[Electroencephalography (EEG) recording techniques and artifact detection in early premature babies].
EEG recording techniques in early premature babies are not very different from those used for full-term neonates. Here, we emphasise the most important points: asepsis precautions, full knowledge of the clinical data and drug therapies, the fundamental role of a well-trained technician in supervising the EEG recording and monitoring the baby. The best electrode positions, the most informative montages and their standardisation between neurophysiological laboratories, are suggested. Artifact detection constitutes an important aspect of EEG signal analysis in preterm babies of less than 30 weeks. It is obviously necessary to discriminate between meaningful information and artefacts. The complexity of the signal in neonates makes artifact detection difficult. We present some characteristic features and describe some methods for eliminating them. We underline the positive aspect of some artifacts and their clinical use. We emphasise the crucial role of the technicians.


Physiological and biochemical studies on the function of 5-methyluridine in the transfer ribonucleic acid of Escherichia coli.
Matched pairs of transductant strains differing by the presence of absence of 5-methyluridine (ribothymidine) (m5U) in their transfer ribonucleic acid (tRNA) were used to study the function of this modified nucleoside in Escherichia coli. Ordinary measurements of growth rate in different media revealed no effect of the loss of m5U in tRNA. A gene located close to trmA (the structural cistron for the methyltransferase that produces m5U in tRNA), however, was found to reduce the growth rates significantly, depending on the medium and the temperature of cultivation. Measurement of codon recognition, macromolecular composition, tRNA binding to the ribosome, and the rate of protein chain elongation in vivo indicated no disadvantage caused by the lack of m5U. The regulation of ilv and his operons seemed also to be unaffected by the absence of m5U in the tRNA. In a mixed population experiment, however, cells possessing m5U in their tRNA seemed to have a distinct advantage over cells lacking this modified nucleoside. This experiment provides the first indication of the overall value of m5U in tRNA.


Library and information services: impact on patient care quality.
The purpose of this paper is to explore library and information service impact on patient care quality. A large-scale critical incident survey of physicians and residents at 56 library sites serving 118 hospitals in the USA and Canada. Respondents were asked to base their answers on a recent incident in which they had used library resources to search for information related to a specific clinical case. Of 4,520 respondents, 75 percent said that they definitely or probably handled patient care differently using information obtained through the library. In a multivariate analysis, three summary clinical outcome measures were used as value and impact indicators: first, time saved; second, patient care changes; and third, adverse events avoided. The outcomes were examined in relation to four information access methods: first, asking librarian for assistance; second, performing search in a physical library; third, searching library's web site; or fourth, searching library resources on an institutional intranet. All library access methods had consistently positive relationships with the clinical outcomes, providing evidence that library services have a positive impact on patient care quality. Electronic collections and services provided by the library and the librarian contribute to patient care quality.


Multiplexed electrochemical detection of three cardiac biomarkers cTnI, cTnT and BNP using nanostructured ZnO-sensing platform.
Development of a label-free multiplexed point-of-care diagnostic device for a panel of cardiac biomarkers - cardiac troponin-T (cTnT), troponin-I (cTnI) and B-type natriuretic peptide (BNP). A nonfaradaic electrochemical immunoassay designed with anisotropic high surface area ZnO nanostructures grown using low-temperature hydrothermal methods was selectively immobilized with capture antibodies. Multiplexed detection in human serum using ZnO nanostructures based on complementary electrochemical measurement techniques - electrochemical impedance spectroscopy and Mott-Schottky. Linear signal response for detection of three biomarkers in human serum with dynamic range of 1 pg/ml-100 ng/ml and limit of detection at 1 pg/ml and low signal response to background interferences was achieved. First demonstration of simultaneous detection of three cardiac biomarkers in clinically relevant range with sensor's analytical performance and linear response of detection showed potential utility in screening clinical samples for early diagnosis of acute myocardial infarction and chronic heart failure.


Method and effect of total knee arthroplasty osteotomy and soft tissue release for serious knee joint space narrowing.
To discuss the method and effect of total knee arthroplasty osteotomy and soft tissue release for serious knee joint space narrowing. Clinical data of 80 patients from October 2013 to December 2014 was selected with a retrospective method. All patients have undergone total knee arthroplasty. Then the X-rays plain film in weight loading was measured before and after operation and osteotomy was performed accurately according to the knee joint scores and the conditions of lower limb alignments. The average angle of tibial plateau osteotomy of postoperative patients was 4.3°, and the corrective angle of soft tissue balancing was 10.7°; the postoperative patients' indicies including range of joint motion, knee joint HSS score, angle between articular surfaces, tibial angle, femoral-tibial angle and flexion contracture were distinctly better than the preoperative indicies (p<0.05) and the differences were statistically significant; the postoperative patients' flexion contracture and range of joint motion were distinctly better than the preoperative indicies (p<0.05) and the differences were statistically significant. The effective release of the soft tissue of the posterior joint capsule under direct vision can avoid excess osteotomy and get satisfactory knee replacement space without influencing the patients' joint recovery.


Speech rate development in Japanese-speaking children and proficiency in mora-timed rhythm.
Development of speech rate is often reported as children exhibiting reduced speech rates until they reach adolescence. Previous studies have investigated the developmental process of speech rate using global measures (syllables per second, syllables per minute, or words per minute) and revealed that development continues up to around 13 years of age in several languages. However, the global measures fail to capture language-specific characteristics of phonological/prosodic structure within a word. The current study attempted to examine the developmental process of speech rate and language-specific rhythm in an elicited production task. We recorded the speech of Japanese-speaking monolingual participants (18 participants each in child [5-, 7-, 9-, 11-, and 13-year-old] and adult groups), who pronounced three types of target words: two-mora, two-syllable words (CV.CV); three-mora, two-syllable words (CVV.CV); and three-mora, three-syllable words (CV.CV.CV), where C is consonant and V is vowel. We analyzed total word duration and differences in two pairs of word types: a pair of three-mora words (to show the effect of syllables) and a pair of two-syllable words (to show the effect of moras). The results revealed that Japanese-speaking children have acquired adult-like word duration before 11 years of age, whereas the development of rhythmical timing control continues until approximately 13 years of age. The results also suggest that the effect of syllables for Japanese-speaking children aged 9 years or under was stronger than that of moras, whereas the effect of moras was stronger after 9 years of age, indicating that the default unit for children in speech rhythm may be the syllable even when the language is mora-based.


Acute severe ulcerative colitis: latest evidence and therapeutic implications.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colorectum which results from a complex interplay between environmental, genetic and microbial factors. One-fifth of patients with UC will experience an acute flare requiring hospitalization. This is a medical emergency and requires prompt recognition and multidisciplinary management. In patients who fail first-line therapy after approximately 3-5 days of intravenous steroids, medical rescue therapy is indicated with either infliximab (IFX) or cyclosporine (CsA). Optimal dosing strategies for IFX are uncertain, with several retrospective studies suggesting an association between an intensified or accelerated IFX induction regimen and lower colectomy rates, although prospective studies are warranted. In patients not responding to medical rescue therapy, or in those with fulminant colitis, urgent colectomy is indicated. Longer prognosis is suboptimal, with half of patients requiring colectomy within 5 years of presentation with acute severe UC (ASUC).


Combined atomic force microscopy and optical microscopy measurements as a method to investigate particle uptake by cells.
We propose a combination of atomic force microscopy (AFM) and optical microscopy for the investigation of particle uptake by cells. Positively and negatively charged polymer microcapsules were chosen as model particles, because their interaction with cells had already been investigated in detail. AFM measurements allowed the recording of adhesion forces on a single-molecule level. Due to the micrometer size of the capsules, the number of ingested capsules could be counted by optical microscopy. The combination of both methods allowed combined measurement of the adhesion forces and the uptake rate for the same model particle. As a demonstration of this system, the correlation between the adhesion of positively or negatively charged polymer microcapsules onto cell surfaces and the uptake of these microcapsules by cells has been investigated for several cell lines. As is to be expected, we find a correlation between both processes, which is in agreement with adsorption-dependent uptake of the polymer microcapsules by cells.


Effect-site concentration of propofol required for LMA-Supreme™ insertion with and without remifentanil: a randomized controlled trial.
A new supraglottic device, the LMA-Supreme™, has recently become available for clinical use. Information on anaesthetic and co-adjuvant requirements for insertion of the LMA-Supreme™ is limited. The present study aimed to evaluate the optimal effect-site concentration of propofol in 50 % (EC50) of adults necessary for successful insertion of the LMA-Supreme™ and to examine remifentanil's effect on propofol requirements. Fifty-eight elective patients (aged 18-60 years; ASA (American Society Anaesthesiologists) physical status classification I and II) scheduled for day surgery were randomly assigned to one of two groups: propofol with saline or propofol with remifentanil. Anaesthesia was induced by target-controlled infusion according to predetermined effect-site concentrations of propofol and remifentanil (5 ng.mL(-1)). The EC50 was calculated using Dixon's up-and-down method. Ten minutes following drug administration, LMA-Supreme™ insertion was attempted without the use of muscle relaxant drugs. In the propofol + saline group, the EC50 of propofol required for LMA-Supreme™ insertion was 6.32 ± 0.67 μg.mL(-1) (95 % CI, 5.69-6.94 μg.mL(-1)). With the addition of remifentanil at an effect-site concentration of 5 ng.mL(-1), the EC50 of propofol required for LMA-Supreme™ insertion was 2.50 ± 0.80 μg.mL(-1) (95 % CI, 1.82-3.17 μg.mL(-1); p < 0.0001). The propofol requirement for smooth insertion of the LMA-Supreme™ was 60 % less when remifentanil (5 ng.mL(-1)) was co-administered. Identified as NCT01974648 at www.clinicaltrials.gov .


Blunted vasodilatory responses in the cutaneous microcirculation of cigarette smokers.
The present study was undertaken to investigate whether chronic smoking alters the vasodilatory capacity in the microcirculation. We assessed, in habitual cigarette smokers, the forearm skin blood flow response to iontophoretically applied acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside. Postocclusive forearm reactive hyperemia was also explored. The skin blood flow responses were determined with a laser-Doppler flowmeter that allowed us to scan the surface after acetylcholine and sodium nitroprusside application. Forty healthy male volunteers were included. Twenty subjects were aged 20 to 35 years and 20 subjects were aged 40 to 60 years. We studied the following 4 groups of 10 subjects each: group 1, younger smokers (mean of 7.2 pack-years); group 2, older smokers (mean of 30 pack-years); group 3, younger nonsmokers; and group 4, older nonsmokers. On the day of the experiment, the subjects of groups 1 and 2 were asked to smoke at least 15 cigarettes from the morning until the afternoon, when the experiments were performed. No significant difference in the studied parameters was observed between younger smokers and younger nonsmokers. In older smokers, however, both acetylcholine- and sodium nitroprusside-induced skin blood flow increases were significantly attenuated in comparison with nonsmokers. Heart rate also was significantly blunted by long-term cigarette smoking in older subjects. These data show that the vasodilatory response of the skin microvasculature is impaired in subjects who have smoked cigarettes for many years. This abnormality involves both endothelium-dependent and endothelium-independent responses.


Design, synthesis and in vitro anticancer activity of novel quinoline and oxadiazole derivatives of ursolic acid.
A series of new quinoline derivatives of ursolic acid were designed and synthesized in an attempt to develop potential anticancer agents. The structures of these compounds were identified by 1H NMR, 13C NMR, IR and ESI-MS spectra analysis. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (MDA-MB-231, Hela and SMMC-7721). From the results, compounds 3a-d displayed significant antitumor activity against three cancer cell lines. Especially, compound 3b was found to be the most potent derivative with IC50 values of 0.61±0.07, 0.36±0.05, 12.49±0.08μM against MDA-MB-231, HeLa and SMMC-7721 cells, respectively, stronger than positive control etoposide. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound 3b could significantly induce the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The cell cycle analysis also indicated that compound 3b could cause cell cycle arrest of MDA-MB-231 cells at G0/G1 phase.


Severe hypernatremic dehydration associated with cerebral venous and aortic thrombosis in the neonatal period.
Severe neonatal hypernatremia is an important electrolyte disorder that has serious effects. Cerebral venous thrombosis and aortic thrombosis are relatively rare in severe neonatal hypernatremic dehydration. The authors report a case of cerebral venous thrombosis, associated with aortic thrombosis revealed by dehydration in a 9-day-old boy. Diagnostic was performed using Doppler ultrasound and imaging techniques. Thrombosis was resolved after anticoagulation treatment with low-molecular weight heparin for 1 month, and then was substituted by oral anticoagulant. The case report is followed by a review of the literature dealing with clinical, aetiological and therapeutic aspects of neonatal thrombosis.


Kinetics and equilibria for the reactions of coenzymes with wild type and the Y70F mutant of Escherichia coli aspartate aminotransferase.
The Y70F mutant of aspartate aminotransferase has reduced affinity for coenzymes compared to the wild type. The equilibrium dissociation constants for pyridoxamine phosphate (PMP) holoenzymes, KPMPdiss, were determined from the association and dissociation rate constants to be 1.3 nM and 30 nM for the wild type and mutant, respectively. This increase in KPMPdiss for Y70F is due to a 27-fold increase in the dissociation rate constant. Pyridoxal phosphate (PLP) association kinetics are complex, with three kinetic processes detectable for wild type and two for Y70F. A directly determined, accurate value of KPLPdiss for wild type enzyme has been difficult to obtain because of the low value of this constant. The values of KPLPdiss for the holoenzymes were determined indirectly through the measured values for KPMPdiss, glutamate-alpha-ketoglutarate half-reaction equilibrium constants, and the equilibrium constant for the transamination of PLP by glutamate catalyzed by Y70F. The values of KPLPdiss obtained by this procedure are 0.4 pM for wild type and 40 pM for Y70F. The increases in KPMPdiss and KPLPdiss for Y70F correspond to delta delta G values of 1.9 and 2.7 kcal/mol, respectively, and are directly attributed to the loss of the hydrogen bond from the phenolic hydroxyl group of Tyr70 to the coenzyme phosphate. The delta G for association of PLP with wild type enzyme is 4.7 kcal/mol more favorable than that for PMP.


Difference in hepatic metabolism of long- and medium-chain fatty acids: the role of fatty acid chain length in the production of the alcoholic fatty liver.
Replacement of dietary triglycerides containing long-chain fatty acids (LCFA) by triglycerides containing medium-chain fatty acids (MCFA) markedly reduced the capacity of alcohol to produce fatty liver in rats. After 24 days of ethanol and MCFA, the increase in hepatic triglycerides was only 3 times that of controls, whereas an 8-fold rise was observed after ethanol and LCFA. The triglyceride fatty acids that accumulated in the liver after feeding of ethanol with MCFA contained only a small percentage of the MCFA; their composition also differed strikingly from that of adipose lipids. To study the mechanism of the reduction in steatosis, we compared oxidation to CO(2) and incorporation into esterified lipids of (14)C-labeled chylomicrons or palmitate-(14)C (representing LCFA), and of octanoate-(14)C (as MCFA) in liver slices and isolated perfused livers, in the presence or absence of ethanol. Ethanol depressed the oxidation of all substrates to CO(2); MCFA, however, was much more oxidized and reciprocally much less esterified than LCFA, with a 100-fold difference in the ratio of esterified lipid-(14)C to (14)CO(2). Furthermore, in hepatic microsomal fractions incubated with alpha-glycerophosphate, octanoate was much less esterified than palmitate. This propensity of MCFA to oxidation rather than esterification represents a likely explanation for the reduction in alcoholic steatosis upon replacement of dietary LCFA by MCFA.


Inorganic polymer photoresist for direct ceramic patterning by photolithography.
A novel negative, inorganic polymer photoresist was demonstrated to be suitable for simple and direct fabrication of tribological SiCN-based ceramic microstructures via UV photolithography and subsequent pyrolysis at 800 degrees C.


Pathology and pathophysiology of chronic obstructive pulmonary disease.
A variety of pathological changes have been observed in the central airways, peripheral airways and lung parenchyma of patients with chronic obstructive pulmonary disease (COPD). The characteristic changes in the central airways include inflammatory cellular infiltration into the airway wall and mucous gland enlargement. In the peripheral airways, various morphological changes are observed, including mucous plugging, epithelial abnormalities, inflammatory cellular infiltrates, fibrosis and distortion; these changes lead to airway narrowing. In the lung parenchyma, emphysema defined as alveolar destruction and airspace enlargement is present. Although the major sites of airflow limitation in patients with COPD are most likely the peripheral airways, lesions in both the peripheral airways and the lung parenchyma contribute to chronic airflow limitations.


Fusion and planarization of bisBODIPY: a new family of photostable near infrared dyes.
We have synthesized a new family of directly-fused bisBODIPY BBP 1 through a key FeCl3-mediated intramolecular oxidative cyclodehydrogenation reaction and its derivatives 2 and 3 from the Knoevenagel reaction. These dyes display effective expansion of π-conjugation over the two BODIPYs due to their locked coplanar conformation, showing intriguing electrochemical and spectroscopic properties, such as intensive absorption/emission bands ranging from 676 to 877 nm and high photostability.


Eosinophilic Cholecystitis presenting with Common Bile Duct Sludge and Cholangitis: A Case Report.
Eosinophilic cholecystitis is a rare post-cholecystectomy inflammatory histopathological condition characterized by more than 90% eosinophilic infiltrate in the gallbladder. We present a case of 27-year female presented with abdominal pain, fever, jaundice, altered mental status, shock, leucocytosis, deranged liver function test, and peripheral blood eosinophilia. The patient underwent cholecystectomy and common bile duct exploration. She developed adult respiratory distress syndrome and hospital-acquired pneumonia. From this, we want to emphasize that eosinophilic cholecystitis and cholangiopathy should be a differential diagnosis in patients presenting with allergy, peripheral eosinophilia, obstructive jaundice that are planned to undergo cholecystectomy that will have early critical care intervention.


Erythropoietin and the regulation of erythropoiesis.
Recent advances in experimental hematology have provided new insight into the physiology of erythropoiesis. Techniques are now available for cloning in vitro the various hematopoietic progenitor cells of both animals and man. Erythropoietin has been purified and a radioimmunoassay for the hormone has been described. In this paper, we discuss the physiology of erythropoietin and erythropoiesis with special emphasis on data obtained through the employment of new technology.


NATURAL VARIATION IN THE EXPRESSION OF THE HEAT-SHOCK PROTEIN HSP70 IN A POPULATION OF DROSOPHILA MELANOGASTER AND ITS CORRELATION WITH TOLERANCE OF ECOLOGICALLY RELEVANT THERMAL STRESS.
Although Hsp70, the principal inducible heat-shock protein of Drosophila melanogaster, has received intense scrutiny in laboratory strains, its variation within natural populations and the consequences of such variation for thermotolerance are unknown. We have characterized variation in first-instar larvae of 20 isofemale lines isolated from a single natural population of D. melanogaster, in which larvae are prone to thermal stress in nature. Hsp70 expression varied more than twofold among lines after induction by exposure to 36°C for one hour, with an estimated proportion of the variation due to genetic differences of 0.24 ± 0.08. Thermotolerance with and without a Hsp70-inducing pretreatment, survival at 25°C, and developmental time also varied significantly. As expected, expression of Hsp70 correlated positively with larval thermotolerance. By contrast, lines in which larval survival was high in the absence of heat stress showed lower than average Hsp70 expression and lower than average inducible thermotolerance. This conditional performance suggests an evolutionary trade-off between thermotolerance and the ability to produce higher concentrations of Hsp70, and survival in a benign environment.


Age-dependent pattern of intermediate filament protein expression in the human pineal gland.
Intermediate filament distribution was studied in children and adult human pineal glands by using immunocytochemistry and immunoblotting. The demonstration of cytokeratin positive cell clusters in the infant pineal gland may be related to ependymal cells arising from the subcommissural organ. The SCO ependymal cells and the ependymal cells in the pineal parenchyma express the neuro-ectoderm specific individual cytokeratins no. 8 and 18. Cytokeratin positive ependymocytes additionally exhibited vimentin and were serotonin negative as revealed by double immunofluorescence labelling. By contrast, in adult pineal glands cytokeratin positive cells were not clustered. An interesting but unexplained increase of neurofilament 68 KD positive nerve fibres was detectable.


Comparison of the Osmotic Virial Equation with the Margules Activity Model for Solid-Liquid Equilibrium.
The main goal of this paper is to compare the general polynomial forms of the osmotic virial equation and the Margules model for the liquid activity coefficients in binary systems. The coefficients/parameters in each model can be calculated based on best fits to experimental phase equilibrium data. Here, the activity coefficient models were combined with the equation of solid-liquid equilibrium. We obtain the coefficients/parameters for the osmotic virial equation and the one- and two-parameter Margules models and compare the accuracy of each model for fitting the experimental data for five water/solute systems: water/glycerol, water/acetic acid, water/propanoic acid, water/mono-ethylene glycol, and water/sulfolane. In obtaining the osmotic virial coefficients, we present a method to fit the equation to the entire range of data including both the ice-formation region and the solute-precipitation region. In expression of the concentration effect of the solute, we showed that the integration constant that arises from the Gibbs-Duhem equation is dependent on the osmotic virial coefficients. The osmotic virial equation is of great interest for its ability to empirically model a very wide range of aqueous solutions and as such is one of the most widely used solution models in biology.


Bis(μ-2-tert-butyl-phenyl-imido-1:2κN:N)chlorido-2κCl-(diethyl ether-1κO)(2η-penta-methyl-cyclo-penta-dien-yl)lithiumtantalum(V).
In the title compound, [LiTa(C(10)H(15))(C(10)H(13)N)(2)Cl(C(4)H(10)O)], the Ta(V) atom is coordinated by a η(5)-penta-methyl-cyclo-penta-dienyl (Cp*) ligand, a chloride ion and two N-bonded 2-tert-butyl-phenyl-imide dianions. With respect to the two N atoms, the chloride ion and the centroid of the Cp* ring, the tantalum coordination geometry is approximately tetra-hedral. The lithium cation is bonded to both the 2-tert-butyl-phenyl-imide dianions and also a diethyl ether mol-ecule, in an approximate trigonal planar arrangement. The Ta⋯Li separation is 2.681 (15) Å. In the crystal, a weak C-H⋯Cl inter-action links the mol-ecules. When compared to the 2,6-diisopropyl-phenyl-imide analogue ('the Wigley derivative') of the title compound, the two structures are conformationally matched with an overall r.m.s. difference of 0.461Å.


Silica Induction of Diverse Inflammatory Proteome in Lungs of Lupus-Prone Mice Quelled by Dietary Docosahexaenoic Acid Supplementation.
Repeated short-term intranasal instillation of lupus-prone mice with crystalline silica (cSiO2) induces inflammatory gene expression and ectopic lymphoid neogenesis in the lung, leading to early onset of systemic autoimmunity and rapid progression to glomerulonephritis. These responses are suppressed by dietary supplementation with the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA). Here, we tested the hypothesis that dietary DHA supplementation suppresses cSiO2-induced inflammatory proteins in bronchoalveolar alveolar lavage fluid (BALF) and plasma of lupus-prone mice. Archived tissue fluid samples were used from a prior investigation in which 6 wk-old lupus-prone female NZBWF1 mice were fed isocaloric diets containing 0 or 10 g/kg DHA for 2 wks and then intranasally instilled with 1 mg cSiO2 or vehicle once weekly for 4 wks. Cohorts were terminated at 1, 5, 9 or 13 wk post-instillation (PI). BALF and plasma from each cohort were analyzed by high density multiplex array profiling of 200 inflammatory proteins. cSiO2 time-dependently induced increases in the BALF protein signatures that were highly reflective of unresolved lung inflammation, although responses in the plasma were much less robust. Induced proteins in BALF included chemokines (e.g., MIP-2, MCP-5), enzymes (e.g., MMP-10, granzyme B), adhesion molecules (e.g., sE-selectin, sVCAM-1), co-stimulatory molecules (e.g., sCD40L, sCD48), TNF superfamily proteins (e.g., sTNFRI, sBAFF-R), growth factors (e.g., IGF-1, IGFBP-3), and signal transduction proteins (e.g., MFG-E8, FcgRIIB), many of which were blocked or delayed by DHA supplementation. The BALF inflammatory proteome correlated positively with prior measurements of gene expression, pulmonary ectopic lymphoid tissue neogenesis, and induction of autoantibodies in the lungs of the control and treatment groups. Ingenuity Pathway Analysis (IPA) revealed that IL-1β, TNF-α, and IL-6 were among the top upstream regulators of the cSiO2-induced protein response. Furthermore, DHA's effects were associated with downregulation of cSiO2-induced pathways involving i) inhibition of ARE-mediated mRNA decay, ii) bacterial and viral pattern recognition receptor activation, or iii) TREM1, STAT3, NF-κB, and VEGF signaling and with upregulation of PPAR, LXR/RXR and PPARα/RXRα signaling. Altogether, these preclinical findings further support the contention that dietary DHA supplementation could be applicable as an intervention against inflammation-driven autoimmune triggering by cSiO2 or potentially other environmental agents.


Synthesis and characterization of fluorescent displacers for online monitoring of displacement chromatography.
One of the major impediments to the implementation of displacement chromatography for the purification of biomolecules is the need to collect fractions from the column effluent for time-consuming offline analysis. The ability to employ direct online monitoring of displacement chromatography would have significant implications for applications ranging from analytical to preparative bioseparations. To this end, a set of novel fluorescent displacers were rationally designed using known chemically selective displacers as a template. Fluorescent cores were functionalized with different charge moieties, creating a homologous library of displacers. These compounds were then tested on two protein pairs, alpha-chymotrypsinogen A/ribonuclease A and cytochrome c/lysozyme, using batch and column displacement experiments. Of the synthesized displacers, two were found to be highly selective while one was determined to be a high-affinity displacer. Column displacements using one of the selective displacers yielded complete separation of both protein pairs while facilitating direct online detection using UV and fluorescence detection. Saturation transfer difference NMR was also carried out to investigate the binding of the fluorescent displacers to proteins. The results indicated a selective binding between the selective displacers and alpha-chymotrypsinogen A, while no binding was observed for ribonuclease A, confirming that protein-displacer binding is responsible for the selectivity in these systems. This work demonstrates the utility of fluorescent displacers to enable online monitoring of displacer breakthroughs while also acting as efficient displacers for protein purification.


Role of Conserved E2 Residue W420 in Receptor Binding and Hepatitis C Virus Infection.
Hepatitis C virus (HCV) enters cells via interactions with several host factors, a key one being that between the viral E2 envelope glycoprotein and the CD81 receptor. We previously identified E2 tryptophan residue 420 (W420) as an essential CD81-binding residue. However, the importance of W420 in the context of the native virion is unknown, as those previous studies predate the infectious HCV cell culture (cell culture-derived HCV [HCVcc]) system. Here, we introduced four separate mutations (F, Y, A, or R) at position 420 within the infectious HCVcc JFH-1 genome and characterized their effects on the viral life cycle. While all mutations reduced E2-CD81 binding, only two (W420A and W420R) reduced HCVcc infectivity. Further analyses of mutants with hydrophobic residues (F or Y) found that interactions with the receptors SR-BI and CD81 were modulated, which in turn determined the viral uptake route. Both mutant viruses were significantly less dependent on SR-BI, and its lipid transfer activity, for virus entry. Furthermore, these viruses were resistant to the drug erlotinib, which targets epidermal growth factor receptor (EGFR) (a host cofactor for HCV entry) and also blocks SR-BI-dependent high-density lipoprotein (HDL)-mediated enhancement of virus entry. Together, our data indicate a model where an alteration at position 420 causes a subtle change in the E2 conformation that prevents interaction with SR-BI and increases accessibility to the CD81-binding site, in turn favoring a particular internalization route. These results further show that a hydrophobic residue with a strong preference for tryptophan at position 420 is important, both functionally and structurally, to provide an additional hydrophobic anchor to stabilize the E2-CD81 interaction. Hepatitis C virus (HCV) is a leading cause of liver disease, causing up to 500,000 deaths annually. The first step in the viral life cycle is the entry process. This study investigates the role of a highly conserved residue, tryptophan residue 420, of the viral glycoprotein E2 in this process. We analyzed the effect of changing this residue in the virus and confirmed that this region is important for binding to the CD81 receptor. Furthermore, alteration of this residue modulated interactions with the SR-BI receptor, and changes to these key interactions were found to affect the virus internalization route involving the host cofactor EGFR. Our results also show that the nature of the amino acid at this position is important functionally and structurally to provide an anchor point to stabilize the E2-CD81 interaction.


Diffusion of CDC's Guidelines to Prevent Tobacco Use and Addiction.
The Center for Disease Control and Prevention's School Guidelines to Prevent Tobacco Use and Addiction were developed, in part, to assist state and local education agencies in adopting and implementing effective school-based tobacco prevention and cessation programs. This project assessed state education agency awareness of and reaction to the Guidelines, and documented efforts to disseminate the Guidelines to local schools. Key informants in 15 state education agencies were interviewed. Respondents reported a fairly high level of receptivity to the Guidelines, numerous benefits and few barriers, and high commitment. Levels of use for the Guidelines varied. Dissemination strategies such as mass mailing or teleconferences are not sufficient to influence the use and integration of Guidelines for school health. The diffusion process requires planned change over time through numerous communication channels and should be monitored at the national, state, and local levels to assess effectiveness and impact.


Time-kill profiles of Enterococcus to antibiotics used for intravitreal therapy.
To determine and then compare the time-kill profiles of Enterococcus to antibiotics used for intravitreal therapy. The time-kill profiles of four endophthalmitis isolates of Enterococcus faecalis, one vancomycin-resistant E. faecalis isolate, and three vancomycin-resistant isolates of E. faecium were determined against vancomycin, amikacin, cefazolin, gentamicin, ampicillin, ciprofloxacin, ceftazidime, clindamycin, and the combinations of vancomycin and amikacin, vancomycin and ceftazidime, vancomycin and gentamicin, vancomycin and ampicillin, cefazolin and gentamicin, and ampicillin and gentamicin. No single antibiotic or combination was bactericidal (defined as 99.9% kill) to all isolates of Enterococcus. Gentamicin was bactericidal to all E. faecalis isolates. None of the tested antibiotics were bactericidal to vancomycin-resistant E. faecium. The time-kill profiles demonstrated that vancomycin and ceftazidime did not produce a 99.9% kill for E. faecalis in this small study. Gentamicin combined with either cefazolin or ampicillin had somewhat better bactericidal activity and should be considered as an alternative therapy. Novel therapy may be necessary to treat endophthalmitis because of vancomycin-resistant Enterococcus, depending on the susceptibility patterns of the individual isolate and the response to initial therapy.


A case study in planning for public health education: the organ and tissue donation experience.
The chasm between the supply and demand of donated organs and tissues continues to grow despite widespread public awareness of transplantation and numerous efforts to educate the public about organ donation. It is fast becoming a significant public health problem in this country. The need for more effective public education is well documented in the literature on transplantation and is a primary objective of organizations in the transplant field. In response to this need, the Division of Organ Transplantation in the Health Resources and Services Administration of the Public Health Service initiated a project to examine the nature and scope of donation education initiatives throughout the country, to identify shortcomings, and to suggest ways the Federal Government could contribute to the effectiveness of public education in organ and tissue donation. The project resulted in the development of a protocol that also is applicable to other health education programs. Its major steps consisted of assessing the status of donation-related public education in the United States, identifying existing needs in donation education by applying principles learned from other public health education programs, and identifying roles that could be assumed to help strengthen the American public's commitment to organ and tissue donation. These roles, which could be adopted by an transplant-related organization, were as broker of knowledge, producer of educational strategies, energizer through communications research, and catalyst by bringing together other groups. This approach to needs assessment and planning may provide useful insights both for those concerned with transplants and for professionals conducting education campaigns related to other public health issues.


ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta.
The first definitive cell fate decision in development occurs at the blastocyst stage with establishment of the trophoblast and embryonic cell lineages. In the mouse, lineage commitment is achieved by epigenetic regulation of a critical gatekeeper gene, the transcription factor Elf5, that reinforces placental cell fate and is necessary for trophoblast stem (TS) cell self-renewal. In humans, however, the epigenetic lineage boundary seems to be less stringent since human embryonic stem (ES) cells, unlike their murine counterparts, harbour some potential to differentiate into trophoblast derivatives. Here, we show that ELF5 is expressed in the human placenta in villous cytotrophoblast cells but not in post-mitotic syncytiotrophoblast and invasive extravillous cytotrophoblast cells. ELF5 establishes a circuit of mutually interacting transcription factors with CDX2 and EOMES, and the highly proliferative ELF5(+)/CDX2(+) double-positive subset of cytotrophoblast cells demarcates a putative TS cell compartment in the early human placenta. In contrast to placental trophoblast, however, ELF5 is hypermethylated and largely repressed in human ES cells and derived trophoblast cell lines, as well as in induced pluripotent stem cells and murine epiblast stem cells. Thus, these cells exhibit an embryonic lineage-specific epigenetic signature and do not undergo an epigenetic reprogramming to reflect the trophoblast lineage at key loci such as ELF5. Our identification of the trophoblast-specific transcriptional circuit established by ELF5 will be instrumental to derive human TS cell lines that truly reflect early placental trophoblast and that will be most beneficial to gain insights into the aetiology of common pregnancy complications, including intra-uterine growth restriction and pre-eclampsia.


A PILOT STUDY OF ANGIOTENSIN II AS PRIMARY VASOPRESSOR IN CRITICALLY ILL ADULTS WITH VASODILATORY HYPOTENSION: THE ARAMIS STUDY.
Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). Results : Mean age was 63 years and median Acute Physiology and Chronic Health Evaluation III score was 65. Ang2 patients had lower ICU mortality (10% vs 26%, P = 0.04); however, their 28- and 90-day mortality was not significantly different (18% vs 29%, P = 0.18; 22% vs 30%, P = 0.39). Peak serum creatinine levels were similar (128 vs 126 μmol/L, P = 0.81), as was the incidence and stage of acute kidney injury (70% vs 74%, P = 0.66), requirement for continuous renal replacement therapy (14% vs 13%, P = 0.84), and risk of major adverse kidney events at 7 days (20% vs 29%, P = 0.30). However, Ang2 patients with prior exposure to renin angiotensin aldosterone system inhibitors had a lower peak serum creatinine ( P = 0.03 for interaction) than conventional vasopressors patients, and serum troponin elevations were less common with Ang2 (8% vs 22%, P = 0.04). The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).


Protracted treatment with diazepam increases the turnover of putative endogenous ligands for the benzodiazepine/beta-carboline recognition site.
DBI (diazepam-binding inhibitor) is a putative neuromodulatory peptide isolated from rat brain that acts on gamma-aminobutyric acid-benzodiazepine-Cl- ionophore receptor complex inducing beta-carboline-like effects. We used a cDNA probe complementary to DBI mRNA and a specific antibody for rat DBI to study in rat brain how the dynamic state of DBI can be affected after protracted (three times a day for 10 days) treatment with diazepam and chlordiazepoxide by oral gavage. Both the content of DBI and DBI mRNA increased in the cerebellum and cerebral cortex but failed to change in the hippocampus and striatum of rats receiving this protracted benzodiazepine treatment. Acute treatment with diazepam did not affect the dynamic state of brain DBI. An antibody was raised against a biologically active octadecaneuropeptide (Gln-Ala-Thr-Val-Gly-Asp-Val-Asn-Thr-Asp-Arg-Pro-Gly-Leu-Leu-Asp-Leu-Lys ) derived from the tryptic digestion of DBI. The combined HPLC/RIA analysis of rat cerebellar extracts carried out with this antibody showed that multiple molecular forms of the octadecaneuropeptide-like reactivity are present and all of them are increased in rats receiving repeated daily injections of diazepam. It is inferred that tolerance to benzodiazepines is associated with an increase in the turnover rate of DBI, which may be responsible for the gamma-aminobutyric acid receptor desensitization that occurs after protracted benzodiazepine administration.


Factors producing various responses to acetylcholine in dog hepatic circulation.
Effect of acetylcholine on hepatic circulation was investigated in 33 mongrel dogs. Mean arterial blood pressure, hepatic artery flow, portal vein pressure and portal vein flow were determined after laparotomy under nembutal anesthesia. In order to analyse the complicated responses in hepatic blood flows to 3 mug of acetylcholine hydrochloride, the peripheral resistance of each vascular system was observed in hypotensive dogs, in vascular obliteration dogs and in portal vein shunting dogs. Observation under a hypotensive condition produced by exsanguination revealed that hepatic artery resistance responded to decrease in hepatic artery pressure in different ways depending on whether the systemic blood pressure was above or below 90 mmHg. Experiments in which the hepatic artery or portal vein were obliterated disclosed that there was a certain regularity in the induction of resistance change in the non-injected one of the two hepatic vessels. The result of shunting the portal vein suggested that the complicated change above mentioned would be the expression of the overlapping two sequential responses. Since these results are difficult to explain merely by the direct response of vascular smooth muscle to acetycholine, the possibility that the hypothetical communication between the hepatic artery and portal vein might be a cholinergic system was discussed.


Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay.
Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management. We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization. Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL). We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.


Inhibitory effects of 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate on allergic inflammatory responses in rat basophilic leukemia cells.
Mast cells play crucial roles in the initiation of allergic inflammatory responses by releasing various mediators such as histamines, cytokines, and leukotrienes. In addition, signaling cascade pathways, such as the mitogen-activated protein kinase (MAPK) pathway, contribute to the regulation of mast cell degranulation. Accordingly, different research strategies have been pursued to develop anti-inflammatory and anti-allergic drugs by regulating these signaling pathways. The development of new drugs that inhibit mast cell degranulation may help in the treatment of allergies. In this study, we investigated the effects of coumarin derivatives on mast cell degranulation. The effect of coumarin derivatives on degranulation in rat basophilic leukemia (RBL)-2H3 cells was determined by a β-hexosaminidase assay and histamine assay. A coumarin derivative 1 (C1), 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate, inhibited degranulation in a dose-dependent manner and demonstrated maximum therapeutic effect when used at 25μM. Additionally, these compounds inhibited the phosphorylation of the extracellular signal-regulated kinase (ERK) pathway. Taken together, these results indicate that 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate inhibits mast cell degranulation by suppressing the activation of the ERK pathway and this inhibitory effect suggests potential therapeutic strategies towards the prevention of allergic disorders.


Dynamics of coupled simplest chaotic two-component electronic circuits and its potential application to random bit generation.
We numerically investigate the possibility of using a coupling to increase the complexity in simplest chaotic two-component electronic circuits operating at high frequency. We subsequently show that complex behaviors generated in such coupled systems, together with the post-processing are suitable for generating bit-streams which pass all the NIST tests for randomness. The electronic circuit is built up by unidirectionally coupling three two-component (one active and one passive) oscillators in a ring configuration through resistances. It turns out that, with such a coupling, high chaotic signals can be obtained. By extracting points at fixed interval of 10 ns (corresponding to a bit rate of 100 Mb/s) on such chaotic signals, each point being simultaneously converted in 16-bits (or 8-bits), we find that the binary sequence constructed by including the 10(or 2) least significant bits pass statistical tests of randomness, meaning that bit-streams with random properties can be achieved with an overall bit rate up to 10×100 Mb/s = 1 Gbit/s (or 2×100 Mb/s =200 Megabit/s). Moreover, by varying the bias voltages, we also investigate the parameter range for which more complex signals can be obtained. Besides being simple to implement, the two-component electronic circuit setup is very cheap as compared to optical and electro-optical systems.


Evaluating a conceptual model-based assignment.
Although all faculty evaluate student assignments, fewer tackle the difficult issue of evaluating its actual usefulness. Wanting to know how their undergraduate community health nursing students were understanding and using a conceptual model in clinical practice, the authors used student journal assignments to evaluate learning and application of the model. They discuss the project's outcomes and subsequent strategies implemented to enhance their own understanding of the model and facilitate improved student learning.


The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex.
Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho)choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N-acetylaspartate in all the models. These changes agree well with the changes in the post-mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.


The complete mitochondrial genome sequence of the Korean hare (Lepus coreanus).
The complete mitogenome of the Korean hare (Lepus coreanus) was determined by the long and accurate polymerase chain reaction and primer-walking methods. The mitogenome of the Korean hare is 17,472 bp in length and contains sequences that encode 13 protein genes, 22 tRNAs, 2 rRNAs and a noncoding control region. The mitogenome is arranged in an identical order to that found in most other vertebrates. All mitochondrial genes are encoded on the heavy strand, except for eight tRNA genes and the ND6 gene. The control region contains putative termination associated elements, conserved sequence blocks and short and long tandem repeats motifs.


Phenomic selection in slash pine multi-temporally using UAV-multispectral imagery.
Genomic selection (GS) is an option for plant domestication that offers high efficiency in improving genetics. However, GS is often not feasible for long-lived tree species with large and complex genomes. In this paper, we investigated UAV multispectral imagery in time series to evaluate genetic variation in tree growth and developed a new predictive approach that is independent of sequencing or pedigrees based on multispectral imagery plus vegetation indices (VIs) for slash pine. Results show that temporal factors have a strong influence on the h2 of tree growth traits. High genetic correlations were found in most months, and genetic gain also showed a slight influence on the time series. Using a consistent ranking of family breeding values, optimal slash pine families were selected, obtaining a promising and reliable predictive ability based on multispectral+VIs (MV) alone or on the combination of pedigree and MV. The highest predictive value, ranging from 0.52 to 0.56, was found in July. The methods described in this paper provide new approaches for phenotypic selection (PS) using high-throughput multispectral unmanned aerial vehicle (UAV) technology, which could potentially be used to reduce the generation time for conifer species and increase the genetic granularity independent of sequencing or pedigrees.


Glycosylation of mammalian neurofilaments. Localization of multiple O-linked N-acetylglucosamine moieties on neurofilament polypeptides L and M.
Neurofilaments are neuronal intermediate filaments that play an important role in the growth and maintenance of large myelinated axons. Mammalian neurofilaments are composed of three polypeptide subunits, designed as NF-L, NF-M, and NF-H, all of which are phosphorylated. Here, we demonstrate by several criteria that neurofilament polypeptides are also modified by an abundant type of intracellular protein glycosylation in which single N-acetylglucosamine monosaccharides are O-glycosidically (O-GlcNAc) linked to serine or threonine residues. In purified neurofilament proteins, the O-GlcNAc modifications occur at a stoichiometry of approximately 0.1 and 0.15 mol of GlcNAc/mol of NF-L and NF-M, respectively. The predominant sites of O-GlcNAc attachment on NF-L and NF-M are identified using proteolysis, purification of the glycopeptides, and subsequent analysis by automated gas-phase sequencing, manual Edman degradation, and laser desorption mass spectrometry. For NF-L, both major sites of glycosylation (Thr21 and Ser27) are located at the NH2-terminal head domain. For NF-M, one major site (Thr48) lies within the NH2-terminal head domain, whereas the other (Thr431) is located at the tail domain. Deletions encompassing these sites have been shown previously to have a dominant detrimental effect upon neurofilament assembly, raising questions about the specific function(s) of the saccharide moieties at these sites. Specific identification of these O-GlcNAc attachment sites has set the stage for more detailed mutagenic analysis of O-GlcNAc functions on neurofilaments.


Effect of bacterial endotoxin lipopolysaccharide treatment on duck Leydig cells.
This study aimed to investigate the effects of bacterial endotoxin lipopolysaccharide (LPS) on hormone production and gene expression in duck Leydig cells and its underlying mechanisms. Leydig cells were collected from 200-day-old mallard ducks and divided into five treatment groups (0, 50, 100, 200, and 400 ng/mL LPS). After treatment with LPS for 6, 12, 24, and 48 h, testosterone, activin, and inhibin levels in the cell supernatants were determined using enzyme-linked immunosorbent assay (ELISA) kits. The expression levels of testosterone synthesis-related genes, including steroidogenic acute regulatory protein (StAR), 3-beta-hydroxysteroid dehydrogenase (3β-HSD), and cytochrome P450 aromatase (P450arom), and reproductive-related genes, including gonadotropin-inhibitory hormone receptor (GnIHR), follicle stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) were detected using quantitative real-time polymerase chain reaction (qRT-PCR). We successfully isolated and cultured duck Leydig cells with cell purity above 90%. Compared with the control group, the levels of testosterone, activin, and inhibin secreted in Leydig cells decreased gradually with increasing LPS concentration. After treatment with LPS, the expression of StAR and 3β-HSD genes in Leydig cells was upregulated at 12 h, and that of GnIHR was upregulated at 24 h; whereas the expression of FSHR and LHR was reduced at 24 h. This study indicates that LPS can inhibit the secretion of hormones and regulate the expression of related genes in duck Leydig cells.


How image quality can be improved: our experience with multidetector computed tomography coronary angiography.
The objective of this study was to investigate the factors that may influence image quality on multidetector computed tomography (MDCT) coronary angiography (CA). Two hundred twenty-four consecutive patients (161 men and 63 women; mean age, 52 years; age range, 34-76 years) evaluated with MDCT CA were included in the study. The evaluation of the quality of the patients' images was mainly based on the contrast material phase (early phase, optimal phase, or late phase) and the level of stepladder artifact (none, acceptable, or unacceptable). In addition, factors such as patient selection, patient preparation, scanning, processing, and steps of analysis, which may be affecting the quality of a final image, were examined independently. Patients who could not achieve sufficient breath-holding despite multiple breath exercises, those with a calcium score of 500 or higher, those with a heart rate greater than 90 bpm after metoprolol administration (because of shortening of the diastolic phase in the most still period), and those whose scanning was not completed were excluded from the study. The results for the remaining 224 patients were evaluated. Based on the contrast phase, there were 66 (29.5%) patients in the first group (early), 93 (41.5%) in the second group (optimal), and 65 (29%) in the third group (late). Among the 224 patients, the images of 152 (67.9%) had no stepladder artifact, those of 67 (29.9%) were of acceptable image quality, and those of 5 (2.2%) were of unacceptable image quality. It is important to obtain high-quality images to achieve correct interpretation with coronary artery CT angiography. This study aimed to describe a technique performed on 224 patients based on an array of factors ranging from patient selection to postprocessing. The results show that patient selection, cooperation with the patient, and breath-holding exercises play a very important role in obtaining the best images. In addition, a proper scanning technique (e.g., placement of electrocardiographic electrodes and contrast material phase) and postprocessing (e.g., reconstruction interval) may also contribute to obtaining high-quality images.


Evaluation of Gd-DTPA-labeled dextran as an intravascular MR contrast agent: imaging characteristics in normal rat tissues.
Dextran covalently linked to moieties of gadolinium diethylenetriamine pentaacetic acid (DTPA), for use as a macromolecular, intravascular blood pool marker for contrast material-enhanced magnetic resonance (MR) imaging was characterized by means of physicochemical and relaxivity measurements and MR imaging in healthy rats. Dextran labeled with 15 Gd-DTPA moities (molecular weight of approximately 75,000 d) had a T1 relaxivity at 0.25 T and 37 degrees C of 157.1 mmol-1.sec-1 per molecule and 10.5 mmol-1.sec-1 per gadolinium atom, more than twice that of unbound Gd-DTPA. Osmolality was 300-350 mOsm/kg at a gadolinium concentration of 0.01 mmol/L. Tissue enhancement was essentially linearly related to injected dose in the gadolinium dose range of 0.01-0.05 mmol/kg of body weight. Approximate typical enhancement values over baseline for normal tissues at 10 minutes after a gadolinium dose of 0.05 mmol/kg were as follows: cardiac muscle, adrenal gland, and liver, 40%-50%; lungs, 160%-200%; renal cortex, 130%; renal medulla, 240%; spleen, 75%; muscle, 15%; and brain, 5%-10%. Projection-subtraction images showed that dextran-(Gd-DTPA)15 remained intravascular for at least 1 hour after injection. The prolonged and easily appreciated levels of tissue enhancement with dextran-(Gd-DTPA)15, at a gadolinium dose less than that routinely used in Gd-DTPA, indicate further evaluation of this macromolecular marker.


[Genetic diversity of P. falciparum and pathogenesis of the severe malarial anaemia in children under 5 years old in the province of Boulgou, Burkina Faso].
The clinical presentation of malaria mainly the severe form may be related to Plasmodium falciparum msp-2 (merozoite surface protein 2) specific family To verify this hypothesis, during the high malaria transmission season in 2001; we analyzed the allelic polymorphism of the msp-2 gene of P. falciparum in children under 5 years old with different presentation of malaria in the regional Hospital and at community level in the Boulgou Province (Burkina Faso). A total of 405 children (107 severe malarial anaemia cases, 102 severe malaria cases without severe anaemia and 196 non severe malaria cases) were enrolled in the study. The frequencies of the FC27 were 89.2% in severe malarial anaemia children group, then 89.7% and 86.9% respectively in severe malaria non anaemic children cases and non severe malaria cases (P = 0.4). The frequencies of the 3D7 were 72.5%; 84.1% and 77% respectively severe malaria non anaemic children, severe malarial anaemia cases and non severe malaria cases (P = 0.7). The complexity of the FC27 genotypes was significantly higher in children with severe malaria (with and without severe anaemia) compared to the non severe malarial children (P << 0.001). No significant difference was pointed up in the complexity of the 3D7 genotypes.


The Perplexity of Synergistic Duality: Inter-molecular Mechanisms of Communication in BCR-ABL1.
Aberrant and proliferative expression of the oncogene BCR-ABL in bone marrow cells is one of the prime causes of Chronic Myeloid Leukemia (CML). It has been established that the tyrosine kinase domain of the BCR-ABL protein is a potential therapeutic target for the treatment of CML. Although the first and second line inhibitors against the enzyme are available, recent studies have indicated that monotherapeutic resistance has become a great challenge. In recent studies, the dual inhibition of BCR-ABL by Nilotinib and Asciminib has been shown to overcome drug resistance. This prompted us to investigate the dynamics behind this novel drug combination. By the utilization of a wide range of computational tools, we defined and compared BCR-ABL's structural and dynamic characteristics when bound as a dual inhibitor system. Conformational ensemble analysis presented a sustained inactive protein, as the activation loop, inclusive of the characteristic Tyr257, remained in an open position due to the unassailable binding of Asciminib at the allosteric site. Nilotinib also indicated stronger binding at the catalytic site in the presence of Asciminib, thus exposing new avenues in treating Nilotinib-resistance. This was in accordance with intermolecular hydrogen bond interactions with key binding site residues GLU399, Asn259 and Thr252. The investigations carried out in this study gave rise to new possibilities in the treatment of resistance in CML, as well as assisting in the design of novel and selective inhibitors as dual anti-cancer drugs.


Effects of Preferential Solvation Revealed by Time-Resolved Magnetic Field Effects.
External magnetic fields can impact recombination yields of photoinduced electron transfer reactions by affecting the spin dynamics in transient, spin-correlated radical pair intermediates. For exciplex-forming donor-acceptor systems, this magnetic field effect (MFE) can be investigated sensitively by studying the delayed recombination fluorescence. Here, we investigate the effect of preferential solvation in microheterogeneous solvent mixtures on the radical pair dynamics of the system 9,10-dimethylanthracene (fluorophore)/N,N-dimethylaniline (quencher) by means of time-resolved magnetic field effect (TR-MFE) measurements, wherein the exciplex emission is recorded in the absence and the presence of an external magnetic field using time-correlated single photon counting (TCSPC). In microheterogeneous environments, the MFE of the exciplex emission occurs on a faster time scale than in iso-dielectric homogeneous solvents. In addition, the local polarity reported by the exciplex is enhanced compared to homogeneous solvent mixtures of the same macroscopic permittivity. Detailed analyses of the TR-MFE reveal that the quenching reaction directly yielding the radical ion pair is favored in microheterogeneous environments. This is in stark contrast to homogeneous media, for which the MFE predominantly involves direct formation of the exciplex, its subsequent dissociation to the magneto-sensitive radical pair, and re-encounters. These observations provide evidence for polar microdomains and enhanced caging, which are shown to have a significant impact on the reaction dynamics in microheterogeneous binary solvents.


Confidence, knowledge, and skills at the beginning of residency. A survey of pathology residents.
To document the pathology learning experiences of pathology residents prior to residency and to determine how confident they were in their knowledge and technical skills. An online survey was distributed to all pathology residency program directors in the United States, who were requested to forward the survey link to their residents. Data were obtained on pathology electives, grossing experience, and frozen section experience. Likert scale questions assessed confidence level in knowledge and skills. In total, 201 pathology residents responded (8% of residents in the United States). Prior to starting residency, most respondents had exposure to anatomic pathology through elective rotations. Few respondents had work-related experience. Most did not feel confident in their pathology-related knowledge or skills, and many did not understand what pathology resident duties entail. Respondents gained exposure to pathology primarily through elective rotations, and most felt the elective experience prepared them for pathology residency. However, elective time may be enhanced by providing opportunities for students to increase hands-on experience and understanding of resident duties.


Serology in autoimmune pancreatitis.
Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic immune-driven, inflammatory process that can involve organs such as the bile duct, salivary glands and lymph nodes, in addition to the pancreas. Many of the presenting signs and symptoms of AIP, including painless jaundice, weight loss and mild epigastric pain, are characteristic of pancreatic adenocarcinoma; thus, obtaining an accurate diagnosis to avoid unnecessary surgery is imperative. AIP responds very well to steroid treatment, although it may recur in up to 20% to 40% of cases. The diagnostic criteria for AIP are histological, radiographic, clinical and laboratory-based in nature. Although no international consensus on diagnostic criteria has yet been made, some of the diagnostic features of AIP include elevated gamma globulin, immunoglobulin, and, in particular, immunoglobulin G4 fraction (IgG4). The search for a distinct serological marker of AIP has included antibodies to a wide range of antigenic stimuli. To date, there have been studies of AIP and antibodies to lactoferrin, carbonic anhydrase isoforms II and IV, pancreatic secretory trypsin inhibitor (PSTI or SPINK) as well as to less sensitive or specific markers of autoimmunity, such as antinuclear antibody and rheumatoid factor. Although there are some preliminary strengths of association with PSTI antibodies, none of these biomarkers appears to be sensitive or specific enough to serve as distinctive evidence of AIP. At the current time, elevations of IgG4 to greater than 280 mg/dL remain the most reliable and reproducible indicator that a patient has AIP.


Genomic epidemiology of SARS-CoV-2 variants during the first two years of the pandemic in Colombia.
The emergence of highly transmissible SARS-CoV-2 variants has led to surges in cases and the need for global genomic surveillance. While some variants rapidly spread worldwide, other variants only persist nationally. There is a need for more fine-scale analysis to understand transmission dynamics at a country scale. For instance, the Mu variant of interest, also known as lineage B.1.621, was first detected in Colombia and was responsible for a large local wave but only a few sporadic cases elsewhere. To better understand the epidemiology of SARS-Cov-2 variants in Colombia, we used 14,049 complete SARS-CoV-2 genomes from the 32 states of Colombia. We performed Bayesian phylodynamic analyses to estimate the time of variants' introduction, their respective effective reproductive number, and effective population size, and the impact of disease control measures. Here, we detect a total of 188 SARS-CoV-2 Pango lineages circulating in Colombia since the pandemic's start. We show that the effective reproduction number oscillated drastically throughout the first two years of the pandemic, with Mu showing the highest transmissibility (Re and growth rate estimation). Our results reinforce that genomic surveillance programs are essential for countries to make evidence-driven interventions toward the emergence and circulation of novel SARS-CoV-2 variants.


Headache diary in the diagnosis of childhood migraine.
The usefulness of a headache diary in the diagnosis of migraine and in the clarification of migraine symptoms was studied in 145 children. These children belong to a 1-year age cohort of 5356 children that has been followed since birth. The children were enrolled in the present study according to their headache status in a questionnaire study at the age of 8 to 9 years, at which time 50 children had migraine, 43 had nonmigrainous headache, and 52 did not have recurrent headache. Information on their present headache status was collected with a face-to-face interview at the age of 11 to 13 years and from a headache diary after the interview. The children kept the diary for 2 to 7 months. Altogether, 72 children had migraine according to the International Headache Society criteria for migraine, either in the interview or in the diary. Eight children were diagnosed only according to the diary (11.1%). Thirty-three children had both migraine attacks and nonmigrainous headache episodes according to the diary, even though they were able to report only one type of headache episode in the interview. The duration of headache episodes was underestimated in the interview, compared to the diary, in the children with migraine. Many children recognized new aura symptoms, associated symptoms, and characteristics of pain when they started to pay attention to these when filling in the diary during the follow-up period. The headache diary is useful in clarifying the features of headache attacks and in the diagnosis of headache types in children.


Frequency tuning and directional sensitivity of tympanal vibrations in the field cricket Gryllus bimaculatus.
Female field crickets use phonotaxis to locate males by their calling song. Male song production and female behavioural sensitivity form a pair of matched frequency filters, which in Gryllus bimaculatus are tuned to a frequency of about 4.7 kHz. Directional sensitivity is supported by an elaborate system of acoustic tracheae, which make the ears function as pressure difference receivers. As a result, phase differences between left and right sound inputs are transformed into vibration amplitude differences. Here we critically tested the hypothesis that acoustic properties of internal transmissions play a major role in tuning directional sensitivity to the calling song frequency, by measuring tympanal vibrations as a function of sound direction and frequency. Rather than sharp frequency tuning of directional sensitivity corresponding to the calling song, we found broad frequency tuning, with optima shifted to higher frequencies. These findings agree with predictions from a vector summation model for combining external and internal sounds. We show that the model provides robust directional sensitivity that is, however, broadly tuned with an optimum well above the calling song frequency. We therefore advocate that additional filtering, e.g. at a higher (neuronal) level, significantly contributes to frequency tuning of directional sensitivity.


Electronic patient-reported outcome systems in oncology clinical practice.
Patient-reported outcome (PRO) questionnaires assess topics a patient can report about his or her own health. This includes symptoms (eg, nausea, fatigue, diarrhea, pain, or frequent urination), physical functioning (eg, difficulty climbing stairs or difficulty fastening buttons), and mental health (eg, anxiety, fear, or worry). Electronic PRO (ePRO) systems are used in oncology clinical care because of 1) their ability to enhance clinical care by flagging important symptoms and saving clinicians time; 2) the availability of standardized methods for creating and implementing PROs in clinics; and 3) the existence of user-friendly platforms for patient self-reporting like tablet computers and automated telephone surveys. Many ePRO systems can provide actionable links to clinical care such as summary reports in a patient's electronic medical record and real-time e-mail alerts to providers when patients report acute needs. This review presents 5 examples of ePRO systems currently in use in oncology practice. These systems support multiple clinical activities, including assessment of symptoms and toxicities related to chemotherapy and radiation, postoperative surveillance, and symptom management during palliative care and hospice. Patient self-reporting is possible both at clinical visits and between visits over the Internet or by telephone. The implementation of an ePRO system requires significant resources and expertise, as well as user training. ePRO systems enable regular monitoring of patient symptoms, function, and needs, and can enhance the efficiency and quality of care as well as communication with patients.


Reversal of photoschedule in spring does not prevent photorefractoriness in Siberian hamsters.
We studied the influence of light-dark (L:D) cycle reversal on daily variations in the brown adipose tissue (BAT) capacity for nonshivering thermogenesis (NST) in Siberian hamsters (Phodopus sungorus). Continuous and simultaneous measurements of BAT temperature (T(BAT)) and preferred ambient temperature (PT(a)) were made after noradrenaline (NA) injections administered every 4 hr. First, hamsters were acclimated for 4 weeks to an ambient temperature (T(a)) of 23 degrees C and 12L:12D, and then to a reversed photoschedule 12D:12L for 8 weeks. The same was done after a 4- and 8-week acclimation period at the same T(a). We found that after photoschedule reversal, the re-entrainment of T(BAT) and PT(a) rhythms preceded re-entrainment of the NST rhythm. The daily rhythms of T(BAT) and PT(a) were fully re-entrained after 4 weeks of acclimation to the reversed photoschedule, but rhythmicity of the response to NA disappeared. This rhythm was restored in hamsters acclimated to a reversed photoschedule for 8 weeks. We suggest that the daily rhythm of NST capacity is not responsible for generating the rhythm of body temperature (T(b)). Rather, it is a result of the daily rhythm of T(b), but adjusts to the new environment more slowly than the T(b) rhythm. When a daily rhythm of NST was present, the increase in T(BAT) after NA injection was inversely correlated with the pre-injection T(BAT). In addition, NA-induced changes in PT(a) reflected the intensity of NST in BAT; namely, increased T(BAT) was correlated with the post-injection decrease in PT(a). When the increase in T(BAT) was large, animals chose a lower T(a) to dissipate excessive heat and prevent overheating. In the course of the experiments, we recorded a decreased mean NST capacity and increased body mass of hamsters. These changes are representative of the time of photorefractoriness and a transition to a summer status. Despite prolonged exposure to an intermediate day length (12 hr of light) and photoschedule reversal, hamsters continued to change towards their summer condition and were able to acclimate to the new D:L cycle.


Antigenic analysis of Haemophilus ducreyi by Western blotting.
Twenty-one strains of Haemophilus ducreyi were analysed by Western blotting using two antisera produced in mice. Common antigens of molecular weights 58, 46, 41, 28, 22 and 16 kDa were detected in all the strains. The antigens were protein in nature, since they could not be detected in whole-cell lysates which had been treated with proteinase K. The H. ducreyi strains showed antigenic cross-reactivity with strains of H. influenzae and H. parainfluenzae, but showed minimal or no cross-reactivity with seven other species of bacteria.


Laparoscopic cryoablation under sonographic guidance for the treatment of small renal tumors.
To evaluate the efficacy of ultrasound-guided laparoscopic cryoablation of small renal tumors. Eleven men and five women with solid renal tumors (mean size 2.6 cm) were treated using laparoscopically monitored cryoablation between October 2000 and October 2002. Nine tumors were left sided and seven right. Ten patients were treated retroperitoneoscopically and six transperitoneally. A double-freeze/active-thaw technique was utilized with two 10-minute freeze cycles. The mean operating time was 188 minutes. There was one open conversion for failure to progress. The mean blood loss was 40 mL. Tumor biopsy demonstrated five renal-cell carcinomas, two oncocytomas, and lesions that either were benign or were not biopsied. The mean hospital stay was 1.9 days with a median stay of 1 day. With a mean follow-up of 9.6 months, all tumors remain nonenhancing and are stable or smaller than the original lesion. Two patients have died of unrelated causes and without evidence of disease. This series of patients adds to the growing body of literature suggesting that cryoablation is a well-tolerated method for treating small renal tumors. Longer follow-up is required to fully define its place in the therapeutic armamentarium.


Suppression of carbon deposition in the iron-catalyzed production of lower olefins from synthesis gas.
Pressure leverage: A tapered-element oscillating microbalance was used to evaluate carbon deposition on a highly selective and active supported iron catalyst for the production of lower olefins. With increasing pressure, the H(2)/CO ratio had a profound effect on the carbon deposition rate and accordingly, conditions leading to minimal carbon deposition, low methane selectivity, and high olefin selectivity were identified.


Phase I/Ib dose-escalation study of avelumab in Chinese patients with advanced solid tumors.
Aim: Data for avelumab (anti-PD-L1 antibody) in Chinese patients are limited. Patients & methods: Phase I/Ib, open-label, dose-escalation study of Chinese patients with advanced solid tumors. Primary study objectives were to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of avelumab. Results: 24 patients received avelumab 3 mg/kg every 2 weeks (Q2W; n = 3), 10 mg/kg Q2W (n = 7), 20 mg/kg Q2W (n = 6) or 10 mg/kg weekly for 12 weeks and then Q2W thereafter (n = 8). MTD was not reached. Avelumab exposure was increased in higher dose groups. Partial responses occurred in two patients (confirmed in one patient); best overall response was stable disease in nine patients. Conclusion: Data for avelumab in Chinese patients with advanced solid tumors were consistent with previous global studies.


Recombination of DNAs in Xenopus oocytes based on short homologous overlaps.
Linear molecules of pBR322 and closely related plasmid DNAs were injected into Xenopus oocyte nuclei. Such molecules were degraded unless their ends were recombined. Non-homologous ends were joined rarely, if at all, but measurable recombination was supported by homologous sequences of less than 10 base pairs (bp). The efficiency of recombination increased as the length and degree of homology improved, in the range of about 8-20 bp. The homologous sequences had to be very close to the original molecular ends (within about 20 bp); internal homologies, even when they included better matches, were never used. These observations are best accommodated by a model of recombination which envisions exonucleolytic resection to expose homologous sequences, followed by annealing of single-stranded tails, tidying up and sealing of the new joint. Some of the recombined plasmids had novel tetracycline resistance genes; their properties give some insight into the function of the tet gene product.


Acidic polysaccharide complexes from purslane, silver linden and lavender stimulate Peyer's patch immune cells through innate and adaptive mechanisms.
Three polysaccharide complexes (PSCs) were isolated from the aerial parts of common purslane (Portulaca oleracea L.), and the flowers of common lavender (Lavandula angustifolia Mill.) and silver linden (Tilia tomentosa Moench) by boiling water extraction and ethanol precipitation. The chemical composition and immunomodulating effects of isolated PSCs were characterized. The chemical characterization revealed that the three samples contain mainly pectic polysaccharides. They exhibited ex vivo intestinal immunomodulating activity through the murine Peyer's patch-mediated bone marrow cell proliferation test at 100μg/ml concentration. At the same time, they stimulated ex vivo human blood T-cell populations (CD4+/CD25+ and CD8+/CD25+), phagocytic leukocytes (CD14+ and CD64+ cells) and induced IL-6 production from human white blood cells and Peyer's patch cells. The herbal PSCs stimulated ex vivo ROS production from whole blood phagocytes and showed unspecific in vitro anti-proliferative activity against normal and A549, HeLa and LS180 tumor cells. This is the first report on immunomodulating studies of linden flower pectins and chemical and biological activity characterization of lavender polysaccharides. Our study demonstrates that similarly to purslane, lavender and silver linden herbal materials contain immunomodulating polysaccharides that could be useful for support of compromised immune system.


[A case of hepatocellular carcinoma treated with specific substance of Maruyama resulting in a partial response].
We treated a 41-year-old man with hepatocellular carcinoma and chronic liver disease. He experienced leg edema. Following additional examinations, we diagnosed the patient with hepatocellular carcinoma and ascites with liver cirrhosis. Due to renal dysfunction, he could not undergo treatment with transcatheter arterial chemoembolization(TACE)or transcatheter arterial infusion(TAI). Therefore, he was treated with specific substance of maruyama(SSM), and survived.


Pharmacogenetic considerations in diseases of cardiac ion channels.
Phenotypic variation within a species arises from differences in genetic makeup between individuals. This inherent diversity empowers the species as a whole to explore and expand into new environmental niches and also to survive new stressors within an ever-changing environment. Paradoxically, one class of stressors currently challenging the human population is therapeutic drugs: medications designed to combat disease are often associated with a host of nonspecific side effects. Following earlier studies of the involvement of some cardiac ion currents in unwanted drug interactions, recent reports have identified not only the ion channel subunits involved but also a range of mutations and single nucleotide polymorphisms in ion channel genes that predispose to both drug-induced and familial cardiac arrhythmia. The tendency for individuals harboring specific, often common, gene variants to succumb to life-threatening cardiac arrhythmia, and the contribution of other factors such as drug interaction to disease etiology in these cases, are discussed here together with potential pharmacogenetic strategies for arrhythmia circumvention and therapy.


Intravenous morphine titration to treat severe pain in the ED.
We assessed the safety of intravenous morphine titration in the emergency setting. A total of 621 consecutive adult patients admitted in the ED with acute severe pain (visual analogue scale pain score > 70) were included. Intravenous morphine titration was administered as a bolus of 2 (body weight < or = 60 kg) or 3 mg (body weight > 60 kg) with 5-minute interval between each bolus. Pain relief was defined as a visual analogue pain score of 30 or lower. The dose of morphine administered was 0.16 +/- 0.10 mg/kg and the median number of boluses was 3. Pain relief was obtained in 512 (82%) patients. Morphine-induced adverse events occurred in 67 patients (11%) without severe adverse event. Titration was interrupted before pain relief had been obtained in 107 (17%) patients. In the remaining 514 patients, pain relief was obtained in 507 (99%) patients. Two variables were significantly associated with no pain relief: major protocol deviation (odds ratio, 17.3; 95% confidence interval, 10.0-30.1) and morphine-induced adverse effect (odds ratio, 13.0; 95% confidence interval, 6.7-25.3). Intravenous morphine titration is a safe and effective option for severe pain when used according to a strict protocol.


Estimation of StilbostatR treatment efficiency in breast cancer by thermography.
Administration of Stilbostat to postmenopasual women with advanced breast cancer markedly improved the clinical state in about 65% of the cases and concomitantly decreased the cutaneous thermic values at the level of the lesions showing a tendency to equalize the values recorded for the symmetrical healthy cutaneous zones. The thermographic test is proposed as a means of estimating the Stilbostat treatment efficiency in breast cancer.


The effect of multiple sclerosis on pure tone thresholds.
The pure tone audiograms of 44 multiple sclerosis (MS) and 44 matched neurological control patients were studied with a view to finding out whether demyelinating disease is associated with decreased acuity to pure tones. The results show that MS patients have essentially normal hearing but auditory acuity at some of the low frequencies was found to be significantly worse in the MS group compared to the control patients. No correlation was found between the affected frequencies and the patients' age, sex and duration of the disease. The differences in thresholds between the control and MS patients were confined to the 25 patients who had clinical evidence of brain stem lesions suggesting that the cause of the abnormality in thresholds is in the brain stem.


Fluorescein angiography: insight and serendipity a half century ago.
It has been 50 years since fluorescein angiography was developed as a clinical procedure by 2 medical students at Indiana University. The story of its discovery and the recognition of its value to ophthalmology involve a combination of insight and serendipity. Fluorescein had been in use clinically for more than half a century, but it took a pulmonary medicine laboratory to provide the stimulus for the development of flash and barrier filters that would make vascular photography practical. The first article was rejected by the ophthalmology literature, but several clinics heard about it and soon documented the enormous diagnostic value of the procedure.


Automatic patient positioning and gating window settings in respiratory-gated stereotactic body radiation therapy for pancreatic cancer using fluoroscopic imaging.
Before treatment delivery of respiratory-gated radiation therapy (RT) in patients with implanted fiducials, both the patient position and the gating window thresholds must be set. In linac-based RT, this is currently done manually and setup accuracy will therefore be dependent on the skill of the user. In this study, we present an automatic method for finding the patient position and the gating window thresholds. Our method uses sequentially acquired anterior-posterior (AP) and lateral fluoroscopic imaging with simultaneous breathing amplitude monitoring and intends to reach 100% gating accuracy while keeping the duty cycle as high as possible. We retrospectively compared clinically used setups to the automatic setups by our method in five pancreatic cancer patients treated with hypofractionated RT. In 15 investigated fractions, the average (±standard deviation) differences between the clinical and automatic setups were -0.4 ± 0.8 mm, -1.0 ± 1.1 mm, and 1.8 ± 1.3 mm in the left-right (LR), the AP, and the superior-inferior (SI) direction, respectively. For the clinical setups, typical interfractional setup variations were 1-2 mm in the LR and AP directions, and 2-3 mm in the SI direction. Using the automatic method, the duty cycle could be improved in six fractions, in four fractions the duty cycle had to be lowered to improve gating accuracy, and in five fractions both duty cycle and gating accuracy could be improved. Our automatic method has the potential to increase accuracy and decrease user dependence of setup for patients with implanted fiducials treated with respiratory-gated RT. After fluoroscopic image acquisition, the calculated patient shifts and gating window thresholds are calculated in 1-2 s. The method gives the user the possibility to evaluate the effect of different patient positions and gating window thresholds on gating accuracy and duty cycle. If deemed necessary, it can be used at any time during treatment delivery.


Primary familial brain calcification with a novel SLC20A2 mutation: Analysis of PiT-2 expression and localization.
Primary familial brain calcification (PFBC) is an autosomal dominant rare disorder characterized by bilateral and symmetric brain calcifications, and neuropsychiatric manifestations. Four genes have been linked to PFBC: SLC20A2, PDGFRB, PDGFB, and XPR1. In this study, we report molecular and clinical data of a PFBC patient carrying a novel SLC20A2 mutation and we investigate the impact of the mutation on PiT-2 expression and function. Sanger sequencing of SLC20A2, PDGFRB, PDGFB, XPR1 led to the identification of a novel duplication of twelve nucleotides (c.1876_1887dup/ p.Trp626_Thr629dup) in SLC20A2 gene. SLC20A2 encodes for a cell membrane transporter (PiT-2) involved in maintenance of inorganic phosphate homeostasis. We performed an analysis of expression and functionality of PiT-2 protein in patient primary cultured fibroblasts. In patient fibroblasts, the mutation does not affect PiT-2 expression but alter sub-cellular localization. The Pi-uptake assay revealed a less Pi depletion in patient than in control fibroblasts, suggesting that SLC20A2 duplication may impair Pi internalization. This is the first study reporting sub-cellular expression analysis of mutant PiT-2 in primary cultured fibroblasts from a PFBC patient, showing that p.Trp626_Thr629dup in SLC20A2 alters PiT-2 sub-cellular localization and reduces Pi-uptake, leading to onset of PFBC in our patient.


Behavioral determinants of occupational exposure to chemical agents.
In the demand-control model (see T. Theorell & R. A. Karasek, 1996), it is hypothesized that workers in active jobs (high demands-high decision latitude) can exert effective coping strategies when confronted with environmental stessors. Thus, when exposed to similar levels of a chemical agent, lower concentrations of this agent in blood could be expected in these workers in comparison with workers in passive jobs. This theory was tested in 2 studies of lead-exposed workers: 18 male Caucasian workers from an electric accumulatory factory and 18 male Caucasian workers from a lead smelting factory. The results did not follow the hypothesized outcomes. In the work environment of the workers in active jobs, lower concentrations of lead in air were measured, but higher levels of lead in blood were observed in these workers. The opposite was true of workers in passive jobs. Differences in hygienic behavior at work may explain these unexpected results.


Phospholipid base exchange activity in the leukocyte membranes of patients with inflammatory disorders.
Phospholipid base exchange and cholinephosphotransferase (CPT) and ethanolaminephosphotransferase (EPT) activities were assessed in the membranes of neutrophils or lymphocytes from patients with various inflammatory disorders. Ethanolamine exchange activity was significantly enhanced in both neutrophils and lymphocytes from patients with active Behçet's disease, active systemic lupus erythematosus (SLE), and severe bacterial infections and slightly enhanced in those from patients with active rheumatoid arthritis (RA), compared with healthy controls. No abnormal findings were found in CPT, EPT, or serine or choline base exchange activities in the leukocytes from any of the diseased groups tested or in the ethanolamine exchange activity of patients with severe viral infections and inactive SLE, RA, and Behçet's disease. The authors have recently demonstrated the enhancement of transmethylation and phospholipase A2 activity in human leukocyte membranes at the height of inflammatory disease states, as well as the activation of leukocyte ethanolamine exchange by bioactive stimulants. These data postulate that phosphatidylethanolamine synthesis by the base exchange reaction may be the precursor of transmethylation and its subsequent activation of phospholipase A2, leading to the induction of arachidonic acid cascade.


Social determinants of quality of elderly life in a rural setting of India.
The aim of this study is to understand the social determinants of quality of elderly life in rural central India and describe their perspectives on various issues related to their quality of life. It was a community-based mixed-methods study in which quantitative (survey) method was followed by qualitative (Focus Group Discussion, FGD). The study was done in field practice area of a Rural Health Training Centre. We decided to interview all the elderly (>60 years) in two feasibly selected wards of village Anji by using the "WHO-Quality of Life (WHOQOL)-brief questionnaire." We used WHOQOL syntax for the calculation of mean values of four domains. Following survey, four FGDs were carried out. The determinants of perceived physical health, amenable for intervention were their currently working status, not being neglected by the family, and involvement in social activities. The determinants for psychological support were health insurance, and their current working status. The determinants for social relations were membership in social group and their present working status. The determinants for perceived environment were membership in social groups and relationship with the family members. In qualitative research, factors such as active life, social activity, spirituality, health care, involvement in decision making, and welfare schemes by the Government were found to contribute to better quality of elderly life. Problems or conflicts in family environment, lack of shelter and financial security, overtapped resources, and gender bias add to negative feelings in old age life. There is a need for intervention at social and family level for elderly friendly environment at home and community level.


Association of MRI Visible Perivascular Spaces and Neurofilament Light Chain: The Framingham Heart Study.
Neurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification. To relate PVS burden according to brain topography and plasma NfL. Framingham Heart Study (FHS) participants with brain MRI and NfL measurements were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) using validated methods and categorized based on counts. A mixed region variable representing high burden PVS in either BG or CSO was assessed. Multivariable linear regression analyses were used to relate PVS burden to log-transformed NfL levels in models adjusted for age, sex, FHS cohort, time between MRI and clinic exam, and image view (model 1), vascular risk factors (model 2), and white matter hyperintensity volume, covert brain infarcts, and cerebral microbleeds (model 3). Among 1,457 participants (68.1±8.5 years, 45% males), NfL levels increased with higher PVS burden. Multivariable analysis showed an association of high PVS burden strictly in BG with NfL (β= 0.117, 95% CI 0.014-0.221; p = 0.027), but attenuated in model 3. The associations were mainly in participants≥65 years (β= 0.122, 95% CI 0.015-0.229, p = 0.026), women (β= 0.156, 95% CI 0.024-0.288, p = 0.021), and APOE ɛ4 non-carriers (β= 0.140, 95% CI 0.017-0.263, p = 0.026). The association of strictly BG high PVS burden with NfL suggests a role for PVS as markers of neuroaxonal injury, but our results are hypothesis generating and require further replication.