16,16-Dimethyl prostaglandin E2 alleviates jejunal microvascular effects of ethanol but not the ethanol-induced inhibition of water, sodium, and glucose absorption.
To examine the relation between ethanol-induced microvascular and absorptive changes, we have investigated the effect of 16,16-dimethyl prostaglandin E2 on the jejunal intraluminal plasma albumin loss (which was taken as a measure of microvascular changes) and the inhibition of water, sodium, and glucose transport caused by intraluminal ethanol. A group of 8 dogs received intravenously 16,16-dimethyl prostaglandin E2 at a dose of 0.1 microgram/kg as a bolus followed by 0.05 microgram/kg.hour for 2 h (prostaglandin-treated group). A second group of 8 dogs received no 16,16-dimethyl prostaglandin E2 (untreated group). In each dog of both groups, one jejunal segment was perfused with an ethanol-free solution (control segment) and an adjacent segment was perfused with the same solution containing 6% (wt/vol) ethanol (ethanol-perfused segment). The albumin loss (mg/g dry gut wt.90 min, mean +/- SE) by the control and the ethanol-perfused segments was 0.76 +/- 0.23 and 8.29 +/- 1.27, respectively, in the untreated group, and 0.66 +/- 0.23 and 4.81 +/- 0.67, respectively, in the prostaglandin-treated group. The ethanol-induced increase in albumin loss was significant in both groups, but was significantly lower (p less than 0.05) in the prostaglandin-treated group than in the untreated group. Intraluminal ethanol depressed net water, sodium, and glucose transport by 74%, 52%, and 22%, respectively, in the untreated group, and by 92%, 65%, and 38%, respectively, in the prostaglandin-treated group. The magnitude of this depression did not differ significantly between the two groups. As 16,16-dimethyl prostaglandin E2 attenuated the ethanol-induced plasma albumin loss, but not the inhibition of water, sodium, or glucose transport, we conclude that the microvascular and the absorptive changes produced by ethanol are not mediated by the same mechanism.


Improved efficacy of some phosphate-based dentin-bonding agents.
The gap-reducing efficacy of four phosphate-based dentin-bonding agents was tested after various treatments of the dentin and/or the bonding agents. The investigation was carried out on extracted human teeth. One of the root surfaces was ground flat, and a cylindrical butt-joint cavity was prepared in the ground dentin surface. It was found that the efficacy of two of the adhesives, presumably being chloro-substituted phosphates, could be markedly improved if the primed dentin was rinsed with copious amounts of water, dried by compressed air, and a second layer of bonding agent applied. The mechanism behind this improvement is assumed to be the formation of hydrogen chloride, which dissolves part of the smear layer.


Consequences of blocking the nerve with a local anaesthetic on the evolution of multiinnervation at the regenerating neuromuscular junction of the rat.
A transient multiinnervation is observed in adult rats during reinnervation of the soleus muscle. Chronic blockage of the sciatic nerve with a cuff of the local anaesthetic lidocaine during reinnervation increases the number of multiply innervated muscle fibres. This result indicates that the selective elimination of redundant nerve terminals is regulated by the activity of the innervated muscle.


Actual standard and further development of an algal fluorescence bioassay.
A measurable result of nearly all influences which affect the primary processes of photosynthesis is a change of the fluorescence emission of a plant. This change of the fluorescence emission due to substances which affect or block photosynthesis is well known since the work of Kautsky (1943). The fluorescence test used here, due to the optical characteristics of the photosynthetic pigments (chlorophyll fluorescence greater than 660 nm), allows the measurement of the fluorescence of algae (Scenedesmus sp./Chlorella sp.). The measurement process is demonstrated. The results show the principal function of the bioassay and its sensitivity. Effects of the algae can be demonstrated at a very low pollutant concentration. The time from the dosage of a toxicant to a clear reaction of the algae is very short (5 min). The aim of the actual research is the determination of the sensitivity of the bioassay to a representative number of chemicals and possible interactions with physical parameters. A connection to a data system, e.g., computer registration of the fluorescence curve and an automated process control, will be the next step.


Visualized changes in respiratory resistance and reactance along a time axis in smokers: a cross-sectional study.
Early detection of changes in respiratory function in smokers is important for the prevention of chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate any changes in the respiratory impedance of smokers with normal FEV1/FVC. We assessed and compared the impedance components, respiratory resistance, and reactance in both the inspiratory and expiratory phases of nonsmokers, smokers, and COPD patients. Approximately 60% of smokers showed elevated resistance and a negative shift in reactance, mainly in the expiratory phase, as observed in COPD patients. Smokers showed an increased gap between the maximum and minimum R5 and X5 values (R5sub, X5sub) in comparison with nonsmokers. Furthermore, R5-R20 was significantly higher in smokers than in nonsmokers. The expiratory-inspiratory gaps in resistance and reactance were also significantly higher in smokers than in nonsmokers. In smokers and COPD patients, the magnitude of expiratory X5 was more negative than that in nonsmokers. In smokers with V·50/V·25≥3, R5-R20 was significantly higher than those in smokers with V·50/V·25<3. Approximately 60% of smokers were shown to exhibit apparent impedance changes despite having normal FEV1/FVC values. Smoking-induced early remodeling of the small airways may be responsible for the observed changes in airway function of smokers. Further studies are necessary to determine if the change in respiratory impedance observed in smokers is an early indicator of COPD.


Effect of selective decontamination of the digestive tract of donor and recipient on the occurrence of murine delayed-type graft-versus-host disease.
In the present study we investigated the occurrence of delayed-type graft-versus-host disease (DT-GvHD) after allogeneic bone marrow transplantation (BMT) between two H-2 incompatible mouse strains. BMT was performed on mice with a conventional intestinal microflora as well as on mice in which the Enterobacteriaceae were selectively eliminated from the intestinal microflora by oral antibiotic treatment. None of the conventional or the selectively decontaminated (SD) chimaeric mice suffering from DT-GvHD died of bacteraemia. While DT-GvHD was mitigated when C3H/He recipient mice were SD-treated, this was not the case when C57B1/6J recipient mice were SD-treated. SD-treatment of the digestive tract of donor mice only mitigated DT-GvHD when the recipients were also SD-treated. We conclude that Enterobacteriaceae in the digestive tract may only play a minor role, if any, in the occurrence of DT-GvHD. Instead, we postulate that in this study DT-GvHD was determined by differences in the composition of the resident intestinal microflora (IM) of both mouse strains together with the cellular composition of the bone marrow graft. The interaction between antigenic components of the recipient's IM and the developing donor immune system in the recipient as a possible cause for DT-GvHD is discussed.


Reliability of the gamma index analysis as a verification method of volumetric modulated arc therapy plans.
We investigate the gamma passing rate (GPR) consistency when applying different types of gamma analyses, linacs, and dosimeters for volumetric modulated arc therapy (VMAT). A total of 240 VMAT plans for various treatment sites, which were generated with Trilogy (140 plans) and TrueBeam STx (100 plans), were retrospectively selected. For each VMAT plan, planar dose distributions were measured with both MapCHECK2 and ArcCHECK dosimeters. During the planar dose distribution measurements, the actual multileaf collimator (MLC) positions, gantry angles, and delivered monitor units were recorded and compared to the values in the original VMAT plans to calculate mechanical errors. For each VMAT plan, both the global and local gamma analyses were performed with 3%/3 mm, 2%/2 mm, 2%/1 mm, 1%/2 mm, and 1%/1 mm. The Pearson correlation coefficients (r) were calculated 1) between the global and the local GPRs, 2) between GPRs with the MapCHECK2 and the ArcCHECK dosimeters, 3) and between GPRs and the mechanical errors during the VMAT delivery. For the MapCHECK2 measurements, strong correlations between the global and local GPRs were observed only with 1%/2 mm and 1%/1 mm (r > 0.8 with p < 0.001), while weak or no correlations were observed for the ArcCHECK measurement. Between the MapCHECK2 and ArcCHECK measurements, the global GPRs showed no correlations (all with p > 0.05), while the local GPRs showed moderate correlations only with 2%/1 mm and 1%/1 mm for TrueBeam STx (r > 0.5 with p < 0.001). Both the global and local GPRs always showed weak or no correlations with the MLC positional errors except for the GPRs of MapCHECK2 with 1%/2 mm and 1%/1 mm for TrueBeam STx and the GPR of ArcCHECK with 1%/2 mm for Trilogy (r < - 0.5 with p < 0.001). The GPRs varied according to the types of gamma analyses, dosimeters, and linacs. Therefore, each institution should carefully establish their own gamma analysis protocol by determining the type of gamma index analysis and the gamma criterion with their own linac and their own dosimeter.


Association of body mass index and uncontrolled blood pressure with cardiovascular mortality in peritoneal dialysis patients.
The association of body mass index (BMI) and blood pressure (BP) control and their interaction with cardiovascular (CV) mortality in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear. We retrospectively analyzed a consecutive series of 1595 incident CAPD patients with hypertension from 2006 to 2013, and followed up through December 2015. The BMI was categorized according to the World Health Organization classification for Asian population. Binary logistic regression was used to assess the relationship between BMI and BP control. Cox's proportional hazards models and competing risk analyses were performed to examine the nassociation of BMI and BP control with CV mortality. In the entire cohort, obesity was unlikely related to increased risk of uncontrolled BP. However, the adjusted hazard ratio (AHR) of CV mortality was increased in individuals with obesity when compared to those with normal weight (AHR 1.56; 95% confidence interval (CI) 1.04-2.34) and in individuals with uncontrolled BP when compared to those with controlled BP (AHR 1.39; (1.02-1.89)). Subgroup analyses showed that the combination of obesity and uncontrolled BP was associated with an increased risk for CV death, when compared to normal weight subjects with uncontrolled BP (AHR 2.35; (1.43-3.86)). Further, subjects with obesity and uncontrolled BP had a nearly threefold increase in risk (AHR 2.57; (1.57-4.20)) for CV death compared to subjects with neither risk factor. These associations persisted in competing risk analyses. In conclusion, the association of obesity with CV mortality was likely to vary with hypertension status among CAPD patients.


Vasoactive intestinal peptide suppresses the NLRP3 inflammasome activation in lipopolysaccharide-induced acute lung injury mice and macrophages.
Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1β, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1β and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1β and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.


Upregulation of genes encoding plastidic isoforms of antioxidant enzymes and osmolyte synthesis impart tissue tolerance to salinity stress in bread wheat.
Wheat genotype Kharchia is a donor for salt tolerance in wheat breeding programs worldwide; however, the tolerance mechanism in Kharchia is yet to be deciphered completely. To avoid spending energy on accumulating organic osmolytes and to conserve resources for maintaining growth, plants deploy sodium (Na+) ions to maintain turgor. The enhanced ability to tolerate excess ion accumulation and ion toxicity is designated as tissue tolerance. In this study, salt-tolerant wheat genotype (Kharchia 65) and sensitive cultivars (HD2687, HD2009, WL711) were exposed to vegetative stage salinity stress (for four weeks). Kharchia 65 showed better tissue tolerance to salinity than the other genotypes based on different physiological parameters. Gene expression and abundance of chloroplast localized antioxidant enzymes and compatible osmolyte synthesis were upregulated by salinity in Kharchia 65. In Kharchia 65, the higher abundance of NADPH Oxidase (RBOH) transcripts and localization of reactive oxygen species (ROS) suggested an apoplastic ROS burst. Expression of calcium signaling genes of SOS pathway, MAPK6, bZIP6 and NAC4 were also upregulated by salinity in Kharchia 65. Considering that Kharchia local is the donor of salt tolerance trait in Kharchia 65, the publically available Kharchia local transcriptome data were analyzed. Our results and the in-silico transcriptome analysis also confirmed that higher basal levels and the stress-induced rise in the expression of plastidic isoforms of antioxidant enzymes and osmolyte biosynthesis genes provide tissue tolerance in Kharchia 65. Thus, in salinity tolerant genotype Kharchia 65, ROS burst mediated triggering of calcium signaling improves Na+ exclusion and tissue tolerance to Na+. The online version contains supplementary material available at 10.1007/s12298-022-01237-w.


Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat.
Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 microg/h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxin-induced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10(-7) M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10(-7) M angiotensin II. The data indicate that blood-borne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood-brain barrier may have regulatory influences on fluid balance during pregnancy in rats.


Sézary's syndrome: report of a case showing peripheral neuropathy and bone marrow fibrosis.
A case of Sézary's syndrome occurred in a 45-year-old man. The unusual noteworthy features in this case are dermal sclerosis, peripheral neuropathy, and bone marrow fibrosis. In two other cases, reviewed here, there was a tendency to fibrosis; therefore, we propose that this process may be an integral part of Sézary's syndrome.


Dopamine 2 receptor C957T and catechol-o-methyltransferase Val158Met polymorphisms are associated with treatment response in electroconvulsive therapy.
Alterations in dopamine levels and dopamine receptors in brain are suggested to be associated with treatment response in electroconvulsive therapy (ECT). Dopamine 2 receptor gene (DRD2) polymorphism C957T (rs6277) and cathechol-o-methyltransferase (COMT) polymorphism Val158Met (rs4680) interaction was studied in 118 patients suffering from major depressive disorder (MDD) treated with ECT and 383 healthy controls. It was found that the combination of COMT Met allele and DRD2 T allele predicted more severe depression in those already affected but did not predict the risk of depression when compared to normal population. The genotype modified the response to ECT. The patients with TT genotype of D2 receptor gene C957T polymorphism combined with COMT gene polymorphism Met/Met genotype did not achieve remission as often as those with CC genotype of DRD2 C957T combined with COMT Val/Val genotype. Thus the interaction of these polymorphisms may be associated with response to ECT.


"APEC blue"--The effects and implications of joint pollution prevention and control program.
To ensure good air quality in Beijing during Asia-Pacific Economic Cooperation (APEC) China 2014, Beijing and its neighboring five provinces and the associated cities were combined under the Joint Prevention and Control of Atmospheric Pollution (JPCAP) program, which implemented rigorous cooperative emission reduction measures. The program was a unique and large-scale artificial experiment that showed that such measures can achieve excellent results, and it led to the popular "APEC blue" catchphrase (i.e., Beijing's skies became blue as pollution levels decreased). This artificial experiment provided the means to effectively conduct JPCAP strategies in the future. Accordingly, our research focused on the characteristics of the six primary pollutants in Beijing. We found that the JPCAP measures directly reduced concentrations of all pollutants except O3. Through correlation analysis, we found that the band distribution of the cities with strong correlations in PM2.5 and PM10 concentrations was affected by wind conditions. Therefore, JPCAP measures should account for specific seasonal and climatic conditions. Based on cluster analysis using the results from the correlation analysis, we divided 13 cities within a 300-km radius of Beijing into different groups according to the similarity of their PM2.5 and PM10 correlation coefficients. For JPCAP measures relevant to PM2.5 and PM10, we found differences in the degrees of collaboration among cities. Therefore, depending upon the pollutant type, the JPCAP strategy should account for the cities involved, the scope of the core area, and the optimal cities to involve in the collaborative efforts based on cost-effectiveness and collaborative difficulty among the involved cities.


Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection.
Highly-pathogenic avian influenza (HPAI) H5N1 and Newcastle disease (ND) viruses are the two most important poultry viruses in the world, with the ability to cause classic central nervous system dysfunction in poultry and migratory birds. To elucidate the mechanisms of neurovirulence caused by these viruses, a preliminary study was design to analyze host's cellular responses during infections of these viruses. An improved mRNA differential display technique (Gene Fishing™) was undertaken to analyze differentially expressed transcripts regulated during HPAI H5N1 and velogenic neurotropic NDV infections of whole brain of chickens. The identification of differentially expressed genes (DEGs) was made possible as this technique uses annealing control primers that generate reproducible, authentic and long PCR products that are detectable on agarose gels. Twenty-three genes were identified to be significantly regulated during infections with both viruses, where ten of the genes have been selected for validation using a TaqMan® based real time quantitative PCR assay. Some of the identified genes demonstrated to be key factors involving the cytoskeletal system, neural signal transduction and protein folding during stress. Interestingly, Septin 5, one of the genes isolated from HPAI H5N1-infected brain tissues has been reported to participate in the pathogenic process of Parkinson's disease. In this limited study, the differentially expressed genes of infected brain tissues regulated by the viruses were found not to be identical, thus suggesting that their neurovirulence and neuropathogenesis may not share similar mechanisms and pathways.


Tolerance and acceptance results of a palladium-103 permanent breast seed implant Phase I/II study.
To test, in a prospective Phase I/II trial, a partial breast irradiation technique using a 103Pd permanent breast seed implant (PBSI) realized in a single 1-h procedure under sedation and local freezing. Eligible patients had infiltrating ductal carcinoma < or = 3 cm in diameter, surgical margin > or = 2 mm, no extensive intraductal component, no lymphovascular invasion, and negative lymph nodes. Patients received a permanent seed implant, and a minimal peripheral dose of 90 Gy was prescribed to the clinical target volume, with a margin of 1.5 cm. From May 2004 to April 2007, 67 patients received the PBSI treatment. The procedure was well tolerated, with 17% of patients having significant pain after the procedure. Only 1 patient (1.5%) had an acute skin reaction (Grade 3 according to the National Cancer Institute Common Toxicity Criteria). The rates of acute moist desquamation, erythema, and indurations were 10.4%, 42%, and 27%, respectively. At 1 year the rate of Grade 1 telangiectasia was 14%. The rate of skin reaction decreased from 65% to 28% when skin received less than the 85% isodose. According to a Radiation Therapy Oncology Group questionnaire, 80-90% of patients were very satisfied with their treatment, and the remainder were satisfied. One patient (1.5%) developed an abscess, which resolved after the use of antibiotics. There was no recurrence after a median follow-up of 32 months (range, 11-49 months). The feasibility, safety, and tolerability of PBSI compares favorably with that of external beam and other partial breast irradiation techniques.


Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma.
Although several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. hMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. Serum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-β, interleukin (IL)-10, tumor necrosis factor-α-stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. Serum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs.


Gastrointestinal Tract Commensal Bacteria and Probiotics: Influence on End-Organ Physiology.
Bacteria represent the earliest form of independent life on this planet. Bacterial development has included cooperative symbiosis with plants (e.g., Leguminosae family and nitrogen fixing bacteria in soil) and animals (e.g., the gut microbiome). It is generally agreed upon that the fusion of two prokaryotes evolutionarily gave rise to the eukaryotic cell in which mitochondria may be envisaged as a genetically functional mosaic, a relic from one of the prokaryotes. This is expressed by the appearance of mitochondria in eukaryotic cells (an alpha-proteobacteria input), a significant endosymbiotic evolutionary event. As such, the evolution of human life has been complexly connected to bacterial activities. Hence, microbial colonization of mammals has been a progressively driven process. The interactions between the human host and the microbiome inhabiting the gastrointestinal tract (GIT) for example, afford the human host the necessary cues for the development of regulated signals that in part are induced by reactive oxygen species (ROS). This regulated activity then promotes immunological tolerance and metabolic regulation and stability, which then helps establish control of local and extraintestinal end-organ (e.g., kidneys) physiology. Pharmacobiotics, the targeted administration of live probiotic cultures, is an advancing area of potential therapeutics, either directly or as adjuvants. Hence the continued scientific understanding of the human microbiome in health and disease may further lead to fine tuning the targeted delivery of probiotics for a therapeutic gain.


Nanoparticular surface-bound PCBs, PCDDs, and PCDFs-a novel class of potentially higher toxic POPs.
In a previous study, Env Sci Poll Res:1-7, 2015 showed that polychlorinated biphenyls (PCBs), polychlorinated dibenzo dioxins (PCDDs), and polychlorinated dibenzo furanes (PCDFs) are found in commercially available (nano) particular titanium dioxide as a result of the fabrication. Here, we give a brief perspective and reason the toxicity of these new classes of persistent organic pollutants (POPs) by reviewing also their nanoparticular properties, such as surface-to-volume ratio, photocatalytic activity, polarity shifts, and stealth effect. These insights point towards a new class of POPs and toxicologic effects, which are related to the size but not a result of nanotechnology itself. We pave the way to the understanding of until now unresolved very complex phenomena, such as the indoor exposure, formation, and transformation of POP and sick-building syndrome. This is a fundamental message for nanotoxicology and kinetics and should be taken into account when determining the toxicity of nanomaterials and POPs separately and as a combination.


Phakometric measurement of ocular surface radii of curvature, axial separations and alignment in relaxed and accommodated human eyes.
Measurements (autokeratometry, A-scan ultrasonography and video ophthalmophakometry) of ocular surface radii, axial separations and alignment were made in the horizontal meridian of nine emmetropes (aged 20-38 years) with relaxed (cycloplegia) and active accommodation (mean +/- 95% confidence interval: 3.7 +/- 1.1 D). The anterior chamber depth (-1.5 +/- 0.3 D) and both crystalline lens surfaces (front 3.1 +/- 0.8 D; rear 2.1 +/- 0.6 D) contributed to dioptric vergence changes that accompany accommodation. Accommodation did not alter ocular surface alignment. Ocular misalignment in relaxed eyes is mainly because of eye rotation (5.7 +/- 1.6 degrees temporally) with small amounts of lens tilt (0.2 +/- 0.8 degrees temporally) and decentration (0.1 +/- 0.1 mm nasally) but these results must be viewed with caution as we did not account for corneal asymmetry. Comparison of calculated and empirically derived coefficients (upon which ocular surface alignment calculations depend) revealed that negligible inherent errors arose from neglect of ocular surface asphericity, lens gradient refractive index properties, surface astigmatism, effects of pupil size and centration, assumed eye rotation axis position and use of linear equations for analysing Purkinje image shifts.


Structure and reactivity of germylene-bridged digold complexes.
The bonding between gold and main-group metallic elements (M) featuring Auδ--Mδ+ polarity, has been studied recently. The gold in the bonds is expected to have the oxidation number of -1, and hence, nucleophilic. However, the knowledge of the reactivity of the gold-metal bonds remains limited. Here, we report digold-substituted germanes of the form of R'2Ge(AuPR3)(AuGeR'2) (3a; R = Me, 3b; R = Et), featuring two Au-Ge(IV) and one Au-Ge(II) bonds. DFT calculations of 3a revealed the existence of high-lying σ(Ge-Au) type HOMO and low-lying LUMO with germylene pπ nature. A pendular motion of AuPR3 group between Ge(IV) and Ge(II) of 3 occurs in the NMR time scale, suggesting that the Ge(II) center has an enhanced electrophilicity to be attacked by the nucleophilic gold (-I) atom. 3a reacts with nucleophilic Cl- and electrophilic MeOTf reagents at Ge(II) and Ge(IV) centers, respectively.


Atomically Dispersed Cu Nanozyme with Intensive Ascorbate Peroxidase Mimic Activity Capable of Alleviating ROS-Mediated Oxidation Damage.
Ascorbate peroxidase (APX) as a crucial antioxidant enzyme has drawn attentions for its utilization in preventing cells from oxidative stress responses by efficiently scavenging H2 O2 in plants. For eliminating the specific inactivation of natural APXs and regulating the catalytic activity, single-atom nanozymes are considered as promising classes of alternatives with similar active sites and maximal atomic utilization efficiency to natural APXs. Herein, graphitic carbon nitride (g-C3 N4 ) anchored with isolated single copper atoms (Cu SAs/CN) is designed as an efficient nanozyme with intrinsic APX mimetic behavior. The engineered Cu SAs/CN exhibits comparable specific activity and kinetics to the natural APXs. Based on the density functional theory (DFT), Cu-N4 moieties in the active center of Cu SAs/CN are determined to exert such favorable APX catalytic performance, in which the electron transfer between Cu and coordinated N atoms facilitates the activation and cleavage of the adsorbed H2 O2 molecules and results in fast kinetics. The constructed Cu SAs/CN nanozyme with superior APX-like performance and high biocompatibility can be applied for effectively protecting the H2 O2 -treated cells against oxidative injury in vitro. These findings report the single-atom nanozymes as a successful paradigm for guiding nanozymes to implement APX mimetic performance for reactive oxygen species-related biotherapeutic.


What gets in the way? Men's perspectives of barriers to mental health services.
This study describes barriers to accessing mental health services among men currently experiencing a mental health concern. Mental health help-seeking survey data from 778 male respondents who self-reported experiencing a mental health concern were analyzed. Of these men, 65% (n = 513) wanted treatment and 35% (n = 265) did not want treatment. The most frequently endorsed barriers to mental health treatment were believing that a lot of people feel sad and down (80%; n = 620), not knowing what to look for in a psychotherapist (counselor; 80%; n = 618) and needing to solve one's own problems (73%; n = 569). Compared with men who wanted help for their mental health concern, those men who did not want help were significantly more likely to be unsure if psychotherapy (counseling) really works or is effective, not tell their physician if they were feeling down or depressed and prefer to solve their own problems. The high endorsement of both structural (e.g., cost) and attitudinal (e.g., beliefs) barriers by respondents suggests that service delivery must adapt to better respond to dominant masculine ideals while also improving men's ease of access into a transparent treatment process.


Pulmonary arterial remodelling by deficiency of peroxisome proliferator-activated receptor-γ in murine vascular smooth muscle cells occurs independently of obesity-related pulmonary hypertension.
Obesity is associated with cardiovascular complications, including pulmonary hypertension (PH). Reports suggest that peroxisome proliferator-activated receptor-γ (PPARγ) has direct action in preventing vascular remodelling in PH. Here we dissected the specific role of high-fat-diet (HFD)-induced obesity and vascular smooth muscle cell (VSMC)-PPARγ for remodelling of small pulmonary arteries. Wild-type (WT) and VSMC-specific PPARγ-knockout (SmPparγ-/-) mice were fed a low-fat-diet (LFD, 10% kcal from fat) or HFD (60% kcal from fat) for 24 weeks. Mice were metabolically phenotyped (e.g. weight development, insulin/glucose tolerance) at the beginning, and after 12 and 24 weeks, respectively. At 24 weeks additionally pulmonary pressure, heart structure, pulmonary vascular muscularization together with gene and protein expression in heart and lung tissues were determined. HFD increased right ventricular systolic pressure (RVSP) to a similar extent in WT and SmPparγ-/- mice. HFD decreased glucose tolerance and insulin sensitivity in both WT and SmPparγ-/- mice. Importantly, the increase in RVSP correlated with the degree of insulin resistance. However, VSMC-PPARγ deficiency increased pulmonary vascular muscularization independently of the diet-induced rise in RVSP. This increase was associated with elevated expression of early growth response protein 1 in heart and osteopontin in lung tissue. Here we demonstrate a correlation of insulin resistance and pulmonary pressure. Further, deficiency of PPARγ in VSMCs diet-independently leads to increased pulmonary vascular muscularization.


Tailoring A Poly(ether sulfone) Bipolar Membrane: Osmotic-Energy Generator with High Power Density.
Osmotic energy, obtained through different concentrations of salt solutions, is recognized as a form of a sustainable energy source. In the past years, membranes derived from asymmetric aromatic compounds have attracted attention because of their low cost and high performance in osmotic energy conversion. The membrane formation process, charging state, functional groups, membrane thickness, and the ion-exchange capacity of the membrane could affect the power generation performance. Among asymmetric membranes, a bipolar membrane could largely promote the ion transport. Here, two polymers with the same poly(ether sulfone) main chain but opposite charges were synthesized to prepare bipolar membranes by a nonsolvent-induced phase separation (NIPS) and spin-coating (SC) method. The maximum power density of the bipolar membrane reaches about 6.2 W m-2 under a 50-fold salinity gradient, and this result can serve as a reference for the design of bipolar membranes for osmotic energy conversion systems.


Identification of CD157-Positive Vascular Endothelial Stem Cells in Mouse Retinal and Choroidal Vessels: Fluorescence-Activated Cell Sorting Analysis.
CD157 (also known as Bst1) positive vascular endothelial stem cells (VESCs), which contribute to vascular regeneration, have been recently identified in mouse organs, including the retinas, brain, liver, lungs, heart, and skin. However, VESCs have not been identified in the choroid. The purpose of this study was to identify VESCs in choroidal vessels and to establish the protocol to isolate retinal and choroidal VESCs. We established an efficient protocol to create single-cell suspensions from freshly isolated mouse retina and choroid by enzymatic digestion using dispase, collagenase, and type II collagenase. CD157-positive VESCs, defined as CD31+CD45-CD157+ cells, were sorted using fluorescence-activated cell sorting (FACS). In mouse retina, among CD31+CD45- endothelial cells (ECs), 1.6 ± 0.2% were CD157-positive VESCs, based on FACS analysis. In mouse choroid, among CD31+CD45- ECs, 4.5 ± 0.4% were VESCs. The CD157-positive VESCs generated a higher number of EC networks compared with CD157-negative non-VESCs under vascular endothelial growth factor (VEGF) in vitro cultures. The EC network area, defined as the ratio of the CD31-positive area to the total area in each field, was 4.21 ± 0.39% (retinal VESCs) and 0.27 ± 0.12% (retinal non-VESCs), respectively (P < 0.01). The EC network area was 8.59 ± 0.78% (choroidal VESCs) and 0.14 ± 0.04% (choroidal non-VESCs), respectively (P < 0.01). The VESCs were located in large blood vessels but not in the capillaries. We confirmed distinct populations of CD157-positive VESCs in both mouse retina and choroid. VESCs are located in large vessels and have the proliferative potential. The current results may open new avenues for the research and treatment of ocular vascular diseases.


[Thoracic outlet syndrome. A study of 45 cases treated between 1975 and 1993].
Since 1970 we have experience of more than 100 cases of the thoracic outlet syndrome. We have rewied 45 patients operated on between 1975 and 1993.The cause, in agreement with the literature, was in 30% a road accident (cervical spine and clavicular disease), in 54% malformations (cervical rib) with a similar frequency of involvement with neurological pathology of the upper limb.We always found a vascular symptomatology, wich increased in shoulder abduction. In 82% of the cases we found an associated neurological deficit. The diagnosis was confirmed with electromyography and arteriography.The treatment was in initially medical and in resistant case, surgery was performed. We have use a supra-clavicular approach with scalenotomy of the scalenus anterior muscle, resection of the distal part of the cervical rib or an anterior fibrous band. We did not do (first operation) a resection of the first rib throught a transaxillary approach, in order to avoid elongation of the brachialplexus roots.We found 80% good results from the opinion of the patients and after clinical examination.We have operated on 6 recurrent cases throught a supra-clavicular approach (fibrous sheath) or by trans axillary approach with resection of the first rib in case of lack of response to scalenotomy.


A geochemical record of the mining history of the Erme Estuary, south Devon, UK.
The concentration of selected trace metals (Cu, Pb and Zn) in salt-marsh sediments from within the Erme Estuary have been measured in order to assess possible historical sources of pollution. The Erme Estuary, south Devon, UK is an Area of Outstanding Natural Beauty and has remained largely unaffected by industrialisation, although a number of small silver-lead mines were in operation in the 1800s. Five cores reveal comparable geochemical profiles. An increase of lead at approximately 40 cm depth is observed, reaching maximum values of 427 ppm. Less distinct trends are revealed by zinc and copper, probably reflecting the lack of widespread mining for ores of these elements within the catchment and possible post-depositional mobility rendering the metal concentrations non-contemporaneous with the chemostratigraphy of lead. The geochemical analysis of the salt-marsh sediments provides a fairly robust chemostratigraphic scheme and the likely sources of mine waste can be pinpointed within the catchment. Based upon reference to the historical mining record of these mines chemostratigraphic dating of the sediments can be achieved in order to provide an estimate of salt-marsh accretion rates and sea-level rise.


A Simple Method that Combines CRISPR and AID to Quickly Generate Conditional Knockouts for Essential Genes in Various Vertebrate Cell Lines.
Cells with a loss-of-function mutation in a gene (knockout cells) are powerful tools for characterizing the function of such gene product. However, for essential genes, conditional knockout cell lines must be generated. The auxin-inducible degron (AID) technique enables us to conditionally and rapidly deplete a target protein from various eukaryotic cell lines. A combination of CRISPR-/Cas9-based gene editing and AID technique allows us to generate AID-based conditional knockout cell lines. Using these two techniques, we recently proposed a simple and quick way to generate conditional knockout cells for essential genes. In this chapter, we introduce the reader to the experimental procedures to generate these AID-based conditional knockout cell lines.


Improving quality of care in less than 1 min: a prospective intervention study on postoperative handovers to the ICU/PACU.
Standardisation of the postoperative handover process via checklists, trainings or procedural changes has shown to be effective in reducing information loss. The clinical friction of implementing these measures has received little attention. We developed and evaluated a visual aid (VA) and >1 min in situ training intervention to improve the quality of postoperative handovers to the intensive care unit (ICU) and postoperative care unit. The VA was constructed and implemented via a brief (<1 min) training of anaesthesiologic staff during the operation. Ease of implementation was measured by amount of information transferred, handover duration and handover structure. 50 handovers were audio recorded before intervention and 50 after intervention. External validity was evaluated by blinded assessment of the recordings by experienced anaesthesiologists (n=10) on 10-point scales. The brief intervention resulted in increased information transfer (9.0-14.8 items, t(98)=7.44, p<0.0001, Cohen's d=1.59) and increased handover duration (81.3-192.8 s, t(98)=6.642, p=0.013, Cohen's d=1.33) with no loss in structure (1.60-1.56, t(98)=0.173, p=0.43). Blinded assessment on 10-point scales by experienced anaesthesiologists showed improved overall handover quality from 7.1 to 7.8 (t(98)=1.89, p=0.031, Cohen's d=0.21) and improved completeness of information (t(98)=2.42, p=0.009, Cohen's d=0.28) from 7.3 to 8.3. An intervention consisting of a simple VA and <1 min instructions significantly increased overall quality and amount of information transferred during ICU/postanaesthetic care unit handovers.


Allergy to Surgical Implants.
Surgical implants are essential elements of repair procedures to correct worn out joints, damaged spinal components, heart and vascular disease, and chronic pain. However, many of the materials that provide stability, flexibility, and durability to the implants are also immunogenic. Fortunately, allergic responses to surgical implants are infrequent. When they do occur, however, the associated pain, swelling, inflammation, and decreased range of motion can significantly impair the implant function. Given the high numbers of joint replacements performed in the developed world, allergic reactions to orthopedic implants form the largest category of allergic responses. The most important allergens in this category include nickel, cobalt, chromium, and bone cement. These allergens are also the most important in reactions to spinal surgeries. Multiple cardiac and neurostimulatory devices are constructed of metals and adhesives that can be sensitizing in some individuals. Implantable pulse generators, important in cardiac pacemakers, gastric stimulators, and neurostimulators, may include components made of stainless steel, titanium alloy, platinum and iridium, epoxy resins, poly methyl methacrylates, and isocyanates, all of which are immunogenic in some patients. Cardiac stents and patches are often made of Nitinol, a composite of nickel and titanium. More surgical procedures are closed using skin glues, which are also capable of triggering a blistering contact dermatitis. Patch testing is the gold standard to determine sensitization, and this review provides a list of standard allergens to test for different implants. The patients most appropriate for testing include (1) pre-operative joint replacement patients with a prior history of skin reactions to metal jewelry, jean snaps, watch bands, metal glass frames, artificial nails, or skin glue; (2) post-operative joint replacement failure patients needing revision without an obvious cause such as infection or mechanical incompatibility; and (3) post-operative cardiac or neurological patients with localized rash, pain, swelling, or inflammation near or over the implant.


Central nervous system catecholamine metabolism in Korsakoff's psychosis.
We attempted to replicate previous reports of impaired central noradrenergic activity in patients with Korsakoff's psychosis. No differences were demonstrated in lumbar cerebrospinal fluid concentrations of norepinephrine or its major metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG), or in the contribution of plasma to cerebrospinal fluid free MHPG in 6 patients with clinically well characterized Korsakoff's psychosis and 8 age-matched healthy, normal volunteers. Likewise, cerebrospinal fluid concentrations of the major metabolites of dopamine (homovanillic acid) and serotonin (5-hydroxyindoleacetic acid) were the same in patients and controls.


Licorice metabolite 18β-glycyrrhetinic acid activates G protein-gated inwardly rectifying K+ channels.
Licorice (liquorice) is a common food additive and is used in Chinese medicine. Excess licorice intake can induce atrial fibrillation. Patients with atrial fibrillation possess constitutively activated G protein-gated inwardly rectifying K+ (GIRK) channels. Whether licorice affects GIRK channel activity is unknown. We aimed to clarify the effects of licorice ingredients on GIRK current and the mechanism of action. A major component of licorice, glycyrrhizic acid (GA), and its metabolite, 18β-glycyrrhetinic acid (18β-GA), were tested. We performed electrophysiological recordings in Xenopus oocytes to examine the effects of GA and 18β-GA on various GIRK subunits (Kir 3.1-Kir 3.4), mutagenesis analyses to identify the crucial residues for drug action and motion analysis in cultured rat atrial myocytes to clarify effects of 18β-GA on atrial functions. GA inhibited Kir 3.1-containing channels, while 18β-GA activated all Kir 3.x subunits. A pore helix residue Phe137 in Kir 3.1 was critical for GA-mediated inhibition, and the corresponding Ser148 in Kir 3.2 was critical for 18β-GA-mediated activation. 18β-GA activated GIRK channel in a Gβγ -independent manner, whereas phosphatidylinositol 4,5-bisphosphate (PIP2 ) was essential for activation. Glu236 located at the cytoplasmic pore of Kir 3.2 appeared to be important to interactions with 18β-GA. In rat atrial myocytes, 18β-GA suppressed spontaneous beating via activation of GIRK channels. GA acts as a novel GIRK inhibitor, and 18β-GA acts as a novel GIRK activator. 18β-GA alters atrial function via activation of GIRK channels. This study elucidates the pharmacological activity of licorice ingredients and provides information for drug design.


The Broad Stroke of Hsp90 Inhibitors: Painting over the RAF Inhibitor Paradox.
The novel Hsp90 inhibitor XL888 is undergoing clinical investigation for use in conjunction with the rapidly accelerated fibrosarcoma (RAF) kinase inhibitor vemurafenib to treat unresectable melanoma. The addition of XL888 to current regimens may serve an additional purpose by blocking the RAF inhibitor paradox. Such activity could reduce adverse events in patients and provide a biomarker for the successful inhibition of Hsp90 target proteins.


IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling.
TH2 cells play a critical role in the pathogenesis of allergic asthma. Established TH2 cells have been shown to resist reprogramming into TH1 cells. The inherent stability of TH2 cells poses a significant barrier to treating allergic diseases. We sought to understand the mechanisms by which CD4(+) T cells from asthmatic patients resist the IL-27-mediated inhibition. We isolated and cultured CD4(+) T cells from both healthy subjects and allergic asthmatic patients to test whether IL-27 can inhibit IL-4 production by the cultured CD4(+) T cells using ELISA. Culturing conditions that resulted in resistance to IL-27 were determined by using both murine and human CD4(+) T-cell culture systems. Signal transducer and activator of transcription (STAT) 1 phosphorylation was analyzed by means of Western blotting and flow cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured by using quantitative PCR. The small interfering RNA method was used to knockdown the expression of Socs3 mRNA. We demonstrated that CD4(+) T cells from asthmatic patients resisted the suppression of IL-4 production mediated by IL-27. We observed that repeated exposure to TH2-inducing conditions rendered healthy human CD4(+) T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. The knockdown of Socs3 mRNA expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated inhibition of IL-4 production. Our findings demonstrate that differentiated TH2 cells can resist IL-27-induced reprogramming toward TH1 cells by downregulating STAT1 phosphorylation and likely explain why the CD4(+) T cells of asthmatic patients are resistant to IL-27-mediated inhibition.


Expression of the recA gene in recombination-deficient (rec-) strains of Escherichia coli.
Basal and induced levels of recA expression in wild-type and isogenic derivatives of Escherichia coli carrying various rec mutations were measured using a low-copy number recApo-lacZ fusion, pKLC3.2. Basal recA expression in wild-type and isogenic derivatives containing single rec- mutations, as well as in the recBCsbcA strain and isogenic recA, recF and recJ derivatives, ranged from 1000 to 3900 units. In the recBCsbcBC strain and isogenic recL and recN derivatives basal recA expressions were 3- to 5-fold higher than that of wild-type cells and were inducible by mitomycin C. Except for the recA and lexA3(lnd-) mutants, recA expression was induced by mitomycin C in wild-type cells and its isogenic recB, recD, recF, recG, recJ, recL, recN, recO and ruv derivatives. RecF was required for induction of recA expression by mitomycin C, but not by naladixic acid in the recBCsbcA and recBCsbcBC genetic backgrounds. In wild-type cells, induction of recA expression by naladixic acid required the recBC, but not the recD function of the RecBCD enzyme. This requirement is suppressed by either an additional sbcA or sbcC mutation, but not by an sbcB mutation.


Paroxysmal positional vertigo.
Paroxysmal positional vertigo (PPV) is the peripheral vertiginous syndrome that is most frequently encountered in clinical practice. It is characterised by paroxysmal vertiginous attacks that are triggered by head movements and last no more than a few seconds, and is often accompanied by nausea and vomiting. The aim of this review is to provide a complete and updated description of the two principal manifestations of the syndrome: posterior semicircular canal (PSC-PPV) and horizontal semicircular canal PPV (HSC-PPV).


Implanted central venous catheter-related acute superior vena cava syndrome: management by metallic stent and endovascular repositioning of the catheter tip.
We describe a case of a 49-year-old woman with stage-IIIB lung adenocarcinoma who experienced an acute superior vena cava syndrome related to an implanted central venous catheter without associated venous thrombosis. The catheter was surgically implanted for chemotherapy. Superior vena cava syndrome appeared after the procedure and was due to insertion of the catheter through a subclinical stenosis of the superior vena cava. Complete resolution of the patient's symptoms was obtained using stent placement and endovascular repositioning of the catheter tip.


Alterations in the polypyrimidine sequence affect the in vitro splicing reactions catalyzed by HeLa cell-free preparations.
The polypyrimidine tract, located at the 3' end of intron 1 of the adenovirus major late transcript, was studied for its role in splicing using cell-free preparations isolated from HeLa cells. A plasmid (pIz) was constructed in which seven purine bases were substituted for pyrimidine bases within the 14-nucleotide polypyrimidine sequence. Runoff transcripts extending to the middle of intron 2 were tested for their ability to support in vitro splicing. The efficiency of these reactions was compared with pre-mRNA transcripts made from the wild-type nonmutated plasmid (p1-2). Neither spliced products nor splicing intermediates were detected in reactions with the pIz pre-mRNA. The formation of the nucleoprotein complexes involved in splicing was examined with this altered pre-mRNA. No 55 S splicing complex was detected and only low levels of the 30 S presplicing complex formed (30-fold less than with wild-type pre-mRNA). However, when a longer runoff transcript was prepared from the polypyrimidine mutated plasmid pIz, spliced RNA was formed. This activity required specific downstream sequences, since transcripts produced from pIz which contained substituted downstream sequences were not spliced. Although intron 2 of the adenovirus major late transcript does not contain a discernible 3' polypyrimidine sequence, pre-mRNA (p2-3) containing this intron was efficiently spliced. However, when the 3' region of intron 2 was substituted for the polypyrimidine sequence of intron 1, the resulting pre-mRNA did not support efficient splicing in vitro. However, when the polypyrimidine sequence of intron 1 was substituted for the sequence at the 3' end of intron 2, efficient splicing occurred, and the rate of formation of splicing intermediates and the accumulation of nucleoprotein complexes was greater than with the wild-type pre-mRNA (p2-3).


Cut the rope: Short-term colonization of mooring lines by fouling community within the port of Livorno (Northern Tyrrhenian Sea, Western Mediterranean), focusing on alien species recruitment.
The early stages of fouling development on artificial substrates were examined for spatial-temporal variation in the commercial and touristic harbours (use destinations) of the port of Livorno (Tuscany, Italy). The experiment was carried out by submerging two types of experimental ropes with different surface textures, considering three times of submersion. Particular attention was paid to the colonization dynamics of non-indigenous species (NIS). The type of rope did not significantly affect fouling development. However, when the NIS assemblage and the whole community were taken into account, the colonization of ropes varied depending on the use destination. The touristic harbour exhibited a degree of fouling colonization higher than the commercial one. NIS were observed in both harbours since the beginning of colonization, eventually achieving higher population densities in the touristic harbour. The use of experimental ropes represents a promising quick cost-effective tool for monitoring of NIS presence in port environments.


Unique gene organization of colubrid three-finger toxins: complete cDNA and gene sequences of denmotoxin, a bird-specific toxin from colubrid snake Boiga dendrophila (Mangrove Catsnake).
Denmotoxin is a colubrid three-finger toxin isolated from the venom of Boiga dendrophila, which exhibits bird-specific neurotoxicity. We have sequenced the full-length cDNA and the gene encoding the precursor of denmotoxin. This is the first glimpse of genomic organization of a colubrid three-finger toxin. Denmotoxin cDNA shows low similarity to elapid three-finger toxins, except for the conserved signal peptide region. The open reading frame of denmotoxin possesses an additional fragment encoding a part of the putative signal peptide followed by an extra long N-terminus. The exon/intron organization of denmotoxin is also different from elapid three-finger toxin genes. The denmotoxin gene contains four exons and three introns, while elapid genes share virtually identical gene organization consisting of three exons and two introns. It appears that Elapidae snakes have lost the extra second exon after the divergence of the snake families.


Immunoprecipitation of insulin receptors by antibodies against Class 1 antigens of the murine H-2 major histocompatibility complex.
Insulin receptors from C57BL/6J mouse (H-2b) liver membranes were specifically labeled with 125I-photo-reactive insulin by UV irradiation. Membranes were solubilized and the capacity of various antibodies reacting with the major histocompatibility complex to immunoprecipitate insulin receptors was tested. About 5% of the labeled receptors were immunoprecipitated by a conventional mouse antiserum against H-2b histocompatibility antigens and by a monoclonal antibody against Class 1 antigens of the H-2b haplotype (Kb and Db). No immunoprecipitation was obtained with a monoclonal antibody against Class 2 antigens of I-Ab or against Class 1 antigens of the H-2k haplotype. Insulin receptors can thus be specifically immunoprecipitated by antibodies against class I histocompatibility antigens.


Complications in laparoscopic surgery.
As laparoscopic surgery gains popularity, it becomes crucial to understand complications associated with the procedure. The potential complications of laparoscopy include those related to laparoscopy and those related to the surgical procedure. As new applications for laparoscopic surgery emerge, it is important for the surgeon to become familiar with potential complications.


The things that do not change.
This issue of Creative Nursing introduces our 2014 theme of Timeless Wisdom, cites each author's contribution to expanding our understanding of Ways of Knowing, and invites article submissions from all walks of nursing life.


Efficacy of intramuscular hydroxocobalamin supplementation in cats with cobalamin deficiency and gastrointestinal disease.
In humans, absorption and tissue retention rates of intramuscularly administered hydroxocobalamin (OH-Cbl) are superior compared to cyanocobalamin (CN-Cbl). Supplementation with OH-Cbl has not been described in cats. To evaluate effects of parenteral OH-Cbl supplementation on clinical signs, serum Cbl and methylmalonic acid (MMA) concentrations in hypocobalaminemic cats with gastrointestinal disease. Twenty-three client-owned cats. Prospective study. Serum Cbl and MMA concentrations were determined at enrollment (t0), immediately before the 4th OH-Cbl IM injection (300 μg, given q2 weeks) (t1), and 4 weeks after the 4th injection (t2). Severity of clinical signs (activity, appetite, vomiting, diarrhea, body weight) was graded at each time point and expressed as clinical disease activity score. Median clinical disease activity score decreased significantly from t0 (6; range, 2-10) to t1 (1; range, 0-6) and t2 (1; range, 0-9). Median serum Cbl concentration increased significantly from 111 pmol/L (range, 111-218; reference range, 225-1451 pmol/L) at t0 to 1612 pmol/L (range, 526-14 756) (P < .001) at t1, and decreased again significantly to 712 pmol/L (range, 205-4265) (P < .01) at t2. Median baseline serum MMA concentration at t0 (802 nmol/L; range, 238-151 000; reference range, 120-420 nmol/L) decreased significantly (P < .001) to 199 nmol/L (range, 29-478) at t1, and was 205 nmol/L (range, 88-734) at t2. Serum MMA concentrations normalized in 22/23 cats at t1, and were not significantly higher at t2 compared to t1. The herein described OH-Cbl injection scheme appears efficacious for normalization of cellular Cbl deficiency in cats with gastrointestinal disease.


Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model.
Intestinal fibrosis associated with Crohn's disease (CD), which a common and serious complication of inflammatory bowel diseases. In this context, heat shock proteins (HSPs) might serve as an alternative treatment because these antigens play important roles in the regulation of effector T cells. We thus evaluated the anti-inflammatory and antifibrotic capacities of an invasive and Hsp65-producing strain-Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65)-in chronic intestinal inflammation to assess its potential as an alternative therapeutic strategy against fibrotic CD. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in BALB/c mice, and the mice were treated orally with L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) via intragastric gavage. The oral administration of this strain significantly attenuated the severity of inflammation and intestinal fibrosis in mice (p < 0.05). These results are mainly justified by reductions in the levels of the pro-fibrotic cytokines IL-13 and TGF-β and increases in the concentration of the regulatory cytokine IL-10. The L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain contributed to reductions in the severity of inflammatory damage in chronic experimental CD, and these findings confirm the effectiveness of this new antifibrotic strategy based on the delivery of therapeutic proteins to inside cells of the host intestinal mucosa.


Lack of pharmacokinetic drug interaction between tenofovir disoproxil fumarate and nelfinavir mesylate.
A study explored the pharmacokinetics of tenofovir (300 mg administered once daily) and nelfinavir (1,250 mg twice daily) when coadministered in 29 healthy volunteers. Tenofovir, nelfinavir, and M8 pharmacokinetics was unaltered when tenofovir and nelfinavir were coadministered, and tenofovir administration did not affect the M8/nelfinavir area under the concentration-versus-time curve over the dosing interval (AUC(tau)) ratio. No interaction between tenofovir and nelfinavir was observed.


Sevoflurane inhibits histone acetylation and contributes to cognitive dysfunction by enhancing the expression of ANP32A in aging mice.
Postoperative cognitive dysfunction (POCD) is a major clinical complication after surgery under general anesthesia, particularly in elderly patients, but the mechanisms remain unclear. We recently found that the anaesthetization of aging C57BL/6 J mice (14-16 months) with sevoflurane (3%, two hours each day for three consecutive days) can induce cognitive dysfunction and synaptic plasticity deficits. Further studies demonstrated that sevoflurane induced ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) overexpression by stimulating C/EBPβ (CCAAT/enhancer binding protein-β), which could suppress histone acetylation at H3K18, H3K14, H4K5, and H4K12 and decrease the binding of H3K18 and H3K14 to the promoters of GluN2B and GluN2A, respectively. These results suggest that sevoflurane can inhibit histone acetylation and contribute to cognitive dysfunction by enhancing the expression of ANP32A in aging mice. Our study provides new insights into aging-associated POCD and potential molecular markers for protection.


Pilot investigation of a novel testing strategy for bleeding in ventricular assist device recipients.
A universal loss of von Willebrand factor (vWF) high-molecular-weight multimers (HMWM) has been demonstrated in continuous-flow left ventricular assist device (HeartMate II) recipients. However, no reliable clinical or laboratory predictors for an increased bleeding tendency in this patient population have been identified. This study evaluated the ability of a new automated latex particle-enhanced immunoturbidimetric vWF activity assay (ALPEIVA) to predict non-surgical bleeding risk in HeartMate II recipients. As part of a prospective multicenter trial, pre-surgical, 7-day, and 30-day post-implantation blood samples were collected from 24 patients. ALPEIVA-assessed vWF activities were compared among patients with and without non-surgical bleeding complications after HeartMate II implantation. Additional laboratory testing included factor VIII activity (FVIII:C), vWF antigen (vWFAg), vWF ristocetin cofactor activity (vWF:RCo), and vWF multimer analysis. All 24 patients had HMWM losses after HeartMate II implantation. Five patients (20%) developed non-surgical bleeding complications between 14 days and 6 months after HeartMate II implantation. Among various laboratory variables, only mean ALPEIVA/vWFAg ratios (referred to as the "bleeding ratio") were significantly lower in patients with clinically relevant bleeding (mean, 0.70 ± 0.06) compared with patients without bleeding (mean, 0.78 ± 0.09; p = 0.02) when measured at 30 days. The post-surgical bleeding ratio could potentially predict non-surgical bleeding risk and guide anti-platelet and anti-coagulation strategies in HeartMate II recipients.


Source identification of surface water pollution using multivariate statistics combined with physicochemical and socioeconomic parameters.
Accurate identification of potential contamination sources of river water is a basis for effective pollution control and sustainable water management. Pollution source identification based on physicochemical-parameters-only method may lead to uncertainty and subjectivity. In this study along with hydrochemistry parameters (HPs), socioeconomic parameters (SPs) were considered as an auxiliary in multivariate statistics to achieve a comprehensive assessment on pollution sources with accurate estimates of source identification and apportionment. Fifteen physicochemical parameters were combined with twelve socioeconomic parameters in multivariate statistics to quantitatively assess potential pollution sources and their contributions to river water pollution. Multivariate statistics in the study included regression analysis, principal component analysis (PCA), and absolute principal component score-multiple linear regression (APCS-MLR). Regression analysis between hydro-chemical parameters and socioeconomic parameters indicated that industrial and population growths were the main factors related to ammonium nitrogen (NH4+-N), total nitrogen (TN) contamination, while total phosphorus (TP) was more correlated with domestic discharge and poultry breeding. Based on the results of PCA, four latent factors were extracted for hydrochemistry parameters (HPs) and socioeconomics parameters (SPs), accounting for 68.59% and 82.40% of the total variance, respectively. With integrating the PCA results of the two parameter groups, pollution sources were ranked as industrial effluents > rural wastewater > municipal sewage > phytoplankton growth and agricultural cultivation. Source apportionment in APCS-MLR revealed that industrial wastewater and rural wastewater averagely contributed 35.68% and 25.08% of pollution, respectively, followed by municipal sewage (18.73%) and phytoplankton pollution (15.13%) with relatively small percentage of unrecognized source. It is concluded that socioeconomic parameters assisting hydrochemistry parameters in multivariate statistics can improve the accuracy and certainty of pollution source identification, supporting decision makers to formulate strategies on protection of river water quality.


Identification of functional genetic variation in exome sequence analysis.
Recent technological advances have allowed us to study individual genomes at a base-pair resolution and have demonstrated that the average exome harbors more than 15,000 genetic variants. However, our ability to understand the biological significance of the identified variants and to connect these observed variants with phenotypes is limited. The first step in this process is to identify genetic variation that is likely to result in changes to protein structure and function, because detailed studies, either population based or functional, for each of the identified variants are not practicable. Therefore algorithms that yield valid predictions of a variant's functional significance are needed. Over the past decade, several programs have been developed to predict the probability that an observed sequence variant will have a deleterious effect on protein function. These algorithms range from empirical programs that classify using known biochemical properties to statistical algorithms trained using a variety of data sources, including sequence conservation data, biochemical properties, and functional data. Using data from the pilot3 study of the 1000 Genomes Project available through Genetic Analysis Workshop 17, we compared the results of four programs (SIFT, PolyPhen, MAPP, and VarioWatch) used to predict the functional relevance of variants in 101 genes. Analysis was conducted without knowledge of the simulation model. Agreement between programs was modest ranging from 59.4% to 71.4% and only 3.5% of variants were classified as deleterious and 10.9% as tolerated across all four programs.


Ultrastructural analysis of membrane-bound polysomes in mouse "nonsecretory" myeloma (nonproducing type).
Using our electron microscopic method of polysome analysis we ascertained the numbers of membrane-bound polysomes and their constituent ribosomes in myeloma cells of J 606 (IgG3) and MOPC315 (IgA) parent cell lines and in their variants that did not produce and, accordingly, secrete either H- or L-chains. Both variants had far fewer membrane-bound polysomes than the respective parent lines. The polysome distribution curve drawn for each of these variants showed one peak at 5-6 ribosomes. In contrast to this finding, the distribution curves for the J 606 and MOPC315 parent lines gave two peaks. These observations on mouse myelomas strongly resembled those on human myelomas.


Validity of a CB-NAAT assay in diagnosing tuberculosis in comparison to culture: A study from an urban area of South India.
•CB-NAAT performance compared in 831 suspected pulmonary and extrapulmonary suspected cases.•The conventional stained smear and CB-NAAT results were compared to the MGIT culture.•Sensitivity and specificity of CB-NAAT was 84.43% and 94.93%.•The rapid results from CB-NAAT confirms its use in the tuberculosis diagnostic algorithm.•The benefits of disease diagnosis and prevention outweighs the price tag of the CB-NAAT tests.•This is more so for the resource poor countries where the burden of the disease is high.


Basic molecular biology.
Rapid advances in molecular biology over the past 20 years have and will continue to impact on the practice of medicine. Advances in molecular biology are having an immense impact in determining the underlying aetiology of lung disease and its treatment. In this review, basic molecular biology techniques will be discussed with examples of how these techniques are used in clinical practice.


Body composition after bone marrow transplantation in childhood.
To describe the body composition and fat distribution of childhood bone marrow transplantation (BMT) survivors at least one year post-transplantation and examine the ability of the Centers for Disease Control and Prevention criteria to identify survivors with elevated body fat percentage. Cross-sectional, descriptive. Pediatric oncology program at a National Cancer Institute-designated comprehensive cancer center. 48 childhood BMT survivors (27 males and 21 females). Measurements included dual-energy x-ray absorptiometry scan, height, weight, and physical activity. Descriptive statistics were reported and mixed-model linear regression models were used to describe findings and associations. Total body fat percentage and central obesity (defined as a ratio of central to peripheral fat of 1 or greater). Fifty-four percent of survivors had body fat percentages that exceeded recommendations for healthy body composition and 31% qualified as having central obesity. Previous treatment with total body irradiation was associated with higher body fat percentage and central obesity, and graft-versus-host disease was associated with lower body fat percentage. The body mass index (BMI) criteria did not correctly identify the BMT survivors who had elevated body fat percentage. Survivors of childhood BMT are at risk for obesity and central obesity that is not readily identified with standard BMI criteria. Nurses caring for BMT survivors should include evaluation of general and central obesity in their assessments. Patient education materials and resources for healthy weight and muscle building should be made available to survivors. Research is needed to develop appropriate interventions.


Analysis of the acid phosphatases of rat sensory ganglia by isoelectric focussing on polyacrylamide gels.
The acid phosphatases of rat spinal and trigeminal ganglia have been separated by isoelectric focussing on polyacrylamide gels into two main classes with pI's of 7.1 and 5.4. A low-pI acid phosphatase is also present in the mouse but not in the guinea pig. Evidence is presented that in the rat the pI 5.4 enzyme represents the nonlysosomal acid phosphatase that has been identified histochemically in one population of sensory neurones. This pI 5.4 acid phosphatase is partly membrane-bound and is selectively depleted by capsaicin administration. In lumbar dorsal root ganglia the enzyme is selectively depleted by sectioning the sciatic nerve and undergoes rapid axonal transport, a greater amount being transported peripherally than centrally. The results are discussed with reference to the possible function of this nonlysosomal acid phosphatase.


Effect of cooling after human cardiac arrest on myocardial infarct size.
The Hypothermia after Cardiac Arrest (HACA) trial assessed whether mild therapeutic hypothermia improved the rate of good neurological recovery in patients after ventricular fibrillation cardiac arrest of presumed cardiac origin. We evaluated the impact of hypothermia on myocardial injury. Re-analysis of a HACA trial subset for our department (cooling, n=55; controls, n=56). Plasma levels of CK, CKMB and ST-scores were used as a measure of infarct size. Area under the curve (AUC) for CK was 28,786U/l x 24 h (IQR 5646-44,998) in the cooling group and 20,373U/l x 24 h (IQR 8211-30,801) for controls (p=0.40), for CKMB AUC was 1691U/l x 24 h (IQR 724-3330) and 1187U/l x 24 h (IQR 490-2469), respectively (p=0.18). The ST score was -40% (IQR [-55]-[+16]) in the cooling group (n=23) and -22% (IQR [-84]-[+33]) for controls (n=24) (p=0.76). When the cooling group was stratified into early (< or =8h) and longer (>8h) time to target temperature, the early group displayed a significantly lower CK 7340U/l x 24 h (IQR 3921-33,753) vs. 38,986U/l x 24 h (IQR 23,945-57,514, p=0.007) and a lower CKMB. Cooling after successful resuscitation for ventricular fibrillation cardiac arrest did not influence infarct size. Cautious interpretation of the subgroup analysis may indicate a favourable trend for early cooling.


Metformin delivery via iontophoresis based on κ-carrageenan cryogels.
Transdermal drug delivery system (TDDS) is the system for transmitting a drug through the skin into the blood circulation. In this work, κ-Carrageenan (κC) was used as the drug matrix material. The porous κC matrices were fabricated by dissolving the κC in deionized water to obtain hydrogels and then using the freeze-dryer to obtain cryogels. The porous (κC) matrices showed interconnected pore sizes varying between 6.05 to 25.8 nm. In the drug release experiments, the drug diffusion coefficient increased and the drug release duration was reduced with decreasing κC concentration due to the larger κC pore sizes. The diffusion coefficient increased with a shorter release time under the applied electric strength of +1.0 V due to the electro-repulsive force between the Metformin and the anode. For the drug release-permeation of the κC 0.8 % v/v cryogel through the pig skin under applied positive electrical potentials, the amounts of drug release-permeation and diffusion coefficients were enhanced with shorter durations relative to without electrical potential. The κC 0.8 % v/v matrix at the applied electric strength of +6.0 V has been shown here to be potential to be used as the Metformin transdermal controlled delivery patch for abdominal obesity and diabetes.


Development of a magnetically aligned regenerative tissue-engineered electronic nerve interface for peripheral nerve applications.
Peripheral nerve injuries can be debilitating to motor and sensory function, with severe cases often resulting in complete limb amputation. Over the past two decades, prosthetic limb technology has rapidly advanced to provide users with crude motor control of up to 20° of freedom; however, the nerve-interfacing technology required to provide high movement selectivity has not progressed at the same rate. The work presented here focuses on the development of a magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI) that combines polyimide "threads" encapsulated within a magnetically aligned hydrogel scaffold. The technology exploits tissue-engineered strategies to address concerns over traditional peripheral nerve interfaces including poor axonal sampling through the nerve and rigid substrates. A magnetically templated hydrogel is used to physically support the polyimide threads while also promoting regeneration in close proximity to the electrode sites on the polyimide. This work demonstrates the utility of magnetic templating for use in tuning the mechanical properties of hydrogel scaffolds to match the stiffness of native nerve tissue while providing an aligned substrate for Schwann cell migration in vitro. MARTEENI devices were fabricated and implanted within a 5-mm-long rat sciatic-nerve transection model to assess regeneration at 6 and 12 weeks. MARTEENI devices do not disrupt tissue remodeling and show axon densities equivalent to fresh tissue controls around the polyimide substrates. Devices are observed to have attenuated foreign-body responses around the polyimide threads. It is expected that future studies with functional MARTEENI devices will be able to record and stimulate single axons with high selectivity and low stimulation regimes.


Trigramin. A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex.
Trigramin, a highly specific inhibitor of fibrinogen binding to platelet receptors, was purified to homogeneity from Trimeresurus gramineus snake venom. Trigramin is a single chain (approximately 9 kDa) cysteine-rich peptide with the Glu-Ala-Gly-Glu-Asp-Cys-Asp-Cys-Gly-Ser-Pro-Ala NH2-terminal sequence. Chymotryptic fragmentation showed the Arg-Gly-Asp sequence in trigramin. Trigramin inhibited fibrinogen-induced aggregation of platelets stimulated by ADP (IC50 = 1.3 X 10(-7)M) and aggregation of chymotrypsin-treated platelets. It did not affect the platelet secretion. Trigramin was a competitive inhibitor of the 125I-fibrinogen binding to ADP-stimulated platelets (Ki = 2 X 10(-8) M). 125I-Trigramin bound to resting platelets (Kd = 1.7 X 10(-7) M; n = 16,500), to ADP-stimulated platelets (Kd = 2.1 X 10(-8) M; n = 17,600), and to chymotrypsin-treated platelets (Kd = 8.8 X 10(-8) M; n = 13,800) in a saturable manner. The number of 125I-trigramin binding sites on thrombasthenic platelets amounted to 2.7-5.4% of control values obtained for normal platelets and correlated with the reduced number of GPIIb-GPIIIa molecules on the platelet surface. EDTA, monoclonal antibodies directed against the GPIIb-GPIIIa complex, and synthetic peptides (Arg-Gly-Asp-Ser and Tyr-Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val) blocked both 125I-fibrinogen binding and 125I-trigramin binding to platelets. Fibrinogen binding was more readily inhibited by these compounds than was trigramin binding. Monoclonal antibodies directed either against GPIIb or GPIIIa molecules did not block the interaction of either ligand with platelets. Reduced, S-pyridylethyl, trigramin did not inhibit platelet aggregation and fibrinogen binding to platelets and it did not bind to platelets, suggesting that the secondary structure of this molecule is critical for expression of its biological activity.


Dual-emission of silicon nanoparticles encapsulated lanthanide-based metal-organic frameworks for ratiometric fluorescence detection of bacterial spores.
Dipicolinic acid (DPA) is employed as a significant biomarker to detect Bacillus anthracis, which can do serious damages to the health of human beings. Hence, it is crucial to develop a fast and highly efficient strategy for DPA monitoring. In this work, based on silicon nanoparticles (Si NPs) and terbium metal-organic frameworks (Tb-MOFs), a hybrid structure (Si NPs/Tb-MOFs) as a novel dual-emitting fluorescence probe was fabricated for ratiometric detection of DPA, where blue light-emitting Si NPs (Ex: 280 nm; Em: 422 nm) are encapsulated into green light-emitting Tb-MOFs (Ex: 280 nm; Em: 547 nm). The optical properties and chemical composition of the as-obtained Si NPs/Tb-MOFs were characterized in detail. The Si NPs/Tb-MOFs probe not merely possesses the merits of a facile synthesis method but also is an excellent fluorescence probe. The response time towards DPA is less than 30 s, revealing that the process of detecting DPA can be completed in such a short time. The limit of detection for DPA is 5.3 nM, which is four orders of magnitude lower than an infectious dosage of anthrax spores for human beings (60 μM). This dual-emitting Si NPs/Tb-MOFs probe with interference-free and self-calibrating properties may be a potential candidate for further development in medical diagnosis. Graphical abstract.


RNA conformational sampling. I. Single-nucleotide loop closure.
We consider the loop-closure problem for nucleic acids and describe an efficient numerical algorithm for closing single-nucleotide loops in nucleic acids. Using six new internal coordinates to represent the nucleotide conformation, which we call the R-representation, the original closure problem with six free torsion angles in each nucleotide can be reduced to one with only four degrees of freedom. Simple numerical techniques have been used to solve the resulting loop-closure equations, and a test of the closure algorithm on a set of RNAs consisting of more than 7000 nucleotides was able to regenerate the native torsion angles in every nucleotide in the test set without exception. We show how the conformational probability density transforms when the original torsion angle representation is mapped onto the new R-representation. We also present statistical evidence showing that the delta and nu(2) torsion angles are coupled, and how this coupling affects the conformation probability density in the R-representation. In addition to the backbone, the same loop-closure algorithm can also be applied to close the ribose ring. The algorithm is freely available at http://tyrosine.use.edu/closure.


Real time wire localization by ultrasound during central line insertion improves accurate positioning in all upper torso sites.
To investigate whether point of care ultrasound can improve central venous catheter tip positioning. A single center retrospective case control study. We compared the precision of central venous catheter tip positioning between two intensive care units while in only one of the units, we used point of care ultrasound for guidewire identification. 207 cases in which central venous catheter was inserted using point of care ultrasound guided method, compared to 192 controls. The primary outcome of correct placement of the central venous catheter tip was significantly higher in the point of care ultrasound guided group (97.6% vs 88.0% p = 0.001). Central venous catheter tip was located too low among 12% of patients in the control group while in only 2.4% of patients in the point of care ultrasound group (p = 0.001). Logistics regression analysis revealed that the correct placement of central venous catheter tip in the point of care ultrasound group versus the control group had an odds ratio of 4.9 (CI 1.6-14.5 P = 0.004). Point of care ultrasound for guidewire identification and localization, while inserting central venous catheter from all upper torso sites, improves precision positioning.


Blood pressure effects of lower abdominal aortic surgery with particular reference to the use of morphine and droperidol in modifying the responses.
Hypertensive responses during operations on the abdominal aorta are common. We have shown that hypertensive changes occur before cross-clamping of the aorta. We have also shown that droperidol modifies the hypertensive changes in operations on the lower aorta. Although further studies are required, our preliminary results show a higher rise of serum epinephrine and norepinephrine levels in one patient receiving morphine, as compared to one patient receiving the same dose per unit body weight of morphine plus droperidol. With maintenance of adequate pre-operative hydration and intra-operative fluid and blood replacement, declamping hypotension was transient in both groups of our patients.


Evaluation of polychlorotrifluoroethylene as sorbent material for on-line solid phase extraction systems: determination of copper and lead by flame atomic absorption spectrometry in water samples.
Polychlorotrifluoroethylene (PCTFE) in the form of beads was applied, as packing material for flow injection on-line column preconcentration and separation systems coupled with flame atomic absorption spectrometry (FAAS). Its performance characteristics were evaluated for trace copper determination in environmental samples. The on-line formed complex of metal with diethyldithiophosphate (DDPA) was sorbed on the PCTFE surface. Isobutyl methyl ketone (IBMK) at a flow rate of 2.8 mL min(-1) was used to elute the analyte complex directly into the nebulizer-burner system of spectrophotometer. The proposed sorbent material reveal, excellent chemical and mechanical resistance, fast adsorption kinetics permitting the use of high sample flow rates up to 15 mL min(-1) without loss of retention efficiency. For copper determination, with 90 s preconcentration time the sample frequency was 30 h(-1), the enhancement factor was 250, which could be further improved by increasing the loading (preconcentration) time. The detection limit (3s) was c(L)=0.07 microg L(-1), and the precision (R.S.D.) was 1.8%, at the 2.0 microg L(-1) Cu(II) level. For lead determination, the detection limit was c(L)=2.7 microg L(-1), and the precision (R.S.D.) 2.2%, at the 40.0 microg L(-1) Pb(II) level. The accuracy of the developed method was evaluated by analyzing certified reference materials and by recovery measurements on spiked natural water samples.


Glial Heterotopia of the Base of Tongue: A Case Report.
Glial heterotopia of oropharynx is a congenital anomaly, whereby ectopic mature glial tissue is found around oropharynx isolated from the brain and spinal cord. Herein we report a rare presentation of a mass at the base of tongue in a neonate. In addition, to underscore the rarity of oropharygeal glial heterotopia, we discuss the dilemma in approaching its diagnosis and management in a neonate.


The effect ofFusarium culmorum /W.G Smith/ andFusarium nivale /Fr./ ces. metabolites on germination, seedlings growth and cytological disturbances of rye, wheat and triticale.
The effects ofF. culmorum andF. Nivale metabolites on grain viability seedlings growth rate, mitotic activity and aberration frequency were studied. It was stated that metabolites which were contained in studiedFusaria culture filtrates decreased seed viability and inhibited growth rate of triticale, rye and wheat seedlings. The decline of mitotic activity and increase of aberration frequency under the effect of studied metabolites were noted. Metabolites of F. culmorum appeared to be more phytotoxic than metabolites ofF. nivale.


Current treatment of HER 2+ metastatic breast cancer.
Historically, HER2-positive breast cancer had a poor prognosis. The development of molecul ar ther apies that target the HER2 receptor has TR ansformed outcomes. Here, the evidence on Anti-HER2 therapies is summarised.


Dietary influences on growth and sexual maturation in premenarchial rhesus monkeys.
The effect of a high-fat diet on growth, sexual maturation, and developmental changes in serum levels of estradiol (E2), growth hormone (GH), somatomedin-C (Sm-C), and insulin were examined in outdoor-housed premenarchial rhesus monkeys. From 16 to 32 months of age, females were fed either a high-fat diet (HFD, N = 5) with 31% calories from fat or a control diet (commercial laboratory chow, N = 10) with 12% of the calories from fat. Maintenance on a HFD did not accelerate physical growth, as all animals exhibited similar increments in body weight, crown-rump length, and weight/height ratios. In contrast, the HFD group exhibited an earlier onset of perineal swelling and menarche despite lower body weights during that time. Moreover, 80% of the HFD animals exhibited an early first ovulation (31-32 months of age) compared with 40% of control animals. These reproductive changes were associated with significant differences in the endocrine profiles of HFD animals. Fasting serum levels of insulin were significantly elevated within 2 months of diet treatment and remained elevated throughout the study period. Levels of Sm-C were elevated relative to those of controls after 3 months of diet treatment, but not thereafter. Serum GH increased after 6 months on the HFD and, overall, concentrations were higher in HFD animals. A significant rise in E2 was observed after only 45 days on the HFD treatment. These concentrations did not differ from 18 to 21 months of age but again were elevated at 27 months in the HFD females. Since these endocrine and physical changes associated with reproductive physiology occurred in the absence of enhanced growth, these data suggest that a high-fat diet may influence the rate of sexual maturation through changes in certain metabolic factors which may act on the developing neuroendocrine system.


Redox-active, organometallic surface-relief gratings from azobenzene-containing polyferrocenylsilane block copolymers.
Organometallic gratings: the ionic self-assembly of metal-containing block-copolymer polyelectrolytes and azobenzene chromophores is exploited for the efficient production of stable photo-induced surface-relief gratings. We show that feature sizes can be tuned using simple redox chemistry, and that the chromophores can be removed during plasma treatment to yield ceramic-based optical materials.


Sulfidised nanoscale zerovalent iron-modified pitaya peel-derived carbon for enrofloxacin degradation and swine wastewater treatment: Combination of electro-Fenton and bio-electro-Fenton process.
In this study, a new Fenton system combining electro-Fenton and bio-electro-Fenton (EF-BEF) processes was proposed for ENR degradation and swine wastewater treatment, and pitaya peel-derived carbon modified with sulfidised nanoscale zerovalent iron (SnZVI) was developed as a catalyst for the system. The as-prepared PPC-800 carbon displayed a hierarchical porous structure (693.5 m2/g), abundant oxygen-containing groups, and carbon defects, which endowed it with a good adsorption capacity, high H2O2 generation capacity (151.9 ± 10.5 mg/L) during the EF period, and good power production performance (194.3 ± 12.50 mW/m2) during the BEF period. When modified with SnZVI, despite the decrease in the adsorption capacity and power output (102.05 ± 4.05 mW/m2), the SnZVI@PPC-2 exhibited the best ENR removal performance with that of 98.9 ± 0.2% in the EF period and 86.2 ± 5.6% during the BEF period. An increase in the current intensity and air flow rate promoted ENR degradation. Finally, swine wastewater was treated using the SnZVI@PPC-2 EF-BEF system, and 97.9 ± 1.3% of the TOC was removed using the combined system.


Third generation quinoline-3-carboxamide transcriptional disrupter of HDAC4, HIF-1α, and MEF-2 signaling for metastatic castration-resistant prostate cancer.
The quinoline-3-carboxamide, Tasquinimod (TasQ), is orally active as a maintenance therapy with an on-target mechanism-of-action via allosteric binding to HDAC4. This prevents formation of the HDAC4/NCoR1/HDAC3 complex, disrupting HIF-1α transcriptional activation and repressing MEF-2 target genes needed for adaptive survival signaling in the compromised tumor micro environment. In phase 3 clinical testing against metastatic castration-resistant prostate cancer(mCRPC), TasQ (1 mg/day) increased time-to-progression, but not overall survival. TasQ analogs were chemically synthesized and tested for activity compared to the parental compound. These included HDAC4 enzymatic assays, qRT-PCR and western blot analyses of gene and protein expression following treatment, in vitro and in vivo efficacy against multiple prostate cancer models including PDXs, pharmacokinetic analyses,AHR binding and agonist assays, SPR analyses of binding to HDAC4 and NCoR1, RNAseq analysis of in vivo tumors, 3D endothelial sprouting assays, and a targeted kinase screen. Genetic knockout or knockdown controls were used when appropriate. Here, we document that, on this regimen (1 mg/day), TasQ blood levels are 10-fold lower than the optimal concentration (≥2 μM) needed for anticancer activity, suggesting higher daily doses are needed. Unfortunately, we also demonstrate that TasQ is an arylhydrocarbon receptor (AHR) agonist, which binds with an EC50 of 1 μM to produce unwanted off-target side effects. Therefore, we screened a library of TasQ analogsto maximize on-target versus off-target activity. Using this approach, we identified ESATA-20, which has ~10-fold lower AHR agonism and 5-fold greater potency against prostate cancer patient-derived xenografts. This increased therapeuticindex nominates ESATA-20 as a lead candidate forclinical development as an orally active third generation quinoline-3-carboxamide analog thatretains its on-target ability to disrupt HDAC4/HIF-1α/MEF-2-dependent adaptive survival signaling in the compromisedtumor microenvironment found in mCRPC.


Posterior curve correction using convex posterior hemi-interbody arthrodesis in skeletally immature patients with scoliosis.
Deformity progression after posterior fusion in skeletally immature patients with scoliosis has remained a topic of debate. It occurs when the anterior segment of the apical zone continues to grow after successful posterior fusion, resulting in progressive bending and rotation of the vertebral bodies. For this reason, circumferential fusion using a combined anterior-posterior approach has been used to prevent this occurrence. The aim of this study was to report instrumented spinal fusion with convex hemi-interbody arthrodesis using a posterior-only approach in Risser stage 0 or 1 scoliosis patients. This is a retrospective study. Three patients presenting scoliosis in Risser stage 0 or 1 were enrolled. Postoperative correction rate, bone union, and pulmonary function were examined. Premenarchal girls aged 11.3-12.2 years underwent surgical procedure. Follow-up after surgery was on 25, 30, and 36 months. The surgical procedure included soft tissue, costotransverse ligament and facet releases, and Ponte osteotomies. Discectomy followed by intervertebral bone grafting were performed across the periapical zone on the convex side. After placement of segmental pedicle screws, deformity correction was achieved by rod derotation, cantilever reduction, direct vertebral derotation distraction and compression technique. Preoperative thoracic Cobb angle measured 81° (range 64-107), which improved to 23° at final follow-up, resulting in a 72% correction. Solid posterior bony fusion was achieved in all cases at final follow-up. No case showed deterioration of axial rotation at the apex radiographically. Postoperative pulmonary function showed increases in forced vital capacity (preoperation: 1.86±0.2L; at 2 years: 2.48±0.1L) and forced expiratory volume in 1 second (preoperation: 1.58±0.2L; at 2 years: 2.11±0.1L). This posterior-only procedure should be considered a suitable option in skeletally immature scoliosis patients where circumferential fusion is indicated and avoiding an anterior thoracotomy is preferable.