ELISA versus LUMINEX assay for measuring mouse metabolic hormones and cytokines: sharing the lessons I have learned.
Enzyme-linked immunosorbent assay (ELISA) has long been the standard for quantitative analysis of metabolic hormones and cytokines. LUMINEX multiplex bead array assays were developed as cost- and time-effective alternatives to ELISA, but they are the only cost- and time-effective if they provide informative data. Here, I show that using half-volume of reagents for an adiponectin single-plex LUMINEX assay and a 6-plex LUMINEX xMAP mouse metabolic bead assay, produces reliable data and increases assay cost-effectiveness. I provide direct comparisons between LUMINEX assay and ELISA for quantitation of mouse leptin and insulin, and evaluate glucagon, GLP-1, IL-6, and TNFα data obtained using the 6-plex LUMINEX assay for a high-fat diet-induced obesity study. Good correlations between assays were obtained for fasting leptin and non-fasting insulin. However, the LUMINEX assay proved unsuitable for quantitating fasting insulin. ELISA proved suitable for quantitating fasting male, but not female, insulin. The LUMINEX assay gave lower values for leptin and higher values for insulin, compared with ELISA. The mouse metabolic LUMINEX assay proved unsuitable for quantitating glucagon, GLP-1, IL-6, and TNFα, due to undetectable levels in most fasting and non-fasting plasma. Overall, quantitative leptin levels were the only reliable data obtained from the mouse metabolic LUMINEX assay.


A rare case of anti-Hu paraneoplastic neurologic syndrome in association with cervical cancer.
Anti-Hu antibodies, also known as ANNA-1, are well characterized in paraneoplastic neuropathies. We present here the first known case of anti-Hu seropositivity, cerebellar ataxia, and sensory neuropathy in association with cervical cancer.


Endogenous retroviral transcripts in myocytes from spontaneously hypertensive rats.
The spontaneously hypertensive rat (SHR) is a well studied animal model of genetic hypertension and heart disease of unknown cause. With the use of differential display, a transcript was found in SHR myocardium that on sequence analysis was identified as an endogenous retrovirus (ERV). ERV gene expression was greater than an order of magnitude increased in adult SHR hearts relative to age-matched normotensive Wistar-Kyoto rats and was further increased in hearts from SHR with heart failure. In situ hybridization studies demonstrated that increased ERV gene expression was localized to myocardial cells. Increases in ERV transcripts in SHR suggest a possible link between inherited proviral elements and genetic hypertensive heart disease.


Increasement of O-acetylhomoserine production in Escherichia coli by modification of glycerol-oxidative pathway coupled with optimization of fermentation.
O-acetylhomoserine (OAH) is an important platform chemical to produce high-valuable chemicals. To improve the production of O-acetylhomoserine from glycerol, the glycerol-oxidative pathway was investigated and the optimization of fermentation with crude glycerol was carried out. The glycerol-uptake system and glycerol-oxidative pathway were modified and O-acetyltransferase from Corynebacterium glutamicum was introduced into the engineered strain to produce O-acetylhomoserine. It was found that overexpression of glycerol 3-phosphate dehydrogenase improved the OAH production to 6.79 and 4.21 g/L from pure and crude glycerol, respectively. And the higher OAH production depending on higher level of transcription of glpD. Two-step statistical approach was employed to optimize the fermentation conditions. The significant effects of glycerol, ammonium chloride and yeast extract were screened applying Plackett-Burman design and were optimized further by employing the Response Surface Methodology. Under optimized conditions, the OAH production was up to 9.42 and 7.01 g/L when pure and crude glycerol were used in shake flask cultivations, respectively. The enzymatic step catalyzing the oxidation of glycerol through GlpD was the key step for OAH production, which served the foundation for realization of a consistent OAH production from crude glycerol in the future.


Variations in the molecular masses of the capsular exopolysaccharides amylovoran, pyrifolan and stewartan.
Erwinia amylovora, causing fire blight of apple, pear and some ornamentals, Erwinia pyrifoliae, causing Asian pear blight, and Pantoea stewartii, causing Stewart's wilt of sweet maize, synthesize capsular extracellular polysaccharides (EPSs) with a high molecular mass. The EPSs are virulence factors and form viscous aggregates, which participate in clogging vessels of infected plants and causing wilting. The sizes of EPSs produced under different environmental growth conditions were determined by analysis with large pore HPLC columns. Their molecular mass of ca. 5 MDa, when isolated from agar plates, decreases to ca. 1 MDa for E. amylovora amylovoran from freeze-dried supernatants from liquid cultures and to 2 MDa for freeze-dried preparations of P. stewartii stewartan. Size changes were also found following growth in various other media and for different strains. Stewartan, amylovoran and E. pyrifoliae pyrifolan were also shown to be completely degraded by a bacteriophage EPS depolymerase.


Activity of selected gluconeogenic and lipogenic enzymes in bovine rumen mucosa, liver and adipose tissue.
The activities of phosphoenolpyruvate carboxykinase, ;malic enzyme', citrate-cleavage enzyme and glucose 6-phosphate dehydrogenase were assayed in homogenates of rumen mucosa, liver and adipose tissue of cattle. Rumen mucosa cytoplasm contained activities of ;malic enzyme' approximately sevenfold those of phosphoenolpyruvate carboxykinase, suggesting that the conversion of propionate into lactate by rumen mucosa involves ;malic enzyme'. Neither starvation for 8 days nor feeding with a concentrate diet for at least 3 months before slaughter produced enzyme patterns in the tissues different from those in cattle given only hay, except that the all-concentrate diet caused increased activities of glucose 6-phosphate dehydrogenase and ;malic enzyme' in adipose tissues. Rumen mucosa, liver and adipose tissue contained phosphoenolpyruvate carboxykinase activity. ;Malic enzyme' was absent in liver. Citrate-cleavage enzyme activity was present in liver and adipose tissue but was quite low in rumen mucosa. Liver contained much less glucose 6-phosphate dehydrogenase activity than rumen mucosa or adipose tissue.


Brief communication: Population data support the adaptive nature of HACNS1 sapiens/neandertal-chimpanzee differences in a limb expression domain.
The 546-base pair enhancer of limb expression HACNS1, which is highly constrained in all terrestrial vertebrates, has accumulated 16 human-specific changes after the human-chimpanzee split. There has been discussion whether this process was driven by positive selection or biased gene conversion, without considering population data. We studied 83 South Amerindian, 11 Eskimo, 35 Europeans, 37 Bantu, and non-Bantu Sub-Saharan speakers, and 28 Brazilian mestizo samples and found no variation in this DNA region. Similar lack of variability in this region was found in four Africans, five Europeans or Euro-derived, two Asians, one Paleo-Eskimo, and one Neandertal sequence, whose whole genomes are publicly available. No difference was found. This result favors the interpretation of past positive and present conservative selection, as would expected in a region which influences Homo-specific traits as important as opposable thumbs, manual dexterity, and bipedal walking. Am J Phys Anthropol, 2010. © 2010 Wiley-Liss, Inc.


[The prevention of neonatal herpes encephalitis: characteristics in a tropical area].
Neonatal herpes infection virus is rare but of poor prognosis. The only way to prevent it, is to practice a prophylactic caesarean section. In medically undeveloped countries, indication of caesarean section should be very prudent because of subsequent risks of uterine rupture. After a short recall about herpes illness, a precise and simple behaviour is proposed.


Role of etheno DNA adducts in carcinogenesis induced by vinyl chloride in rats.
Vinyl chloride, a hepatocarcinogen in humans and rodents, can form promutagenic etheno bases in DNA after metabolic activation. The formation of 1,N6-ethenoadenine (epsilon A) and 3,N4-ethenocytosine (epsilon C) was measured in adult Sprague-Dawley rats by immunoaffinity purification and 32P-postlabelling. A highly variable background was found in all tissues from untreated animals: the mean molar ratios of epsilon A:A and epsilon C:C in DNA ranged from 0.043 x 10(-8) to 31.2 x 10(-8) and from 0.062 x 10(-8) to 20.4 x 10(-8), respectively. After exposure to 500 ppm vinyl chloride by inhalation (4 h/day, 5 days/week for 8 weeks), increased levels of epsilon A were found in the liver, lung, circulating lymphocytes and testis, the mean (+/- SD) of induced levels (treated-control values) being (4.1 +/- 1.5) x 10(-8) for these tissues. No increase in the epsilon A:A ratio was observed in kidney, brain or spleen. The levels of epsilon C increased in all the tissues examined except the brain. The mean value of the induced epsilon C:C ratios was (7.8 +/- 1.2) x 10(-8) for the liver, kidney, lymphocytes and spleen, and these ratios were higher in the lung (28 x 10(-8)) and testis (19 x 10(-8)). The results suggest a variable repair capacity for epsilon A or epsilon C in different tissues. The results are discussed in relation to published studies on the accumulation and persistence of etheno bases in the liver during and after exposure to vinyl chloride and on mutation spectra in the ras and p53 genes in liver tumours induced by vinyl chloride. In addition, we show that the linear relationship established for monofunctional alkylating agents between their carcinogenic potency in rodents and their covalent binding index for promutagenic bases in hepatic DNA holds for vinyl chloride. It is concluded that etheno bases are critical lesions in hepatocarcinogenesis induced by vinyl chloride. For a better understanding of the mechanism of action of this compound, further work is needed on the role of DNA repair pathways and of endogenous lipid peroxidation products in the formation and persistence of etheno bases in vivo.


Toward the conservation of the endemic monotypic fish genus Aulopyge from the Balkan Dinaric karst: Integrative assessment of introduced and natural population.
The complex biogeographical history of the Balkan Peninsula caused remarkable freshwater fish diversity and endemism, among which Cyprinidae fish dominate. The Dinaric karst was a Pleistocene refugium and it harbors ancient and endemic cyprinids, including Aulopyge huegelii, a sole representative of its genus. Being highly distributionally restricted, it faces various threats that promote a critical decline in population abundance and even population extinction. Phenotypic and molecular diversity of the introduced (Šator Lake, Šator Mountain) and natural (Studena River, Duvanjsko Polje) populations of Dalmatian barbelgudgeon from Bosnia and Herzegovina was studied by using two mitochondrial genes and morphometric traits (linear and geometric morphometrics). Nonparametric ANOVA showed that two analyzed populations significantly differed in six linear measurements, except snout length and postorbital head length. Contrary to centroid size, two populations were found to be significantly different in body shape. Deformation grids indicated that individuals from Studena River are characterized by wider and slightly shorter body comparing to individuals from Šator Lake. Incongruence in cytochrome c oxidase subunit I (COI) and cytochrome b (cyt b) mitochondrial DNA (mtDNA) variation was observed since a common COI haplotype was observed, while four and three cyt b haplotypes were registered in Šator Lake and Studena River, respectively. Since it was demonstrated that cyt b mtDNA was a faster evolving gene, we encourage its use in intraspecies studies, especially for evaluating the connectivity of fragmented populations and for studying the evolutionary footprint of the processes incorporated into the distinctive evolution of Aulopyge. Finally, findings herewith provide a firm basis for designing a long-term sustainable conservation strategy for endemic species in Dinaric karst.


Palladium-catalyzed cross-coupling reactions of silanolates: a paradigm shift in silicon-based cross-coupling reactions.
This paper chronicles the conceptual development, proof of principle experiments, and recent advances in the palladium-catalyzed cross-coupling reactions of the conjugate bases of organosilanols. The discovery that led to the design and refinement of this process represents a classical illustration of how mechanistic studies can provide a fertile ground for the invention of new reactions. On the basis of a working hypothesis (which ultimately proved to be incorrect) and the desire to effect silicon-based cross-coupling without the agency of fluoride activation, a mild and practical palladium-catalyzed cross-coupling of alkenyl-, aryl-, and heteroaryl silanolates has been developed. The mechanistic underpinnings, methodological extensions, and the successful applications of this technology to the synthesis of complex molecules are described.


Comparison of meniscal T1rho- and T2*-relaxation times in professional female volleyball players and healthy controls using 3T MRI: A pilot study.
Comparison of meniscal T1rho- and T2*-relaxation times in professional female volleyball players and healthy controls to determine if relaxation times are prolonged in athletes due to compositional meniscal alterations based on extensive and repetitive joint loading. The right knee of 20 asymptomatic professional female volleyball players and 20 female controls were examined at 3T MRI. T1rho- and T2*-measurements were performed in sagittal orientation. For quantitative measurements, two readers independently defined two consecutive central slices with the greatest area of the anterior and posterior horn of the lateral (AHLAT; PHLAT) and medial meniscus (AHMED; PHMED). Both readers repeated measurements after a six-week interval on the original MR images. Statistical analysis included intraclass correlation coefficient (ICC), Wilcoxon signed-rank-, Shapiro-Wilk- & Kolmogorov-Smirnov- and Mann-Whitney U-tests. Mean T1rho-relaxation times in the PHMED were significantly prolonged in professional female volleyball players when compared to controls (24.2 ± 4.0 vs 21.1 ± 2.6 ms; p < 0.005). There were no significant differences for the remaining three meniscal horns. T2*-relaxation times revealed no significant differences between athletes and controls. Prolonged T1rho-relaxation times in the PHMED of female volleyball players did not correlate with significant change in T2*-relaxation times within all meniscal subregions. Reproducibility levels were excellent in all segments (Interobserver-ICC: 0.93-0.97 and intraobserver-ICC: 0.97-0.99). T1rho-relaxation times were significantly increased in the PHMED of female volleyball players, potentially indicating a predilection to early degenerative meniscal changes. T1rho may serve as a sensitive biomarker at detecting early compositional meniscal alterations in athletes.


Ground adaptive standing controller for a powered transfemoral prosthesis.
The scope of this work is the design and verification of a new standing controller for a powered knee and ankle prosthesis. The controller is based upon a finite-state impedance control approach previously developed by the authors. The controller provides a comprehensive standing behavior that incorporates ground adaptation for unlevel terrain. An amputee subject tested the controller with a powered prosthesis for a variety of standing conditions. Results indicate that the powered prosthesis can estimate the ground slope within ±1 degree over a range of ±15 degrees, and that it can provide appropriate joint impedances for standing on slopes within this range.


Epitope-labeled soluble human interleukin-5 (IL-5) receptors. Affinity cross-link labeling, IL-5 binding, and biological activity.
The human receptor for the potent eosinophilopoietic cytokine interleukin-5 (IL-5) consists of two components: a 60-kDa ligand-binding alpha chain (IL-5 alpha R) and a 130-kDa beta chain (IL-5 beta R). Three ectodomain constructs of the alpha chain (alpha RED) bearing C-terminal epitope tags were engineered and expressed in baculovirus-infected Sf9 cells. Each recombinant alpha chain was secreted into the medium, maximum expression occurring 72 h post-infection. The various soluble alpha chains were shown by affinity cross-link labeling and competition with unlabeled IL-5 to bind recombinant human (rh) 125I-IL-5 specifically with an ED50 of 2-5 nM. The epitope tag provided a simple purification of the receptor from conditioned medium using immunoaffinity chromatography. The purified material had an apparent molecular mass of 43 kDa and was heterogeneously glycosylated. Sedimentation analysis revealed a 1:1 association of the purified epitope-tagged soluble receptor with its ligand, resulting in the formation of a 70-74-kDa complex. Circular dichroism analysis revealed that the soluble alpha chain existed with a significantly ordered structure consisting of 42% beta-sheet and 6% alpha-helix. Such analyses combined with fluorescence spectrometry suggested that ligand-receptor complex formation in solution resulted in minimal conformational changes, consistent with the suggestion that the membrane-associated form of the alpha chain itself has minimal signal transduction capability. Surface plasmon resonance studies of the interaction of the purified alpha RED with immobilized rhIL-5 revealed a specific, competable interaction with a dissociation constant of 9 nM. Preincubation of an IL-5-dependent cell line with the epitope-tagged alpha RED also dose-dependently neutralized rhIL-5-induced proliferation. These data demonstrate that biologically active epitope-tagged recombinant soluble IL-5 receptors are facile to produce in large quantities and may have therapeutic utility in the modulation of IL-5-dependent eosinophilia in man.


Activation of sea-urchin sperm motility is accompanied by an increase in the creatine kinase exchange flux.
The kinetics of the creatine kinase (CK) reaction were studied in suspensions of quiescent and active, intact sea-urchin spermatozoa in artificial seawater, using 31P-NMR magnetization transfer. In inactive sperm, no CK-mediated exchange flux was detected, whereas in activated motile sperm, the forward pseudo-first-order rate constant was 0.13+/-0.04 s-1 at 10 degrees C, corresponding to a steady-state CK flux of 3.1+/-0.5 mM.s-1. Intracellular pH shifted from 6.6+/-0.1 to 7.6+/-0.1 upon activation. The phosphocreatine (PCr)/ATP and PCr/Pi ratios were only marginally reduced in activated sperm, whereas the estimated cytosolic free ADP concentration increased remarkably from 9 microM in quiescent, to 114 microM in activated spermatozoa. The elevation of CK flux upon sperm activation is discussed in the light of the proposition that in sea-urchin spermatozoa, which are fuelled entirely by oxidative phosphorylation, high-energy phosphate transport is mediated by a 'CK/PCr shuttle'.


On the statistical reliability of letter-chart visual acuity measurements.
To determine boundary values of test-retest reliability and sensitivity to acuity change that are unlikely to be exceeded in any clinical situation, for a popular visual acuity chart (Lighthouse/ETDRS) with three scoring methods; to discuss general methodological issues associated with statistical accuracy of optotype chart testing; and to link measures of test reliability to measures of sensitivity to change. Five highly practiced subjects were tested using a computer-controlled acuity testing system in a procedure designed to reduce measurement error. Subjects read the computerized chart 156 times, yielding a sample of 78 test-retest comparisons. Under conditions likely to minimize variability, visual acuity may, with 95% confidence, be ascertained only within +/- 0.1 log units, using this chart with the recommended letter-by-letter scoring. Detecting a significant change in visual acuity requires about +/- 0.14 log units for the same degree of confidence. These measurements may be viewed as approaching the upper limit of reliability of this letter chart. Reliability probably is considerably less in typical usage.


Use of a pneumonia management tool to manage children with pneumonia at the first level health care facilities.
To describe the application and evaluation of Pneumonia Management Tool (PMT) to manage children with non-severe pneumonia (NSP) at the first level health care (FLHC) facilities according to the standard case management (SCM) guidelines for acute respiratory infections (ARI). The ARI SCM guidelines were simplified to a PMT and used by health workers at 14 FLHC facilities to assess, manage and monitor children with NSP and to educate caretakers on home care and follow-up visits. The district supervisors provided on the job support to various cadres of health workers of both public and private facilities. Of 949 children with NSP, 940 (99%) were successfully treated at FLHC facilities. Caretakers found PMT useful and of 1888 follow-up visits: 1872 (99.2%) brought PMT copy; 1627 (86.2%) brought their children to the facility; 1799 (95.3%) were on time and; 1857 (98.4%) had maintained antibiotic compliance. Using PMT, health workers adherence to SCM guidelines improved from 14% at baseline to 29% after training and 65% with on the job support. The practices remained similar among various cadres of health workers. Health workers used PMT in managing children with NSP, counselling caretakers on home care, follow-up visits and monitoring the treatment outcome. District level supervision helped to maintain a uniform skill enhancement.


Alpha2-macroglobulin from an Atlantic shrimp: biochemical characterization, sub-cellular localization and gene expression upon fungal challenge.
In this study, we report on the isolation and characterization of an alpha2-macroglobulin (α2M) from the plasma of the pink shrimp Farfantepenaeus paulensis, its sub-cellular localization and transcriptional changes after infection by fungi. The molecular mass of the α2M was estimated at 389 kDa by gel filtration and 197 kDa by SDS-PAGE, under reducing conditions, suggesting that α2M from F. paulensis consists of two identical sub-units, covalently linked by disulphide bonds. The N-terminal amino acid sequence of the α2M from F. paulensis was very similar to those of other penaeid shrimps, crayfish and lobster (70-90% identity) and to a less extent with that of freshwater prawn (40% identity). A monoclonal antibody raised against the Marsupenaeus japonicus α2M made it possible to demonstrate that α2M of F. paulensis is stored in the vesicles of the shrimp granular hemocytes (through immunogold assay). Quantitative real-time PCR (qPCR) analysis showed that α2M mRNA transcripts significantly increased 24 h after an experimental infection with the shrimp pathogen Fusarium solani and it returned to the basal levels at 48 h post-injection. This is the first report on a α2M characterization in an Atlantic penaeid species and its expression profile upon a fungal infection.


Mapping the Influence of the Gut Microbiota on Small Molecules across the Microbiome Gut Brain Axis.
Microbes exert influence across the microbiome-gut-brain axis through neurotransmitter production, induction of host immunomodulators, or the release or induction of other microbial or host molecules. Here, we used mass spectrometry imaging (MSI), a label-free imaging tool, to map molecular changes in the gut and brain in germ-free, antibiotic-treated and control mice. We determined spatial distribution and relative quantification of neurotransmitters and their precursors in response to the microbiome. Using untargeted MSI, we detected a significant change in the levels of four identified small molecules in the brains of germ-free animals compared to controls. However, antibiotic treatment induced no significant changes in these same metabolites in the brain after 1 week of treatment. This work exemplifies the utility of MSI as a tool for the study of known and discovery of novel, mediators of microbiome-gut-brain axis communication.


Experimental evidence of contagious stretching and ingroup bias in budgerigars (Melopsittacus undulatus).
Previous observational research suggests that stretching is contagious in budgerigars (Melopsittacus undulatus). Here we report the first experimental evidence of this response through a reanalysis of a previous experiment testing for contagious yawning in this species. Using a repeated measures design, 16 birds were tested as pairs alongside familiar and unfamiliar conspecifics with and without visual barriers. Our results show that stretching behavior was temporally clustered only when the birds could see one another, corroborating previous observational findings supporting contagion. Additionally, for the first time, we show an ingroup bias in this response. That is, while the overall frequency of stretching did not significantly differ as a function of conspecific familiarity, contagious stretching was only present when cage mates were paired together. These findings are discussed in relation to recent research studying social cognition in this species. (PsycINFO Database Record


[Guided endodontic access of calcified root canal by laser melting templates].
The aim of this study is to treat calcified root canal and assess the accuracy of guided endodontics using laser melting templates. Two cases with calcified anterior teeth were treated with laser melting templates. Cone beam computed tomography (CBCT) was used to scan the maxillary teeth of patients before surgery to establish the root canal system model. The maxillary impression of the patient was made and it was scanned by a 3D scanner. The CBCT scans were matched with surface scans of plaster model. Mimics 19.0 and 3-matic 11.0 software were used to design the virtual planning to access cavities. The templates were produced by laser melting 3D printing. Access cavity was prepared under the guidance of laser melting template. Then the deviations of planned and prepared cavities in three dimensions and angle were measured. The two teeth obtained satisfactory results. The first case had a angle deviation of 1.77°, a drilling base deviation of 0.403-0.497 mm, and a tip of 0.433-0.537 mm. The second case had a angle deviation of 3.26°, a drill base deviation of 0.18-0.347 mm, and a tip of 0.310-0.463 mm. Laser melting template-guided endodontics is an effective technique for the treatment of calcified root canal and can be used as a new strategy for the treatment of calcified canal.


Light-dependent kinetics of 2-carboxyarabinitol 1-phosphate metabolism and ribulose-1,5-bisphosphate carboxylase activity in vivo.
The light-dependent kinetics of the apparent in vivo synthesis and degradation of 2-carboxyarabinitol 1-phosphate (CA1P) were studied in three species of higher plants which differ in the extent to which this compound is involved in the light-dependent regulation of ribulose-1,5-bisphosphate carboxylase (Rubisco) activity. Detailed studies with Phaseolus vulgaris indicate that both the degradation and synthesis of this compound are light-stimulated, although light is absolutely required only for CA1P degradation. We hypothesize that the steady state level of CAIP at any particular photon flux density (PFD) represents a pseudo-steady state balance between ongoing synthesis and degradation of this compound. The rate of CA1P synthesis in P. vulgaris and the resultant reduction in the total catalytic constant of Rubisco were maximal at 200 micromoles quanta per square meter per second following a step decrease from a saturating PFD, and substantially faster than the rate of synthesis in the dark. Under these conditions an amount of CA1P equivalent to approximately 25% of the Rubisco catalytic site content was synthesized in less than 1 minute. The rate of synthesis was reduced at higher or lower PFDs. In Beta vulgaris, the rate of CA1P synthesis at 200 micromoles quanta per square meter per second was substantially slower than in P. vulgaris. In Spinacea oleracea, an apparent noncatalytic tight-binding of RuBP to deactivated sites on the enzyme was found to occur following a step decrease in PFD. When dark acclimated leaves of P. vulgaris were exposed to a step increase in PFD, the initial rate of CA1P degradation was also found to be dependent on PFD up to a maximum of approximately 300 to 400 micromoles quanta per square meter per second. The rate of degradation of this compound was similar in B. vulgaris. In S. oleracea, a step increase in PFD resulted in noncatalytic RuBP binding to Rubisco followed by an apparent release of RuBP and activation of the enzyme. The in vivo rate of change of Rubisco activity in response to an increase or decrease in PFD was similar between species despite the differences between species in the mechanisms used for the regulation of this enzyme's activity.


Photosensitization of Eretmapodites quinquevittatus Theobald (Diptera: Culicidae) eggs and larvae with Photofrin II.
The susceptibility of Eretmapodites quinquevittatus eggs and larvae to photosensitization with Photofrin II (PII) was determined. Hatching rates of eggs (5 min to 2 h after oviposition with no PII exposure) exposed to solutions of PII (90 micrograms/ml) in the dark for 12 h, before photoirradiation for 72 h. were very similar to those of untreated controls (P > 0.05). Hatching rates of eggs (5 min after oviposition with no PII exposure) exposed to PII (90 micrograms/ml) and photoirradiated simultaneously for 72 h were significantly lower than for untreated controls (P < 0.05). Permeability of the egg to PII diminishes as the eggs age and the serosal cuticle becomes mature. Eretmapodites quinquevittatus larvae were killed after exposure to PII (90 micrograms/ml) that had been previously photoirradiated for 1-11 days. The effect was age and size related. First-instar to early 3rd-instar larvae were killed when exposed to PII (90 micrograms/ml) with no photoirradiation.


Geriatrics on the run: rationale, implementation, and preliminary findings of a Belgian internal liaison team.
This article describes the rationale, implementation, interventions and preliminary findings of a Belgian interdisciplinary internal liaison team in a 1470-bed teaching hospital. The motive to start the team was threefold: the ageing of the inhospital population, the conclusion that health care professionals working on non-geriatric wards often lack the necessary skills to deal with older patients' needs and Belgian law, obliging each general hospital to set up an internal liaison team. Our team aims at detecting geriatric patients at risk, assisting health care professionals in caring for older patients and sensitizing them regarding optimal geriatric care. The article explains the underlying philosophy and strategy for implementation, focusing on the concepts of reciprocity, flexibility and cooperation. The preliminary results are based on a process evaluation of 719 consultations carried out from November 2004 to November 2006, a time registration, and a Strengths, Weaknesses, Opportunities, and Threats analysis (SWOT). Although our data are preliminary and the implementation of the team was pragmatic rather than research driven, they provide insight into the development, implementation, functioning and interventions of a Belgian interdisciplinary internal liaison team.


[Reversibility of myocardiopathy induced by incessant supraventricular tachycardia in children after radiofrequency ablation].
The so called tachycardia-induced cardiomyopathy may develop as a complication of persistent abnormal high rates. It is especially common in patients who have either a permanent form of junctional reciprocating tachycardia or an ectopic atrial tachycardia. Radiofrequency catheter ablation has become established as an effective and safe treatment to eliminate both arrhythmias. Four children aged from 3 months to 8 years, who had incessant tachyarrhythmias and left ventricular dysfunction (shortening fraction of mean +/- SD, 21.7 +/- 1.2%) underwent radiofrequency catheter ablation. The youngest patient had permanent junctional reciprocating tachycardia caused by a left posteroseptal pathway. She was presented with severe heart failure that did not improve with digoxin and amiodarone. The other patients had palpitations and exercise intolerance. Two of them had an ectopic atrial tachycardia caused by a single atrial focus localized in the left atrial appendage apex and the orifice of the right atrial appendage respectively. The other patient had the permanent form of junctional reciprocating tachycardia caused by a right posteroseptal pathway. All four patients underwent one successful ablation. The average procedure mean time was 3.7 hours with an fluoroscopy time of 44 minutes. There were no complications. Subsequently shortening fraction improved progressively. After a mean follow-up of 21.7 months all patients are asymptomatic without medical treatment. Radiofrequency catheter ablation is the therapy of choice in children with either the permanent form of junctional reciprocating tachycardia or ectopic atrial tachycardia refractory to medical treatment. The tachycardia-induced cardiomyopathy is reversible after the elimination of the arrhythmia. The presence of tachycardia-induced cardiomyopathy is an indication for radiofrequency ablation even in small infants.


Toxicity of smoke extracts towards A549 lung cells: role of acrolein and suppression by carbonyl scavengers.
The noxious 3-carbon electrophile acrolein forms on combustion of diverse organic matter including synthetic polymers such as polyethylene. While known to play a key role in smoke inhalation injury (SII), the molecular basis for the pulmonary toxicity of high dose acrolein-containing smoke is unclear. As a result, drug interventions in SII are poorly directed against pathogenetic smoke toxicants such as acrolein. The first aim of this study was to confirm a role for acrolein in the acute toxicity of smoke extracts towards A549 lung cells by monitoring adduction of known acrolein targets and the expression of acrolein-inducible genes. A second aim was to evaluate carbonyl scavengers for their abilities to protect cell targets and block smoke extract toxicity. Extracts were prepared by bubbling smoke released by smouldering polyethylene through a buffered saline-trap. Acrolein levels in the extracts were estimated via HPLC after derivatisation with 2,4-dinitrophenylhydrazine. Extracts were highly toxic towards A549 cells, eliciting greater ATP depletion than an equivalent concentration of acrolein alone. The toxicity was accompanied by pronounced carbonylation of several cytoskeletal targets, namely vimentin and keratins-7, -8 and -18. Western blotting revealed that polyethylene combustion products also upregulated several acrolein-responsive protein markers, including GADD45beta, NQO1, HMOX, Hsp70, Nur77 and Egr1. Several carbonyl scavengers (bisulfite, d-penicillamine, hydralazine and 1-hydrazinoisoquinoline) strongly attenuated smoke extract toxicity, with bisulfite suppressing both the adduction and cross-linking of intermediate filament targets. Bisulfite also suppressed the cytotoxicity of smoke extracts when detected using real-time monitoring of cellular impedance. These findings confirm a key role for acrolein in smoke cytotoxicity and suggest drugs that block acrolein toxicity deserve further investigation as possible interventions against SII.


Immunomodulation of human B cells following treatment with intravenous immunoglobulins involves increased phosphorylation of extracellular signal-regulated kinases 1 and 2.
In the treatment of autoimmune diseases, intravenous Igs (IVIg) are assumed to modulate immune cells through the binding of surface receptors. IVIg act upon definite human B cell populations to modulate Ig repertoire, and such modulation might proceed through intracellular signaling. However, the heterogeneity of human B cell populations complicates investigations of the intracellular pathways involved in IVIg-induced B cell modulation. The aim of this study was to establish a model allowing the screening of IVIg signal transduction in human B cell lines and to attempt transposing observations made in cell lines to normal human B lymphocytes. Nine human B cell lines were treated with IVIg with the goal of selecting the most suitable model for human B lymphocytes. The IgG(+) DB cell line, whose response was similar to that of human B lymphocytes, showed reduced IVIg modulation following addition of PD98059, an inhibitor of extracellular signal-regulated protein kinase 1/2 (ERK1/2). The IVIg-induced ERK1/2 phosphorylation was indeed proportional to the dosage of monomeric IVIg used when tested on DB cells as well as Pfeiffer cells, another IgG(+) cell line. In addition, two other intermediates, Grb2-associated binder 1 (Gab1) and Akt, showed increased phosphorylation in IVIg-treated DB cells. IVIg induction of ERK1/2 phosphorylation was finally observed in peripheral human B lymphocytes, specifically within the IgG(+) B cell population. In conclusion, IVIg immunomodulation of human B cells can thus be linked to intracellular transduction pathways involving the phosphorylation of ERK1/2, which in combination with Gab1 and Akt, may be related to B cell antigen receptor signaling.


Personal and interpersonal risk factors in the consumption of illicit drugs by marginal adolescents and young people from juvenile gangs.
Marginal populations are groups which are known to present higher risks of drug consumption. It is possible to identify adolescents and young people from juvenile gangs that constitute this group. The purpose of this study was to analyze the effect of personal and interpersonal risk factors of drug consumption in 175 marginal adolescents and young people who belong to juvenile gangs in Mexico. Results showed a significant effect of personal factors on drug use, with an estimated variation of 26.1%. The factors that presented the highest rates were: gender, age and mental problems. The interpersonal factors (relationships with friends who have maladaptive behaviors and inappropriate relationships with parents) showed an effect with an estimated variation of 15%. These results will allow for reflection and, in the future, the elaboration of adequate preventive programs aimed at this group of young people.


Postarthroscopic arthrofibrosis of the shoulder.
Arthrofibrosis after shoulder surgery may be challenging to treat. Certain factors, including diabetes and history of keloid formation, predispose patients to the development of postoperative arthrofibrosis. Etiologies include rotator cuff repair, labral repair, capsulorrhaphy, shoulder arthroplasty, and proximal humerus fracture fixation. Systematic evaluation with thorough history and physical examination is essential to determine the proper treatment and to counsel patients on expectations for recovery. Nonoperative treatment focused on physical therapy is the first step in management. Manipulation under anesthesia may be an effective treatment for failure of physical therapy regimens in idiopathic adhesive capsulitis, however it is less successful in cases of postsurgical adhesions. In cases of postoperative stiffness, treatment options include arthroscopic and open capsular releases. Adequate postoperative pain control and adherence to a rigorous physical therapy regimen are integral to the success of surgical release. Surgical treatment is effective in the majority of patients with postsurgical arthrofibrosis.


Opioid-Induced Pronociceptive Signaling in the Gastrointestinal Tract Is Mediated by Delta-Opioid Receptor Signaling.
Opioid tolerance (OT) leads to dose escalation and serious side effects, including opioid-induced hyperalgesia (OIH). We sought to better understand the mechanisms underlying this event in the gastrointestinal tract. Chronic in vivo administration of morphine by intraperitoneal injection in male C57BL/6 mice evoked tolerance and evidence of OIH in an assay of colonic afferent nerve mechanosensitivity; this was inhibited by the δ-opioid receptor (DOPr) antagonist naltrindole when intraperitoneally injected in previous morphine administration. Patch-clamp studies of DRG neurons following overnight incubation with high concentrations of morphine, the µ-opioid receptors (MOPr) agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or the DOPr agonist [D-Ala2, D-Leu5]-Enkephalin evoked hyperexcitability. The pronociceptive actions of these opioids were blocked by the DOPr antagonist SDM25N but not the MOPr antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 The hyperexcitability induced by DAMGO was reversed after a 1 h washout, but reapplication of low concentrations of DAMGO or [D-Ala2, D-Leu5]-Enkephalin restored the hyperexcitability, an effect mediated by protein kinase C. DOPr-dependent DRG neuron hyperexcitability was blocked by the endocytosis inhibitor Pitstop 2, and the weakly internalizing DOPr agonist ARM390 did not cause hyperexcitability. Bioluminescence resonance energy transfer studies in HEK cells showed no evidence of switching of G-protein signaling from Gi to a Gs pathway in response to either high concentrations or overnight incubation of opioids. Thus, chronic high-dose opioid exposure leads to opioid tolerance and features of OIH in the colon. This action is mediated by DOPr signaling and is dependent on receptor endocytosis and downstream protein kinase C signaling.SIGNIFICANCE STATEMENT Opioids are effective in the treatment of abdominal pain, but escalating doses can lead to opioid tolerance and potentially opioid-induced hyperalgesia. We found that δ-opioid receptor (DOPr) plays a central role in the development of opioid tolerance and opioid-induced hyperalgesia in colonic afferent nociceptors following prolonged exposure to high concentrations of MOPr or DOPr agonists. Furthermore, the role of DOPr was dependent on OPr internalization and activation of a protein kinase C signaling pathway. Thus, targeting DOPr or key components of the downstream signaling pathway could mitigate adverse side effects by opioids.


Potential for Non-Contact ACL Injury Between Step-Close-Jump and Hop-Jump Tasks.
This study aimed to compare the kinematics and kinetics during the landing of hop-jump and step-close-jump movements in order to provide further inferring that the potential risk of ACL injuries. Eleven elite male volleyball players were recruited to perform hop-jump and step-close-jump tasks. Lower extremity kinematics and ground reaction forces during landing in stop-jump tasks were recorded. Lower extremity kinetics was calculated by using an inverse dynamic process. Step-close-jump tasks demonstrated smaller peak proximal tibia anterior shear forces during the landing phase. In step-close-jump tasks, increasing hip joint angular velocity during initial foot-ground contact decreased peak posterior ground reaction force during the landing phase, which theoretically could reduce the risk of ACL injury. Key pointsThe different landing techniques required for these two stop-jump tasks do not necessarily affect the jump height.Hop-jump decreased the hip joint angular velocity at initial foot contact with ground, which could lead to an increasing peak posterior GRF during the landing phase.Hop-jump decreased hip and knee joint angular flexion displacement during the landing, which could increase the peak vertical loading rate during the landing phase.


Brain morphometry and IQ measurements in preterm children.
Although IQ is thought to remain relatively stable in the normal population, a decline in IQ has been noted in children born preterm. It is not clear, however, to what extent the inclusion of children with clear neurological damage has influenced these findings. We examined IQ scores obtained in childhood and then again in adolescence from a group of children born at 30 weeks gestation or less who had been classified as neurologically normal at 7.5-8 years. They showed a significant decline in mean IQ scores over time. MRI scans obtained from a subset of children at adolescence were read as normal in approximately 50% of cases and, in the others, there were no consistent relationships between radiological abnormalities and IQ results. Such children can, however, have relatively subtle brain abnormalities that are not seen on conventional MRI, and we hypothesized that these would be related to declines in IQ. Voxel-based morphometry (VBM) analyses of the MRI scans revealed that absolute IQ scores were related to areas in both the parietal and temporal lobes. The analyses also showed that frontal and temporal lobe regions were associated with the decline in VIQ, while occipital and temporal lobe regions (including the hippocampi) were associated with the decline in PIQ. Hippocampal volume measurements were consistent with the VBM findings. We concluded that preterm children are at risk of declining IQ over time even if they have not suffered obvious neurological damage and that the decline is associated with specific neural regions. Whether this is true of children born at >30 weeks gestation and what other factors predispose to this decline have yet to be determined.


Ultrasound imaging with bolus delivered contrast agent for the detection of angiogenesis and blood flow irregularities.
Highly increased blood flow and vascularity after angiogenic gene therapy have raised concerns of shunting and hemangioma-like blood pool formation that might decrease effective perfusion and ruin the beneficial effects of the therapy. Contrast enhanced ultrasound is a promising noninvasive tool for studying skeletal muscle perfusion. The objectives of the present study were to test bolus and infusion administrations of ultrasound microbubble contrast media in imaging vascular growth in skeletal muscle and assess the functionality of vessels grown with angiogenic gene therapy. Contrast enhanced ultrasound was used to study changes in skeletal muscle perfusion in normal and gene-transduced rabbit hindlimbs 6 days after gene transfer. Adenoviral gene transfer of VEGF (10e(9)-10e(11) viral particles) or β-galactosidase control gene (10e(11) viral particles) was done under anesthesia and induced up to 16-fold increases in relative tissue perfusion. Contrast intensity versus time curves were plotted and analyzed for contrast kinetics. Bolus administration of the contrast media was highly feasible in analyzing skeletal muscle blood flow and its kinetics. Maximal signal intensity of the bolus signal reflected relative changes in both blood flow and volume equally to the infusion method. Flow irregularities were detected after angiogenic gene therapy. In conclusion, bolus delivery of ultrasound contrast agent is highly feasible for the relative analysis of both quantity and quality of blood flow after angiogenic gene therapy. The kinetics of blood flow can and should be studied more extensively in both preclinical and clinical trials of angiogenic gene therapy since there is increasing evidence of flow irregularities in angiogenic vessels.


The relation between mild leg-length inequality and able-bodied gait asymmetry.
The causes of able-bodied gait asymmetries are unclear. Mild (< 3 cm) leg-length inequality (LLI) may be one cause of these asymmetries; however, this idea has not been thoroughly investigated. The purpose of this study was to investigate the nature of the relationship between LLI and able-bodied gait asymmetries. We hypothesized that subjects (n = 26) with relatively large LLI, quantified radiographically, would display less symmetrical gait than subjects with relatively small LLI. Gait asymmetries for joint kinematics and joint kinetics were determined using standard gait analysis procedures. Symmetry coefficients were used to quantify bilateral gait symmetry for sagittal-plane hip, knee, and ankle joint angles, moments, and powers. A Pearson product-moment correlation coefficient (r) was used to evaluate the relationship between LLI and the aforementioned symmetry coefficients. Also, these symmetry coefficients were compared between subjects with relatively small LLI (LLI < 1 cm; n = 19) and relatively large LLI (LLI ≥ 1 cm; n = 7). Statistically significant relationships were observed between LLI and the symmetry coefficient for knee joint moment (r = -0.48) and power (r = -0.51), and ankle joint moment (r = -0.41) and power (r = -0.42). Similarly, subjects with relatively large LLI exhibited significantly lower symmetry coefficients for knee joint moment (p = 0.40) and power (p = 0.35), and ankle joint moment (p = 0.40) and power (p = 0.22) than subjects with relatively small LLI. Degree of bilateral symmetry for knee and ankle joint kinetics appears to be related to LLI in able- bodied gait. This finding supports the idea that LLI is one cause of able-bodied gait asymmetries. Other factors, however, are also likely to contribute to these gait asymmetries; these may include other morphological asymmetries as well as asymmetrical neuromuscular input to the lower limb muscles. Key pointsModerate negative relationships were observed between mild limb-length inequality and gait symmetry for knee and ankle moment and power.Subjects with relatively large mild limb-length inequality (between 1.0 and 2.3 cm) exhibited significantly less symmetrical gait for knee and ankle joint moment and power than subjects with relatively small mild limb-length inequality (< 1 cm).These results indicate that the degree of symmetry for knee and ankle joint kinetics appears to be related to mild limb-length inequality in able-bodied gait.These results further our understanding of normal human walking and provide important background information for future studies on gait pathology associated with mild limb-length inequality.


Glutamate Genetics in Obsessive-Compulsive Disorder: A Review.
Obsessive-compulsive disorder (OCD) is common and debilitating with patients exhibiting persistent intrusive thoughts (obsessions), repetitive ritualistic behaviours (compulsions) and anxiety. While it is known that OCD is highly heritable, the specific genetic risk factors for OCD are still largely unknown. The etiology of OCD has also not been fully elucidated but there is growing evidence that glutamate signaling dysfunction in the cortico-striatal-thalamo-cortical (CSTC) circuitry plays a role in its pathogenesis. We conducted a focused review of recent literature on the role of glutamate genes in OCD. There have been several recent discoveries in the SAPAP (DLGAP) family, SLC1A1, and GRIN/GRIK families of proteins related to OCD. There is growing evidence supporting a role for genetic variation leading to dysfunctional glutamate signaling in OCD. Based on this new evidence we hypothesize that sustained glutamatergic neurotransmission in key areas of the brain may be contributing to the etiology of OCD.


An audit of morbidity and mortality associated with foreign body aspiration in children from a tertiary level hospital in Northern India.
There is paucity of data regarding the morbidity and mortality of rigid bronchoscopy in children for foreign body (FB) retrieval from India. The aim was to audit data regarding anaesthetic management of rigid bronchoscopy in children and associated morbidity and mortality. Hospital records of all patients below 18 years of age undergoing rigid bronchoscopy for suspected FB aspiration (FBA) between January 1, 2002 and December 31, 2011 were audited to assess their demographic profile, anaesthetic management, complications, and postoperative outcomes. The children were divided into early and late diagnosis groups depending on whether they presented to the hospital within 24 hours of FBA, or later. One hundred and forty children, predominantly male (75%), with an average age of 1-year and 8 months, presented to our hospital for rigid bronchoscopy during the study period. Majority of children presented in the late diagnosis group (59.29% vs. 40.71%). The penetration syndrome was observed in 22% of patients. Majority of patients aspirated an organic FB (organic: Inorganic FB = 3:1), with peanuts being the most common (49.28%). A significantly higher number of children presented with cough (P = 0.0001) and history of choking (P = 0.0022) in the early diagnosis group and crepitations (P = 0.0011) in the late diagnosis group. Major complications included cardiac arrest (2.1%), pneumothorax (0.7%), and laryngeal oedema (9.3%). The average duration of hospitalization in our series was 3.08 ± 0.7 days. Foreign body aspiration causes considerable morbidity, especially when diagnosis is delayed.


Therapeutic value of bovine saliva in wound healing: a histomorphological study.
Biopsies were collected from the control (normal saline solution treated) and saliva treated wounds (back and loin region) of calves on 3rd, 7th, 14th, 21st and 28th days post-wounding. A faster connective tissue and epidermal regeneration was observed in saliva treated group. The inflammatory response was subdued as early as on 3rd day. On the 14th day the test wounds were covered with a dense layer of fibroblast and collagen and epidermal growth started. On 21st day the condensation of collagen and vascularization of the scar tissue was further augmented. By 28th day, the wounds were completely filled and nearly 85% of the wound surface was covered with epidermis.


Influence of pressure transducer protrusion depth on pressure measurements of shock waves in shock tubes.
This note investigates how small changes in the protrusion depth of a pressure transducer affect the pressure measurement of a moving shock wave. Measurements are undertaken with Kistler, Kulite, and PCB sensors in flush, recessed, and protruded sensor positions. Measurements of both absolute pressure and Mach number are shown to be insensitive to sensor protrusion depth. An assessment of sensor response time indicates a significantly shorter reaction time for the Kulite and PCB sensors compared with the Kistler sensor.


Remaining challenges in predicting patient outcomes for diffuse large B-cell lymphoma.
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is an aggressive malignancy with heterogeneous outcomes. Diverse methods for DLBCL outcomes assessment ranging from clinical to genomic have been developed with variable predictive and prognostic success.Areas covered: The authors provide an overview of the various methods currently used to estimate prognosis in DLBCL patients. Models incorporating cell of origin, genomic features, sociodemographic factors, treatment effectiveness measures, and machine learning are described.Expert opinion: The clinical and genetic heterogeneity of DLBCL presents distinct challenges in predicting response to therapy and overall prognosis. Successful integration of predictive and prognostic tools in clinical trials and in a standard clinical workflow for DLBCL will likely require a combination of methods incorporating clinical, sociodemographic, and molecular factors with the aid of machine learning and high-dimensional data analysis.


The effect of acute exercise on undercarboxylated osteocalcin in obese men.
The purpose of this study was to examine if the reduction in glucose post-exercise is mediated by undercarboxylated osteocalcin (unOC). Obese men were randomly assigned to do aerobic or power exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC. Osteocalcin (OC) in its undercarboxylated (unOC) form may contribute to the regulation of glucose homeostasis. As exercise reduces serum glucose and improves insulin sensitivity in obese individuals and individuals with type 2 diabetes (T2DM), we hypothesised that this benefit was partly mediated by unOC. Twenty-eight middle-aged (52.4 ± 1.2 years, mean ± SEM), obese (BMI = 32.1 ± 0.9 kg m(-2)) men were randomly assigned to do either 45 min of aerobic (cycling at 75% of VO(2peak)) or power (leg press at 75% of one repetition maximum plus jumping sequence) exercises. Blood samples were taken at baseline and up to 2 h post-exercise. At baseline, unOC was negatively correlated with glucose levels (r = -0.53, p = 0.003) and glycosylated haemoglobin (HbA1c) (r = -0.37, p = 0.035). Both aerobic and power exercises reduced serum glucose (from 7.4 ± 1.2 to 5.1 ± 0.5 mmol L(-1), p = 0.01 and 8.5 ± 1.2 to 6.0 ± 0.6 mmol L(-1), p = 0.01, respectively). Aerobic exercise significantly increased OC, unOC and high-molecular-weight adiponectin, while power exercise had a limited effect on OC and unOC. Overall, those with higher baseline glucose and HbA1c had greater reductions in glucose levels after exercise (r = -0.46, p = 0.013 and r = -0.43, p = 0.019, respectively). In a sub-group of obese people with T2DM, the percentage change in unOC levels was correlated with the percentage change in glucose levels post-exercise (r = -0.51, p = 0.038). This study reports that the reduction in serum glucose post-acute exercise (especially aerobic exercise) may be partly related to increased unOC.


Effect of Increased IL-1β on Expression of HK in Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by decreased glucose metabolism and increased neuroinflammation. Hexokinase (HK) is the key enzyme of glucose metabolism and is associated with mitochondria to exert its function. Recent studies have demonstrated that the dissociation of HK from mitochondria is enough to activate the NOD-like receptor protein 3 (NLRP3) inflammasome and leads to the release of interleukin-1β (IL-1β). However, the effect of increased IL-1β on the expression of HK is still unclear in AD. In this paper, we used positron emission tomography (PET), Western blotting and immunofluorescence to study the glucose metabolism, and the expression and distribution of HK in AD. Furthermore, we used lipopolysaccharide (LPS), nigericin (Nig), CY-09 and lonidamine (LND) to treat N2a and N2a-sw cells to investigate the link between IL-1β and HK in AD. The results show decreased expression of HK and the dissociation of HK from mitochondria in AD. Furthermore, a reduction of the expression of IL-1β could increase the expression of HK in AD. These results suggest that inhibiting inflammation may help to restore glucose metabolism in AD.


Botulinum Toxin in Aesthetic Medicine: Myths and Realities.
Several formulations of Botulinum toxin serotype A (BoNT-A) for aesthetic indications are available, with numbers likely to increase. Preparations are not interchangeable, based on dose unit comparisons. Numerous myths and misconceptions regarding the use of BoNT-A for aesthetic indications have arisen, which this review aims to lay to rest. This review assesses evidence for and against each of the most common myths regarding BoNT use in aesthetics. BoNT-A neurotoxin/protein complexes are irrelevant to the toxin's therapeutic/aesthetic indications. BoNT-A neurotoxin/protein complexes do not influence movement from injection site or immunogenicity. Any relationship between neutralizing antibody formation and clinical response is complex and clinicians should consider other factors that may induce an apparent loss of clinical response. Diffusion appears predominately, perhaps exclusively, dose dependent. Careful placement and correct dosing optimizes likelihood of good outcomes. Manufacturers recommend reconstitution of products with sterile nonpreserved saline. However, compelling evidence suggests that reconstitution using preserved saline dramatically improves patient comfort without compromising efficacy. Several post-treatment instructions/restrictions are widely used despite the lack of evidence, but muscle activity after injection may be beneficial. Cooling the treatment area might hinder BoNT-A translocation and should probably be abandoned. The existing evidence suggests that experienced users should achieve equivalent results regardless of BoNT-A formulation, but additional, well-designed, adequately powered, controlled randomized studies should be performed.


Magnetic resonance spectroscopy study of the antioxidant defense system in schizophrenia.
Accumulating evidence suggests that oxidative stress associated with impaired metabolism of the antioxidant glutathione (GSH) plays a key role in the pathophysiology of schizophrenia. Magnetic resonance spectroscopy (MRS) is one of the brain-imaging techniques that can quantitatively measure bioactive substances such as GSH in the intact human brain. Four different measurement sequences including double quantum coherence (DQC) filtering, MEscher-GArwood Point-RESolved Spectroscopy (MEGA-PRESS), Stimulated Echo Acquisition Mode (STEAM), and PRESS have been used to evaluate the (1)H-MRS measurement of GSH in the brains of patients with schizophrenia. Although the results of these studies were somewhat diverse, a negative correlation between brain GSH levels and the severity of negative symptoms in schizophrenia patients suggests that increasing the brain GSH levels might be beneficial for schizophrenia patients with negative symptoms. Moreover, a recent double-blind, placebo-controlled study demonstrated that add-on of N-acetyl-l-cysteine (NAC), a precursor of GSH, to antipsychotics improved the negative symptoms and reduced the side effects (akathisia) in patients with chronic schizophrenia. MRS study of the antioxidant defense system in schizophrenia still remains in the infantile stage; future studies are needed to examine the brain GSH level before and after NAC treatment, and thereby to provide direct evidence of the induced production of GSH in the living brain.


One important way to get the best performance from staff.
Good communication about expectations is essential to encouraging the best performance from staff. An excellent tool for fostering this communication is the performance evaluation. Used correctly, it can open a dialogue that can lead to agreement between the supervisor and staff member on areas that need to be improved and ways to do so.


Menstrual cycle effects on cortisol responsivity and emotional retrieval following a psychosocial stressor.
This article is part of a Special Issue "Estradiol and cognition". Laboratory-induced stress produces elevations in cortisol and deficits in memory, especially when stress is induced immediately before retrieval of emotionally valent stimuli. Sex and sex steroids appear to influence these stress-induced outcomes, though no study has directly compared the effects of laboratory-induced stress on cortisol and emotional retrieval across the menstrual cycle. We examined the effect of psychosocial stress on cortisol responsivity and emotional retrieval in women tested during either the follicular phase (low estradiol and progesterone) or the luteal phase (higher estradiol and progesterone). Forty women (50% White; age 18-40 years) participated in the study; 20 completed the task during the luteal phase and 20 during the follicular phase. Psychosocial stress was induced with the Trier Social Stress Test (TSST). On the day before the TSST, participants learned two lists of word pairs to 100% criterion. The next day, participants recalled one list after the control condition and the other after the TSST. Women in the follicular phase, but not the luteal phase, demonstrated a significant cortisol response to the TSST. There was a stress-induced decrease in emotional retrieval following the TSST, but this effect was not modified by menstrual phase. However, regression and correlational analyses showed that individual differences in stress-induced cortisol levels were associated with impaired emotional retrieval in the follicular phase only. The present findings indicate that cortisol responsivity and the impairing effects of cortisol on emotional memory are lower when levels of estradiol and progesterone are high compared to when levels are low.


Flip-flop of oleic acid in a phospholipid membrane: rate and mechanism.
Flip-flop of protonated oleic acid molecules dissolved at two different concentrations in membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine is studied with the aid of molecular dynamics simulations at a time scale of several microseconds. Direct, single-molecule flip-flop events are observed at this time scale, and the flip-flop rate is estimated at 0.2-0.3 μs(-1). As oleic acid molecules move toward the center of the bilayer during flip-flop, they undergo gradual, correlated translational, and rotational motion. Rare, double-flipping events of two hydrogen-bonded oleic acid molecules are also observed. A two-dimensional free energy surface is obtained for the translational and rotational degree of freedom of the oleic acid molecule, and the minimum energy path on this surface is determined. A barrier to flip-flop of ~4.2 kcal/mol is found at the center of the bilayer. A two-dimensional diffusion model is found to provide a good description of the flip-flop process. The fast flip-flop rate lends support to the proposal that fatty acids permeate membranes without assistance of transport proteins. It also suggests that desorption rather than flip-flop is the rate-limiting step in fatty acid transport through membranes. The relation of flip-flop rates to the evolution of ancestral cellular systems is discussed.


Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex vivo expanded haematopoietic stem cells.
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34+ cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34+ and CD34+ CD38- cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1). Moreover, in vivo analysis demonstrates that PD reduces engraftment capacity of ex vivo expanded CD34+ cells. Notably, when ERK pathway is blocked in UCB-MNCs, spontaneous erythroid differentiation is promoted, found in concomitant with increasing number of burst-forming unit-erythroid colony (BFU-E) as well as enhancement of erythroid glycophorin-A marker. These results are in total conformity with up-regulation of some erythroid enhancer genes (TAL1, GATA2, LMO2) and down-regulation of some erythroid repressor genes (JUN, PU1) as well. Taken together, our results support the idea that MEK/ERK pathway has a critical role in achieving the correct balance between self-renewal and differentiation of UCB cells. Also, we suggest that inhibition of ERK signalling could likely be a new key for erythroid induction of UCB-haematopoietic progenitor cells.


A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model.
Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment.


Muscle Oxidative Capacity in Vivo Is Associated With Physiological Parameters in Trained Rowers.
Purpose: The muscle oxygen uptake (mV˙O2) kinetics following exercise, measured by near-infrared spectroscopy, has been used as a functional evaluation of muscle oxidative metabolism. This study aimed to determine the mV˙O2 off-kinetics and verify the relationship of the recovery rate of mV˙O2 (k) with time-trial performance and different aerobic parameters in trained rowers. Methods: Eleven male rowers (age: 20 ± 3 years; V˙O2max: 4.28 ± 0.35 L·min-1) used a rowing ergometer to perform (I) an incremental test to determine the maximal oxygen uptake (V˙O2max) and peak power output (Ppeak); (II) several visits to determine maximal lactate steady state (MLSS); and (III) a 2000-m rowing ergometer performance test. Also, one test to determine mV˙O2 off-kinetics of the vastus lateralis muscle using a repeated arterial occlusions protocol. Results: The mV˙O2 generated a good monoexponential fit (R2 = 0.960 ± 0.030; SEE = 0.041 ± 0.018%.s-1). The k of mV˙O2 (2.06 ± 0.58 min-1) was associated with relative V˙O2max (r = 0.79), power output at MLSS (r = 0.76), and Ppeak (r = 0.83); however, it was not related with 2000-m rowing performance (r = -0.38 to 0.52; p > .152). Conclusion: These findings suggest that although not associated with rowing performance, the mV˙O2 off-kinetics determined after a submaximal isometric knee extension may be a practical and less-exhaustive approach than invasive responses and incremental tests to assess the muscle oxidative metabolism during a training program.


Activity levels of B-esterases in the tadpoles of 11 species of frogs in the middle Paraná River floodplain: implication for ecological risk assessment of soybean crops.
Soybean fields provide habitats for many species of amphibians. However, the persistence and health of amphibian populations may be at risk from the increasing use of pesticides and other agricultural chemicals. We examined the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterases (CbEs) in 11 syntopic species of larval anurans. In vitro effects of malaoxon causing 50% BChE inhibition (IC(50)) were also studied. In addition, we calculated a relative risk index (RI) based on the geographic distributions of the anurans, the phenology of soybean cultivation, and basal enzymatic values related to potential pesticide detoxification. Among the 11 species, AChE activity varied from 17.5 ± 1.6 to 68.2 ± 4.7 nmol min(-1) mg(-1) protein (PT). BChE activity also varied significantly, ranging from 3.3 ± 0.4 to 7.5 ± 0.4 nmol min(-1) mg(-1)PT. Both measures of CbE activities varied widely (CbE α-NA: 2.1 ± 0.5-12.4 ± 1.1 nmol min(-1) mg(-1) PT; CbE-4NPV: 21.8 ± 1.8-102.6 ± 7.9 nmol min(-1) mg(-1) PT). We also corroborate that lower BChE activity levels for the tadpoles were associated at minor IC(50) values. The results of this study demonstrate significant variation in enzymatic levels among several tadpole species and intermediate to high RI values for 7 species. Based on these results, it appears that a conversion of native ecosystems to soybean crops may lead to increased ecological risk for anuran amphibians.


Microneedles in Drug Delivery: Progress and Challenges.
In recent years, an innovative transdermal delivery technology has attracted great interest for its ability to distribute therapeutics and cosmeceuticals for several applications, including vaccines, drugs, and biomolecules for skin-related problems. The advantages of microneedle patch technology have been extensively evaluated in the latest literature; hence, the academic publications in this area are rising exponentially. Like all new technologies, the microneedle patch application has great potential but is not without limitations. In this review, we will discuss the possible limitations by highlighting the areas where a great deal of improvements are required. Emphasising these concerns early on should help scientists and technologists to address the matters in a timely fashion and to use their resources wisely.


Anatomical site-specific modalities for hyperthermia.
The clinical application of hyperthermia in the treatment of deep-seated tumors remains an empirical science. The pleomorphic nature of the neoplasms and the great diversity in the anatomy and physiology of the individual tumor locations make the treatment of nearly every neoplasm a unique challenge. A wide variety of devices is required, both for the administration of hyperthermia and for the measurement of the temperatures achieved. At Stanford University, these include the BSD Medical Corp. annular phased array system, an isospherical ultrasound device, and interstitial radiofrequency for deep heating. Ultrasound transducers and a variety of microwave applicators are used for superficial hyperthermia. Six illustrative case studies, selected from the 91 patients treated in our program since October 1981, are presented, with discussion and comparison of treatment devices. Difficulties in deep heating were encountered in several instances, believed secondary to the thickness of the s.c. fat, the relatively high heat-induced tumor blood flow, and the presence of adjacent bone. It is suggested that ultimate improvement in clinical results will be possible once a better understanding is achieved of such anatomical and physiological factors.


Behavioral processes underlying the decline of narcissists' popularity over time.
Following a dual-pathway approach to the social consequences of grandiose narcissism, we investigated the behavioral processes underlying (a) the decline of narcissists' popularity in social groups over time and (b) how this is differentially influenced by the 2 narcissism facets admiration and rivalry. In a longitudinal laboratory study, participants (N = 311) first provided narcissism self-reports using the Narcissistic Personality Inventory and the Narcissistic Admiration and Rivalry Questionnaire, and subsequently interacted with each other in small groups in weekly sessions over the course of 3 weeks. All sessions were videotaped and trained raters coded participants' behavior during the interactions. Within the sessions participants provided mutual ratings on assertiveness, untrustworthiness, and likability. Results showed that (a) over time narcissists become less popular and (b) this is reflected in an initially positive but decreasing effect of narcissistic admiration as well as an increasing negative effect of narcissistic rivalry. As hypothesized, these patterns of results could be explained by means of 2 diverging behavioral pathways: The negative narcissistic pathway (i.e., arrogant-aggressive behavior and being seen as untrustworthy) plays an increasing role and is triggered by narcissistic rivalry, whereas the relevance of the positive narcissistic pathway (i.e., dominant-expressive behavior and being seen as assertive) triggered by narcissistic admiration decreases over time. These findings underline the utility of a behavioral pathway approach for disentangling the complex effects of personality on social outcomes.


Effect of Patient-Specific Coronary Flow Reserve Values on the Accuracy of MRI-Based Virtual Fractional Flow Reserve.
The purpose of this study is to investigate the effect of varying coronary flow reserve (CFR) values on the calculation of computationally-derived fractional flow reserve (FFR). CFR reflects both vessel resistance due to an epicardial stenosis, and resistance in the distal microvascular tissue. Patients may have a wide range of CFR related to the tissue substrate that is independent of epicardial stenosis levels. Most computationally based virtual FFR values such as FFRCT do not measure patient specific CFR values but use a population-average value to create hyperemic flow conditions. In this study, a coronary arterial computational geometry was constructed using magnetic resonance angiography (MRA) data acquired in a patient with moderate CAD. Coronary flow waveforms under rest and stress conditions were acquired in 13 patients with phase-contrast magnetic resonance (PCMR) to calculate CFR, and these flow waveforms and CFR values were applied as inlet flow boundary conditions to determine FFR based on computational fluid dynamics (CFD) simulations. The stress flow waveform gave a measure of the functional significance of the vessel when evaluated with the physiologically-accurate behavior with the patient-specific CFR. The resting flow waveform was then scaled by a series of CFR values determined in the 13 patients to simulate how hyperemic flow and CFR affects FFR values. We found that FFR values calculated using non-patient-specific CFR values did not accurately predict those calculated with the true hyperemic flow waveform. This indicates that both patient-specific anatomic and flow information are required to accurately non-invasively assess the functional significance of coronary lesions.


Globally Optimal Inlier Set Maximization for Atlanta World Understanding.
In this work, we describe man-made structures via an appropriate structure assumption, called the Atlanta world assumption, which contains a vertical direction (typically the gravity direction) and a set of horizontal directions orthogonal to the vertical direction. Contrary to the commonly used Manhattan world assumption, the horizontal directions in Atlanta world are not necessarily orthogonal to each other. While Atlanta world can encompass a wider range of scenes, this makes the search space much larger and the problem more challenging. Our input data is a set of surface normals, for example, acquired from RGB-D cameras or 3D laser scanners, as well as lines from calibrated images. Given this input data, we propose the first globally optimal method of inlier set maximization for Atlanta direction estimation. We define a novel search space for Atlanta world, as well as its parametrization, and solve this challenging problem using a branch-and-bound (BnB) framework. To alleviate the computational bottleneck in BnB, i.e., the bound computation, we present two bound computation strategies: rectangular bound and slice bound in an efficient measurement domain, i.e., the extended Gaussian image (EGI). In addition, we propose an efficient two-stage method which automatically estimates the number of horizontal directions of a scene. Experimental results with synthetic and real-world datasets have successfully confirmed the validity of our approach.


Monosomy 22 in rhabdoid or atypical tumors of the brain.
Cytogenetic studies of three rare childhood brain tumors were performed. Two children presented with pure rhabdoid tumors. The third child had a tumor composed of a mixture of rhabdoid elements with neuroepithelial, epithelial, and mesenchymal tissue - an atypical teratoid tumor. All three tumors demonstrated monosomy 22 as the only cytogenetic abnormality. The cytogenetic findings suggest that loss of a gene or genes on chromosome 22 may be involved in the initiation or progression of these malignant tumors. Further studies on additional fresh tumor specimens are warranted; however, it is possible that cytogenetic studies may be used as an additional means of diagnosing rhabdoid or atypical teratoid tumors of the brain.


Iridium-catalysed ortho-H/D and -H/T exchange under basic conditions: C-H activation of unprotected tetrazoles.
The first examples of selective ortho-directed C-H activation with unprotected 2-aryltetrazoles are described. A new base-assisted protocol for iridium(i) hydrogen isotope exchange catalysis allows access to ortho-deuterated and tritiated tetrazoles, including the tetrazole-containing pharmaceutical, Valsartan. Preliminary mechanistic studies are also presented.


[A clinical x-ray analysis of the results of using titanium mandibular endoprostheses].
Late results of repair surgery are analyzed in 40 patients with segmented mandibular defects of different origin. Titanium constructions were used for repair of defects in 21 patients and in 19 others combined endoprostheses were used, consisting of the crest of the patient's iliac bone and a titanium carcass. Check-ups 1.5-2 years after repair showed a higher reliability of combined endoprostheses.


Compacting the density matrix in quantum dynamics: Singular value decomposition of the surprisal and the dominant constraints for anharmonic systems.
We introduce a practical method for compacting the time evolution of the quantum state of a closed physical system. The density matrix is specified as a function of a few time-independent observables where their coefficients are time-dependent. The key mathematical step is the vectorization of the surprisal, the logarithm of the density matrix, at each time point of interest. The time span used depends on the required spectral resolution. The entire course of the system evolution is represented as a matrix where each column is the vectorized surprisal at the given time point. Using the singular value decomposition (SVD) of this matrix, we generate realistic approximations for the time-independent observables and their respective time-dependent coefficients. This allows for a simplification of the algebraic procedure for determining the dominant constraints (the time-independent observables) in the sense of the maximal entropy approach. A non-stationary coherent initial state of a Morse oscillator is used to introduce the approach. We derive the analytical exact expression for the surprisal as a function of time, and this offers a benchmark for comparison with the accurate but approximate SVD results. We discuss two examples of a Morse potential of different anharmonicities, H2 and I2 molecules. We further demonstrate the approach for a two-coupled electronic state problem, the well-studied non-radiative decay of pyrazine from its bright state. Five constraints are found to be enough to capture the ultrafast electronic population exchange and to recover the dynamics of the wave packet in both electronic states.


[Surveillance of nosocomial infections in a cardiology hospital].
To describe a nosocomial infection surveillance in a cardiology and thoracic diseases hospital in Northern Mexico during its initial months of activity. Retrospective report of nosocomial infection surveillance performed by the infection control team with patient visits, clinical records, microbiology reports, and direct information obtained by health personnel. General and specific infection rates were analyzed by the chi 2 test and the Student t test. General infection rate was 4.99 during the 17 month period. Monthly infection rates changed significantly during infection control team vacations. By site of infection, surgical wound infection were the most common (1.14), followed by urinary tract infections (1.08), and bacteremia (0.72). However, when we grouped bacteremias and other catheter related infections, this intravascular access related infections were the most frequent (1.73). Gram positive organisms were most commonly isolated in nosocomial infections, except in pneumonias (gram negative organism) and urinary tract infections (Candida spp.). Mortality related to nosocomial infection was high (21.7%), and at least one third of those deaths was directly related to the infection. In hospital stay and cost were also increase with nosocomial infections. Nosocomial infection is common in interventional cardiology hospitals, producing high mortality and rising costs and length of stay. We need a more effective nosocomial infections surveillance system to eliminate changes in monthly case detection produced by the infection control team vacations, since this under-registry could result in lost of control of nosocomial infections and epidemic outbreak emergence.


Physiological reflux and venous diameter change in the proximal lower limb veins during a standardised Valsalva manoeuvre.
the aim of this study was to provide normal values for venous diameter at rest, and venous diameter and physiologic venous reflux during a standardised Valsalva manoeuvre. The impact of the patient's sex, body mass index (BMI), and family history was investigated. eighty legs of 40 healthy volunteers were investigated in a supine position. The median age was 28 years (range 20-66 years). The common femoral vein (CFV), the proximal superficial femoral vein (SFV) and the proximal long saphenous vein (LSV) were investigated by duplex sonography. The following parameters were assessed: resting diameter (VDrest) and maximum diameter (VDmax) as well as reflux time (tr) during the Valsalva manoeuvre. The Valsalva manoeuvre was elicited by a forceful expiration into a tube system. The standard values used were a pressure of 30 mmHg, established within 0.5 seconds (s) and maintained over a time period of at least 3 s. mean VDrest and VDmax were 8.3+/-2.2 and 11.1+/-2.8 mm in the CFV, 5.9+/-1. 3 and 7.2+/-1.6 mm in the SFV and 3.5+/-0.9 and 4.3+/-1.4 mm in the LSV. Mean values for tr were 0.61+/-0.63 s in the CFV, 0.25+/-0.26 s in the SFV and 0.28+/-0.40 s in the LSV. A BMI >22.5 kg/m2 was associated with statistically significant larger values for VDrest and tr. If adjusted for BMI, tr in the SFV and the LSV did not differ by sex. For healthy subjects with first-degree relatives suffering from varicose veins (n=19), mean VDrest in the SFV as well as VD in the LSV was significantly larger (p=0.02, 0.05, respectively). Coefficients of variation for repeated measurements (VDrest, VDmax, tr) in the same segment varied between 3.3% and 16. 4% for the three investigated sites. normal values for VDrest and VDmax as well as reflux time during a standardised Valsalva manouevre were assessed in the proximal lower limb veins. The influences of BMI, sex and family history were investigated. The described standardised Valsalva manoeuvre led to highly reproducible results and can be recommended for further research projects or as a routine procedure for the assessment of venous reflux.


CD40- and HLA-DR-mediated cell death pathways share a lot of similarities but differ in their use of ADP-ribosyltransferase activities.
CD40 and HLA-DR molecules are two major components of the immune system, and their engagement on several cell types leads to various cellular events that modulate cell function. In this study, we demonstrate that signaling via these molecules leads to a rapid B cell death. CD40-mediated cell death was mainly observed in Epstein-Barr virus (EBV)-transformed B cell lines, whereas, HLA-DR-induced response can be triggered in normal activated B cells as well as in EBV-transformed B cell lines. Cell death induced via both molecules does not require de novo protein synthesis, but involves the integrity of the cytoskeleton. The sensitivity of CD40- and HLA-DR-mediated cell death to various inhibitors is very similar to that previously reported for tumor necrosis factor receptor (TNFR)- and Fas-triggered apoptosis; however, caspases leading to poly(ADP-ribose) polymerase cleavage are not implicated in this response. Both B cell death forms do not involve Fas-Fas ligand and TNF-TNFR systems, but require LFA-1-independent cell-cell interactions mediated by still undefined molecules. Although CD40- and HLA-DR-mediated cell death appears to follow a common pathway, inhibitors of poly- and mono-ADP-ribosyltransferase activity differentially affect these responses. Defining the molecules involved in CD40- and HLA-DR-mediated death will provide a possible interrelation between the different B cell death programs that can lead to a better comprehension of regulation of B cell functions.


Urinary Tract Infection after Elective Spine Surgery: Timing, Predictive Factors, and Outcomes.
Retrospective review of prospectively collected data. The aim of this study was to investigate risk factors associated with the timing of urinary tract infection (UTI) after elective spine surgery, and to determine whether postoperative UTI timing affects short-term outcomes. Urinary tract infection (UTI) is a common post-surgical complication; however, the predominant timing, location, and potential differential effects have not been carefully studied. We analyzed elective spine surgery patients from 2012 to 2018 in the ACS National Surgical Quality Improvement Program (NSQIP). We grouped patients with postoperative UTI by day of onset relative to discharge, to create cohorts of patients who developed inpatient UTI and post-discharge UTI. We compared both UTI cohorts with a control (no UTI) population and with each other to identify differences in baseline characteristics including demographic, comorbidity and operative factors. We performed multivariate logistic regression to identify predictors of UTI in each cohort and to assess adjusted risks of poor outcomes associated with UTI timing. A total of 289,121 patients met inclusion criteria and 0.88% developed UTI (n = 2553). Only 31.6% of UTIs occurred before discharge (n = 806), with 68.4% occurring after discharge (n = 1747). The inpatient UTI cohort had significantly longer operative time, more fusion procedures, more posterior procedures, and more procedures involving the lumbar levels than the post-discharge cohort. Predictors of inpatient UTI included procedure type, spine region, and approach. Predictors of post-discharge UTI included length-of-stay and discharge destination. Both UTI cohorts were significantly associated with sepsis; however, post-discharge UTI carried a higher odds (adjusted odds ratio [aOR] = 24.90, 95% confidence interval [CI] = 21.05-29.45, P < 0.001 vs. aOR = 14.31, 95% CI = 11.09-18.45, P < 0.001). Inpatient UTI was not associated with 30-day readmission, although post-discharge UTI was (aOR = 8.23, 95% CI = 7.36-9.20, P < 0.001). Conversely, inpatient UTI was associated with increased odds of 30-day mortality (aOR = 3.23, 95% CI = 1.62-6.41, P = 0.001), but post-discharge UTI was not. Predictive factors and outcomes differ based on timing of UTI after elective spine surgery. Before discharge, procedure -specific details predict UTI, but after discharge they do not. These findings suggest that traditional thinking about UTI prevention may need modification.Level of Evidence: 3.


Unlocking hospital gridlock.
Hospitals should identify barriers to timely patient discharges. Benchmarking hospital data with best-practice hospital experience can help in developing recommendations for improvement. Solutions include developing revised discharge policies and procedures, establishing and communicating a discharge time, and setting a deadline for physicians to write orders for discharge and discharge-dependent tests.


The Effects of Synbiotic Supplementation on Carotid Intima-Media Thickness, Biomarkers of Inflammation, and Oxidative Stress in People with Overweight, Diabetes, and Coronary Heart Disease: a Randomized, Double-Blind, Placebo-Controlled Trial.
Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidant actions. The aim of this study was to evaluate the effects of synbiotic supplementation on carotid intima-media thickness (CIMT), biomarkers of inflammation, and oxidative stress in people with overweight, diabetes, and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was conducted and involved 60 people with overweight, diabetes, and CHD, aged 50-85 years old. Participants were randomly allocated into two groups to take either synbiotic supplements containing three probiotic bacteria spices Lactobacillus acidophilus strain T16 (IBRC-M10785), Lactobacillus casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 109 CFU/g each) plus 800 mg inulin or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention period to determine metabolic variables. After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly reduced serum high-sensitivity C-reactive protein (hs-CRP) (- 3101.7 ± 5109.1 vs. - 6.2 ± 3163.6 ng/mL, P = 0.02), plasma malondialdehyde (MDA) (- 0.6 ± 1.0 vs. - 0.1 ± 0.3 μmol/L, P = 0.01), and significantly increased nitric oxide (NO) levels (+ 7.8 ± 10.3 vs. - 3.6 ± 6.9 μmol/L, P < 0.001). We did not observe any significant changes of synbiotic supplementation on other biomarkers of oxidative stress and CIMT levels. Overall, synbiotic supplementation for 12 weeks among people with overweight, diabetes, and CHD had beneficial effects on serum hs-CRP, plasma NO, and MDA levels; however, it did not have any effect on other biomarkers of oxidative stress and CIMT levels.


Association of constitutive nuclear factor-kappaB activation with aggressive aspects and poor prognosis in cervical cancer.
Although nuclear factor-kappaB (NF-kappaB) is generally believed to be involved in carcinogenesis, the relationship between NF-kappaB activation and progression of cervical cancer in clinical settings has not been reported. In this study, we investigated the association of NF-kappaB activation with aggressive aspects and prognosis in cervical cancer. Nuclear factor-kappaB subunits p65 and p50 were detected in 159 paraffin tissues including normal cervical, precancerous (squamous intraepithelial lesions), and cervical carcinoma tissues by immunohistochemistry. Nuclear factor-kappaB nuclear translocation and DNA-binding activity in precancerous or carcinoma tissues were examined by Western blot and electrophoretic mobility shift assay, respectively. A gradual NF-kappaB activation from normal cervical epithelial cells to precancerous and carcinoma cells was detected by immunohistochemistry (nuclear expression of p65 and p50, P < 0.001), Western blot (NF-kappaB nuclear translocation), and electrophoretic mobility shift assay (enhanced DNA-binding activity). In 79 cancer tissues, increased nuclear p65, an active NF-kappaB form, was correlated with poor tumor grade, lymphatic metastasis, interstitial invasion, and larger tumor size (P < 0.05). Similarly, increased nuclear p50 was correlated with poor tumor grade, interstitial invasion, and larger tumor size (P < 0.05). Moreover, increased nuclear p65 was associated with lower survival rate in patients with cancer (P < 0.05). Constitutive NF-kappaB activation is correlated to tumor progression, aggressive behaviors, and poor prognosis in cervical cancer, suggesting that NF-kappaB is a tumor promoter, a prognostic indicator, and a possible therapeutic target for this malignant disease.


Nursing consultation protocol for patients after myocardial revascularization: influence on anxiety and depression.
The objective was to evaluate the influence of the Nursing Consultation Protocol in aspects of anxiety and depression in patients after myocardial revascularization using the Hospital Anxiety and Depression scale (HAD). A randomized clinical trial developed in the outpatient clinic of a public hospital in Fortaleza-Ceará. One hundred and forty six patients, who underwent myocardial revascularization, composed the population, providing the sample of 39 patients in the control group (CG) and 39 in the intervention group (IG). The results were presented in tables. Anxiety had a mean of 5.41 in the CG and a median of 5 and a mean in the IG of 5.21 and a median of 4. Depression predominated in the CG, with a mean 4.82 and a median of 4, while the IG had a mean of 3.79 and a median of 3. It was found that people monitored in accordance with the Nursing Consultation Protocol had a lower percentage of anxiety and depression after six months.


Use of sustainable chemistry to produce an acyl amino acid surfactant.
Surfactants find wide commercial use as foaming agents, emulsifiers, and dispersants. Currently, surfactants are produced from petroleum, or from seed oils such as palm or coconut oil. Due to concerns with CO(2) emissions and the need to protect rainforests, there is a growing necessity to manufacture these chemicals using sustainable resources In this report, we describe the engineering of a native nonribosomal peptide synthetase pathway (i.e., surfactin synthetase), to generate a Bacillus strain that synthesizes a highly water-soluble acyl amino acid surfactant, rather than the water insoluble lipopeptide surfactin. This novel product has a lower CMC and higher water solubility than myristoyl glutamate, a commercial surfactant. This surfactant is produced by fermentation of cellulosic carbohydrate as feedstock. This method of surfactant production provides an approach to sustainable manufacturing of new surfactants.


Calcitonin gene-related peptide increases the blood flow of port-wine stains and improves continuous-wave dye laser treatment.
Ten patients with port-wine stains were treated with continuous-wave dye laser before and after treatment with the vasodilatory compound calcitonin gene-related peptide. The patients were given calcitonin gene-related peptide as an intravenous infusion or as a regional intravenous infusion. Six uniformly colored test sites, each 5 x 10 mm, located within a port-wine stain were selected for clinical evaluation. Laser treatment of these areas was performed on one occasion with three different energy densities: 15, 30, and 45 J/cm2. The port-wine stain circulation was monitored with a laser Doppler flowmeter before and after calcitonin gene-related peptide infusion and immediately after laser treatment. The cosmetic result was evaluated and judged as excellent, desirable, or undesirable. It was shown that calcitonin gene-related peptide is able to induce a long-lasting increase in blood flow in the vascular bed of port-wine stains and that the immediate postlaser laser Doppler flow values may serve as an indication of the outcome of laser therapy. The cosmetic result was often better in the group treated with calcitonin gene-related peptide compared with controls, and an excellent result also was achievable with the use of lower levels of energy.