Gene therapy for primary immunodeficiencies.
For over 40 years, primary immunodeficiencies (PIDs) have featured prominently in the development and refinement of human allogeneic hematopoietic stem cell transplantation. More recently, ex vivo somatic gene therapy using autologous cells has provided remarkable evidence of clinical efficacy in patients without HLA-matched stem cell donors and in whom toxicity of allogeneic procedures is likely to be high. Together with improved preclinical models, a wealth of information has accumulated that has allowed development of safer, more sophisticated technologies and protocols that are applicable to a much broader range of diseases. In this review we summarize the status of these gene therapy trials and discuss the emerging application of similar strategies to other PIDs.


Cross-sectional study of quadriceps properties and postural stability in patients with chronic stroke and limited vs. non-limited community ambulation.
Background: Changes in the paretic-side metabolism post-stroke and quadriceps muscle mechanical properties favour muscle wasting, affecting postural instability and walking impairment. Further clarification is needed in subjects post-stroke who show limited or non-limited community ambulation. Objectives: To analyze between-limb differences in quadriceps muscle thickness, strength and thigh cutaneous temperature, as well as investigate postural stability in subjects with chronic stroke and limited vs. non-limited community ambulation and compared against healthy controls. Methods: In this controlled cross-sectional study, 26 participants with chronic hemiparesis post-stroke (divided in a slow gait group (SG<0.8 m/s) (n = 13) and a fast gait group with full community ambulation speed (FG≥0.8 m/s)) and 18 healthy people were recruited. Thigh surface temperature, rectus femoris (RF) and vastus intermedius (VI) muscles thickness, quadriceps' isometric maximal voluntary contraction and postural stability were measured. Results: The SG presented significantly lower RF (P = .019) and VI (P = .006) muscle thickness, less peak force (P < .001) and lower temperature (P = .002) in the paretic vs the non-paretic limb. The FG showed significantly lower VI thickness (P = .036) and peak force (P < .001) in the paretic vs the non-paretic limb. Regarding balance, all indices were worse in the SG versus the FG and CG. Conclusions: Subjects of the FG, despite showing full community ambulation speed, had less quadriceps strength and VI muscle thickness but not RF muscle wasting in the paretic limb. The paretic VI muscle wasting may be an important factor to reach normal walking. The SG showed between-limb differences in all the studied variables and the worst postural stability.


Nonlocal product rules for percolation.
Despite original claims of a first-order transition in the product rule model proposed by Achlioptas et al. [Science 323, 1453 (2009)], recent studies indicate that this percolation model, in fact, displays a continuous transition. The distinctive scaling properties of the model at criticality, however, strongly suggest that it should belong to a different universality class than ordinary percolation. Here we introduce a generalization of the product rule that reveals the effect of nonlocality on the critical behavior of the percolation process. Precisely, pairs of unoccupied bonds are chosen according to a probability that decays as a power law of their Manhattan distance, and only that bond connecting clusters whose product of their sizes is the smallest becomes occupied. Interestingly, our results for two-dimensional lattices at criticality shows that the power-law exponent of the product rule has a significant influence on the finite-size scaling exponents for the spanning cluster, the conducting backbone, and the cutting bonds of the system. In all three cases, we observe a clear transition from ordinary to (nonlocal) explosive percolation exponents.


Quercetin improves the imbalance of Th1/Th2 cells and Treg/Th17 cells to attenuate allergic rhinitis.
Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.


Anomalous segmental pulmonary vein: additional V6 behind the bronchus intermedius draining into the superior pulmonary vein.
Anatomical variations of pulmonary venous drainage have been widely described in the literature in order to perform safe thoracic surgical procedures. We report a case of anomalous vein from the superior segment of the right lower lobe running in the posterior mediastinum and draining into the superior pulmonary vein. As the patient showed a usual right inferior pulmonary vein, formed by the union of the superior segment right lower lobe vein (V6) and the common basal vein joining the left atrium, the uncommon segmental pulmonary vein described was named: additional V6. It was identified preoperatively and recognized intraoperatively during thoracoscopic right lower lobectomy and lymph node dissection performed for lung cancer treatment. Diagnostic imaging and careful surgical dissection are helpful tools to avoid intraoperative bleeding and other complications during thoracic surgical procedures due to unrecognized vascular anomalies.


Ileal starch digestibility of different cereal grains fed to growing pigs.
The objective of the present study was to determine, in growing pigs, the ileal starch digestibility and ileal digestible starch content of 8 different genotypes of barley, rye, triticale, and wheat each. Therefore, 4 experiments were conducted with 34 ileally cannulated growing pigs (initial BW of 24 to 32 kg) in total. The experimental diets were formulated to contain 1 of the 8 genotypes of each cereal grain at an inclusion level of 95%. Cereal grains were ground through a 2-mm sieve and were the sole dietary source of starch. All diets were supplemented with plant oil, minerals and vitamins, and titanium dioxide as an indigestible marker. The experiments were arranged either as a row-column design with 8 periods of 6 d each and 9 pigs (for barley and wheat) or according to an 8 × 8 Latin square design with 8 periods of 6 (rye) or 7 d (triticale) and 8 pigs. Experimental periods comprised 4 (barley, rye, and wheat) or 5 d (triticale) for adaptation followed by 2 d for ileal digesta collection. The daily feed intake amounted to 4% of pigs' average BW, corresponding to about 3 times the animals' energy requirement for maintenance (106 kcal of ME [as-fed basis]/kg of metabolic BW). Ileal starch digestibility was different ( < 0.05) within barley and triticale genotypes, with values ranging between 90.1 and 95.0% for barley and between 96.5 and 98.1% for triticale and tended to differ within rye genotypes ( < 0.1). Ileal digestible starch content was different ( < 0.05) within all cereal grains. On average, ileal starch digestibility amounted to 92.7, 95.0, 97.3, and 92.2% for barley, rye, triticale, and wheat, respectively, and was different among cereal grains ( < 0.001). Average ileal digestible starch content was greatest ( < 0.001) in triticale (68.3%, DM basis) followed by wheat (66.1%, DM basis), rye (61.1%, DM basis), and barley (57.6%, DM basis). Differences in ileal starch digestibility and ileal digestible starch content within and among grain genotypes may reflect variations in contents of several fiber fractions such as NDF, ADF, and nonstarch polysaccharides (NSP). For most cereal grains, ileal starch digestibility and ileal digestible starch content decreased ( < 0.05) with increasing contents of soluble, insoluble, and total NSP. In conclusion, in the present study, triticale is superior when compared with the other cereal grains due to its relatively low fiber and high starch content and its high ileal starch digestibility values.


The inhibitory effect of D-glucosamine on thymidine kinase in chick embryo retinas and HeLa cells.
D-Glucosamine markedly inhibits thymidine incorporation into the TCA-insoluble fraction and thymidine kinase activity in HeLa cells. Both the inhibitory effects are also observed in isolated retinas of chick embryos. In this case the inhibitory effects are age-dependent and the magnitude of the responses decreases with embryonic development. In addition the time of exposure to D-glucosamine which is necessary to reveal the inhibitory effect on thymidine kinase increases with the age of the embryos.


Near-infrared spectroscopy for divertor plasma diagnosis and control in DIII-D tokamak.
New near infrared (NIR) spectroscopic measurements performed in the DIII-D tokamak divertor plasma suggest new viable diagnostic applications: divertor recycling and low-Z impurity flux measurements, a spectral survey for divertor Thomson scattering (DTS) diagnostic, and Te monitoring for divertor detachment control. A commercial 0.3 m spectrometer coupled to an imaging lens via optical fiber and a InGaAs 1024 pixel array detector enabled deuterium and impurity emission measurements in the range 800-2300 nm. The first full NIR survey identified D, He, B, Li, C, N, O, Ne lines and provided plasma Te, ne estimates from deuterium Paschen and Brackett series intensity and Stark line broadening analysis. The range 1.000-1.060 mm was surveyed in high-density and neon seeded divertor plasmas for spectral background emission studies for λ = 1.064 μm laser-based DTS development. The ratio of adjacent deuterium Paschen-α and Brackett Br9 lines in recombining divertor plasmas is studied for divertor Te monitoring aimed at divertor detachment real-time feedback control.


Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis.
Early studies suggested that TR4 nuclear receptor might play important roles in the skeletal development, yet its detailed mechanism remains unclear. We generated TR4 knockout mice and compared skeletal development with their wild type littermates. Primary bone marrow cells were cultured and we assayed bone differentiation by alkaline phosphatase and alizarin red staining. Primary calvaria were cultured and osteoblastic marker genes were detected by quantitative PCR. Luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, and electrophoretic mobility shift assays (EMSA) were performed to demonstrate TR4 can directly regulate bone differentiation marker osteocalcin. We first found mice lacking TR4 might develop osteoporosis. We then found that osteoblast progenitor cells isolated from bone marrow of TR4 knockout mice displayed reduced osteoblast differentiation capacity and calcification. Osteoblast primary cultures from TR4 knockout mice calvaria also showed higher proliferation rates indicating lower osteoblast differentiation ability in mice after loss of TR4. Mechanism dissection found the expression of osteoblast markers genes, such as ALP, type I collagen alpha 1, osteocalcin, PTH, and PTHR was dramatically reduced in osteoblasts from TR4 knockout mice as compared to those from TR4 wild type mice. In vitro cell line studies with luciferase reporter assay, ChIP assay, and EMSA further demonstrated TR4 could bind directly to the promoter region of osteocalcin gene and induce its gene expression at the transcriptional level in a dose dependent manner. Together, these results demonstrate TR4 may function as a novel transcriptional factor to play pathophysiological roles in maintaining normal osteoblast activity during the bone development and remodeling, and disruption of TR4 function may result in multiple skeletal abnormalities.


Gelation in Photoinduced ATRP with Tuned Dispersity of the Primary Chains.
We investigated gelation in photoinduced atom transfer radical polymerization (ATRP) as a function of Cu catalyst loading and thus primary chain dispersity. Using parallel polymerizations of methyl acrylate with and without the addition of a divinyl crosslinker (1,6-hexanediol diacrylate), the approximate values of molecular weights and dispersities of the primary chains at incipient gelation were obtained. In accordance with the Flory-Stockmayer theory, experimental gelation occurred at gradually lower conversions when the dispersity of the primary chains increased while maintaining a constant monomer/initiator/crosslinker ratio. Theoretical gel points were then calculated using the measured experimental values of dispersity and initiation efficiency. An empirical modification to the Flory-Stockmayer equation for ATRP was implemented, resulting in more accurate predictions of the gel point. Increasing the dispersity of the primary chains was found not to affect the distance between the theoretical and experimental gel points and hence the extent of intramolecular cyclization. Furthermore, the mechanical properties of the networks, such as equilibrium swelling ratio and shear storage modulus showed little variation with catalyst loading and depended primarily on the crosslinking density.


Erratum: Bioactivity of Diterpens from the Ethyl Acetate Extract of Kingiodendron pinnatum Rox. Hams.
[This corrects the article on p. 287 in vol. 8, PMID: 27695270.].


A study of critical incident analysis as a route to the identification of change necessary in clinical practice: addressing the theory-practice gap.
This paper examines the analysis of critical incidents to assess to what extentpost-registration students are able, through reflection, to identify areas of practice in need of improvement. Discussion centres on the students' ability to reflect on their writing and link such reflection to ways in which changes can be facilitated. Concerns around the theory-practice gap are central to the research, and the use of this teaching strategy is discussed in relation to issues that arise from identification of the practice gap. Cormack's (1983, 1996) technique of analysing critical incidents is used to classify the data, and the areas of discussion are grouped around three main headings relevant to the process of change. It is clear from the data that areas in need of change are identified, but it is more difficult to assess to what extent the process directly informs practice. The conclusion highlights the need for further research that examines whether or not change is apparent in the students' practice area.


Electrophoresis of soft particles with hydrophobic inner core grafted with pH-regulated and highly charged polyelectrolyte layer.
Electrophoresis of core-shell composite soft particles possessing hydrophobic inner core grafted with highly charged polyelectrolyte layer (PEL) has been studied analytically. The PEL bears pH-dependent charge properties due to the presence of zwitterionic functional groups. The dielectric permittivity of the PEL and bulk aqueous medium were taken to be different, which resulted in the ion-partitioning effect. Objective of this study was to provide a simple expression for the mobility of such core-shell soft particles under Donnan limit where the thickness of the PEL well exceeds the electric double layer thickness. Going beyond the widely used Debye-Hückel linearization, the nonlinear Poisson-Boltzmann equation coupled with Stokes-Darcy-Brinkman equations was solved to determine the electrophoretic mobility. The derived expression further recovers all the existing results for the electrophoretic mobility under various simplified cases. The graphical presentation of the results illustrated the impact of pertinent parameters on the electrophoretic mobility of such a soft particle.


Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life.
Newborns and unvaccinated infants, compared to other age groups, are more susceptible to pertussis infection, manifesting severe symptoms leading to a higher mortality. The recent increase in pertussis cases demands more effective strategies to overcome this major health problem. In parallel with maternal-immunization, neonatal-immunization (NI) is a strategy needing revision. Here, using the intranasal-challenge-mouse-model we evaluated the protective capacity of NI in both naïve-mice and those with maternally acquired immunity. We tested our acellular-vaccine-candidate based on outer-membrane-vesicles derived from Bordetella pertussis (OMVP) that induces Th2-profile but also the recommended Th-profile for protection: Th1/Th17-profile and CD4 T-memory-cells that reside in the lungs. Commercial acellular-vaccine (aP) and whole cell-vaccine (wP) inducing mainly Th2-profile and Th1-profile, respectively, were also tested. Analyzing the induced immunity and protection capability of NI included in 1- or 2-dose schedules with the same or different types of vaccine, we detected that the aP-vaccine administered in either single- or 2-dose schedules protected against sublethal B. pertussis infection. Schedules consisting of doses of aP neonatally and of OMVP or wP vaccine during infancy greatly reduced bacterial lung colonization while inducing the highest levels of high-avidity anti-pertussis toxin (PTx) IgG. That OMVP or wP neonatal dose did not interfere with the protection of transferred maternal immunity was especially encouraging. Moreover, OMVP- or wP used as a neonatal dose enhanced the quality of the humoral immune response in immunized pups. Antibodies generated by OMVP-or wP-vaccinated mice born to aP-immunized mothers were of higher avidity than those from mice that harbored only maternal immunity; but when mothers and neonates were immunized with the same aP-vaccine, the humoral response in the neonates was partially suppressed through the blunting of the level of anti-PTx IgG induced by the neonatal aP dose. These results demonstrated that neonatal immunization is a possible strategy to be considered to improve the current pertussis epidemiology. For neonates without maternal-immunity, mixed-vaccination schedules that include the aP- and OMVP-vaccines appear to be the most appropriate to induce protection in the pups. For offspring from immune mothers, to avoid blunting-effect, NI should be carried out with vaccines other than those applied during pregnancy.


Glutathione reductase activity and isoforms in leaves and roots of wheat plants subjected to cadmium stress.
The behavior of glutathione reductase (GR, EC 126.96.36.199) activity and isoforms were analyzed in wheat (Triticum aestivum L.) leaves and roots exposed to a chronic treatment with a toxic cadmium (Cd) concentration. A significant growth inhibition (up to 55%) was found in leaves at 7, 14 and 21 days, whereas roots were affected (51%) only after three weeks. Wheat plants grown in the presence of 100microM Cd showed a time-dependent accumulation of this metal, with Cd concentration being 10-fold higher in roots than in leaves. Nevertheless, lipid peroxidation was augmented in leaves in all experiments, but not in roots until 21 days. Cadmium treatment altered neither the GR activity nor the isoform pattern in the leaves. However, GR activity increased 111% and 200% in roots at 7 and 14 days, respectively, returning to control levels after 21 days. Three GR isoforms were found in roots of control and treated plants, two of which were enhanced by Cd treatment at 7 and 14 days, as assessed by activity staining on native gels. The changes in the isoform pattern modified the global kinetic properties of GR, thereby decreasing significantly (2.5-fold) the Michaelis constant (K(m)) value for oxidized glutathione. Isozyme induction was not associated with an enhancement of GR mRNA and protein expression, indicating that post-translational modification could occur. Our data demonstrated that up-regulation of GR activity by the induction of distinctive isoforms occurs as a defense mechanism against Cd-generated oxidative stress in roots.


Molecular dynamics and analytical Langevin equation approach for the self-diffusion constant of an anisotropic fluid.
We carried out a molecular-dynamics (MD) study of the self-diffusion tensor of a Lennard-Jones-type fluid, confined in a slit pore with attractive walls. We developed Bayesian equations, which modify the virtual layer sampling method proposed by Liu, Harder, and Berne (LHB) [P. Liu, E. Harder, and B. J. Berne, J. Phys. Chem. B 108, 6595 (2004)]. Additionally, we obtained an analytical solution for the corresponding nonhomogeneous Langevin equation. The expressions found for the mean-squared displacement in the layers contain naturally a modification due to the mean force in the transverse component in terms of the anisotropic diffusion constants and mean exit time. Instead of running a time consuming dual MD-Langevin simulation dynamics, as proposed by LHB, our expression was used to fit the MD data in the entire survival time interval not only for the parallel but also for the perpendicular direction. The only fitting parameter was the diffusion constant in each layer.


[The prevalence of hyperlipidemia and obesity in Vienna health examinations 1986].
A random sample of 20% of people taking part in the free health check-ups provided by the city of Vienna in 1986 (707 men and 1022 women), aged 20 to 79 years (mean age men 48.1 +/- 15.8, women 49.6 +/- 15.1 respectively) were retrospectively evaluated to determine coronary heart disease risk according to the recommendations of the Austrian Cholesterol Consensus Conference. Age-standardized mean total-cholesterol is 230.0 mg/dl in men and 235.8 mg/dl in women. Age-standardized percentage of normal lipid levels (i.e. total-cholesterol below 200 mg/dl) is 29.7% in men, 25.7% in women respectively. The high-risk group (i.e. total-cholesterol more than 250 mg/dl) has an age-standardized prevalence of 28.5% in men and 35.8% in women. The age-standardized percentage of obesity according to the guidelines of the National Institutes of Health is 14.2 in men, 17.2 in women respectively. The comparison of age-standardized men-values of total-cholesterol, LDL-cholesterol, triglycerides and Quetelet-index, as well as normal lipid levels according to the Austrian recommendations and percentage of obesity, in the age groups 20 to 39, 40 to 59 and 60 to 79 years shows a statistical significant difference of each parameter between age-group 20 to 39 and age-group 40 to 59 in men, but no significant difference in any parameter between age-group 40 to 59 and 60 to 79 in men. On the contrary in women differences are significant between age-group 20 to 39 and 40 to 59, as well as between age-group 40 to 59 and 60 to 79 in each parameter.(ABSTRACT TRUNCATED AT 250 WORDS)


[May-Hegglin anomaly--from genome research to clinical laboratory].
The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS) and Fechtner syndrome (FTNS), are rare disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like cytoplasmic inclusions in granulocytes. Epstein syndrome (EPS) is another autosomal dominant macrothrombocytopenia associated with Alport syndrome but without leukocyte inclusions. We previously mapped the locus for MHA on chromosome 22q12.3-q13.2 by genome-wide linkage analysis and found that MYH9, the gene for the nonmuscle myosin heavy chain-A (NMMHCA), is responsible for the disorder, by positional cloning. Mutations of MYH9 have also been found in SBS, FTNS, and EPS; the term "MYH9 disorders" has been proposed, but clear phenotype-genotype relationships were not found. We developed an immunofluorescence technique for conventional air-dried peripheral blood smears and studied the neutrophil NMMHCA localization in MYH9 disorders. Abnormal subcellular localization of NMMHCA was observed in every neutrophil from individuals with MYH9 mutations and the localization pattern was classified into three groups according to the number, size, and shape of the NMMHCA-positive granules. Patients without neutrophil inclusions on conventional May-Grünwald-Giemsa-stained blood smears but with abnormal NMMHCA localization on immunofluorescence analysis had MYH9 mutations. In contrast, patients with EPS and isolated macrothrombocytopenia with normal NMMHCA localization had no MYH9 mutations. Immunofluorescence analysis of neutrophil NMMHCA is useful as a novel screening test for the differential diagnosis of macrothrombocytopenia and clear hematopathological classification of MYH9 disorders.


Clinical characteristics of infantile hemangiomas with aggressive, persistent, and destructive ulceration.
Ulceration is a common complication of infantile hemangioma (IH). Severe, persistent ulceration occurs in a minority of patients. This study aims to characterize the clinical features of IH with aggressive ulceration (AU). Multicenter retrospective study of clinical features of IH with AU. Thirty-five patients with AU were identified and included in the study. The majority of AU occurred in segmental IH (23/35, 65%). Segmental IH with AU were large (≥10 cm2 ; 16/23, 69%, p < .001) with a thin (<3 mm) superficial component (16/23, 69%, p < .001). Localized IH with AU had a thick (>3 mm) superficial component (11/12, 92%, p < .001). All diaper area IH with AU (9/35) were segmental with thin superficial component (100%, p = .02). IH with AU in the head/neck (10/35) were more commonly localized (67%) and mixed (62.5%), while segmental, thick superficial morphology was more common on trunk (9/35) and upper extremities (7/35). IH resulting in AU differ in clinical features by anatomic site. Those in the diaper area are nearly always segmental with thin superficial component, whereas other sites tend to be localized, mixed, with thick superficial component. These distinct phenotypes may prove useful in the clinical setting for physicians to identify patterns of IH ulceration with increased risk of aggressive, persistent ulceration.


Using a 3% Proton Density Fat Fraction as a Cut-Off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results From Histopathology Analysis.
It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (1H-MRS), instead of collecting and analyzing liver biopsy specimens to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of 1H-MRS PDFF in the measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, 1H-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (≥6 mo) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereologic point counts (SPCs). We correlated the 1H-MRS PDFF findings with SPCs (r = 0.92; P < .001). 1H-MRS PDFF results correlated with histopathology results (ρ = 0.87; P < .001), and SPCs correlated with histopathology results (ρ = 0.88; P < .001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values less than 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve noninvasive detection of steatosis.


Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.
Faropenem medoxomil is the first oral penem in a new class of beta-lactam antibiotics. Faropenem medoxomil has excellent in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of treatment with faropenem medoxomil is as clinically and bacteriologically effective as 10 days of treatment with cefuroxime axetil. One study showed faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety profile of faropenem medoxomil is similar to that of most comparators. Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal flora leads to less diarrhea and other adverse events than coamoxicillin-clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little requirement for dosage adjustments in the typical acute rhinosinusitis population.


Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy.
Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive paralysis and death. There is currently no resolutive therapy. We have developed a treatment in which we combined the effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT 1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with HCT 1026 of two murine models for limb girdle and Duchenne muscular dystrophies (alpha-sarcoglycan-null and mdx mice). In both models, HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down disease progression. HCT 1026 acted by reducing inflammation, preventing muscle damage, and preserving the number and function of satellite cells. HCT 1026 was significantly more effective than the corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined therapies with donor or autologous, genetically corrected stem cells.


Dietary management of patients with a high-output stoma.
A stoma enables faeces and flatus to be passed through a small surgically formed aperture in the abdominal wall, and may be temporary or permanent. However, in some cases, the output of a stoma can exceed normal limits. Without appropriate management, a high-output stoma can lead to dehydration, electrolyte disturbances and malnutrition in patients. Interventions to manage a high-output stoma include the use of oral rehydration solutions, restriction of hypotonic fluids and dietary modifications. This article reviews the causes of high-output stomas, and describes the assessment and management options available to nurses.


Collapsin response mediator protein-2 is associated with neurofibrillary tangles in Alzheimer's disease.
Intraneuronal accumulation of paired helical filaments (PHF) is considered to be closely related to the neuronal loss observed in brains of patients affected with Alzheimer's disease. The central issue is whether PHF formation itself causes or accelerates the neuronal perikaryal and neuritic degeneration or whether they are simply the consequence of preceding degeneration. We sought to address the issue in part by characterizing the PHF-associated molecules and thus raised a number of monoclonal antibodies to neurofibrillary tangles. One monoclonal antibody, 3F4, strongly reacted with neurofibrillary tangles and some plaque neurites but few neuropil threads. This monoclonal antibody labeled a 65-kDa protein, but not tau or ubiquitin, on a Western blot of human brain extract and immunoprecipitated the same protein. The peptides released from the purified 65-kDa protein had the same sequences as those of a newly identified protein, human collapsin response mediator protein-2. Incorporation into neurofibrillary tangles may deplete soluble, cytosolic human collapsin response mediator protein-2 and lead to abnormal neuritic and/or axonal outgrowth of the tangle-bearing neuron, thus accelerating the neuritic degeneration in Alzheimer's disease.


Aerobic bacterial nosocomial infections in paediatric surgical patients at a tertiary health institution in Lagos, Nigeria.
This study was undertaken to determine nosocomial bacterial infections (NI) in surgical patients in a developing country using the detailed option of the Center for Disease Control (CDC) surgical patient surveillance technique. From 1994 - 1995. Paediatrics surgical patients at the Lagos University Teaching Hospital (LUTH) were prospectively monitored for NI at all body sites. Standard definitions of NI were used, and NI sites were categorised by type of operation. A total of 304 NI occurred in 245 out of 664 surgical patients investigated. SSI (77.3 %) and urinary tract infections (19.1%) were in preponderance. Seventy three per cent of SSI were superficial incisions, 20.5% organ/space and 6.8% deep incisions. The overall wound infection rate was 30.9%. The SSI rate for emergency surgery was 35.6% and 26.5% for elective procedures. Rates within each wound class were 20.2, 23.8, 51.9 and 52.8% respectively and 17, 37.6, 43.4 and 47. 1% for patients with ASA scores of I II III and IV in that order. The SSI rates for patients with scores of 0, 1, 2 and 3 were 20.4; 43.5, 57.1 and 75% respectively. Mean infection rates in the various wound classes were highly correlated with the number of risk factors present. Klebsiella pneumoniae (38. 7%), Escherichia coli (22.7%), Pseudomonas aeruginosa (16.8%) and Staphylococcus aureus (10. 7%) were the most common pathogens.


Activating and relaxing music entrains the speed of beat synchronized walking.
Inspired by a theory of embodied music cognition, we investigate whether music can entrain the speed of beat synchronized walking. If human walking is in synchrony with the beat and all musical stimuli have the same duration and the same tempo, then differences in walking speed can only be the result of music-induced differences in stride length, thus reflecting the vigor or physical strength of the movement. Participants walked in an open field in synchrony with the beat of 52 different musical stimuli all having a tempo of 130 beats per minute and a meter of 4 beats. The walking speed was measured as the walked distance during a time interval of 30 seconds. The results reveal that some music is 'activating' in the sense that it increases the speed, and some music is 'relaxing' in the sense that it decreases the speed, compared to the spontaneous walked speed in response to metronome stimuli. Participants are consistent in their observation of qualitative differences between the relaxing and activating musical stimuli. Using regression analysis, it was possible to set up a predictive model using only four sonic features that explain 60% of the variance. The sonic features capture variation in loudness and pitch patterns at periods of three, four and six beats, suggesting that expressive patterns in music are responsible for the effect. The mechanism may be attributed to an attentional shift, a subliminal audio-motor entrainment mechanism, or an arousal effect, but further study is needed to figure this out. Overall, the study supports the hypothesis that recurrent patterns of fluctuation affecting the binary meter strength of the music may entrain the vigor of the movement. The study opens up new perspectives for understanding the relationship between entrainment and expressiveness, with the possibility to develop applications that can be used in domains such as sports and physical rehabilitation.


How much basic science content do second-year medical students remember from their first year?
While most medical students generally perform well on examinations and pass their courses during the first year, we do not know how much basic science content they retain at the start of their second year and how that relates to minimal competency set by the faculty. In the fall of 2014, before starting their second-year courses, 27 medical students volunteered to participate in a study of long-term retention of the basic sciences by taking a "retention exam" after a delay of 5-11 months. The overall mean performance when the students initially answered the 60 multiple choice questions (MCQs) was 82.8% [standard deviation (SD) = 7.4%], which fell to 50.1% (SD = 12.1%) on the retention exam. This gave a mean retention of 60.4% (SD = 12.8%) with the retention for individual students ranging from 37 to 81%. The majority of students (23/27; 85%) fell below the minimal level of competency to start their second year. Medical educators should be more aware of the significant amount of forgetting that occurs during training and make better use of instructional strategies that promote long-term learning such as retrieval practice, interleaving, and spacing.


Interleukin-6 Signaling in Atherosclerosis: From Molecular Mechanisms To Clinical Outcomes.
Interleukin-6 (IL-6) is a cytokine centrally involved in several immune responses and it has been recognized as a driver of enhanced atherothrombotic risk. Immunity and inflammation are intrinsically involved in atherosclerosis progression. This generated 'inflammation hypothesis', which is now validated in large-scale clinical trials. Abundant evidence supports the distinctive role of IL-6 in coronary artery disease. The focus on this cytokine stems from epidemiological studies linking high plasma concentrations of IL-6 with greater risk for adverse cardiovascular events, genetic studies which implicate a causative role of IL-6 in atherosclerosis and murine data which support the involvement of IL-6 in various pathophysiological cascades of atherothrombosis. The fact that high IL-6 levels are equivalent to increased cardiovascular risk created an unmet need to address those who are at 'residual inflammatory risk'. Moreover, the opposing effects of IL-6 underlined the importance of deciphering specific signaling cascades, which may be responsible for different effects. Finally, murine data and some small clinical trials highlighted the possibility of reversing the pro-atherogenic effects of IL-6 by directly targeting it. While IL-1 blockage was proved effective, it is reasonable to examine if moving more downstream in the inflammation cascade could be more selective and effective than other anti-inflammatory therapies. In the present review, we examine the role of IL-6 as a biomarker of 'residual inflammatory risk', its vital role in the pathophysiology of atherosclerosis progression and the possibility of targeting it to stall coronary artery disease progression.


Additive Classical Capacity of Quantum Channels Assisted by Noisy Entanglement.
We give a capacity formula for the classical information transmission over a noisy quantum channel, with separable encoding by the sender and limited resources provided by the receiver's preshared ancilla. Instead of a pure state, we consider the signal-ancilla pair in a mixed state, purified by a "witness." Thus, the signal-witness correlation limits the resource available from the signal-ancilla correlation. Our formula characterizes the utility of different forms of resources, including noisy or limited entanglement assistance, for classical communication. With separable encoding, the sender's signals across multiple channel uses are still allowed to be entangled, yet our capacity formula is additive. In particular, for generalized covariant channels, our capacity formula has a simple closed form. Moreover, our additive capacity formula upper bounds the general coherent attack's information gain in various two-way quantum key distribution protocols. For Gaussian protocols, the additivity of the formula indicates that the collective Gaussian attack is the most powerful.


Urban mosquito management administration: Mosquito (Diptera: Culicidae) habitat surveillance and questionnaire survey in Wuhan, Central China.
Creating National Sanitary City (CNSC) promotes appearance, environment sanitation and public health including vector management of cities in China. However, vector management especially mosquito management and the related administrative productivity of Patriotic Health Campaign System (PHCS) of National Sanitary Cities (NSCs) were questioned by many pest control professionals and citizens. In this study, we studied mosquito management of NSCs taking Wuhan as an example. The study aimed to (1) determine the distribution and abundance of immature mosquito habitats in built-up areas of Wuhan and (2) better understand the related administration procedure in CNSC. Immature mosquito habitat surveillance was carried out in randomly selected premises of driving schools (DSs), schools or kindergartens (SKs), property management residential areas (PMRAs), construction sites (CSs), wide roads with storm drains (WRSDs) and urban creeks (UCs) in built-up areas of Wuhan from July to October 2015 followed by questionnaire interviews with one each of premise occupants and district departments responsible for mosquito management in these premises. Total of 64.1 km of route were inspected in 36 DSs, 36 SKs, 36 PMRAs, 36 CSs and 36 segments of WRSD and 2,158 potential mosquito habitats with 749 (35%) mosquito-positive habitats were found. The route index (RI) was 11.7, which was 14.6 times higher than the grade C criteria for vector density control (RI = 0.8 positive habitats/km) in CNSC. Occupants of 36 DSs, 36 SKs, 36 PMRAs, 34 CSs were interviewed and 77% of them reported no difference in mosquito infestation in their premises since 2013 and 80% of them knew about the responsibility and arrangements of PHCS of mosquito management in their premises. Only 15% had the awareness of larval source reduction strategy and 14% had implemented it. Receipt the electronic/paper edition of CNSC vector management specifications from the PHCS was very low (13%) and an official notification or bulletin for rectification mosquito-positive habitats was also very low (5%). Of the 75 responsible district departments interviewed, about half (55%) reported that they had held training courses/meetings related to CNSC vector management, the majority (96%) reported that they had not carried out independent on-site supervision of premises under their jurisdiction. No differences in larval indices were found between premises which were administrative intervened and with no administrative intervention. The administrative intervention of PHCS had not evidently improved mosquito management of the premises in built-up areas in Wuhan. It is a violation of the original intention of the National Patriotic Health Campaign Committee in organizing CNSC programs. To combat mosquito borne diseases, and to improve the quality of life of residents, we recommend that PHCS honestly reveals defects in urban mosquito management and seriously takes those exposed defects. The PHCS should strengthen Patriotic Health Campaign activities by strict adherence to NSC standards. Further research on sustained promotion of urban mosquito management of NSCs, which focus on effective administration, as well as on improvement of related sectors of NSC standards should be carried out.


Lipoprotein-associated phospholipase A2 and AGEs are associated with cardiovascular risk factors in women with history of gestational diabetes mellitus.
Although most women with gestational diabetes mellitus (GDM) return to normal glucose tolerance after delivery, they have increased risk of cardiometabolic diseases. This study aimed to evaluate the relationships between plasma levels of Lp-pla2 and AGEs and cardiometabolic risk factors in women with GDM. 190 women with GDM (cases) and 80 healthy women (controls) were enrolled. Demographic and clinical data were collected and analyzed about 2 years after the delivery. Of the 190 cases, 19 (10%), 38 (20%) and 10 (5%) had type 2 diabetes mellitus, metabolic syndrome and hypertension after delivery, respectively. There were significant differences in variables between cases and controls: Lp-pla2 (pg/mL) 1991.5 ± 905.3 versus 1527.0 ± 799.8; AGEs (ng/mL) 403.0 ± 208.6 versus 321.8 ± 150.3. The plasma Lp-pla2 and AGEs levels were positively correlated with metabolic indexes in women with previous GDM. Women with GDM have increased risk of cardiometabolic disease. AGEs and Lp-pla2 could be utilized as novel biomarkers to identify at an early stage of women with increased risk of metabolic and cardiovascular disease.


Minocycline effects in patients with active trachoma.
Minocycline has a unique solubility in lipids and may reach therapeutic concentrations in tears and saliva. In two consecutive prospective double-masked clinical trials that were carried out in two villages in Saudi Arabia, we assessed the effects of oral minocycline in the treatment of trachoma and compared its effects with those of topical tetracycline ointment in the first study and to tetracycline ointment and placebo in the second study. A total of 178 eyes in 96 patients were included. The age range was 7 to 14 years, with a mean age of 9 years. All patients underwent complete ophthalmologic evaluation. School children were divided into two groups in a double-masked fashion. The first group received either oral minocycline or topical tetracycline 1% ointment and the second group was divided into three subgroups, each receiving one of the following therapeutic modalities: oral minocycline, topical tetracycline ointment, or placebo ointment. All patients were evaluated before initiation of therapy, at three weeks and at 12 months following treatment. Therapy was continued for a period of five weeks. These two double-masked field-based clinical trials have shown both minocycline given orally and tetracycline ointment given topically were effective in decreasing the intensity of inflammation due to trachoma. Oral minocycline was found to be equally effective as topical tetracycline ointment in the treatment of trachoma at three weeks. Minocycline, however, was found to be superior to topical tetracycline when patients were evaluated one year after therapy (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Benign intracranial hypertension and facial diplegia.
Benign intracranial hypertension (BIH) may occasionally be associated with false localizing cranial nerve palsies. Abducens nerve palsies reportedly occur in 10% to 60% of patients with BIH, whereas other cranial nerve palsies occur much less frequently. We treated a woman with benign intracranial hypertension and facial diplegia who showed complete resolution of her cranial nerve palsies after control of her elevated intracranial pressure with a lumboperitoneal shunt. The pathophysiologic course of cranial nerve palsies in patients with BIH is uncertain but in most cases probably represents a nonspecific pressure-related phenomenon, as was clearly demonstrated in this patient. The clinical association of BIH and facial diplegia has not, to our knowledge, been reported previously.


Return to sport after total or unicompartmental knee arthroplasty: An informative guide for residents to patients.
Knee arthroplasty survival rate - either UKA or TKA - is currently 95%, greater than it was ten years ago, but has not been specifically evaluated in very active patients practicing sport at a high intensity.The terms and conditions of return to physical activities are decided by the surgeon, the rehabilitation or Sports Medicine doctor, who needs to make sure that postoperative rehabilitation has been conducted optimally. Specifically, range of movement must be complete, muscular strengthening has to be sufficient and balance must be recovered by proprioception. Only after this stage (i.e. three to six months after surgery) can physical activities be resumed.Return to sport must be gentle and progressive, with moderate activities limited to short sessions. Progressively the patient will be able to return to intermediate activities, provided that he/she possesses the adequate level of technique for the sport.This up-to-date review for young surgeons and residents aims to provide an informative guide for patients regarding sport following knee arthroplasty. Cite this article: EFORT Open Rev 2017;2:496-501. DOI: 10.1302/2058-5241.2.170037.


The emergent generation effect and hypermnesia: influences of semantic and nonsemantic generation tasks.
The generation effect is moderated by experimental design, affecting recall in within-subjects designs but typically not in between-subjects designs. However, N. W. Mulligan (2001) found that the generation effect emerged over repeated recall tests in a between-subjects design, calling into question the generality of this limiting condition. In addition, the generate condition but not the read condition produced hypermnesia (increased recall over tests). The present experiments demonstrate that semantic-based (semantic-associate and category-associate) generation tasks produce this pattern of results whereas nonsemantic (letter transposition, rhyme, word fragment) generation tasks do not. Thus, the emergent generation effect appears to be a byproduct of semantic elaboration rather than a direct product of generation. In addition, high- and low-imagery words produced equivalent hypermnesia and emergent generation effects, arguing against a mediating role for imagistic encoding. Finally, there is no evidence of an emergent generation effect for nonwords, another traditional limiting condition of the generation effect.


Terahertz response of dipolar impurities in polar liquids: on anomalous dielectric absorption of protein solutions.
A theory of radiation absorption by dielectric mixtures is presented. The coarse-grained formulation is based on the wave-vector-dependent correlation functions of molecular dipoles of the host polar liquid and a density structure factor of the solutes. A nonlinear dependence of the dielectric absorption coefficient on the solute concentration is predicted and originates from the mutual polarization of the liquid surrounding the solutes by the collective field of the solute dipoles aligned along the radiation field. The theory is applied to terahertz absorption of hydrated saccharides and proteins. While the theory gives an excellent account of the observations for saccharides, without additional assumptions and fitting parameters, experimental absorption coefficient of protein solutions significantly exceeds theoretical calculations with dipole moment of the bare protein assigned to the solute and shows a peak against the protein concentration. A substantial polarization of protein's hydration shell, resulting in a net dipole moment, is required to explain the disagreement between theory and experiment. When the correlation function of the total dipole moment of the protein with its hydration shell from numerical simulations is used in the analytical model, an absorption peak, qualitatively similar to that seen in experiment, is obtained. The existence and position of the peak are sensitive to the specifics of the protein-protein interactions. Numerical testing of the theory requires the combination of dielectric and small-angle scattering measurements. The calculations confirm that "elastic ferroelectric bag" of water shells observed in previous numerical simulations is required to explain terahertz dielectric measurements.


Advancing the functional utility of PAR-CLIP by quantifying background binding to mRNAs and lncRNAs.
Sequence specific RNA binding proteins are important regulators of gene expression. Several related crosslinking-based, high-throughput sequencing methods, including PAR-CLIP, have recently been developed to determine direct binding sites of global protein-RNA interactions. However, no studies have quantitatively addressed the contribution of background binding to datasets produced by these methods. We measured non-specific RNA background in PAR-CLIP data, demonstrating that covalently crosslinked background binding is common, reproducible and apparently universal among laboratories. We show that quantitative determination of background is essential for identifying targets of most RNA-binding proteins and can substantially improve motif analysis. We also demonstrate that by applying background correction to an RNA binding protein of unknown binding specificity, Caprin1, we can identify a previously unrecognized RNA recognition element not otherwise apparent in a PAR-CLIP study. Empirical background measurements of global RNA-protein crosslinking are a necessary addendum to other experimental controls, such as performing replicates, because covalently crosslinked background signals are reproducible and otherwise unavoidable. Recognizing and quantifying the contribution of background extends the utility of PAR-CLIP and can improve mechanistic understanding of protein-RNA specificity, protein-RNA affinity and protein-RNA association dynamics.


Aromatase expression and cell proliferation following injury of the adult zebra finch hippocampus.
Estrogens can be neuroprotective following traumatic brain injury. Immediately after trauma to the zebra finch hippocampus, the estrogen-synthetic enzyme aromatase is rapidly upregulated in astrocytes and radial glia around the lesion site. Brain injury also induces high levels of cell proliferation. Estrogens promote neuronal differentiation, migration, and survival naturally in the avian brain. We suspect that glia are a source of estrogens promoting cell proliferation after neural injury. To explore this hypothesis, we examined the spatial and temporal relationship between glial aromatase expression and cell proliferation after neural injury in adult female zebra finches. Birds were ovariectomized and given a blank implant or one filled with estradiol; some birds were also administered an aromatase inhibitor or vehicle. All birds received penetrating injuries to the right hippocampus. Twenty-four hours after lesioning, birds were injected once with BrdU to label mitotically active cells and euthanized 2 h, 24 h, or 7 days later. The brains were processed for double-label BrdU and aromatase immunocytochemistry. Injury-induced glial aromatase expression was unaffected by survival time and aromatase inhibition. BrdU labeling was significantly reduced at 24 h by ovariectomy and by aromatase inhibition; effects were partially reversed by E2 replacement. Irrespective of ovariectomy, the densities of aromatase immunoreactive astrocytes and BrdU-labeled cells at known distances from the lesion site were highly correlated. These data suggest that injury-induced glial aromatization may influence the reorganization of injured tissue by providing a rich estrogenic environment available to influence cellular incorporation.


Survey on Metals Contained in Stainless Steel Kitchenware and Tableware.
Stainless steel kitchenware and tableware on sale in Japan were investigated. Surface elemental composition ratios of 172 samples were analyzed by the fluorescence X-ray method. High levels of manganese (9.59-20.03%)were detected in 17 samples. This finding was confirmed by ICP analysis. Next, we conducted migration tests. Samples conformed to the Italian Specific Migration Limits. Moreover, lead and antimony were not detected in these samples, in accordance with the Japanese Food Sanitation Law.


Borrmann effect in photonic crystals.
We present the experimental observation of the optical Borrmann effect in 1D porous silica-based photonic crystals (PhC) composed of several hundreds of dielectric layers with different porosity. Two mechanisms of the effect are demonstrated, which involve the optical losses associated with light scattering and absorption in nanoporous layers. Absorption is introduced by a small amount of silicon in partially annealed porous silicon PhC. We show that the PhC transmittance increases substantially under the Bragg diffraction condition, which is a manifestation of the Borrmann effect. The observed effects along with their polarization sensitivity are confirmed by numerical calculations.


Localization of stx, a determinant essential for high-level production of shiga toxin by Shigella dysenteriae serotype 1, near pyrF and generation of stx transposon mutants.
Hfr strains of Shigella dysenteriae serotype 1 were constructed by transient integration of an RP4 plasmid derivative carrying transposon Tn501 into the Shigella chromosome through Tn501-mediated cointegration. The Hfr strains were mated with Escherichia coli K-12 recipients carrying various auxotrophic markers, and E. coli recombinants which had received prototrophic Shigella genes were selected. Some of the E. coli transconjugants produced high levels of a cytotoxin which was neutralized by both polyclonal and monoclonal anti-Shiga toxin sera. The determinant for Shiga toxin production, designated stx, was first transferred to E. coli K-12 and then mapped by Hfr crosses to the trp-pyrF region located at 30 min on the E. coli chromosome. Bacteriophage P1-mediated transduction analysis of stx gave the following gene order: trp-pyrF-stx. The level of Shiga toxin production in E. coli Stx+ transconjugants and transductants was as high as that of the parental S. dysenteriae 1 strain. Stx- mutants of an Stx+ E. coli transductant were generated by random in vivo insertion mutagenesis with a Tn10 derivative transposon, Tn-mini-kan, followed by P1 cotransduction of the kanamycin resistance and PyrF+ markers into a pyrF Stx+ E. coli K-12 recipient. One stx::Tn-mini-kan transposon mutation was transferred by P1 transduction from this E. coli Stx- mutant to an E. coli K-12 Hfr strain and in turn transferred by conjugation to the original S. dysenteriae 1 strain plus two others. All kanamycin-resistant recombinants of S. dysenteriae 1 had lost their ability to produce high levels of Shiga toxin. A gene that specifies high-level Shiga toxin production is thus located near pyrF on the chromosome of S. dysenteriae 1. Stx- mutants of S. dysenteriae 1 exhibited full virulence in the Serény test.


Antitumor effects and hematotoxicity of C60-Cis-Pt nanocomplex in mice with Lewis lung carcinoma.
Cisplatin (Cis-Pt) is a widely used anticancer drug but its therapeutic efficiency is limited by hemato-, cardio-, hepato-, nephro- and neurotoxicity. Complexation of Cis-Pt with C60 fullerene nanoparticle will allow to enhance the antitumor activity of the drug and to reduce its side toxic effects. To estimate the antitumor effects of С60-Cis-Pt nanocomplex in Lewis lung carcinoma (LLC) and analyze hematological toxicity in tumor-bearing mice. Complexation of C60 fullerene and Cis-Pt molecule was studied by computer simulation. С60-Cis-Pt nanocomplex was i.p. injected to LLC-bearing mice in a total dose of 7.5 mg/kg (C60:Cis-Pt as 3.75:3.75 mg/kg). The survival of tumor-bearing mice and the relative reduction of tumor weight was recorded. Blood indices were determined using the Particle Counter PCE-210 automatic hematology analyzer. Computer simulation demonstrated the formation of С60-Cis-Pt nanocomplex in physiological medium and its stability due to the hydrophobic interactions. Treatment with C60-Cis-Pt nanocomplex increased survival time of LLC-bearing mice by 32%, normalized hemoglobin content (up to 100 g/l), erythrocyte and platelet count as compared to the untreated LLC-bearing mice. Tumor weight decreased by 35.5%; the mitotic index of tumor cells decreased by 78%, and apoptotic index increased by 75%. The revealed effects of the C60-Cis-Pt nanocomplex were more pronounced than the effects of Cis-Pt or C60 fullerene alone in equivalent dose. Treatment with C60-Cis-Pt nanocomplex prolonged the survival of LLC-bearing mice and reduced anemia in LLC-bearing mice.


Differential proteomics of Helicobacter pylori associated with autoimmune atrophic gastritis.
Atrophic autoimmune gastritis (AAG) is a condition of chronic inflammation and atrophy of stomach mucosa, for which development can be partially triggered by the bacterial pathogen Helicobacter pylori (HP). HP can cause a variety of gastric diseases, such as duodenal ulcer (DU) or gastric cancer (GC). In this study, a comparative proteomic approach was used by two-dimensional fluorescence difference gel electrophoresis (DIGE) to identify differentially expressed proteins of HP strains isolated from patients with AAG, to identify markers of HP strain associated with AAG. Proteome profiles of HP isolated from GC or DU were used as a reference to compare proteomic levels. Proteomics analyses revealed 27 differentially expressed spots in AAG-associated HP in comparison with GC, whereas only 9 differential spots were found in AAG-associated HP profiles compared with DU. Proteins were identified after matrix-assisted laser desorption ionization (MALDI)-TOF and peptide mass fingerprinting. Some AAG-HP differential proteins were common between DU- and GC-HP (peroxiredoxin, heat shock protein 70 [HSP70], adenosine 5'-triphosphate [ATP] synthase subunit α, flagellin A). Our results presented here may suggest that comparative proteomes of HP isolated from AAG and DU share more common protein expression than GC and provide subsets of putative AAG-specific upregulated or downregulated proteins that could be proposed as putative markers of AAG-associated HP. Other comparative studies by two-dimensional maps integrated with functional genomics of candidate proteins will undoubtedly contribute to better decipher the biology of AAG-associated HP strains.


[Azilsartan Medoxomil Capabilities in Arterial Hypertension and Obesity].
Arterial hypertension (AH) is one of the most common cardiovascular disease. Angiotensin II (AT II), the hormone of renin-angiotensin-aldosterone system, realizes its negative effects through AT 1 receptors - application point of angiotensin receptor blockers (ARB). Due to different dissociation AT 1 receptors properties some ARBs are more effective than others. Multiply multicenter randomized and observational studies approve the effectiveness and safety of azilsartan medoxomil in patients with AH 1-2 grade. Several preclinical studies have shown the additional properties of azilsartan, including increase of insulin sensitivity, cardio- and nephron protection in obesity. In our clinical case we showed the positive influence of azilsartan medoxomil on clinic and ambulatory blood pressure, 24-hour aortic stiffness parameters, longitudinal left ventricular strain in patient with AH and obesity.


CD44 crosslinking-mediated matrix metalloproteinase-9 relocation in breast tumor cells leads to enhanced metastasis.
CD44 plays a major role in multiple physiological processes, including cell-cell adhesion, cell-substrate interaction, lymphocyte homing, and tumor metastasis. It has been reported that highly expressed CD44 in certain types of tumors is associated with the hematogenic spread of tumor cells. The ability of CD44 to bind hyaluronan has been shown to correlate with tumor cell invasiveness, and it is likely that this ability may enhance tumor cell migration at several points during metastasis. However, the mechanism as to how CD44 stimulates metastasis remains unknown. The human breast tumor cell line, MDA-MB-435s, was used to investigate the effect of antibody-mediated CD44 crosslinking on the cellular level and localization of matrix metalloproteinase-9 (MMP-9). Confocal microscopy and immunocytochemical analyses were performed to demonstrate colocalization of CD44 and MMP-9 after CD44 crosslinking. Furthermore, the CD44-MMP-9 complex was purified by immunoprecipitation. G8 myoblast monolayers were employed to evaluate the invasiveness of human breast tumor cells after CD44 crosslinking in the presence or absence of protease inhibitors. CD44 crosslinking augmented the level of MMP-9 in the membrane of human breast tumor cells and clustering of CD44 serves as an MMP-9 docking molecule allowing MMP-9 to retain its concentrated proteolytic activity on the cell surface. Furthermore, crosslinking of CD44 enhances the ability of breast tumor cells to invade G8 myoblast monolayers and migrate through the basal membranes which was inhibited in the presence of anti-MMP-9 antibody or the MMP inhibitors GM6001 or 1,10-phenanthroline. This study demonstrates for the first time that CD44 crosslinking leads to an enhanced level and relocation of MMP-9 in human breast tumor cells accompanied by increased tumor invasion and metastasis.


Golgi and electronmicroscopic studies of spongiform encephalopathy.
Golgi impregnations of cerebral biopsies from two patients suffering from Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) revealed striking loss of dendritic spines of pyramidal neurons and unusual focal spherical distensions of dendritic and axonal processes. Light and electronmicroscopic studies disclosed spongiform changes, which seemed to be caused by intracytoplasmic vacuoles and expansion of the plasmalemmal membranes of neurons and astrocytes. Although the diagnostic biopsies were performed at a markedly symptomatic stage of the disease, there was no evidence of neuronal cell loss. Neuronal changes in Golgi impregnations of cerebral cortex from hamsters infected with scrapie were essentially identical to those in the human biopsies. The loss of dendritic spines of pyramidal cells and spherical swellings of axons and dendrites thus seem to be characteristic of spongiform encephalopathies, and probably account in part for the clinical neurologic manifestations, which may be severe in the relative absence of neuronal death.


Relationship between Nonhepatic Serum Ammonia Levels and Sepsis-Associated Encephalopathy: A Retrospective Cohort Study.
Nonhepatic hyperammonemia often occurs in patients with sepsis. Ammonia plays an essential role in the occurrence of hepatic encephalopathy. However, the relationship between nonhepatic serum ammonia levels and sepsis-associated encephalopathy (SAE) remains unclear. Thus, we aimed to evaluate the association between serum ammonia levels and patients with SAE. Data of critically ill adults with sepsis who were admitted to the intensive care unit were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) between 2008 and 2019 and retrospectively analyzed. Data of patients with sepsis patients and serum ammonia not related to acute or chronic liver disease were not included. Data from 720 patients with sepsis were included. SAE was found to have a high incidence (64.6%). After adjusting for other risk factors, a serum ammonia level of ≥45 μmol/L (odds ratio (OR): 3.508, 95% confidence interval (CI): 2.336-5.269, p < 0.001) was found to be an independent risk factor for patients with SAE; moreover, as the serum ammonia level increased, the hospital mortality of SAE gradually increased in a certain range (serum ammonia <150 μmol/L). Serum ammonia levels of ≥45 μmol/L were associated with higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment (SOFA) scores in patients with SAE. Besides, our study found that patients with SAE used opioid analgesics (OR:3.433, 95% CI: 1.360-8.669, p = 0.009) and the SOFA scores of patients with SAE (OR: 1.126, 95% CI: 1.062-1.194, p < 0.001) were significantly higher than those without SAE. Nonhepatic serum ammonia levels of ≥45 μmol/L evidently increased the incidence of SAE. Serum ammonia levels should be closely monitored in patients with sepsis.


A Global View of Digital Replantation and Revascularization.
Survival rates of digital replantation vary in different regions and countries, and Asian surgeons see more challenging cases and have developed some unique methods. Replantation of multiple digits in one or both hands can follow a structure-by-structure method or a digit-by-digit method. For replanting all 10 digits, 3 or 4 teams should be organized. Flow-through flaps, often venous flaps, can be taken from the distal forearm or lower extremity to repair defects of soft tissues and arteries. A pedicled digital artery flap from the adjacent digit can also repair tissue defects and supply blood to the replanted digit.


Tubulointerstitial Injury and Drugs of Abuse.
Drug abuse is widespread in many populations, and patients abusing illicit substances are at a significantly increased risk of kidney injury. The tubulointerstitial compartment is a common target of these nephrotoxic agents. This review will cover some of the common illicit drugs and will focus on the tubulointerstitial injuries seen in the setting of drug abuse. Agents addressed in this review are synthetic cannabinoids, "bath salts," ecstasy, anabolic steroids, inhaled solvents, heroin, and cocaine. The most frequent biopsy findings are those of acute tubular necrosis and acute interstitial nephritis. Unfortunately, histology is often unable to sufficiently narrow the differential diagnosis and point to a single likely cause. A high suspicion for drug abuse as a potential cause of kidney injury is needed to identify the patients for whom this is the cause of their kidney failure. Toxicology screens are often of little use in identifying patients using emerging drugs of abuse.


A theoretical study of ternary indole-cation-anion complexes.
The simultaneous interactions of an anion and a cation with a π system were investigated by MP2 and M06-2X theoretical calculations. Indole was chosen as a model π system for its relevance in biological environments. Two different orientations of the anion, interacting with the N-H and with the C-H groups of indole, were considered. The four cations (Na(+), NH4(+), C(NH2)3(+) and N(CH3)4(+)) and the four anions (Cl(-), NO3(-), HCOO(-) and BF4(-)) included in the study are of biological interest. The total interaction energy of the ternary complexes was calculated and separated into its two- and three-body components and all of them are further divided into their electrostatic, exchange, repulsion, polarization and dispersion contributions using the local molecular orbital-energy decomposition analysis (LMO-EDA) methodology. The binding energy of the indole-cation-anion complexes depends on both ions, with the cation having the strongest effect. The intense cation-anion attraction determines the geometric and energetic features in all ternary complexes. These structures, with both ions on the same side of the π system, show an anti-cooperative interaction. However, the interaction is not only determined by electrostatics, but also the polarization contribution is important. Specific interactions like the one established between the anion and the N-H group of indole or the proton transfer between an acidic cation and a basic anion play a significant role in the energetics and the structure of particular complexes. The presence of the polar solvent as modelled with the polarizable continuum model (PCM) does not seem to have a significant effect on the geometry of the ternary complexes, but drastically weakens the interaction energy. Also, the strength of the interaction is reduced at a faster rate when the anion is pushed away, compared to the results obtained in the gas phase. The combination of PCM with the addition of one water molecule indicates that the PCM method properly reproduces the main energetic and geometrical changes, even at the quantitative level, but the explicit hydration allows refining the solvent effect and detecting cases that do not follow the general trend.


A Novel Therapeutic Mechanism of Imipridones ONC201/ONC206 in MYCN-Amplified Neuroblastoma Cells via Differential Expression of Tumorigenic Proteins.
Neuroblastoma is the most common extracranial nervous system tumor in children. It presents with a spectrum of clinical prognostic measures ranging from benign growths that regress spontaneously to highly malignant, treatment evasive tumors affiliated with increased mortality rates. MYCN amplification is commonly seen in high-risk neuroblastoma, rendering it highly malignant and recurrence prone. In our current study, we investigated the therapeutic potential of small molecule inducers of TRAIL, ONC201, and ONC206 in MYCN-amplified IMR-32 and non-MYCN-amplified SK-N-SH human neuroblastoma cell lines. Our results exhibit potent antitumor activity of ONC201 and ONC206 via a novel inhibition of EGF-induced L1CAM and PDGFRβ phosphorylation in both cell lines. Drug treatment significantly reduced cellular proliferation, viability, migration, invasion, tumorsphere formation potential, and increased apoptosis in both cell lines. The protein expression of tumorigenic NMYC, Sox-2, Oct-4, FABP5, and HMGA1 significantly decreased 48 h post-drug treatment, whereas cleaved PARP1/caspase-3 and γH2AX increased 72 h post-drug treatment, compared with vehicle-treated cells in the MYCN-amplified IMR-32 cell line. We are the first to report this novel differential protein expression after ONC201 or ONC206 treatment in human neuroblastoma cells, demonstrating an important multitarget effect which may yield added therapeutic benefits in treating this devastating childhood cancer.


Effects of Pax3 and Pax7 expression on muscle mass in the Pekin duck (Anas platyrhynchos domestica).
This study aimed to investigate whether the differential expression of muscle development-related genes is one of the reasons why muscle development differs between Pekin, Jianchang, and Heiwu ducks, which are all domesticated duck breeds (Anas platyrhynchos domestica) breeds. At 2 weeks of age, the RNA expression of paired box 7 (Pax7), paired box 3 (Pax3), myogenic differentiation antigen (MYOD), and myogenin (MYOG) genes were measured by quantitative polymerase chain reaction, and Pax3 and Pax7 protein levels were detected by western blot assay. Myofiber morphology was investigated using paraffin-embedded muscle sections. At 8 weeks of age, 30 ducks of each breed were slaughtered for meat quality determination. The results revealed that Pax3 and Pax7 expression levels at both the RNA and protein levels were high in the Pekin duck. In addition, MYOG expression levels in the Jianchang duck were significantly higher than in the other two duck breeds (P < 0.05). There were no significant differences in MYOD expression levels between the breeds (P > 0.05). Myofiber diameter and cross-sectional area were the largest in the Pekin duck and the smallest in the Heiwu duck. There were significant differences in slaughter data between these breeds, and muscle content was greatest in the Pekin duck. The results indicate that the muscle content of three different duck breeds is associated with the expression of satellite-cell marker genes.


Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes.
The mammalian SWI/SNF chromatin remodeling complex is a heterogeneous collection of related protein complexes required for gene regulation and genome integrity. It contains a central ATPase (BRM or BRG1) and various combinations of 10-14 accessory subunits (BAFs for BRM/BRG1 Associated Factors). Two distinct complexes differing in size, BAF and the slightly larger polybromo-BAF (PBAF), share many of the same core subunits but are differentiated primarily by having either AT-rich interaction domain 1A/B (ARID1A/B in BAF) or ARID2 (in PBAF). Using density gradient centrifugation and immunoprecipitation, we have identified and characterized a third and smaller SWI/SNF subcomplex. We termed this complex GBAF because it incorporates two mutually exclusive paralogs, GLTSCR1 (glioma tumor suppressor candidate region gene 1) or GLTSCR1L (GLTSCR1-like), instead of an ARID protein. In addition to GLTSCR1 or GLTSCR1L, the GBAF complex contains BRD9 (bromodomain-containing 9) and the BAF subunits BAF155, BAF60, SS18, BAF53a, and BRG1/BRM. We observed that GBAF does not contain the core BAF subunits BAF45, BAF47, or BAF57. Even without these subunits, GBAF displayed in vitro ATPase activity and bulk chromatin affinity comparable to those of BAF. GBAF associated with BRD4, but, unlike BRD4, the GBAF component GLTSCR1 was not required for the viability of the LNCaP prostate cancer cell line. In contrast, GLTSCR1 or GLTSCR1L knockouts in the metastatic prostate cancer cell line PC3 resulted in a loss in proliferation and colony-forming ability. Taken together, our results provide evidence for a compositionally novel SWI/SNF subcomplex with cell type-specific functions.


Hypervitaminosis a in pediatric hematopoietic stem cell patients requiring renal replacement therapy.
Chronic renal failure patients have been known to develop vitamin A toxicity, but a descriptive study of hypervitaminosis A in patients with acute renal failure (ARF) has not yet been published. The authors observed hypervitaminosis A in pediatric hematopoietic stem cell transplant (HSCT) patients. All HSCT patients admitted between January 2001 and May 2006 who experienced ARF, received renal replacement therapy (RRT), and had a vitamin A level drawn were included in this retrospective, descriptive study. Molar ratios of vitamin A and retinol-binding protein (RBP) were calculated to more accurately assess vitamin A status. Nineteen patients met the criteria for this study. At initial testing (generally between days 6 and 10 after initiation of RRT), 17 of the 19 patients had abnormally elevated vitamin A levels for their age. Molar ratios of vitamin A to RBP were elevated in 6 patients at initial testing. Prescribed vitamin A intake information (parenteral and enteral) was available for most patients; all but 3 had an average daily intake greater than 2000 IU/kg over the 30 days prior to RRT initiation. Many patients had symptoms possibly related to vitamin A toxicity, although interpretation of hair, skin, and liver abnormalities are difficult to ascertain in HSCT patients. Seven patients had other findings that may have been associated with vitamin A toxicity. Children undergoing HSCT who receive nutrition support (predominantly parenteral nutrition), experience ARF, and require RRT are at risk for hypervitaminosis A and toxicity.


[The elimination of hydroxyethyl starch 200/0.5, dextran 40 and oxypolygelatine (author's transl)].
After withdrawal of 400 ml whole blood and subsequent infusion of 500 ml of a colloidal plasma substituent, the intravascular and renal colloid elimination was investigated in 40 test subjects. The individual colloidal solutions could no longer be demonstrated in the intravascular space after the following times: 10% hydroxyethyl starch 200/0.5 (anthrone method) after six weeks, 10% dextran 40 (anthrone method) after two weeks, 6% hydroxyethyl starch 200/0.5 (anthrone method) after four weeks and 5.5% oxypolygelatine (hydroxyproline method) after two days. Colloidal plasma substitutes are polydisperse solutions with various molecular weights and degree of hydroxyethylation and therefore, also have a large number of different elimination constants. With repeated application, the intravascular colloid concentration shifts in favour of the molecules with a longer half life which are difficult to eliminate. The elimination of the clinically employed dextran 40 and oxypolygelatine solution could be best described with an open two-compartment model. As a result of its greater heterogeneity, the elimination of the moderately high molecular weight hydroxyethyl starch 200/0.5 could only be characterized approximately even assuming three elimination constants. In the first four days, the hydroxyethyl starch 200/0.5 was more rapidly eliminated compared to dextran 40. However, subsequently a very much lower elimination from the intravascular space was found for about 3% of the administered hydroxyethyl starch 200/0.5. Oxypolygelatine was eliminated especially rapidly. Accordingly, the greatest renal clearance was found for oxypolygelatine, which showed a close relation to the molecular weight. On the other hand, a rapid elimination simultaneously is followed by a correspondingly lower volume effect.


Silver nanoparticle-base lateral flow immunoassay for rapid detection of Staphylococcal enterotoxin B in milk and honey.
A silver nanoparticle (AgNP)-based sandwich-type lateral flow immunoassay (LFIA) was evaluated for rapid detection of Staphylococcal enterotoxin B (SEB) in milk and honey. The role of trisodium citrate dihydrate (TSC) in the formation of Ag/TSC nanoparticles was established using UV-Vis spectroscopy. The association of silver with TSC in Ag/TSC nanoparticles was studied by the decrease in the intensity of anodic peak potential at 0.47 V and shift to 0.30 V in cyclic voltammetry (CV). The morphological, compositional and interaction studies of the AgNPs conjugated with the anti-SEB polyclonal antibody (Ag-sAb) was established using transmission electron microscopy (TEM) and X-ray photo electron spectroscopy (XPS) measurements. The visible detection limit and optical detection limit of the SEB test strip were 0.5 and 0.125 ppm, respectively, in SEB standard solution. This assay showed no cross-reaction with Staphylococcal enterotoxin A, Staphylococcal enterotoxin C or Salmonella typhi. Finally, the SEB test strip was effectively applied for the detection of SEB in spiked liquid milk and viscous honey, with optical detection limits of 0.25 and 0.5 ppm, respectively.


Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity.
Silymarin (Sm) is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps) were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100(®) polymer (Rohm Pharma GmbH, Darmstadt, Germany). Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 μmol/g in hepatic tissue due to Smnps.


Nurses' Experience of Patient Care in Multibed Hospital Rooms: Results From In-Depth Interviews With Nurses After Further Education in Anesthesia.
The purpose of this study was to investigate and explore nurse's previous experiences of patient care in MBRs before their further education in anesthesia. Qualitative research. Data were collected through three focus group interviews using content data analysis. Maintaining patient privacy, providing conditions for communication between health care professionals and patients, and undertaking daily practical care were stated as the main problems in MBR care. Inferior conditions for providing sensitive information and communication with proxies, especially in association with language problems, were frequently encountered. Patient's proxies could facilitate several problematic issues in MBR care. The present study characterized well-defined and easily recognizable clinical problems experienced in the care of patients in an MBR setting from a nurse's perspective. The opinion shared by most nurses was that the inability to implement privacy, dignity, and sound communication with patients should be taken into account in future hospital designs. General dissatisfaction with work environment, increased stress, and the risk of errors in care may otherwise follow.


(2-Chloro-4-nitro-benzoato)(methanol)triphenyl-tin(IV).
In the title complex, [Sn(C(6)H(5))(3)(C(7)H(3)ClNO(4))(CH(4)O)], the five-coordinate Sn(IV) atom exists in a trigonal-bipyramidal environment, formed by a monodentate carboxyl-ate group, three phenyl rings and a methanol mol-ecule. The axial sites are occupied by the O atoms of the methanol mol-ecule and the carboxyl-ate group, while the equatorial plane is formed by the C atoms of three phenyl rings. The benzene ring of the 2-chloro-4-nitro-benzoate ligand makes dihedral angles of 66.18 (7), 74.71 (7) and 77.39 (7)° with respect to the three phenyl rings. In the crystal, the mol-ecules are linked via inter-molecular O-H⋯O and C-H⋯O hydrogen bonds into a column along the b axis.


Korean Nursing Students' Acquisition of Evidence-Based Practice and Critical Thinking Skills.
Evidence-based practice (EBP) is essential for enhancing nurses' quality of care. We identified Korean nursing students' practices, attitudes, and knowledge concerning EBP, as well as their critical thinking disposition (CTD). The EBP Questionnaire (EBPQ) was administered to a convenience sample of 266 nursing students recruited from four nursing schools in Seoul and its metropolitan area. Average EBPQ and CTD total scores were 4.69 ± 0.64 and 3.56 ± 0.32, respectively. Students who were ages ⩾23 years, male, and satisfied with their major demonstrated higher EBPQ and CTD scores. EBPQ scores were significantly correlated with CTD scores (r = .459, p < .01), and CTD was an explanatory factor of EBP (adjusted R2 = 0.200). It is necessary to develop comprehensive teaching strategies to help nursing students improve their CTD and information utilization skills, as well as integrate EBP in undergraduate programs to enhance nurses' EBP abilities. [J Nurs Educ. 2018;57(1):21-27.].


Homemade Candy Plug Using a Zenith Alpha Thoracic Stent-Graft for False Lumen Distal Occlusion in Acute-on-Chronic Type B Aortic Dissection.
Purpose: To report a candy-plug technique using a Zenith Alpha stent-graft to occlude the distal false lumen in a patient with a complicated chronic type B aortic dissection. Case Report: A 50-year-old male smoker presented with chest pain due to rapidly growing complicated chronic type B aortic dissection. Computed tomography angiography (CTA) showed the dissection extending from distal to the origin of the left subclavian artery (LSA) down to the left femoral artery. There was fusiform aneurysmal dilatation of the proximal descending aorta measuring up to 5.8 cm in diameter. He underwent left carotid-subclavian artery bypass, thoracic endovascular aortic repair with a Zenith Alpha stent-graft, a left common carotid artery chimney, and embolization of the proximal LSA. Serial CTA showed persistent false lumen flow. A decision was made to occlude the distal large false lumen using the candy-plug technique. A 44×125-mm Zenith Alpha stent-graft was used to prepare the candy plug. A gutter leak and a type Ia endoleak were embolized via a left brachial artery approach. At 2.5 years, imaging showed the candy plug in position, no endoleak, and the thrombosed false lumen in the thoracic aorta reduced in size. Conclusion: The candy-plug technique is useful in facilitating complete occlusion of the false lumen in chronic aortic dissection, which avoids an open procedure and the risk of higher morbidity.


Quantum chemical studies of protein structure.
Quantum chemical methods now permit the prediction of many spectroscopic observables in proteins and related model systems, in addition to electrostatic properties, which are found to be in excellent accord with those determined from experiment. I discuss the developments over the past decade in these areas, including predictions of nuclear magnetic resonance chemical shifts, chemical shielding tensors, scalar couplings and hyperfine (contact) shifts, the isomer shifts and quadrupole splittings in Mössbauer spectroscopy, molecular energies and conformations, as well as a range of electrostatic properties, such as charge densities, the curvatures, Laplacians and Hessians of the charge density, electrostatic potentials, electric field gradients and electrostatic field effects. The availability of structure/spectroscopic correlations from quantum chemistry provides a basis for using numerous spectroscopic observables in determining aspects of protein structure, in determining electrostatic properties which are not readily accessible from experiment, as well as giving additional confidence in the use of these techniques to investigate questions about chemical bonding and chemical reactions.


Classicula: the teleomorph of Naiadella fluitans.
A new genus, Classicula, and a new species, Classicula fluitans, are described in the Urediniomycetes for the teleomorph of Naiadella fluitans. Classicula fluitans forms transversely septate basidia with subapically swollen sterigmata and long fusiform basidiospores. An integrated analysis of morphological, ultrastructural and molecular data indicates that Classicula fluitans is a member of the Urediniomycetes. Among the Urediniomycetes, Classicula fluitans shares the formation of simple septal pores associated with microbodies and tremelloid haustorial cells only with the hyphomycete Jaculispora submersa. In addition, in our molecular phylogenetic analyses with at least two representatives of all known urediniomycetous groups, Classicula fluitans appears together with Jaculispora submersa in a statistically well-supported cluster. Accordingly, the family Classiculaceae and the order Classiculales are proposed to accommodate these fungi in the Urediniomycetes.


Living alone and depression: the modifying role of the perceived neighborhood environment.
Older adults who live alone are more likely to report feelings of depression than those who live with a spouse or other family members. This study examines the effects of residential status and perceived neighborhood characteristics on depression in middle-aged and older adults. This study is based on a probability sample of 1049 adults aged 55-98 years (M = 69 years) residing in Allegheny County, Pittsburgh, PA, USA in 2014. Thirty percent of participants reported living alone. We tested a multivariate model using living alone (vs. living with a family member or others) and perceived neighborhood physical and social quality as predictors of depressive symptomatology while controlling for age, sex, race, education, and disability. Living alone (compared to living with a family member) was associated with elevated levels of depressive symptomatology. However, perceptions of neighborhood social quality moderated this association. Living alone was more highly associated with depression when the perceived social quality of the neighborhood was low. Neighborhood social quality was not associated with depression among older adults who lived with a family member. Perceptions of neighborhood physical quality were not significantly associated with depression. Perceptions of good neighborhood social quality is important for adults who live alone, in terms of fewer symptoms of depression.


Importance of temporal heterogeneity in assessing the contraction abnormalities associated with acute myocardial ischemia.
A number of recent two-dimensional echocardiographic studies have attempted to relate quantitative changes in short-axis left ventricular radial wall motion to underlying myocardial ischemia/infarction. The significance of temporal variation in the contraction sequence within these ischemic regions in the overall evaluation of segmental left ventricular dysfunction, however, remains undefined. To assess this, we examined the motion of 192 individual radii that intersected known ischemic segments at 16.7 msec intervals from end-diastole to end-systole. The studies were performed in 13 dogs 1 hr after acute coronary ligation (six of the left anterior descending and seven of the circumflex coronary artery). Zones of infarction were confirmed by triphenyltetrazolium chloride staining at the termination of the experiment and by a corresponding decrease of more than 75% in myocardial perfusion at the 1 hr sampling period. Dyskinesis (defined for each radius as negative or outward excursion relative to the end-diastolic reference on two consecutive fields) was noted along 168 of 192 radii (88%) at some point in the contraction sequence. The maximal outward or dyskinetic motion occurred most commonly in the fourth decile of the normalized contraction sequence. In 147 of the 168 dyskinetic radii (88%) the maximal outward motion occurred during the first half of systole while in only two radii in one animal was the maximal outward motion noted at end-systole. The total number of radii showing dyskinetic motion at any given point in the contraction sequence likewise varied with time. Although again the greatest number of radii showed abnormal motion during the fourth decile of the normalized contraction sequence, only 66 of 168 or 39% remained dyskinetic to end-systole. No relationship was observed between the point of maximal dyskinesis (time-weighted average of all dyskinetic radii for a given animal) and (1) the total number of radii showing dyskinesis, (2) the total number of radii within the infarct zone, or (3) the infarct area expressed as a percent of the slice area. The major factor determining persistence of dyskinesis to end-systole for any radius was the maximal outward motion of the endocardial segment at the point of maximal dyskinesis. Therefore, simple measurement of endocardial excursion from end-diastole to end-systole may fail to detect important wall motion abnormalities and, in some cases, may miss dyskinetic segments completely.


Oligorecurrence Non-small Cell Lung Cancer After Failure of First-Line Chemotherapy: Computed Tomography-Guided 125I Seed Implantation vs. Second-Line Chemotherapy.
Purpose: To compare the efficacy and safety of computed tomography (CT)-guided 125I seed implantation with second-line chemotherapy in treatment of oligorecurrence non-small cell lung cancer after failure of first-line chemotherapy. Methods: Data of oligorecurrence non-small cell lung cancer patients after failure of first-line chemotherapy at two institutions were retrospectively reviewed from January 2013 to July 2018. A total of 53 patients who received the treatment of 125I seed implantation or second-line chemotherapy were eligible for this study. In group A, 25 patients, 84 lesions, received CT-guided permanent 125I seed implantation, whereas in group B, 28 patients, 96 lesions, received second-line chemotherapy. The outcomes were measured in terms of disease control rate, overall survival, quality of life, and complications. Results: The median follow-up period was 13 months (range, 5-42 months). Disease control rate in group A was higher than that in group B (70.8 vs. 42.3%, P = 0.042) at 6 months after treatment. The median overall survival was 12.8 months (95% confidence interval, 10.5-15.1 months) in group A and 15.2 months (95% confidence interval, 12.2-18.2 months) in group B, with no significant difference (P = 0.847). Since the fourth month, the number of patients in group A with a non-decreasing Karnofsky Performance Scale score was more than that in group B (P < 0.05). The incidence of grade 3 or higher complications especially hematologic toxicity in group A was significantly lower than that in group B (P < 0.05). Conclusion: Radioactive 125I seed implantation is safe and feasible in selected non-small cell lung cancer patients with oligorecurrence after failure of first-line chemotherapy and seems to provide a better long-term quality of life in these patients compared with second-line chemotherapy.


The effects of sulindac and diclofenac in essential hypertension controlled by treatment with a beta blocker and/or diuretic.
A placebo-controlled, double blind crossover study of the non-steroidal anti-inflammatory drugs (NSAIDs) sulindac and diclofenac was conducted in 16 patients with essential hypertension that was controlled by treatment with a beta blocker, a diuretic or co-administration of both. In 4 cases, another antihypertensive agent (prazosin or verapamil) was also co-administered. In every patient, plasma creatinine concentration was less than 0.14 mmol/l (normal range 0.07-0.12 mmol/l). Sulindac and diclofenac were each given for 7 weeks. Diclofenac caused a decrease of borderline significance in plasma aldosterone concentration. Neither NSAID altered the mean values for systolic or diastolic blood pressure, body weight, plasma electrolyte concentrations, urate clearance, creatinine clearance or plasma renin activity. However, rises in plasma creatinine concentration and falls in creatinine clearance occurred during NSAID therapy in three individual subjects. No significant differences were observed in this study between the effects on renal function or blood pressure of sulindac and diclofenac, both of which appear not to interfere with the antihypertensive actions of beta blockers and diuretics.