocytochemistry and Western-blotting. Contrasted with NIH-3T3 cells transfected with empty plasmid, the effect of high-level HSP90 on cell proliferation and cell cycle was analyzed by MTT method and flow cytometry. The rising level of HSP90 was shown by immunocytochemistry and Western-blotting. Compared with control, the growth of HSP90 highly expressing cell line slowed down and the DNA content of S phase was lower. The NIH-3T3 derived cell line, which stably expressed high level of HSP90 was established. The effect of high-level HSP90 on cell proliferation was to retard cell growth by affecting cell cycle.


Identification of a unique ethidium bromide binding site on yeast tRNAPhe by high resolution (300 MHz) nuclear magnetic resonance.
The binding of ethidium bromide to yeast tRNAPhe has been studied by high resolution (300 MHz) proton nuclear magnetic resonance. Under appropriate experimental conditions one ethidium bromide is bound to each tRNA and two resonances from ring NH protons are shifted upfield. These observations taken in conjunction with the low-field spectrum of yeast tRNAPhe show that the unique ethidium bromide binding site is located between base pairs AU6 and AU7 of the amino acid acceptor stem. This information should be of value in understanding the way in which ethidium bromide binding alters the biochemical properties of the tRNA molecules.


Clinical and Analytical Evaluation of the Alinity m HR HPV Assay within the VALGENT-3 Framework.
Only clinically validated human papillomavirus (HPV) tests should be used in cervical cancer screening. VALGENT provides a framework to validate new HPV tests. In the VALGENT-3 study, the clinical accuracy of the recently launched Abbott Alinity m HR HPV assay (Alinity m) to detect cervical precancerous lesions was assessed against the standard comparator test (Hybrid Capture 2; HC2) and against two previously validated alternative comparator tests (Abbott RealTime HR HPV and Roche cobas 4800 assays). Validation was conducted using 1,300 consecutive cervical samples from women attending an organized population-based cervical screening program enriched with 300 cytologically abnormal samples. Overall high-risk HPV test concordance was assessed by kappa values; the concordance for HPV-16 and HPV-18 was assessed for Alinity m, RealTime, and cobas, and the Linear Array (Roche) was used for more detailed genotyping concordance. In the total study population, the relative sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ of Alinity m compared to HC2 was 1.02 (95% confidence interval [CI], 0.99 to 1.06) and 1.03 (95% CI, 0.99 to 1.06), respectively. The relative specificity for nondiseased subjects (≤CIN1) was 1.01 (95% CI, 1.00 to 1.02) (all pnon-inferiority ≤ 0.001). Alinity m showed noninferior clinical accuracy among women 30 years or older when cobas or RealTime was used as a comparator. HPV genotype-specific concordance between Alinity m and the three comparator tests showed excellent agreement, with kappa values ranging from 0.82 to 1.00. In conclusion, Alinity m fulfills the international accuracy requirements for use in cervical cancer screening and shows excellent HPV genotype-specific concordance with three clinically validated HPV tests.


miR-532 promoted gastric cancer migration and invasion by targeting NKD1.
Gastric cancer is one of the most common human malignant neoplasms, especially in China, its regulatory mechanism is important to develop new therapy approaches. miRNAs have been demonstrated to regulate gastric cancer progression. We found miR-532 was overexpressed in gastric cancer tissues and cells. Wound healing and transwell assay revealed that its overexpression promoted gastric cancer cell migration and invasion, its knockdown inhibited gastric cancer cell migration and invasion. Wnt/β-catenin antagonist naked cuticle homolog 1 (NKD1) was the target of miR-532, miR-532 inhibited NKD1 expression. TOP/FOP luciferase activity analysis suggested miR-532 also increased Wnt/β-catenin pathway activity. Overexpression miR-532 and NKD1 inhibited gastric cancer cell migration and invasion, consistent with miR-532 knockdown. These findings revealed miR-532 promoted gastric cancer cell migration and invasion through inhibiting NKD1 and activated Wnt/β-catenin pathway. We provide a potential target for gastric cancer therapy.