title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Electrochemiluminescence detection of dichlorvos pesticide in luminol-CTAB medium. | A simple, novel electrochemiluminescence (ECL) method for the detection of dichlorvos pesticide (DDVP) with high sensitivity was discovered. Detection was carried out in a static ECL system, in which a glassy carbon electrode was selected as the working electrode. ECL parameters, including the concentrations of cetyrltrimethylammonium bromide and luminol, the solution pH, and the scan rate of the applied potential, were optimized. Under these optimal conditions, the linear response of ECL-emission versus DDVP concentration was valid in the range 5-8000 ng/L (r(2)=0.9982) with a relative standard deviation of 4.3% at 2000 ng/L (n=10), yielding a detection limit (S/N=3) of 0.42 ng/L. The ECL emission was caused by a radical reaction process, in which the dissolved oxygen in the luminol solution reacted with the DDVP and generated free radicals. The free radicals reacted with the luminol anion and yielded the luminol radical. The approach presented was successfully applied to the determination of DDVP residues in vegetable samples. | 18,761,159 |
Optimization of serotonin imprinted polymers and recognition study from platelet rich plasma. | Molecularly imprinted polymers using serotonin as the template molecule was prepared for selective recognition from platelet rich plasma by non-covalent imprinting approach. Four different monomers (methacrylic acid, acrylamide, 4-vinylpyridine and 2-acrylamido-2-methylpropane sulfonic acid) and acetonitrile and DMSO as porogen were investigated for the first time by bulk polymerization. The molecularly imprinted polymer which was prepared by acrylamide/methacrylic acid had the largest imprinting factor for serotonin. The affinity and specificity of these polymers were evaluated by equilibrium binding experiments. The effect of polarity of the solvents was examined by polymers binding capacity and imprinting factor. According to the Scatchard analysis the K(d) and Q(max) values were calculated as 1.95 micromoll(-1) and 19.129 micromolg(-1), respectively. The polymer was tested to evaluate serotonin from platelet rich plasma and 70% serotonin recovery was found. | 18,761,170 |
A systematic study on extraction of total arsenic from down-scaled sample sizes of plant tissues and implications for arsenic species analysis. | An easily feasible, species-conserving and inexpensive protocol for the extraction of total arsenic and arsenic species from terrestrial plants was designed and applied to the investigation of accumulation and metabolization of arsenite (As(III)), arsenate (As(V)), monomethylarsonate (MMA(V)), and dimethylarsinate (DMA(V)) by the model plant Tropaeolum majus. In contrast to existing extraction methods hazardous additives and elaborate procedures to enhance the extraction yields were omitted. The proposed protocol is suited to down-scale the sample sizes used for the extractions and to promote a compartmentally resolved analysis of the arsenic distribution within individual leaves, leaf stalks, and stems instead of the conventional extraction of pooled samples. In a two-step extraction, the high extraction efficiencies (85-92%) for arsenic achieved by phosphate buffer from larger amounts (200mg) of homogenized leaf material in a one-step extraction, could be enhanced to 94-100% in a second extraction step. A strong dependence of the arsenic extractability on the type of arsenic species accumulated in the tissue as well as on the type of the tissue (leaf, leaf stalk, stem) was found. For the extraction of 5mm long segments cut from individual leaves without previous homogenization of the plant parts yields between 75 and 93% depending on arsenic species prevailing in the cells were obtained using 1 or 10mM phosphate buffer. The total extraction and analysis protocol was validated using a standard reference material as well as by spiking experiments. The arsenic species analysis by IC/ICPMS revealed a number of nine unidentified metabolites in the plant extracts in addition to the species MMA(V), DMA(V), As(III), and As(V) that were provided to the plants during their growth phase. | 18,761,183 |
Laparoscopic radical cystectomy. | The application of laparoscopic techniques to radical cystectomy has been a recent and natural evolution of successful laparoscopic applications in renal surgery and prostatectomy. The authors' ongoing international registry comprises over 700 cases from 14 countries. Most laparoscopic radical cystectomy (LRC) operations are performed using standard laparoscopic technique, with a minority of hand-assisted or robotic-assisted procedures. This article attempts to provide an overview of the current status of LRC, with technical details, modifications, and results of various techniques as reported by the authors' group and other groups. | 18,761,199 |
Remifentanil-propofol versus fentanyl-propofol for monitored anesthesia care during hysteroscopy. | To compare the efficacy of remifentanil-propofol with that of fentanyl-propofol for monitored anesthesia care during hysteroscopy. Prospective, randomized study. Operating room and postanesthesia care unit of a university hospital. 30 ASA physical status I and II adult patients undergoing hysteroscopic procedures. After propofol infusion, patients received a bolus of remifentanil (group R, 0.5 microg/kg) or fentanyl (group F, 1 microg/kg) 4 minutes before starting the procedure and then received a continuous infusion of remifentanil (group R, 0.05 microg/kg per min) or bolus doses of fentanyl (group F, 0.5 microg/kg). Patients in group R had lower pain scores than patients in group F (0-0 vs 0-7, P < 0.05) and more stable blood pressures (74 +/- 15 vs 85 +/- 9 mmHg, P < 0.05) one minute after the start of the procedure. However, no differences were observed in other variables (recovery profiles and satisfaction scores). Remifentanil seems to be a safe and effective analgesic adjunct for monitored anesthesia care of hysteroscopic surgery. | 18,761,238 |
Frequency of electrocardiographic changes indicating myocardial ischemia during elective cesarean delivery with regional and general anesthesia: detection based on continuous Holter monitoring and serum markers of ischemia. | To determine the frequency of electrocardiographic (ECG) changes and to assess the occurrence of myocardial ischemia during elective cesarean delivery with either regional or general anesthesia. Randomized, prospective, single-blinded clinical trial. Large referral hospital. 40 ASA physical status I and II term parturients. Patients were divided randomly into two groups as follows: the regional anesthesia group (group 1, n = 20) and the general anesthesia group (group 2, n = 20). In each case, continuous ECG was done using a 7-lead Holter monitor in the operating room, continuing for 24 hours after surgery. All Holter traces were analyzed by a study-blinded cardiologist. Blood samples were collected preoperatively (baseline) and at one, 5, and 24 hours postoperatively. Serum troponin T, creatinine kinase-MB, and myoglobin levels were measured. Two patients in group 1 (10%) and one patient in group 2 (5%) showed one mm ST-segment depression for two to 5 minutes. In all 40 cases, troponin T levels were in the normal range at all time points studied. In both groups, mean serum creatinine kinase-MB and myoglobin levels at one and 5 hours postoperatively were significantly higher than at baseline (P < 0.05). These high CK-MB and myoglobin levels were returned to normal ranges at the end of the study period; none of these women showed ST-segment changes. The ST-segment changes are not frequent in healthy women undergoing elective cesarean delivery during either regional or general anesthesia, and we found no evidence of myocardial injury. | 18,761,242 |
Intravenous remifentanil and propofol for gastroscopy. | To evaluate the efficiency and safety of intravenous (i.v.) remifentanil and propofol for gastroscopy in healthy adults. Randomized, double-blinded study. Endoscopy Center, West China Hospital, Sichuan University (Chengdu, People's Republic of China). 199 adult ASA physical status I and II patients. Patients were randomly allocated to either the fentanyl group (n = 99) or the remifentanil group (n = 100). Patients received either fentanyl 0.5 microg/kg or remifentanil 0.5 microg/kg, followed by a bolus injection of one mg/kg of propofol. The subsequent doses of propofol were 0.5 mg/kg when the patient was conscious or body movement appeared. Noninvasive blood pressure, heart rate, arterial pulse oxygen saturation, and respiratory rate were recorded before gastroscopy and at two-minute intervals until the end of the gastroscopy procedure. Patients were asked to evaluate their level of cognition using the Digit-Symbol Substitution Test score before gastroscopy and at 10 minutes after discontinuation of the drug injection. Recovery time was significantly shorter in the remifentanil group than in the fentanyl group (P < 0.05). Postoperative Digit-Symbol Substitution Test scores were significantly higher in the remifentanil group than in the fentanyl group (P < 0.01). Total dosage of propofol given in the remifentanil group was significantly less than it was in the fentanyl group (P < 0.01). Frequency of apnea was significantly higher in the remifentanil group (P < 0.05). There were no significant differences in frequency of hypoxemia, bag ventilation, or body movement between the two groups (P > 0.05). Intravenous remifentanil and propofol were more efficient for gastroscopy than i.v. fentanyl and propofol. | 18,761,243 |
Relationship of sustained brain natriuretic peptide release after reperfused acute myocardial infarction with gated SPECT infarct measurements and its connection with collagen turnover and left ventricular remodeling. | The relationship among plasma brain natriuretic peptide (BNP), markers of extracellular matrix (ECM) remodeling, and left ventricular (LV) dilation after reperfused acute myocardial infarction is poorly known. Echocardiogram, plasma BNP, and ECM degradation markers (serum amino-terminal telopeptide of type I procollagen and type III procollagen and carboxy-terminal telopeptide of type I procollagen [ICTP]) were evaluated in 34 patients at days 1, 3, and 30 after first reperfused acute myocardial infarction. At 1 month, infarct size and severity and LV volume were measured by sestamibi gated single photon emission computed tomography. Patients were stratified according to day 3 BNP levels into 2 groups: group 1 (n = 17) had BNP values over the median value, and group 2 (n = 17) had BNP values under the median value. Infarct size and severity were similar in the 2 groups. LV volumes increased in group 1 but decreased in group 2 (P < .01). BNP values, LV volume/mass index, and infarct size were independent predictors of 1-month LV dilation (beta = .58 [P = .001], beta = .41 [P = .01], and beta = .32 [P = .03], respectively). Levels of serum amino-terminal propeptide of type I procollagen and type III procollagen were similar in both groups. The level of ICTP increased significantly in group 1 only, and after 3 days, it was higher (P < .01) than in group 2. In group 1 ICTP significantly interacted with the relationship between BNP release and serial changes in LV volumes (F = 4.87, P = .03). ICTP is related to elevated BNP level independently of infarct size and severity and interacts with the relationship between BNP and LV dilation. BNP levels could play a role in LV remodeling by favoring ECM degradation. | 18,761,267 |
Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction. | Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities have higher degrees of dyssynchrony measured by median phase SD (45.5 degrees vs 27.7 degrees, P < .0001) and bandwidth (117.0 degrees vs 73.0 degrees, P = .0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1 degrees vs 34.7 degrees, P < .0001) and bandwidth (136.5 degrees vs 99.0 degrees, P = .0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD (r = 0.50) and bandwidth (r = 0.40). Mechanical dyssynchrony (phase SD >43 degrees) was 43.2%. HF patients with perfusion abnormalities or prolonged QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy. | 18,761,269 |
Dolphin natures, human virtues: MacIntyre and ethical naturalism. | Can biological facts explain human morality? Aristotelian 'virtue' ethics has traditionally assumed so. In recent years Alasdair MacIntyre has reintroduced a form of Aristotle's 'metaphysical biology' into his ethics. He argues that the ethological study of dependence and rationality in other species--dolphins in particular--sheds light on how those same traits in the typical lives of humans give rise to the moral virtues. However, some goal-oriented dolphin behaviour appears both dependent and rational in the precise manner which impresses MacIntyre, yet anything but ethically 'virtuous'. More damningly, dolphin ethologists consistently refuse to evaluate such behaviour in the manner MacIntyre claims is appropriate to moral judgement. In light of this, I argue that virtues--insofar as they name a biological or ethological category--do not name a morally significant one. | 18,761,281 |
"Curiously parallel": analogies of language and race in Darwin's Descent of man. A reply to Gregory Radick. | In the second chapter of The descent of man (1871), Charles Darwin interrupted his discussion of the evolutionary origins of language to describe ten ways in which the formation of languages and of biological species were 'curiously' similar. I argue that these comparisons served mainly as analogies in which linguistic processes stood for aspects of biological evolution. Darwin used these analogies to recapitulate themes from On the origin of species (1859), including common descent, genealogical classification, the struggle for existence, and natural selection, among others. Skeptical of this interpretation, Gregory Radick sees the naturalistic account of language formation in the Descent comparisons as reinforcing Darwin's idea that languages and the races of mankind have both undergone progressive development. (The opposite view was that modern-day primitive peoples had degenerated from an originally civilized condition.) Yet the details of Darwin's language-species comparisons, as well as the polemical context in which they appear, show that they were not aimed at so limited a function. Rather, they addressed issues related to species transmutation in general. | 18,761,287 |
Caste and maternal health care service use among rural Hindu women in Maitha, Uttar Pradesh, India. | The objective of this study was to examine the association between caste and maternal health care service use among rural Hindu women in India. We analyzed data from the Morbidity and Performance Assessment, a population-based cross-sectional study, for 482 Hindu women who were pregnant during January 1998 to January 1999 in Maitha, Uttar Pradesh, India. Maternal health care service use among both upper and lower caste women was very low. Upper caste women were almost three times more likely to use antenatal care (odds ratio [OR] = 2.72; 95% confidence interval [CI], 1.40-5.30), tetanus toxoid (OR = 2.50; 95% CI, 1.48-4.21), and contraceptives (OR = 2.66; 95% CI, 1.28-5.54) and almost five times (OR = 4.77; 95% CI, 1.81-12.54) more likely to have a trained birth attendant compared to the lower caste women. Caste was a significant determinant of tetanus toxoid use and trained birth attendant even after adjusting for sociodemographic factors. Besides caste, maternal literacy was the one sociodemographic factor that was significantly associated with the use of all maternal health care services. Information dissemination and awareness generation can improve the use of subsidized maternal health care services among women of all caste groups. | 18,761,290 |
Acute death due to hyperextension injury of the cervical spine caused by falling and slipping onto the face. | This retrospective study presents findings of cases involving fatal injuries, in which the victim was found dead at the scene, resulting from cervical hyperextension force attributable to a fall from a low height. External postmortem examination of 14 victims revealed that abrasions and lacerations of the face or the forehead are typical indicators of a direct impact. Either a disruption at the disk space or a transverse fracture of the vertebral body was apparent in the spinal column. The most frequent disk disruption injury occurred at the inter-vertebral space between C4 and C5, and double disruptions were observed in four instances. The damaged cord demonstrated central hemorrhage; moreover, axonal fragmentation and neuronal chromatolysis in the white matter column were evident histopathologically. The elderly victims (mean age, 64.7 years), many of whom displayed elevated blood alcohol levels, experienced the injury consequent to a fall from a low height, a fall during bicycling or slipping on a slope under accidental circumstances. | 18,761,315 |
An enhancer required for transcription of the Col6a1 gene in muscle connective tissue is induced by signals released from muscle cells. | Collagen VI is a survival factor for skeletal muscle produced by endomysial cells and localized in connective tissue around muscle fibers. Mutations of its genes (COL6A1, COL6A2 and COL6A3) cause two muscular disorders, Bethlem myopathy and Ullrich disease. Expression of Collagen VI is highly dynamic during development, suggesting that developmental and homeostatic cues of the muscle microenvironment are relevant to confine its expression in this tissue. In face of the large body of work highlighting the relevance for human diseases of the adhesion of muscle cells with their surrounding extracellular matrix, remarkably little is known on how myogenic cells control gene expression in the connective tissue cells that produce such matrix. By expressing promoter-lacZ constructs in transgenic mice, we identify a Col6a1 gene enhancer region that is necessary for activation of transcription in connective tissue cells associated with skeletal muscle. By means of a lacZ transgenic mouse line crossed in metD/D mutant background, in which muscles of limb buds fail to form, we provide evidence that the presence of cells of the myogenic lineage is needed for enhancer activation in mesenchymal cells. Accordingly, lack of myogenic cells in limb buds of metD/D mice reduces Collagen VI deposition in connective tissue. The Col6a1 enhancer characterized here is conserved in mammals and may be relevant in some cases of heritable diseases of Collagen VI. | 18,761,340 |
Cutaneous leishmaniasis caused by Leishmania infantum transmitted by Phlebotomus tobbi. | Transmission of cutaneous leishmaniasis (CL) caused by Leishmania infantum was studied in South Anatolia, Turkey. Small, non-ulcerating lesions prevailed and patients were negative in rK39 tests for antibody detection for human visceral leishmaniasis (VL). The most abundant sand fly species, Phlebotomus tobbi, was found positive for Leishmania promastigotes with a prevalence of 1.4% (13 out of 898 dissected females). The isolated strains were identical with those obtained from patients with CL and were typed as L. infantum. Phylogenetic analysis revealed similarity to MON-188 and a clear difference from the MON-1 clade. Blood-meal identification showed that P. tobbi feeds preferentially on cattle and humans. This finding, the high number of CL patients and relative scarcity of dogs in the focus, suggests that the transmission cycle could be anthroponotic. | 18,761,342 |
Attenuation of the cardiovascular and metabolic complications of obesity in CD14 knockout mice. | Although toll-like receptors (TLR) are known to mediate the metabolic complications of obesity, the mechanisms underlying its activation remain largely unknown. The present study analyzed a model of diet-induced obesity in mice lacking the TLR4/TLR2 co-receptor CD14. Six-week-old male mice lacking CD14 (n = 16) were allocated to either a control diet or a high-fat high-simple carbohydrate diet (5.4 kcal/g; 35% fat; 35% sucrose), and compared with C57BL/6 (WT; n = 15) controls. After 12 weeks, body composition, basal sympathetic activity, non-invasive blood pressure and glucose tolerance were evaluated. Hepatic and adipose tissues were collected for mRNA quantification, histology and LPS incubation. In both WT and CD14 knockout mice, obesity was accompanied by TLR2 and TLR4 upregulation. However, obese mice lacking CD14 presented decreased lipid and macrophage content in hepatic and adipose tissues, lower urinary levels of noradrenaline, decreased systolic blood pressure, reduced fasting plasma glucose and blunted glucose intolerance, compared with obese WT group. In the presence of exogenous sCD14, adipose tissue incubation with LPS-induced TLR2 and TNF-alpha upregulation in both WT and CD14 knockout obese mice. In our model of diet-induced obesity, mice lacking CD14 showed lower adiposity and hepatic steatosis, improved glucose homeostasis, blunted sympathetic overactivity and reduced blood pressure elevation. This was observed in the presence of preserved TLR4 and TLR2 gene expression, and intact TLR4 signaling pathways. These results suggest that CD14-mediated TLR activation might contribute to the cardiovascular and metabolic complications of obesity. | 18,761,356 |
A delay reaction-diffusion model of the dynamics of botulinum in fish. | A model of interaction between fish and a bacterium (Clostridium botulinum) responsible for avian botulism is introduced, considering diffusion of both fish and bacterium in water. The fish population moves randomly in water. Death fish disintegrate in water, at different locations, causing bacteria to diffuse through water and infect other fish. Existence of uniform steady states is investigated and the linearized stability of the positive uniform steady state is analyzed. A Hopf bifurcation is proved to occur from the uniform steady state when the bifurcation parameter, here the time delay, passes through a critical value and diffusion coefficients satisfy some conditions, that induces time oscillations of the populations. Comments on diffusion-driven instability are provided, and numerical simulations are carried out to illustrate the results. | 18,761,358 |
A Micro-Electrode Array device coupled to a laser-based system for the local stimulation of neurons by optical release of glutamate. | Optical stimulation is a promising approach to investigate the local dynamic responses of cultured neurons. In particular, flash photolysis of caged compounds offers the advantage of allowing the rapid change of concentration of either extracellular or intracellular molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. We describe here the use of an ultra-violet (UV) laser diode coupled to an optical fibre for the local activation of caged compounds combined with a Micro-Electrode Array (MEA) device. Local uncaging was achieved by UV irradiation through the optical fibre previously positioned by using a red laser diode. The size of the stimulation was determined using caged fluorescein, whereas its efficacy was tested by studying the effect of uncaging the neurotransmitter glutamate. Uncaged glutamate evoked neuronal responses that were recorded using either fluorescence measurements or electrophysiological recordings with MEAs, thus showing the ability of our system to induce local neuronal excitation. This method allows overcoming the limitations of the MEA system related to unfocused electrical stimulation and induction of electrical artefacts. In addition, the coupling of a UV laser diode to an optical fibre allows a precise local stimulation and a quick change of the stimulation point. | 18,761,373 |
Liquid state machines and cultured cortical networks: the separation property. | In vitro neural networks of cortical neurons interfaced to a computer via multichannel microelectrode arrays (MEA) provide a unique paradigm to create a hybrid neural computer. Unfortunately, only rudimentary information about these in vitro network's computational properties or the extent of their abilities are known. To study those properties, a liquid state machine (LSM) approach was employed in which the liquid (typically an artificial neural network) was replaced with a living cortical network and the input and readout functions were replaced by the MEA-computer interface. A key requirement of the LSM architecture is that inputs into the liquid state must result in separable outputs based on the liquid's response (separation property). In this paper, high and low frequency multi-site stimulation patterns were applied to the living cortical networks. Two template-based classifiers, one based on Euclidean distance and a second based on a cross-correlation were then applied to measure the separation of the input-output relationship. The result was over a 95% (99.8% when nonstationarity is compensated) input reconstruction accuracy for the high and low frequency patterns, confirming the existence of the separation property in these biological networks. | 18,761,392 |
Molecular cloning and functional characterization of cynomolgus monkey multidrug resistance-associated protein 2 (MRP2). | The monkey is an important experimental model in the pharmacological evaluation of new drugs. We isolated monkey multidrug resistance-associated protein 2 (MRP2) cDNA to examine expression profiles among various tissues and measured ATPase activity to assess substrate specificity. The amino acid sequence encoded by monkey MRP2 cDNA was very similar (96% identity) to the reported human MRP2 cDNA (GenBank accession no. NM_000392). The tissue distribution of MRP2 in monkeys was partially different from that in humans. We found relatively high expression of MRP2 in the monkey kidney and small intestine using Northern blotting. Substrate specificity was compared between human and monkey MRP2. The affinity of 17beta-estradiol 17-(beta-d-glucuronide), methotrexate, vinblastine, and probenecid to monkey MRP2 was higher than that to human MRP2. Functional and expression differences between human and monkey MRP2 should be incorporated into the evaluation of candidate drugs. | 18,761,402 |
The salt tolerant yeast Zygosaccharomyces rouxii possesses two plasma-membrane Na+/H+-antiporters (ZrNha1p and ZrSod2-22p) playing different roles in cation homeostasis and cell physiology. | Antiporters exporting Na(+) and K(+) in exchange for protons are conserved among yeast species. The only exception so far has been Zygosaccharomyces rouxii, an osmotolerant species closely related to Saccharomyces cerevisiae. Z. rouxii was described as possessing one plasma-membrane antiporter transporting only Na(+) (ZrSod2-22p in the CBS 732(T) type strain). We report the characterization of a second gene, ZrNHA1, encoding a new K(+)(Na(+))/H(+)-antiporter capable of both K(+) and Na(+) export. Synteny analyses suggested that ZrSOD2-22 originated by single duplication of the ZrNHA1 gene. Substrate specificities and transport properties of ZrNha1p and ZrSod2-22p were compared upon heterologous expression in S. cerevisiae, and then directly in Z. rouxii. Deletion mutants and phenotype analyses revealed that ZrSod2-22 antiporter is important for Na(+) detoxification, probably together with ZrEna1 ATPase; ZrNha1p is indispensable to maintain potassium homeostasis and ZrEna1p is not, in contrast to the situation in S. cerevisiae, involved in this function. | 18,761,413 |
Monoprotection of diols as a key step for the selective synthesis of unequally disubstituted diamondoids (nanodiamonds). | The monoprotection (desymmetrization) of diamondoid, benzylic, and ethynyl diols has been achieved using fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) under acidic conditions. This practical acid-catalyzed S(N)1 reaction opens the door for the synthesis of novel bifunctional diamondoids. With diamantane as an example, we show that the resulting monoethers can be used to prepare selectively, for instance, amino or nitro alcohols and unnatural amino acids. These are important compounds in terms of the exploration of electronic, pharmacological, and material properties of functionalized nanodiamonds. | 18,761,438 |
Fluorescence imaging of intracellular cadmium using a dual-excitation ratiometric chemosensor. | We described here a coumarin-based dual-excitation ratiometric probe for cadmium, CadMQ. This fluorescence sensor has high quantum yields of 0.59 and 0.70 in the metal-free and Cd2+-bound forms, respectively, and has a dissociation constant of 0.16 nM for Cd2+. CadMQ is cell permeable and locates within the acidic compartments of the cells. We further show that CadMQ is a useful tool to ratiometrically probe the change in the intracellular Cd2+ levels with the use of two excited wavelengths. | 18,761,452 |
Asymmetric intramolecular arylcyanation of unactivated olefins via C-CN bond activation. | The enantioselective, intramolecular arylcyanation of unactivated olefins via C-CN bond activation has been accomplished using a Ni(0) catalyst and BPh3 co-catalyst. High enantioselectivities are achieved using TangPHOS as a chiral ligand. This method allows the generation of two new C-C bonds and one new quaternary carbon stereogenic center in a single synthetic step, converting readily available benzonitrile substrates into 1,1-disubstituted indanes in 49-85% yield and 92-97% ee. | 18,761,453 |
The technique, validity and clinical use of the sweep VEP. | Vision scientists have concentrated on studying two visual functions when it comes to assessing the sensory visual development in human: visual acuity and contrast sensitivity. The methods used to measure these visual functions can be either behavioral or electrophysiological. A relatively new technique for measuring the visual acuity and contrast sensitivity electrophysiologically is the sweep visual evoked potential (sVEP). This paper is a review of the literature on the sVEP technique: stimulus parameters, threshold determination, validity and reliability of sVEP are discussed. Different studies using the sVEP to study the development of visual acuity, contrast sensitivity, and vernier acuity are presented. Studies have demonstrated that the sVEP is a potentially important tool for assessing visual acuity and contrast sensitivity in non-verbal individuals with disorders affecting their visual system. | 18,761,477 |
Assessing the optical performance of multifocal (diffractive) intraocular lenses. | While the optical performance of monofocal refractive lenses can be measured quite easily, more efforts are required to assess the performance of multifocal lenses, due to imaging to several foci. The purpose of this study was to develop a rugged test setup for evaluation of the optical properties of intraocular lenses (IOLs) in conformity to the International Standard ISO 11979. We built a test setup in order to measure the point spread function and to determine the modulation transfer function (MTF) of IOLs. We measured three multifocal IOLs with (1) a diffraction limited model cornea and (2) an individualized aspheric model cornea which shows a significant amount of spherical aberration. All the three IOL samples tested showed a different impact of spherical aberration on the MTF. The bispheric lenses (Alcon and Dr Schmidt) showed a degradation of the MTF and Strehl ratio with model (2) compared to model (1). In contrast, the MTF of the Tecnis lens, which has a prolate aspheric front surface, improved dramatically in combination with model (2). We demonstrated the functional capability of our measurement system by presentation of a set of working examples. Two different model corneas were used to study the influence of spherical aberration on the MTF of our working examples. An aspheric model cornea, which had already been shown to be suitable for testing monofocal aspherics, was shown to be well suited for testing aspheric multifocal lenses. | 18,761,484 |
Extranodal gammadelta-T-cell lymphoma in a dog with leishmaniasis. | An 8-year-old intact male mongrel dog with alopecia and weight loss was referred to the Veterinary Faculty of Naples. The dog had pale mucous membranes, enlarged prescapular lymph nodes, and splenomegaly. Laboratory abnormalities included anemia, thrombocytopenia, and hyperglobulinemia. Bone marrow aspirate smears contained numerous Leishmania amastigotes and an immunofluorescent antibody titer was strongly positive (1:1280) for leishmaniasis. The dog was treated with a combination of meglumine antimoniate and allopurinol for 60 days and showed clinical improvement. Two months after the end of treatment the dog was again referred because of relapse of leishmaniasis and the presence of a firm subcutaneous mass on the medial right thigh. Based on cytologic examination of fine needle aspirates of the mass, a diagnosis of large-cell lymphoma was made. Flow cytometry of tumor cells revealed gammadelta-T-cell lymphoma with a CD5+, CD3+, TCRgammadelta+, CD4-, CD8-, CD45RA+ immunophenotype. Using nested PCR, amastigotes were not detected in the neoplastic tissue. An association between leishmaniasis and hematopoietic tumors has been described rarely. gammadelta-T cells may be involved in the host response to this parasite, and prolonged antigenic stimulation and chronic immunosuppression (typical of leishmaniasis) play a crucial role in the etiopathogenesis of T-cell lymphoma. | 18,761,522 |
What is your diagnosis? Biopsy impression smear of a hepatic mass in a yearling Thoroughbred filly. | A 1-year-old Thoroughbred filly was presented to the Cornell University Hospital for Animals with a 10-day history of fever, diarrhea, inappetance, and hypodipsia. Clinical pathology abnormalities found by the referring veterinarian included erythrocytosis, hyperproteinemia, and increased serum gamma-glutamyltransferase and lactate dehydrogenase activities. At Cornell University, the laboratory abnormalities were confirmed and also included thrombocytosis and hypoglycemia. Erythrocytosis persisted despite vigorous fluid therapy. Ultrasound examination revealed an extremely enlarged liver with abnormal echogenicity and a 21 x 25-cm hepatic mass with varied echogenicity. Imprints of an ultrasound-guided biopsy of the mass revealed a neoplastic epithelial population of uncertain origin, although the cells did not resemble hepatocytes. Together with the presenting signs, signalment, ultrasonographic findings, and persistent erythrocytosis, the cytologic findings were considered to be most consistent with hepatoblastoma. Histopathologic examination of the mass at necropsy confirmed the diagnosis and findings also included bone marrow erythroid hyperplasia. Serum erythropoietin concentration was 28.0 mU/mL (reference interval 1.0-11.8 mU/mL), supporting erythropoietin production by the tumor and secondary inappropriate erythrocytosis. To our knowledge, this report is the first to document secondary erythrocytosis with increased erythropoietin concentration in a horse with hepatoblastoma, and also the first to describe the cytopathologic features of this rare tumor. | 18,761,530 |
Long-term safety, tolerability, and efficacy of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder. | To evaluate the long-term safety, tolerability, and efficacy of imidafenacin, a novel anti-muscarinic agent, in Japanese patients with overactive bladder. Men and women who had overactive bladder symptoms were enrolled for open-label treatment with 0.1 mg of imidafenacin twice daily for 52 weeks; the safety and efficacy of the treatment regimen were assessed. A total of 478 patients received the treatment and 376 patients completed the 52-week program. Imidafenacin was well tolerated, the most common adverse event being a dry mouth (40.2% of the patients). Compared with short-term treatment, long-term treatment did not produce an increase in the frequency of adverse events. Imidafenacin had no significant effects on the corrected QT interval, vital signs, results from laboratory tests, or post-void residual volume. A significant efficacy of imidafenacin was observed from week 4 through week 52. After 52 weeks, imidafenacin produced mean changes from baseline in the number of incontinence episodes (-83.51%), urgency incontinence episodes (-84.21%), voiding frequency (-2.35 micturitions/day), urgency episodes (-70.53%), and volume voided per micturition (28.99 mL). There were also significant reductions from baseline in all domains of the King's Health Questionnaire. Favorable safety, tolerability, and efficacy profiles for 0.1 mg of imidafenacin administered twice daily were maintained over 52 weeks in Japanese patients with overactive bladder. | 18,761,536 |
Eggshell pigmentation pattern in relation to breeding performance of blue tits Cyanistes caeruleus. | 1. We test the consequences, in terms of breeding success and parental effort, of eggshell pigmentation pattern in a hole-nesting bird, the blue tit Cyanistes caeruleus that lays eggs asymmetrically speckled with reddish spots (maculated eggs). 2. We assess the effect of distribution of spots (pigment 'spread') and spot size and pigment intensity (pigment 'darkness') on eggshell physical properties and breeding parameters concerning nestling condition, investment of parents in offspring care and reproductive output in two different habitat types: a deciduous oakwoodland and an evergreen forest. 3. Blue tit clutches with more widely distributed spots showed a thicker eggshell, a shorter incubation period, a lesser amount of mass loss per day and a higher hatching probability than those with spots forming a 'corona' ring. While eggs with larger and darker (more pigment intensity) spots showed a thicker eggshell and a shorter incubation period. In the light of 'signal function hypothesis', these egg traits may reflect female health status and, consequently, this could affect male parental effort. 4. Here we show supports for some of the necessary assumptions of this hypothesis. We found a positive relationship between egg pigment 'spread' and male but not female provisioning rates per day. On the other hand, pigment 'darkness' of blue tits' clutches was positively related to female tarsus length, while pigment 'spread' was positively related to clutch size, male body mass and nestling tarsus length. Our study shows that eggshell pigment 'spread' can be used as an indicator of clutch quality. Further investigations are needed to understand the role of calcium availability as possible causal agent of deviant eggs and its relation to the maculation phenomenon. | 18,761,537 |
Abortive aphthous-like oral lesions: an underreported initial presentation of pemphigus vulgaris. | Pemphigus vulgaris (PV) usually presents as non-healing, painful oral erosions, but transient or aphtha-like lesions are not exceptional at the very beginning of the disease leading to the common misdiagnosis of recurrent aphthous stomatitis (RAS). We designed this cross-sectional, questionnaire-based study to evaluate this underreported yet important presentation of PV. One hundred and eighty-five consecutive PV patients were interviewed and a questionnaire, comprising items related to the natural history of oral lesions, was filled in for each. Fourteen patients who had taken steroids (topical or systemic) before their final diagnosis were excluded. Twenty-three per cent of patients gave a history of transient aphthous-like lesions; 95% of them were misdiagnosed as aphthae. These lesions were especially reported by patients aged 40 years or older (P < 0.047). PV should be kept in mind as a rare differential diagnosis of transient oral ulcerations. We recommend careful observation of these patients and performing indirect immunofluorescence or desmoglein ELISA and even biopsy in atypical cases, to rule out PV especially in older patients and predisposed ethic groups. To find out the differential aspects of RAS and aphthous-like PV, a cohort study on RAS patients is suggested. | 18,761,538 |
Polymorphisms of interleukin-1 and interleukin-2 genes in patients with gastric cancer in Korea. | Interleukin (IL)-1 gene polymorphism has been reported to be associated with the increment of gastric cancer (GC) and the decrement of duodenal ulcers (DU). In addition, IL-2 is known to induce Helicobacter pylori (H. pylori)-associated gastric atrophy, but it is not known whether IL-2 gene polymorphism increases the risk of GC (GC) or peptic ulcer diseases. Therefore, we compared the genotypes of IL-1B, IL-1RN, and IL-2 gene polymorphisms with risk of gastric ulcers (GU), GC, and DU in Korean patients. In total, 116 GU, 122 GC, and 104 DU patients were included consecutively and compared with 100 healthy controls. Polymorphisms of the IL-1B-511/-31 gene, the penta-allelic variable number of tandem repeats of the IL-1RN gene, and the IL-2-330 gene were analyzed by polymerase chain reaction with restriction fragment length polymorphism or confronting two-pair primers methods. The age-sex-adjusted odds ratios (OR) for the IL-1B-511 T genotype relative to the C/C genotype (OR = 0.82, 95% confidence interval [CI] 0.41-1.65), IL-1RN*2 genotype relative to the L/L genotype (OR = 0.85, 95% CI 0.41-1.78), and IL-2-330 T genotype relative to the G/G genotype (OR = 1.94, 95% CI 0.76-4.96) were not increased in GC. There was also no significant difference in the genotypes of these cytokine polymorphisms between the study group (GU or DU) and control group. In addition, genotypic frequency was not associated with H. pylori positivity and histological type of GC. IL-1B-511, IL-1RN, and IL-2 genetic polymorphisms were not important contributors to the pathogenesis of GU, GC, and DU in Korean patients. | 18,761,558 |
Development of a re-positionable aortic stent-valve: a preliminary study in swine. | Placement of aortic stent-valves in the proper position is difficult due to the high velocity and oscillation of blood flow and anatomical characteristics. To address this problem, a re-positionable stent-valve was designed and examined in a preliminary animal experiment. Protocols for this animal study were approved by the institutional Animal Care and Use Committee. An umbrella-shaped polyurethane valve was attached at the tip of newly devised re-positionable metallic stent. The prosthesis (re-positionable stent-valve) was implanted in 5 female pigs via the right carotid artery using a 10-F introducer (Group A). As a control, the stent-without-valve was implanted in 4 female pigs (Group B). Efficacy of the valve was assessed by aortography and aortic pressure measurement. Animals were sacrificed 1 hour after stent-valve implantation for macroscopic examination. The stent-valve was successfully implanted in all pigs. In Group A, aortography showed good function of the polyurethane valve. No significant change in diastolic pressure was noted during valve testing. In Group B, aortography and aortic pressure measurement showed massive aortic regurgitation following dysfunction of the native aortic leaflets. Post-mortem examination showed small amounts of thrombus inside the polyurethane umbrella in Group A. Placement of the re-positionable stent-valve seems feasible and effective. However, the problem of thrombus formation inside the umbrella valve should be solved in future studies. | 18,761,562 |
The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. | In April 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine partnered to sponsor a 2-day workshop to revisit nomenclature, interpretation, and research recommendations for intrapartum electronic fetal heart rate monitoring. Participants included obstetric experts and representatives from relevant stakeholder groups and organizations. This article provides a summary of the discussions at the workshop. This includes a discussion of terminology and nomenclature for the description of fetal heart tracings and uterine contractions for use in clinical practice and research. A three-tier system for fetal heart rate tracing interpretation is also described. Lastly, prioritized topics for future research are provided. | 18,761,565 |
Immediate implant placement: clinical decisions, advantages, and disadvantages. | Implant placement in fresh extraction sockets in conjunction with appropriate guided bone regeneration is well documented. The decision to extract teeth and replace them with immediate implants is determined by many factors, which ultimately affect the total treatment plan. The goal of this article is to review some of the important clinical considerations when selecting patients for immediate implant placement, and to discuss the advantages and disadvantages of this mode of therapy. | 18,761,580 |
Psychophysiological assessment of sexual function in women after radiotherapy and total mesorectal excision for rectal cancer: a pilot study on four patients. | The potential contribution of psychological and anatomical changes to sexual dysfunction in female patients following short-term preoperative radiotherapy (5 x 5 Gy) and total mesorectal excision (TME) is not clear. Aim. In this study we assessed female sexual dysfunction in patients who underwent radiotherapy and TME for rectal cancer. Genital arousal was assessed using vaginal videoplethysmography. Sexual functioning was examined in four patients who had rectal cancer and underwent radiotherapy and TME. All investigations were done at least 15 months after treatment. The results were compared with an age-matched group of 18 healthy women. The patients and healthy controls showed comparable changes in vaginal vasocongestion during sexual arousal, though three out of four patients showed a lower mean spectral tension (MST) of the vaginal pulse compared with healthy controls. Subjective sexual arousal was equivalent between the two groups. In this study the changes of genital and subjective sexual arousal after erotic stimulus condition between patients and healthy controls were not different, though lower MST of the vaginal pulse was found in three out of four patients compared with healthy women. Additional work, however, must be performed to clarify the mechanisms of sexual dysfunction following treatment of rectal cancer. | 18,761,589 |
Circadian variation of rectal sensitivity and gastrointestinal peptides in healthy volunteers. | The aim of our study was to identify diurnal variation of perception of rectal distension and the release of gastroenteropancreatic hormones. In 12 healthy male volunteers (25 years, range 22-32), a rectal balloon distension was performed. Rectal perception thresholds (minimal, urge and pain) and rectal compliance were double-measured with a computer-controlled barostat at seven standardized time points during the day (from 16.00 to 14.00 hours the following day). Blood samples were taken 30 min before and after each rectal distension procedure to determine plasma levels of cholecystokinin (CCK), pancreatic polypeptide (PP) and motilin. Sensory thresholds for urge and pain varied significantly with the time of day, with higher threshold levels in the evening than in the morning hours. Bowel wall compliance showed as well-significant variance at pain threshold and was higher during daytime than in the evening or at night. In contrast to motilin, release of CCK and PP also showed a significant variation depending on daytime. Perception of rectal distension stimuli as well as compliance was independent of intake of food and peptide hormone levels, but CCK and PP levels increased with food, and PP levels decreased with rectal distension. Significant differences in the perception of rectal distension stimuli for urge and pain depending on daytime were found, but the release of gastrointestinal peptides seemed not to be involved. This circadian variation needs to be taken into account in patients and volunteer studies. | 18,761,628 |
Insulin detemir is characterized by a more reproducible pharmacokinetic profile than insulin glargine in children and adolescents with type 1 diabetes: results from a randomized, double-blind, controlled trial. | Insulin detemir (detemir) has previously been shown to be associated with lower within-subject variability compared with other basal insulin preparations in adults with type 1 diabetes mellitus (T1DM). This randomized, double-blind, crossover trial compared the within-subject variability of detemir and insulin glargine (glargine) in pharmacokinetic properties in children and adolescents with T1DM. The trial enrolled 32 children and adolescents (19 girls and 13 boys; mean +/- SD: age 13 +/- 2.5 yr and T1DM duration 6.3 +/- 3.0 yr) with a hemoglobin A1c (HbA1c) of 7.9 +/- 1.0%. Participants were randomized to a specific treatment sequence in which a dose of 0.4 U/kg of detemir and glargine was injected subcutaneously 24 h apart at each of two dosing visits. Insulin concentrations were measured at frequent intervals for a period of 16-h post-dosing. Detemir showed statistically significantly less within-subject variability compared with glargine with a 3.1-fold and 2.9-fold lower coefficient of variation (CV, %) for the area under the concentration-time curve [AUC((0-16) (h))] and the maximum concentration (C(max)), respectively. Separate analyses demonstrated a 2.5-fold and 2.9-fold lower CV (%) with detemir in children (8-12 yr) and a 4-fold and 3.8-fold lower CV (%) with detemir in adolescents (13-17 yr). No safety concerns were raised during the trial. In conclusion, within-subject variability in pharmacokinetic properties was significantly lower for detemir than for glargine in children and adolescents with T1DM. This indicates a less variable absorption with detemir, which is expected to be associated with a more predictable therapeutic effect also in this population. | 18,761,644 |
Assessment of risk factors of poor metabolic control in type 1 diabetic children assisted in a public hospital in Argentina. | To evaluate predictive risk variables of poor diabetes control that are present at the onset of the disease. A prospective cohort study was carried out in a population of children with type 1 diabetes mellitus by means of a survey with information related to the clinical control of the patients, the sociodemographic and economic situations of their families, and the importance that the families attached to health care. The sample population had had the disease for over 2 yr, had no associated pathology, and was followed in an Argentinean hospital. Data from 148 patients, 71 male (48%), were collected, with a mean hemoglobin A1c (HbA1c) of 9.3 +/- 1.62%. Patients with HbA1c <8.4% (25th percentile) were considered as having better metabolic control (BC), and those with HbA1c >10% (75th percentile) were considered with poorer control (PC). PC was significantly associated with the fact that the patients' biological parents did not live together (p = 0.01) and had not done the diabetic education together at debut of diabetes (p = 0.007). A linear regression model was used to analyze predictors of BC: presence of both parents during diabetes instruction (OR: 3.82), both parents lived together with the patient (OR: 2.39), and lower age of patients (OR: 0.89). Predictors of PC were unsatisfied basic food needs (OR: 4.33) and mothers' low level of education (OR: 2.13). This study showed that socioeconomic and familial factors were strongly associated with metabolic control, and they will allow us to make an early detection of those patients who are more susceptible of having poor progression of diabetes. | 18,761,645 |
The role of p53 in pigmentation, tanning and melanoma. | p53 has a central role in skin pigmentation and may impact on melanoma at all stages, however, as it's mutation frequency in melanoma is low, it's role has been somewhat under-appreciated. During normal skin function, p53 in the keratinocyte is a transducer of the skin tanning signal and an essential component of what is effectively a keratinocyte-melanocyte signaling cycle that regulates skin pigmentation. It is clear that this cycle functions optimally in skin of dark pigmentation. When melanin biosynthesis is genetically disrupted in skin of white complexion, we propose that this cycle operates as a promoter of melanocyte proliferation. The cell autonomous function of p53 in melanocytes is not well described, however, the balance of the evidence suggests that p53 is an effective tumor suppressor and the myriad of mechanisms by which the p53 pathway may be dysregulated in tumors attests to it importance as a tumor suppressor. In this review, we outline the known mechanisms that impair p53 itself and its immediate regulators or target genes during melanomagenesis. Due to the importance of this pathway, it is clear that p53 disruptions may relate directly to a patient's prognosis. This pathway will continue to be a focus of investigation, particularly with respect to targeted experimental chemotherapeutics. | 18,761,658 |
Linkage and association study of late-onset Alzheimer disease families linked to 9p21.3. | A chromosomal locus for late-onset Alzheimer disease (LOAD) has previously been mapped to 9p21.3. The most significant results were reported in a sample of autopsy-confirmed families. Linkage to this locus has been independently confirmed in AD families from a consanguineous Israeli-Arab community. In the present study we analyzed an expanded clinical sample of 674 late-onset AD families, independently ascertained by three different consortia. Sample subsets were stratified by site and autopsy-confirmation. Linkage analysis of a dense array of SNPs across the chromosomal locus revealed the most significant results in the 166 autopsy-confirmed families of the NIMH sample. Peak HLOD scores of 4.95 at D9S741 and 2.81 at the nearby SNP rs2772677 were obtained in a dominant model. The linked region included the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), which has been suggested as an AD candidate gene. By re-sequencing all exons in the vicinity of CDKN2A in 48 AD cases, we identified and genotyped four novel SNPs, including a non-synonymous, a synonymous, and two variations located in untranslated RNA sequences. Family-based allelic and genotypic association analysis yielded significant results in CDKN2A (rs11515: PDT p = 0.003, genotype-PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p. | 18,761,660 |
Diversity and expression of nitrogen fixation genes in bacterial symbionts of marine sponges. | Marine sponges contain complex assemblages of bacterial symbionts, the roles of which remain largely unknown. We identified diverse bacterial nifH genes within sponges and found that nifH genes are expressed in sponges. This is the first demonstration of the expression of any protein-coding bacterial gene within a sponge. Two sponges Ircinia strobilina and Mycale laxissima were collected from Key Largo, Florida and had delta(15)N values of c. 0-1 per thousand and 3-4 per thousand respectively. The potential for nitrogen fixation by symbionts was assessed by amplification of nifH genes. Diverse nifH genes affiliated with Proteobacteria and Cyanobacteria were detected, and expression of nifH genes affiliated with those from cyanobacteria was detected. The nifH genes from surrounding seawater were similar to those of Trichodesmium and clearly different from the cyanobacterial nifH genes detected in the two sponges. This study advances understanding of the role of bacterial symbionts in sponges and suggests that provision of fixed nitrogen is a means whereby symbionts benefit sponges in nutrient-limited reef environments. Nitrogen fixation by sponge symbionts is possibly an important source of new nitrogen to the reef environment that heretofore has been neglected and warrants further investigation. | 18,761,667 |
Steering patients to safer hospitals? The effect of a tiered hospital network on hospital admissions. | To determine if a tiered hospital benefit and safety incentive shifted the distribution of admissions toward safer hospitals. A large manufacturing company instituted the hospital safety incentive (HSI) for union employees. The HSI gave union patients a financial incentive to choose hospitals that met the Leapfrog Group's three patient safety "leaps." The analysis merges data from four sources: claims and enrollment data from the company, the American Hospital Association, the AHRQ HCUP-SID, and a state Office of the Insurance Commissioner. Changes in hospital admissions' patterns for union and nonunion employees using a difference-in-difference design. We estimate the probability of choosing a specific hospital from a set of available alternatives using conditional logistic regression. Patients affiliated with the engineers' union and admitted for a medical diagnosis were 2.92 times more likely to select a hospital designated as safer in the postperiod than in the preperiod, while salaried nonunion (SNU) patients (not subject to the financial incentive) were 0.64 times as likely to choose a compliant hospital in the post- versus preperiod. The difference-in-difference estimate, which is based on the predictions of the conditional logit model, is 0.20. However, the machinists' union was also exposed to the incentive and they were no more likely to choose a safer hospital than the SNU patients. The incentive did not have an effect on patients admitted for a surgical diagnosis, regardless of union status. All patients were averse to travel time, but those union patients selecting an incentive hospital were less averse to travel time. Patient price incentives and quality/safety information may influence hospital selection decisions, particularly for medical admissions, though the optimal incentive level for financial return to the plan sponsor is not clear. | 18,761,676 |
Contact-dependent growth inhibition requires the essential outer membrane protein BamA (YaeT) as the receptor and the inner membrane transport protein AcrB. | Contact-dependent growth inhibition (CDI) is a phenomenon by which bacterial cell growth is regulated by direct cell-to-cell contact via the CdiA/CdiB two-partner secretion system. Characterization of mutants resistant to CDI allowed us to identify BamA (YaeT) as the outer membrane receptor for CDI and AcrB as a potential downstream target. Notably, both BamA and AcrB are part of distinct multi-component machines. The Bam machine assembles outer membrane beta-barrel proteins into the outer membrane and the Acr machine exports small molecules into the extracellular milieu. We discovered that a mutation that reduces expression of BamA decreased binding of CDI+ inhibitor cells, measured by flow cytometry with fluorescently labelled bacteria. In addition, alpha-BamA antibodies, which recognized extracellular epitopes of BamA based on immunofluorescence, specifically blocked inhibitor-target cells binding and CDI. A second class of CDI-resistant mutants identified carried null mutations in the acrB gene. AcrB is an inner membrane component of a multidrug efflux pump that normally forms a cell envelope-spanning complex with the membrane fusion protein AcrA and the outer membrane protein TolC. Strikingly, the requirement for the BamA and AcrB proteins in CDI is independent of their multi-component machines, and thus their role in the CDI pathway may reflect novel, import-related functions. | 18,761,695 |
The major and minor wall teichoic acids prevent the sidewall localization of vegetative DL-endopeptidase LytF in Bacillus subtilis. | Cell separation in Bacillus subtilis depends on specific activities of DL-endopeptidases CwlS, LytF and LytE. Immunofluorescence microscopy (IFM) indicated that the localization of LytF depended on its N-terminal LysM domain. In addition, we revealed that the LysM domain efficiently binds to peptidoglycan (PG) prepared by chemically removing wall teichoic acids (WTAs) from the B. subtilis cell wall. Moreover, increasing amounts of the LysM domain bound to TagB- or TagO-depleted cell walls. These results strongly suggested that the LysM domain specifically binds to PG, and that the binding may be prevented by WTAs. IFM with TagB-, TagF- or TagO-reduced cells indicated that LytF-6xFLAG was observed not only at cell separation site and poles but also as a helical pattern along the sidewall. Moreover, we found that LytF was localizable on the whole cell surface in TagB-, TagF- or TagO-depleted cells. These results strongly suggest that WTAs inhibit the sidewall localization of LytF. Furthermore, the helical LytF localization was observed on the lateral cell surface in MreB-depleted cells, suggesting that cell wall modification by WTAs along the sidewall might be governed by an actin-like cytoskeleton homologue, MreB. | 18,761,696 |
Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid. | Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histological features of the disease such as Lewy body like inclusions and long-term inflammatory changes are lacking. Fornai et al. [Proc. Natl Acad. Sci. USA 102 (2005), 3413] suggested that continuous delivery of MPTP with Alzet osmotic minipumps may possibly circumvent these problems. Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable. | 18,761,710 |
Constitutive histamine H2 receptor activity regulates serotonin release in the substantia nigra. | The substantia nigra pars reticulata (SNr) forms a principal output from the basal ganglia. It also receives significant histamine (HA) input from the tuberomammillary nucleus whose functions in SNr remain poorly understood. One identified role is the regulation of serotonin (5-HT) neurotransmission via the HA-H(3) receptor. Here we have explored regulation by another HA receptor expressed in SNr, the H(2)-receptor (H(2)R), by monitoring electrically evoked 5-HT release with fast-scan cyclic voltammetry at carbon-fiber microelectrodes in SNr in rat brain slices. Selective H(2)R antagonists (inverse agonists) ranitidine and tiotidine enhanced 5-HT release while the agonist amthamine suppressed release. The 'neutral' competitive antagonist burimamide alone was without effect but prevented ranitidine actions indicating that inverse agonist effects result from constitutive H(2)R activity independent of HA tone. H(2)R control of 5-HT release was most apparent (from inverse agonist effects) at lower frequencies of depolarization (< or = 20 Hz), and prevailed in the presence of antagonists of GABA, glutamate or H(3)-HA receptors. These data reveal that H(2)Rs in SNr are constitutively active and inhibit 5-HT release through H(2)Rs on 5-HT axons. These data may have therapeutic implications for Parkinson's disease, when SNr HA levels increase, and for neuropsychiatric disorders in which 5-HT is pivotal. | 18,761,715 |
Assessment of the effectiveness of radon screening programs in reducing lung cancer mortality. | The present study was aimed at assessing the health consequences of the presence of radon in Quebec homes and the possible impact of various screening programs on lung cancer mortality. Lung cancer risk due to this radioactive gas was estimated according to the cancer risk model developed by the Sixth Committee on Biological Effects of Ionizing Radiations. Objective data on residential radon exposure, population mobility, and tobacco use in the study population were integrated into a Monte-Carlo-type model. Participation rates to radon screening programs were estimated from published data. According to the model used, approximately 10% of deaths due to lung cancer are attributable to residential radon exposure on a yearly basis in Quebec. In the long term, the promotion of a universal screening program would prevent less than one death/year on a province-wide scale (0.8 case; IC 99%: -3.6 to 5.2 cases/year), for an overall reduction of 0.19% in radon-related mortality. Reductions in mortality due to radon by (1) the implementation of a targeted screening program in the region with the highest concentrations, (2) the promotion of screening on a local basis with financial support, or (3) the realization of systematic investigations in primary and secondary schools would increase to 1%, 14%, and 16.4%, respectively, in the each of the populations targeted by these scenarios. Other than the battle against tobacco use, radon screening in public buildings thus currently appears as the most promising screening policy for reducing radon-related lung cancer. | 18,761,730 |
Carcinoid tumour of the appendix in children: a case report. | Carcinoids are the most common tumours of the appendix. These tumours show prevalence in white children. The clinical presentation of the appendiceal carcinoids is similar to that of acute appendicitis, although in many cases the tumour is diagnosed incidentally during an operation. The diagnosis should be confirmed histologically. The prognosis in patients with local disease is excellent. In small lesions isolated appendicectomy is considered as the most appropriate treatment, while in larger lesions right colectomy should be performed. We report a case of a carcinoid tumour in the tip of the appendix of a thirteen year old girl which was diagnosed intraoperatively. The patient received isolated appendicectomy due to the small size of the lesion. Ten years after the operation there is no evidence of recurrence or metastases, and the patient is considered free of disease. | 18,761,734 |
Methodology capture: discriminating between the "best" and the rest of community practice. | The methodologies we use both enable and help define our research. However, as experimental complexity has increased the choice of appropriate methodologies has become an increasingly difficult task. This makes it difficult to keep track of available bioinformatics software, let alone the most suitable protocols in a specific research area. To remedy this we present an approach for capturing methodology from literature in order to identify and, thus, define best practice within a field. Our approach is to implement data extraction techniques on the full-text of scientific articles to obtain the set of experimental protocols used by an entire scientific discipline, molecular phylogenetics. Our methodology for identifying methodologies could in principle be applied to any scientific discipline, whether or not computer-based. We find a number of issues related to the nature of best practice, as opposed to community practice. We find that there is much heterogeneity in the use of molecular phylogenetic methods and software, some of which is related to poor specification of protocols. We also find that phylogenetic practice exhibits field-specific tendencies that have increased through time, despite the generic nature of the available software. We used the practice of highly published and widely collaborative researchers ("expert" researchers) to analyse the influence of authority on community practice. We find expert authors exhibit patterns of practice common to their field and therefore act as useful field-specific practice indicators. We have identified a structured community of phylogenetic researchers performing analyses that are customary in their own local community and significantly different from those in other areas. Best practice information can help to bridge such subtle differences by increasing communication of protocols to a wider audience. We propose that the practice of expert authors from the field of evolutionary biology is the closest to contemporary best practice in phylogenetic experimental design. Capturing best practice is, however, a complex task and should also acknowledge the differences between fields such as the specific context of the analysis. | 18,761,740 |
Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study. | To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 - 39 days) and the median total RT dose was 40 Gy (range, 36 - 60 Gy). Median lacrimal gland exposure was 35.9 Gy (range, 16.8 - 42.6 Gy). Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome. | 18,761,746 |
Primary carcinoid tumour of nasal septum. | We present the first reported case of primary carcinoid tumour of the nasal septum. Case report of our experience of a carcinoid tumour of the nasal septum. We discuss our clinical, radiological and pathological findings. An 83-year-old woman presented with a history of left-sided nasal blockage. Clinical examination showed a unilateral, left-sided nasal polyp. Further imaging and histological analysis confirmed this to be a carcinoid tumour. Carcinoid tumours outside the gastrointestinal tract are rare. There have been reports of carcinoid tumours in the head and neck region, but no published cases occurring in the nasal septum. Our management involved wide surgical resection with regular follow up to monitor for recurrence and for the development of carcinoid syndrome. Four years from initial presentation, the patient remained free of the primary tumour and had displayed no signs or symptoms suggestive of carcinoid syndrome. To the authors' best knowledge, and after searching the world literature, the presented case represents the first report of primary carcinoid tumour of the nasal septum. Despite its rarity, this tumour should be considered as part of the differential diagnosis, as timely recognition and intervention are critical for successful treatment. | 18,761,767 |
Porcine circoviruses: a minuscule yet mammoth paradox. | Porcine circovirus type 2 (PCV2) is the primary causative agent for porcine circovirus-associated disease (PCVAD). PCVAD has been the cause of considerable economic losses to the pork industry worldwide. The disease is primarily characterized by wasting, enlarged lymph nodes, jaundice and weight loss in affected weanling pigs. Several other complex syndromes involving reproductive failure, enteritis, pneumonia and necrotizing dermatitis have also been associated with PCV2 infection. Lymphoid depletion, which is the hallmark lesion of PCVAD, predisposes the host to immunosuppression. Disease progression is further complicated by co-infections with other bacterial and viral pathogens. Despite the availability of effective vaccines for the last 2 years, newly emerging strains of the virus have been reported to cause more severe outbreaks in parts of the USA and Canada. While knowledge of the biology and pathogenesis of PCV2 has progressed considerably over the last 12 years since the disease was recognized, many questions still remain to be answered. | 18,761,774 |
[Effects of occupation on health of traffic policemen in a city]. | To investigate the health and work status of traffic policemen in a city, and analyze the effect of the occupation on health of them. The prevalent investigation was used to investigate the health status of on-the-job traffic policemen and the effect of the occupation on the health of traffic policemen was studied. Among 4486 traffic policemen, 1604 working outside. The average time of working outside was (12.0 +/- 7.9) years and the average time of standing was (7.0 +/- 1.7) hours/day. The incidence of naso-pharyngitis, arthropathy, photosensitive dermatitis, heat stroke and chilblain, noise-induced deafness in the outside-traffic policemen were higher than that of the policemen working indoors. Eye diseases were higher in those who worked outside for 20-25 years. The varicosis of the lower extremity was higher in those who stood outside over 4 hours every day. The average period of onset of disease was 7-8 years. The occupational stress of outside-traffic policemen was bigger in the city. The environmental pollution and the bad condition are the risky factors of 8 kinds of diseases among traffic policemen. The average period of onset of the disease is 7-8 years. | 18,761,799 |
[Application of the medicine profile in an ambulatory setting]. | A person with a digital signature can access his or her own personal electronic medicinal profile (PEM) which can also be accessed by the person's prescribing doctors. The PEM provides an overview and contains an overview of the prescription medicine sold to the patient over the previous two years. Randomly-selected geriatric ambulatory patients were included. Accordance between physicians' medication records and the PEM was calculated. Moreover, the prescribing ambulatory doctor and the patient's general practitioner were asked if the PEM could contribute with non-recognized information about patients' prescription medicine. We found a 13-20% discrepancy between physicians' medication records and PEMs, involving 50-60% of the patients. In most cases, access to the PEM significantly corrected the discrepancies. Discrepancies were neither correlated to gender, age nor to the amount of prescription medicine. Discrepancies were judged to be serious or influential. The PEM provides insight into unrecognized information about patients' prescription medicine and access to the PEM bridges the gap between primary and secondary health care. Easier access to the digital signature, inclusion of over-the-counter drugs, and improved protection against misuse would further improve the PEM and ensure access to updated drug information. | 18,761,822 |
[Transient elastography for diagnosing liver fibrosis]. | Liver fibrosis is a known complication to chronic liver diseases. The reference method for diagnosing and assessing the progression of fibrosis or cirrhosis is histological examination of liver tissue. Since there is a slight but significant risk from every invasive procedure, a non-invasive method has been sought. Transient elastography is a new noninvasive method of assessing fibrosis by measuring liver stiffness. The method is described in the article, as well as its diagnostic sensitivity and specificity, and the reproducibility is briefly discussed by evaluating some studies. | 18,761,829 |
[Breakfast habits and overweight in Danish schoolchildren. The role of socioeconomic positions]. | The prevalence of adolescent overweight has increased dramatically, and in many industrialised countries overweight is most prevalent in lower socioeconomic positions (SEP). It is therefore important to examine determinants of overweight and to understand the mechanisms behind social patterning. Several studies show that skipping breakfast is a risk factor for overweight. However, it is unknown whether this association is consistent across SEP. The aim was to examine the association between the frequency of eating breakfast and overweight among Danish adolescents and to examine whether the association differs between different SEP. The study is a cross-sectional school survey including all 11, 13, and 15-year-olds in a random sample of schools in Denmark, participation rate 89.3%, n=4,824. The study was the sixth Danish contribution to the international research project Health Behaviour in School-aged Children (HBSC). SEP was measured by parental occupational class and the frequency of breakfast was measured by the weekly number of weekdays on which breakfast was eaten. Skipping breakfast is associated with overweight. The OR (95% CI) for overweight was 1.80 (1.38-2.36) among students who only ate breakfast 0-1 weekday per week. Frequent consumption of breakfast is less protective against overweight among low-SEP schoolchildren than high-SEP schoolchildren. No former studies have analysed the influence of SEP on the association between skipping breakfast and overweight. We found that frequent consumption of breakfast is most protective against overweight among high-SEP schoolchildren. | 18,761,839 |
[Analysis of deaths during hospitalization and after discharge from hospital]. | Analysis of deaths during and up to one month after discharge from hospital. For 2006, all deaths during and up to one month after discharge were identified for patients admitted to hospital in Roskilde or Køge. Age, acute or planned hospitalisation, duration of in-hospital stay, department of discharge and main diagnose were registered. Out of 50,302 hospitalisations, 2.2% had a fatal outcome during hospitalisation, whereas 2.1% died within the following month. During hospitalisation, the proportion of deaths among patients with either planned or acute admission was 1.1% and 2.6%, respectively. For several diagnose groups the risk of death during the first month after discharge was higher than that of fatal outcome during hospitalisation. The diagnose groups most frequently related to fatal outcome were cancers, infectious diseases, cardiovascular diseases and respiratory diseases. Pneumonia was the most prevalent benign diagnosis for fatal cases during hospitalisation. Data are provided for mortality related to diagnose and age group. The incidence of fatal outcome increased with the length of in-patient stay. Analysis of fatality rates also during planned hospitalisations and within the first month after acute as well as planned hospitalisations should be in focus when planning quality improvement projects. | 18,761,842 |
[Whole-body magnetic resonance angiography]. | Whole-body magnetic resonance angiography (WB-MRA) is a new approach for diagnosing atherosclerosis. Through utilisation of fast whole-body MRI systems, the arterial system, excluding the intracranial and coronary arteries, can be investigated in one examination. WB-MRA has the potential of replacing conventional catheter-based angiography in the diagnostic workup of patients with atherosclerotic disease. Developments in MRI contrast agents and MRI systems may further improve WB-MRA. | 18,761,843 |
[Rabies in a cat in Greenland]. | We describe the first case of rabies diagnosed in a cat in Greenland. The cat showed aggressive behaviour one month after the visit of a rabid fox on the premises. Rabies is enzootic in Greenland, the arctic fox being the natural host of rabies virus. Cats are imported in increasing numbers to Greenland and the reported case stresses the need for concern in relation to a hitherto unrecognised risk of exposure to rabies virus and stresses the need to comply with the obligatory anti-rabies vaccination regimes for cats in Greenland. | 18,761,847 |
[Clinical aspects of Tourette syndrome]. | Tourette syndrome (TS) is a hereditary, chronic, neurobiological disease, characterized by the presence of motor and vocal tics. The disease is often accompanied by other symptoms: Attention Deficit Hyperactive Disorder (ADHD), Obsessive Compulsive Disorder (OCD), sleeping disorders, learning disabilities, speech disfluencies, outbursts of extreme anger and behavioural problems. Treatment must be multidisciplinary. The most disabling symptom should be treated medically and the drug of first choice depends on the pathophysiology of this symptom. | 18,761,861 |
[Complicated course after conservative treatment of incarcerated inguinal hernia]. | We report a case of intestinal perforation due to manual reduction of incarcerated inguinal hernia. Explorative laparotomy was delayed and first attempted after 21 hours. The patient died as a result of peritonitis. If conservative treatment of incarcerated inguinal hernia is considered, this should be done with caution. When successful, possibility of reduction of non-vital organ should be eliminated. Patient must be informed about symptoms and risks, otherwise hospitalisation can be considered. | 18,761,865 |
[Intestinal duplication--an important differential diagnosis to intussusception]. | This is a case report on a 6-month-old child with an intestinal duplication cyst (ID), initially diagnosed as intussusception. As the patient failed to improve clinically after an apparently successful enema reduction, surgery was performed and an ID was found causing compression and strangulation of the ileum. ID should be considered in small children presenting with acute abdomen. This history also emphasises the need to consider alternative diagnosis to intussusception when initial enema reduction fails to relieve symptoms. | 18,761,866 |
[Surgical correction of pectus carinatum]. | Pectus carinatum (PC) is a protrusion of the sternum due to overgrowth of the costal cartilages. It can have considerable psychological and somatic impact on the patient. Many physicians are unaware of the beneficial effects and low comorbidity related to surgical correction and therefore erroneously advise patients against the operation. We report the preliminary experience with 26 consecutive patients operated for PC at our Department between 1 April 2006 and 1 April 2007. Surgery was performed by a modified Ravitch and Welch technique. The mean age was 15 years (13-21), and 92% of the patients were boys. We obtained excellent cosmetic results in the majority of patients (92%), no major complications, no major pain complaints and short hospital stays for all patients. Patients who are psychologically or physically impaired by this deformity should be referred for surgical evaluation. | 18,761,868 |
[Primary childhood vasculitis--new classification criteria]. | Primary vasculitis is seen in both adults and children, but some of the diseases like Kawasaki disease occur primarily in children. The Chapel Hill Classification Criteria for primary vasculitis refers to the size of vessels but has not been validated in children. Recently, new criteria for the classification of childhood vasculitides have been proposed by a working group of the Pediatric Rheumatology European Society and the EULAR Standing Committee on Paediatric Rheumatology. This review describes primary vasculitides from a pediatric perspective referring to the new consensus criteria. | 18,761,873 |
Salmonella infections associated with reptiles: the current situation in Europe. | Salmonella infections are caused by consumption of contaminated food, person-to-person transmission, waterborne transmission and numerous environmental and animal exposures. Specifically, reptiles and other cold blooded animals (often referred to as "exotic pets") can act as reservoirs of Salmonella, and cases of infection have been associated with direct or indirect contact with these animals. Approximately 1.4 million human cases of Salmonella infection occur each year in the United States and it has been estimated that 74,000 are a result of exposure to reptiles and amphibians. Regular case reports of reptile-associated salmonellosis in the US are available for the period 1994-2002. Cases of Salmonella infection attributed to direct or indirect contact with reptiles or other exotic pets have been described in a number of European countries, too but a more comprehensive overview of the magnitude of this problem in Europe is lacking. In total, 160,649 human cases of salmonellosis were reported in 2006 in the then 25 European Union Member States, Bulgaria, Romania, Iceland, Liechtenstein and Norway. | 18,761,944 |
p53 strikes mTORC1 by employing sestrins. | The guardian of the genome (p53) elicits cell-cycle checkpoints in response to genotoxic stress. p53 also induces a metabolic checkpoint by inhibiting the mammalian target of rapamycin complex 1 (mTORC1). Recent results by Budanov and Karin, (2008) reveal that p53 exerts its effect on mTORC1 through sestrin1 and sestrin2. | 18,762,019 |
TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. | Calcium signaling controls multiple cellular functions and is regulated by the release from internal stores and entry from extracellular fluid. In bone, osteoclast differentiation is induced by RANKL (receptor activator of NF-kappaB ligand)-evoked intracellular Ca(2+) oscillations, which trigger nuclear factor-activated T cells (NFAT) c1-responsive gene transcription. However, the Ca(2+) channels involved remain largely unidentified. Here we show that genetic ablation in mice of Trpv4, a Ca(2+)-permeable channel of the transient receptor potential (TRP) family, increases bone mass by impairing bone resorption. TRPV4 mediates basolateral Ca(2+) influx specifically in large osteoclasts when Ca(2+) oscillations decline. TRPV4-mediated Ca(2+) influx hereby secures intracellular Ca(2+) concentrations, ensures NFATc1-regulated gene transcription, and regulates the terminal differentiation and activity of osteoclasts. In conclusion, our data indicate that Ca(2+) oscillations and TRPV4-mediated Ca(2+) influx are sequentially required to sustain NFATc1-dependent gene expression throughout osteoclast differentiation, and we propose TRPV4 as a therapeutic target for bone diseases. | 18,762,026 |
Microtensile bond strengths and scanning electron microscopic evaluation of self-adhesive and self-etch resin cements to intact and etched enamel. | The longevity of indirect adhesively cemented restorations is directly related to the bond quality of resin cements to dental tissues. Bonding to cervical enamel can generate significantly lower bond strengths than bonding to other enamel areas. The effect of enamel pretreatment on bond strengths of self-etch and self-adhesive resin cements to cervical enamel remains undetermined. The purpose of this study was to evaluate cervical enamel bond strengths of self-adhesive, self-etch resin cements according to acid pretreatment, using a total-etch resin cement as the control. The proximal surfaces of 20 extracted molars were sectioned to obtain 40 enamel rectangles with an area of 8.0 x 4.0 mm. The rectangular enamel specimens were assigned to 1 of 5 enamel experimental groups: intact enamel + RelyX Unicem (UN), etched enamel + UN (UNpa), intact enamel + Multilink (ML), etched enamel + ML (MLpa), and the total-etch-based RelyX ARC (RX; control group). Standard 8.0 x 4.0 x 6.0-mm composite resin blocks (Z250) were cemented to all specimens. The bonded enamel surfaces were sectioned into sticks with a cross-section of 0.8 +/-0.2 mm(2) and tested to failure in tension mode at a crosshead speed of 1 mm/min. The data were submitted to 1-way analysis of variance (ANOVA), followed by Tukey's HSD post hoc test (alpha=.05). Additionally, the enamel etching pattern was investigated for all experimental groups using field-emission electron microscopy. Statistical analysis showed significant differences among different resin cements (P<.001) and phosphoric acid etching (P<.002). The highest mean (SD) bond strengths were obtained with UNpa (32.92 (4.23)) > RX (19.40 (9.47)). Acid etching of enamel before application of self-etch resin cement did not improve the mean bond strengths (SD) for self-etch resin cement [ML (5.38 (5.97)); MLpa (5.23 (1.1))]. Self-adhesive and self-etch resin cements yielded the lowest significant mean bond strengths (SD) when applied on intact enamel: UN (13.03 (2.82)) > ML (5.38 (5.97)). Scanning electron microscopy showed a consistent etching pattern for phosphoric acid-etched specimens. Self-etch and self-adhesive resin cements applied directly to intact enamel showed inconsistent areas of etching. Etching cervical enamel surfaces resulted in significantly higher bond strengths for self-adhesive resin cement. For self-etch resin cement, etching did not improve bond strength. | 18,762,032 |
Reprint of "Cortical reorganization of language functioning following perinatal left MCA stroke" [Brain and Language 105 (2008) 99-111]. | Functional MRI was used to determine differences in patterns of cortical activation between children who suffered perinatal left middle cerebral artery (MCA) stroke and healthy children performing a silent verb generation task. Ten children with prior perinatal left MCA stroke (age 6-16 years) and ten healthy age matched controls completed an executive language activation task. fMRI scans were acquired on a 3T scanner using T2* weighted gradient echo, echo-planar imaging (EPI) sequence. Random effects analysis and independent component analysis (ICA) were used to compute activation maps. Both analysis methods demonstrated alternative activation of cortical areas in children with perinatal stroke. Following perinatal stroke, typical left dominant productive language areas in the inferior frontal gyrus were displaced to anatomical identical areas in the right hemisphere (p=.001). In addition, stroke patients showed more bilateral activation in superior temporal and anterior cingulate gyri and increased activation in primary visual cortex when compared to healthy controls. There was no relation between lesion size and the degree of right hemisphere activation. ICA showed that the healthy controls had a negative correlation with the time course in the right inferior frontal gyrus in the same region that was activated in stroke subjects. This functional MRI study in children revealed novel patterns of cortical language reorganization following perinatal stroke. The addition of ICA is complementary to Random Effects Analysis, allowing for the exploration of potential subtle differences in pathways in functional MRI data obtained from both healthy and pathological groups. | 18,762,059 |
Transstyloid, translunate fracture-dislocation of the wrist: case report. | Earlier reports have described characteristic fracture-dislocation patterns of the carpus and distal radius. Most result from a fall onto an outstretched arm, with an applied force directed in a radial-to-ulnar direction across the wrist. We present the clinical, radiographic, and arthroscopic findings noted with an unusual pattern of injury resulting from a force applied at the ulnar side of the wrist. | 18,762,109 |
Precontoured fixed-angle volar distal radius plates: a comparison of anatomic fit. | To compare distal radius volar fixed-angle plates for anatomic fit. Twenty embalmed radii were stripped of soft tissues. The volar lip (watershed line) on the volar distal radius served as a reference line. Seven volar fixed-angle plates were tested (Acumed Acu-loc Standard, Hand Innovations DVRAW and DVRAN, Synthes Juxta-articular [JA], Synthes Extra-articular [EA], Trimed Volar Bearing, Zimmer Volar Lateral Column). Four parameters of anatomic fit were studied: (1) site of best fit; (2) percent plate contact; (3) pin-subchondral bone distance; and (4) extraosseous penetrations. The Wilcoxon signed rank test and Pearson's correlation coefficient were used to compare interobserver plate placement. A Kruskal-Wallis analysis of variance was used to compare percent plate contact and pin-subchondral bone distance across all plates. The Bonferroni correction for multiple comparisons was used to compare pin-subchondral bone distances for all possible plate combinations. There was no difference between observers for plate placement. Each plate had a specific site of best fit, and the 7 plates varied widely in best fit location. Percent contact (range, 3% to 6%) between plates was significantly different. Pin-subchondral bone distance across all plates was significantly different. Analysis of all possible plate combinations showed that the Synthes EA pin-subchondral bone distances were significantly different than those of all plates except Zimmer. Amongst the 140 plate insertions, the radiocarpal joint was penetrated in 17, the styloid in 7, (with 6 associated with the DVRAW plate), and the distal radioulnar joint in 9 (all associated with the DVRAW plate). There was considerable variation in ideal plate location among the 7 plates tested. Total contact was minimal for all plates tested. The Synthes EA pin-subchondral bone distance was significantly greater than those of other plates tested. Joint penetration was relatively common, necessitating use of fluoroscopy and proper plate width. | 18,762,111 |
Metalloproteinase gene expression correlates with clinical outcome in Dupuytren's disease. | We have previously demonstrated that gene expression levels of matrix metalloproteinases (MMPs), related metalloproteinases "a disintegrin and metalloproteinase with thrombospontin motifs" (ADAMTSs), and tissue inhibitors of metalloproteinases (TIMPs) differed when comparing palmar fascia from 19 patients with Dupuytren's disease (DD) with 19 disease-free controls. We undertook to investigate whether the extent of this altered gene expression was related to clinical outcome. All the patients with DD were followed up for an average of 14 months from their primary fasciectomy. Clinical outcome was scored by measuring range of motion to assess total extension deficit (fixed flexion deformity [FFD] of the affected digit), total further flexion, and grip strength, and using 3 validated outcome scores: the Disability of Arm, Shoulder and Hand (DASH) questionnaire, the Michigan Hand Questionnaire (MHQ), and the Vancouver Scar Scale (VSS). We found a considerable correlation between levels of gene expression of several of the MMPs (MMP2, MMP13, MMP14, MMP16, MMP 19) and ADAMTSs (ADAMTS2, ADAMTS4, ADAMTS5, ADAMTS14, ADAMTS16) and the recurrence of FFD over the follow-up period. The expression of all these genes had been shown to be increased in DD samples compared with controls. We also found that the expression levels of several of these genes correlated with 2 other preoperative measurements, total further flexion (digital roll-up) and grip strength. These findings suggest that gene expression levels of key MMPs and ADAMTSs could be used to predict 1-year clinical outcome in terms of recurrent FFD of the affected finger following fasciectomy for DD. This implies that knowledge of these expression levels could be used to direct appropriate surgical and adjuvant intervention for DD. This study also provides further evidence to support the functional link between metalloproteinase gene expression and symptomatic progression or recurrence. Prognostic IV. | 18,762,113 |
Imaging motor imagery: methodological issues related to expertise. | Mental imagery (MI) is the mental rehearsal of movements without overt execution. Brain imaging techniques have made it possible to identify the brain regions that are activated during MI and, for voluntary motor tasks involving hand and finger movements, to make direct comparison with those areas activated during actual movement. However, the fact that brain activation differs for different types of imagery (visual or kinetic) and depends on the skill level of the individual (e.g., novice or elite athlete) raises a number of important methodological issues for the design of brain imaging protocols to study MI. These include instructing the subject concerning the type of imagery to use, objective measurement of skill level, the design of motor tasks sufficiently difficult to produce a range of skill levels, the effect of different environments on skill level (including the imaging device), and so on. It is suggested that MI is more about the neurobiology of the development of motor skills that have already been learned, but not perfected, than it is about learning motor skills de novo. | 18,762,138 |
A roadmap for drug discovery and its translation to small molecule agents in clinical development for tuberculosis treatment. | Drug discovery and development, from an initial disease treatment concept to a new drug application (NDA), is a complex, lengthy and expensive process. In this review we discuss the key stages of drug discovery and early development, including target identification and validation, assay development and screening, confirmed hits to leads, lead optimization, and progressing development candidates to an investigational new drug (IND) filing. We also provide particular examples of how this process is beginning to assist in the development of small molecule treatments for tuberculosis, by summarizing the status of the clinical development of several newer classes of drugs. These include the fluoroquinolones, oxazolidinones, diarylquinolines, and nitroimidazo-oxazoles and -oxazines. | 18,762,151 |
Subunit mass fingerprinting of mitochondrial complex I. | We have employed laser induced liquid bead ion desorption (LILBID) mass spectrometry to determine the total mass and to study the subunit composition of respiratory chain complex I from Yarrowia lipolytica. Using 5-10 pmol of purified complex I, we could assign all 40 known subunits of this membrane bound multiprotein complex to peaks in LILBID subunit fingerprint spectra by comparing predicted protein masses to observed ion masses. Notably, even the highly hydrophobic subunits encoded by the mitochondrial genome were easily detectable. Moreover, the LILBID approach allowed us to spot and correct several errors in the genome-derived protein sequences of complex I subunits. Typically, the masses of the individual subunits as determined by LILBID mass spectrometry were within 100 Da of the predicted values. For the first time, we demonstrate that LILBID spectrometry can be successfully applied to a complex I band eluted from a blue-native polyacrylamide gel, making small amounts of large multiprotein complexes accessible for subunit mass fingerprint analysis even if they are membrane bound. Thus, the LILBID subunit mass fingerprint method will be of great value for efficient proteomic analysis of complex I and its assembly intermediates, as well as of other water soluble and membrane bound multiprotein complexes. | 18,762,163 |
Effects of novel antituberculosis agents on OmpF channel activity. | Nanopore forming proteins spanning the outer membrane mediate in the diffusion of hydrophilic chemicals through the hydrophobic bacterial cell wall. In this study, the effects of two novel anti-TB derivatives, ethyl alpha-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-ylthio] acetates and propyl alpha-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-ylthio] acetates, on OmpF channel reconstituted in artificial bilayers were evaluated by voltage clamp technique. Surprisingly, ethyl derivative (MIC > or = 6.75 microg/ml) showed no effects on OmpF channel activity but the propyl derivative (MIC=0.39 microg/ml) reduced the channel conductance considerably and changed the gating pattern of the channel. The findings obtained here at molecular level, might shed light on better understanding of the actual mechanism(s) by which the novel anti-TB agents permeate through the cell wall of the Mycobacterium tuberculosis. | 18,762,173 |
Cathepsin D: a cellular roadmap. | Cathepsin D is a normal and major component of lysosomes, it is found in almost all cells and tissues of mammals. Present review describes different events in cellular life of cathepsin D mainly its biosynthesis, co-translational and posttranslational modifications, targeting to lysosomes and proteolytic processing and maturation within lysosomes. | 18,762,174 |
Regulation of antiapoptotic MCL-1 function by gossypol: mechanistic insights from in vitro reconstituted systems. | Small-molecule drugs that induce apoptosis in tumor cells by activation of the BCL-2-regulated mitochondrial outer membrane permeabilization (MOMP) pathway hold promise for rational anticancer therapies. Accumulating evidence indicates that the natural product gossypol and its derivatives can kill tumor cells by targeting antiapoptotic BCL-2 family members in such a manner as to trigger MOMP. However, due to the inherent complexity of the cellular apoptotic network, the precise mechanisms by which interactions between gossypol and individual BCL-2 family members lead to MOMP remain poorly understood. Here, we used simplified systems bearing physiological relevance to examine the impact of gossypol on the function of MCL-1, a key determinant for survival of various human malignancies that has become a highly attractive target for anticancer drug design. First, using a reconstituted liposomal system that recapitulates basic aspects of the BCL-2-regulated MOMP pathway, we demonstrate that MCL-1 inhibits BAX permeabilizing function via a "dual-interaction" mechanism, while submicromolar concentrations of gossypol reverse MCL-1-mediated inhibition of functional BAX activation. Solution-based studies showed that gossypol competes with BAX/BID BH3 ligands for binding to MCL-1 hydrophobic groove, thereby providing with a mechanistic explanation for how gossypol restores BAX permeabilizing function in the presence of MCL-1. By contrast, no evidence was found indicating that gossypol transforms MCL-1 into a BAX-like pore-forming molecule. Altogether, our findings validate MCL-1 as a direct target of gossypol, and highlight that making this antiapoptotic protein unable to inhibit BAX-driven MOMP may represent one important mechanism by which gossypol exerts its cytotoxic effect in selected cancer cells. | 18,762,177 |
Activation of protein kinase C enhances NMDA-induced currents in primary cultured cerebellar granule cells: Effect of temperature and NMDA NR2 subunit composition. | The purpose of this study was to determine the effect of protein kinase C (PKC) activation by 100 nM phorbol 12-myristate 13-acetate (PMA) on N-methyl-d-aspartate (NMDA) receptor function with the whole-cell patch-clamp technique. Receptors expressed in primary cultured cerebellar granule cells at days in vitro that result in different NMDA NR2A and NR2B subunit composition were assessed. The effect of temperature during PMA exposure on NMDA-induced current amplitudes as well as PMA-induced translocation of PKC isoform-specific immunoreactivity was also assessed. We observed that PMA augmented NMDA-induced peak current amplitude regardless of NR2 subunit composition and augmentation of NMDA-induced steady-state current amplitudes was only observed in 13 and older days in vitro cerebellar granule cells. PMA treatment did not affect the desensitized state (steady-state to peak current ratios) of the receptor. Augmentation of NMDA-induced current amplitude was seen by 12.5 min PMA exposure, a time that corresponded with translocation of all PMA-sensitive PKC isoform immunoreactivity. PMA exposure at 37 degrees C resulted in a significant enhancement of NMDA-induced current amplitude compared to augmentation of receptor function following a PMA exposure at 23 degrees C. Translocation of PKC immunoreactivity was also greatly attenuated at 23 degrees C compared to treatment at 37 degrees C. While our data support previous observations that activation of PKC by PMA enhances NMDA receptor function, this augmentation does not appear to be dependent upon NR2 subunit composition. Furthermore our data emphasize the importance of conducting experiments at physiological temperatures when assessing PKC effects on native NMDA receptors. | 18,762,183 |
Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase. | Tanshinone IIA is an important ingredient in the herb danshen (Salvia miltiorrhiza), which has been used to treat cardiovascular diseases such as atherosclerosis and angina for hundreds of years in China. There are numerous reports that TIIA has anti-oxidant properties but the chemical structure indicates that TIIA is fully oxidized. Here, we test the hypothesis that TIIA alters the expression and/or activity of specific anti-oxidation enzymes to protect cells from oxidant damage. We utilized J774 macrophages to model cellular responses to TIIA when challenged with H(2)O(2). Expression and activity levels of several anti-oxidation enzymes were investigated and the only system modulated by TIIA was glutathione peroxidase (GPx). GPx-1 mRNA levels were significantly increased by TIIA but not the vitamin E analogue, Trolox. GPx activities were also significantly increased by TIIA. Mercaptosuccinic acid inhibited GPx activity and the protective effect of TIIA was attenuated. Thus, TIIA protects cultured macrophages from H(2)O(2)-induced cell death and protection is mediated in large part by TIIA induction of GPx gene expression and activity. Because of the importance of GPx in health and because TIIA is able to modulate GPx activity to some extent in cell culture, we suggest that TIIA is a worthwhile candidate for further study in animal models of atherosclerosis and eventually in human prospective trials. | 18,762,198 |
Distribution and neurochemical characterization of neurons within the nucleus of the solitary tract responsive to serotonin agonist-induced hypophagia. | Pharmacological compounds enhancing serotonergic tone significantly decrease food intake and are among the most clinically efficacious treatments for obesity. However, the central mechanisms through which serotonergic compounds modulate feeding behavior have not been fully defined. The primary relay center receiving visceral gastrointestinal information in the central nervous system is the nucleus of the solitary tract (NTS) in the caudal brainstem. Here we investigated whether the classic anorectic serotonin receptor agonist m-chloro-phenylpiperazine (mCPP) enhances the activity of metabolically sensitive NTS neurons. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation in rats, we observed that mCPP significantly and dose-dependently activated a discrete population of caudal NTS neurons at the level of the area postrema (AP). In particular, this pattern of FOS-IR induction was consistent with the location of catecholamine-containing neurons. Dual-labeling performed with FOS-IR and the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) revealed that mCPP induced FOS-IR in 83.7% of TH-IR containing neurons in the NTS at the level of the AP. The degree of activation of TH neurons was strongly negatively correlated with food intake. Moreover, this activation was specific to catecholamine neurons, with negligible induction of cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), or neurotensin neurons. NTS catecholaminergic neurons relay visceral gastrointestinal signals to both the lateral hypothalamus (LHA) and paraventricular nucleus of the hypothalamus (PVH), where these signals are integrated into autonomic and hormonal responses regulating food intake. The data presented here identify a novel mechanism through which a serotonin receptor agonist acting in the caudal brainstem may regulate ingestive behavior. | 18,762,217 |
Oral creatine supplementation attenuates L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats. | L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson patients after a prolonged treatment with levodopa (L-DOPA). Since previous transcriptome and proteomic studies performed in the rat model of LID suggested important changes in striatal energy-related components, we hypothesize that oral creatine supplementation could prevent or attenuate the occurrence of LID. In this study, 6-hydroxydopamine-lesioned rats received a 2% creatine-supplemented diet for 1 month prior to L-DOPA therapy. During the 21 days of L-DOPA treatment, significant reductions in abnormal involuntary movements (AIMs) have been observed in the creatine-supplemented group, without any worsening of parkinsonism. In situ hybridization histochemistry and immunohistochemistry analysis of the striatum also showed a reduction in the levels of prodynorphin mRNA and FosB/DeltaFosB-immunopositive cells in creatine-supplemented diet group, an effect that was dependant on the development of AIMs. Further investigation of the bioenergetics' status of the denervated striatum revealed significant changes in the levels of creatine both after L-DOPA alone and with the supplemented diet. In conclusion, we demonstrated that combining L-DOPA therapy with a diet enriched in creatine could attenuate LID, which may represent a new way to control the motor complications associated with L-DOPA therapy. | 18,762,218 |
The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization. | Only a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines. | 18,762,221 |
Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects. | Three independent, phase 1 clinical trials were conducted in Australia and in USA to assess the safety and immunogenicity of sanofi pasteur dengue vaccine candidates. In this context, Dengue 1-4 and Yellow Fever 17D-204 (YF 17D)-specific CD4 and CD8 cellular responses induced by tetravalent chimeric dengue vaccines (CYD) were analyzed in flavivirus-naive or flavivirus-immune patients. Tetravalent CYD vaccine did not trigger detectable changes in serum pro-inflammatory cytokines, whatever the vaccinees immune status, while inducing significant YF 17D NS3-specific CD8 responses and dengue serotype-specific T helper responses. These responses were dominated by serotype 4 in naive individuals, but a booster vaccination (dose #2) performed 4 months following dose #1 broadened serotype-specific responses. A similar, broader response was seen after primary tetravalent immunization in subjects with pre-existing dengue 1 or 2 immunity caused by prior monovalent live-attenuated dengue vaccination. In all three trials, the profile of induced response was similar, whatever the subjects' immune status, i.e. an absence of Th2 response, and an IFN-gamma/TNF-alpha ratio dominated by IFN-gamma, for both CD4 and CD8 responses. Our results also showed an absence of cross-reactivity between YF 17D or Dengue NS3-specific CD8 responses, and allowed the identification of 3 new CD8 epitopes in the YF 17D NS3 antigen. These data are consistent with the previously demonstrated excellent safety of these dengue vaccines in flavivirus-naive and primed individuals. | 18,762,226 |
The effects of childhood disruptive disorder comorbidity on P3 event-related brain potentials in preadolescents with ADHD. | The present study examined the degree to which the P300 component of the visual brain event-related potential and associated task performance deficits often observed in children with attention-deficit hyperactivity disorder (ADHD) are attributable to comorbid childhood disruptive disorders using a community sample of 11-year olds from the Minnesota Twin Family Study. Subjects were divided into "ADHD-pure" (ADHD without oppositional defiant disorder, ODD, or conduct disorder, CD), "ADHD-comorbid" (ADHD with ODD or CD), and comparison (no childhood disruptive disorder) groups using DSM-III-R diagnoses. Results showed that ADHD-comorbid but not ADHD-pure subjects displayed significant P3 amplitude reduction and poorer task performance compared to controls. No group effects for P3 latency or reaction time were seen. Although ADHD-comorbid children had marginally more ADHD symptoms compared to ADHD-pure children, this did not account for their reduced P3, suggesting that the observed neurobehavioral deficits reflected the effects of co-occurring childhood disruptive disorders. | 18,762,228 |
The F-domain of estrogen receptor-alpha inhibits ligand induced receptor dimerization. | The role of the carboxyl terminal F-domain of estrogen receptor (ERalpha) is uncertain, but evidence suggests that this region may impart internal restraint on ER dimerization in the presence of 17beta-estradiol (E2). To identify the C-terminal residues affecting human ERalpha activation, we created a series of deletions and examined E2 induced receptor dimerization and transactivation. Deletion of the final 24 C-terminal amino acids of the F-domain (Delta7b) yielded a fivefold increase in dimerization, when compared to wild type (wt) ERalpha in the presence of 2nM E2, utilizing a yeast two-hybrid assay. This increase in dimerization is similar to that observed when the entire F-domain was deleted. Measurement of mutant:mutant homodimer formation yielded similar increases compared to mutant:wt interactions. Interestingly, a point mutation at the C-terminus (mut 3) showed increases in dimerization comparable to that of Delta7b in the presence of nanomolar amounts of E2. However, at sub-nanomolar levels of E2, mut 3 behaved similarly to wt ERalpha, whereas Delta7b maintained striking increases in dimerization. Determination of E2 binding affinity (Kd) constants revealed only marginal differences for wt and F-domain mutants, suggesting that the F-domain affects dimerization directly. We also observed enhanced interaction of F domain mutants with p160 family coactivator SRC1. Finally, transcriptional regulation of estrogen responsive reporters, 2XERE-LacZ and 3XERE-Luc in yeast and mammalian cells, respectively, reflected the increased propensity for dimerization by F domain mutants. Together, these data indicate that the C-terminal amino acids of ERalpha are critical for attenuation of E2 induced receptor dimerization and transcriptional activity. | 18,762,230 |
Interaction of mitoxantrone with human serum albumin: spectroscopic and molecular modeling studies. | Mitoxantrone (MTX) is a clinically used antitumor anthracycline, which is made available to the target tissues by transport protein human serum albumin (HSA). Being less toxic unlike other member of this family, its binding characteristics are therefore of immense interest. The circular dichroism (CD), fluorescence and Fourier transform infrared (FTIR) spectroscopies were employed to elucidate the mode and the mechanism for this interaction. MTX binding is characterized by one high affinity binding site with the association constants of the order of 10(5). Correlation between stability of N-MTX (drug bound N form of HSA) and B-MTX (drug bound B form of HSA) complexes with drug distribution has been discussed. The molecular distance, r, between donor (HSA) and acceptor (MTX) was estimated according to Forster's theory of non-radiation energy transfer. The features of MTX induced structural perturbation of human serum albumin (HSA) has been studied in detail by CD and FTIR analysis. Domain I was assigned to possess high affinity binding site for MTX. Molecular docking showed that the MTX binds HSA to a non-classical drug binding site. The binding dynamics was expounded by synchronous fluorescence, thermodynamic parameters and molecular modeling, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces, stabilizes the interaction. | 18,762,252 |
In vitro human plasma distribution of nanoparticulate paclitaxel is dependent on the physicochemical properties of poly(ethylene glycol)-block-poly(caprolactone) nanoparticles. | In this study, we synthesized and characterized two methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL) amphiphilic diblock copolymers, both based on MePEG with a molecular weight of 5000 g/mol (114 repeat units) and PCL block lengths of either 19 or 104 repeat units. Nanoparticles were formed from these copolymers by a nanoprecipitation and dialysis technique. The MePEG(114)-b-PCL(19) copolymer was water soluble and formed micelles that had a hydrodynamic diameter of 40 nm at all copolymer concentrations tested, and displayed a relatively low core microviscosity. The practically water insoluble MePEG(114)-b-PCL(104) copolymer formed nanoparticles with a larger hydrodynamic diameter, which was dependent on copolymer concentration, and possessed a higher core microviscosity than the MePEG(114)-b-PCL(19) micelles, characteristic of nanospheres. The micelles solubilized a maximum of 1.6% w/w of the hydrophobic anticancer agent, paclitaxel (PTX), and released 92% of their drug payload over 7 days, as compared to the nanospheres, which solubilized a maximum of 3% w/w of PTX and released 60% over the same period of time. Both types of nanoparticles were found to be hemocompatible, causing only minimal hemolysis and no changes in plasma coagulation times as compared to control. Upon in vitro incubation in human plasma, PTX solubilized by micelles had a plasma distribution similar to free drug. The majority of PTX was associated with the lipoprotein deficient plasma (LPDP) fraction, which primarily consists of albumin and alpha-1-acid glycoprotein. In contrast, nanospheres were capable of retaining more of the encapsulated drug with significantly less PTX partitioning into the LPDP fraction. | 18,762,253 |
Can type-1 responses against intracellular pathogens be T helper 2 cytokine dependent? | While control of intracellular pathogens, such as the protozoan Leishmania, is dependent on the generation of type-1 immune responses, the role of T helper 2 cytokines in the disease process is more controversial. Traditionally these cytokines were perceived as counter-regulating type-1 responses and promoting disease exacerbation. Nevertheless a substantial body of evidence now exists suggesting that the development of effective type-1 immunity can involve the significant involvement of the Th2 cytokines IL-4 and IL-13. This article reviews, using Leishmania species in particular, the circumstances under which these cytokines can promote protective type-1 immunity. | 18,762,265 |
Cellular uptake of lipoproteins and persistent organic compounds--an update and new data. | There are a number of interactions related to the transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs including the pesticide p,p'-dichlorodiphenyltrichloroethane (DDT), and especially its metabolite p,p'-dichlorodiphenyldichloroethene (DDE), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of low-density lipoproteins (LDL) and [(14)C]DDT. The receptor function was further evaluated by adding the 40kDa receptor-associated protein (RAP) which blocks receptor activity. The results showed that [(14)C]DDT uptake was decreasing when the LDL concentration was increasing. There was no strong evidence for a receptor-mediated uptake of the [(14)C]DDT-lipoprotein complex. To conclude, DDT travels in the blood stream and can cross cell membranes while being transported as a DDT-lipoprotein complex. The lipoproteins do not need receptors to cross cell membranes since passive diffusion constitutes a major passageway. | 18,762,293 |
Methods for the determination of phenolic brominated flame retardants, and by-products, formulation intermediates and decomposition products of brominated flame retardants in water. | Brominated flame retardants (BFRs) are the chemicals of high importance within the REAch framework. In addition to polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA), other BFRs such as bromophenols, intermediates in FR formulation like bromoanilines, and their brominated and non-brominated by-products such as bromoanisoles, bromotoluenes, bromoalkanes and 1,5,9-cyclododecatriene, respectively should be monitored and controlled because of their toxicity and their very low odour and taste thresholds, below sub-nanogram-per liter levels. In the present study several analytical methods for the simultaneous determination, i.e., combining one single sample treatment and one analysis step, of these compounds in water have been developed, optimized and evaluated. The methods involve a (pre-concentration)-extraction technique, such as liquid-liquid (LLE), solid-phase (SPE), headspace (HS) extraction or solid-phase microextraction (SPME), followed by gas chromatography (GC)-mass spectrometry (MS) analysis with either electron capture negative ionization (ECNI) or electron impact (EI) as ionization techniques. ECNI is more sensitive than EI for analytes with more than one bromine atom. HS and SPME were previously optimized by means of a multifactorial experimental design. Extraction temperature and the liquid/headspace volume ratio were the most significant factors in HS extraction. In SPME, the variables studied were the nature of the fiber, the mode of extraction and the extraction temperature. Polydimethylsiloxane (PDMS) fibers appeared to be more suitable than carboxen-polydimethylsiloxane (CAR-PDMS) for the analysis of the target compounds with more than one bromine atom. The extraction of 2,4-dibromoaniline was only achieved in a direct immersion mode, in which the optimal extraction temperature was 60 degrees C. The methods LLE-GC-(ECNI)MS, LLE-GC-(EI)MS, SPE-GC-(ECNI)MS, SPE-GC-(EI)MS, HS-GC-(EI)MS and SPME-GC-(EI)MS were evaluated in terms of linearity, precision, detection limits and trueness. All methods, with the exception of HS-GC-(EI)MS, were linear in a range of at least two orders of magnitude, giving recoveries above 75% and detection limits at the low ng/L level for most of the target analytes. SPE-GC-(ECNI)MS is the most sensitive and reliable method for the determination of most of the bromine compounds, whereas SPE-GC-(EI)MS is the most suitable to quantify the three isomers of 1,5,9-cyclododecatriene. Both methods together with SPME-GC-(EI)MS (for qualitative confirmation) were applied to water samples from the Western Scheldt (The Netherlands), where 2,6-dibromophenol and 2,4,6-tribromoanisole could be detected at levels higher than their respective odour thresholds. | 18,762,297 |
[Cerebrovascular diseases and... skin abnormalities that disclose the diagnosis]. | In many cases, the diagnostic work-up after a stroke can be greatly enhanced by a thorough examination of the skin, since vasculitis or vasculopathies, even if inherited, may affect cerebral vessels and the skin. Skin abnormalities differ depending on familial history, age of the patient, stroke subtype (cerebral infarct or hemorrhage), and etiology (cervical dissection, cardiac myxoma or small artery disease...). | 18,762,305 |
Laser ultrasonic diagnostics of residual stress. | Ultrasonic NDE is one of the most promising methods for non-destructive diagnostics of residual stresses. However the relative change of sound velocity, which is directly proportional to applied stress, is extremely small. An initial stress of 100 MPa produces the result of deltaV/V approximately 10(-4). Therefore measurements must be performed with high precision. The required accuracy can be achieved with laser-exited ultrasonic transients. Radiation from a Nd-YAG laser (pulse duration 7 ns, pulse energy 100 microJ) was absorbed by the surface of the sample. The exited ultrasonic transients resembled the form of laser pulses. A specially designed optoacoustic transducer was used both for the excitation and detecting of the ultrasonic pulses. The wide frequency band of the piezodetector made it possible to achieve the time-of-flight measurements with an accuracy of about 0.5 ns. This technique was used for measuring of plane residual stress in welds and for in-depth testing of subsurface residual stresses in metals. Plane stress distribution for welded metallic plates of different thicknesses (2-8 mm) and the subsurface stress distribution for titanium and nickel alloys were obtained. The results of conventional testing are in good agreement with the laser ultrasonic method. | 18,762,308 |
Partitioning and granulometric distribution of metal leachate from urban traffic dry deposition particulate matter subject to acidic rainfall and runoff retention. | Vehicular transportation coupled with urban hydrology is a significant source as well as vector of particulate matter (PM) and particulate-bound metal inventories in urban systems. This study examines the granulometric distribution of metals from dry deposition PM generated from 17 dryfall periods and equilibrium metal partitioning with runoff PM distribution from eight rainfall-runoff events at an urban inter-state watershed in Baton Rouge, LA. Dry deposition PM is a coarse non-uniform gradation with a d(50 m)=304 microm and a peak surface area at 106 microm. Results indicate acid rain is not a significant metal contributor to runoff but is capable of leaching metals from PM to runoff. Retained runoff partitioning resulted in particulate-bound predominance for As, Cd, Cr, Cu, Pb, and Zn while Ca and Mg remained predominately dissolved. The finer PM fraction (<75 microm) generates the highest metal concentrations and the highest metal mass is associated with the coarser fraction (>75 microm). This coarse fraction is also the most labile when exposed to acidic rainfall; generating up to 90% of the total metal mass leached from the entire PM gradation. Comparing dry deposition and runoff PM of equal mass and size gradation, retained runoff PM is enriched with metals (except Pb). Results indicate the labile coarse fraction of dry deposition PM can be a significant source of metal leaching while runoff PM (mobilized dry deposition PM) stored in a BMP can be metal-enriched with the potential for re-leaching or scour. | 18,762,311 |
Short- and long-term effects of immunization against gonadotropin-releasing hormone, using Improvac, on sexual maturity, reproductive organs and sperm morphology in male pigs. | The objective of this study was to determine the short and long term effects of a gonadotropin-releasing hormone (GnRH) vaccine (Improvac Pfizer Ltd.), on sexual maturity, development of the reproductive organs, and the morphology of caudal epididymal spermatozoa in non-castrated male pigs. The pigs were slaughtered 4, 16 or 22 weeks after the second Improvac vaccination. A total of 80 crossbred non-castrated male pigs were included in this study comprising two experiments, a short-effect (Experiment 1) and a long-effect (Experiment 2). The first experiment included 56 pigs, 24 of them were maintained as controls and 32 were vaccinated twice, and slaughtered 4 weeks after the second vaccination. The second experiment included 24 pigs, 12 controls and 12 vaccinated twice, and slaughtered either 16 weeks (n=6) or 22 weeks (n=6) after the second vaccination. None of the immunized pigs was sexually mature at slaughter, i.e. 4, 16 or 22 weeks after second vaccination. Corresponding results of the control pigs showed that 50% had reached sexual maturity at the age corresponding to 4 weeks after the second vaccination, and 100% at slaughter 16, respectively, 22 weeks after vaccination. At 4, 16 and 22 weeks after second vaccination both testes weight and bulbourethral length were significantly reduced (p<0.001). The percentages of proximal droplets and abnormal heads were significantly lower in the control pigs than in the immunized pigs at slaughter 4 weeks after vaccination, whereas distal droplets were higher. For the other morphological parameters no significant differences were seen, but all mean values except for acrosome defects were numerically lower in the control pigs compared with the immunized pigs. For pigs slaughtered 16 or 22 weeks after vaccination, the vaccination effect was significant for percentages of proximal droplets, distal droplets, acrosome defects, acrosome abnormality and abnormal heads (p=0.017-0.001). The immunization clearly disrupted the number and morphology of the interstitial Leydig cells, lasting throughout the study period (4-22 weeks after vaccination). Spermatogenesis was also clearly affected in the immunized pigs, to various degrees, from mild disruption (spermatocyte loss, decrease of the normal number of layers of germ cells) to severe loss of germ cells including tubuli with Sertoli cells-only (complete disappearance of germ cells), also covering the entire study period. The results indicated that the effect of immunization persisted for at least 22 weeks after the second vaccination. | 18,762,333 |
Evaluation of polymerization shrinkage and hydroscopic expansion of fiber-reinforced biocomposites using optical fiber Bragg grating sensors. | Polymerization shrinkage of dental composite materials is recognized as one of the main reasons for the development of marginal leakage between a tooth and filling material. In addition, hydroscopic expansion due to water sorption is known to cause instability in dental materials. Several methods have been proposed to quantify the polymerization shrinkage and hydroscopic expansion. However, in the case of anisotropic materials, such as unidirectional fiber-reinforced composites (FRCs), the measurement method must allow for the discrimination of the shrinkage or expansion in the two orthogonal directions. In this work, optical fiber sensors were employed to study strains in dental materials induced by polymerization shrinkage and hydroscopic expansion. Four dental materials were evaluated in this study: unfilled BisGMA/TEGDMA-based resin, Z250 dental restorative composite, unidirectional and bidirectional fiber reinforced composites. The changes in the linear strain due to the polymerization shrinkage and hydroscopic expansion were monitored in real-time using embedded optical fiber Bragg grating (FBG) sensors. The polymerization shrinkage was monitored during the light curing process. FBG sensors were also used to record the hydroscopic expansion of the samples which were immersed in water up to 132 days. Unfilled polymer resin had the highest polymerization shrinkage of 0.84%. Unidirectional FRC had a relatively high shrinkage in the transverse direction with respect to the reinforcing fibers (0.41%) whereas the shrinkage along the reinforcing fibers was small (0.02%). Bidirectional FRC showed a low shrinkage value (0.03%). For most tested materials the hydroscopic expansion seemed to compensate for the polymerization shrinkage. Fiber Bragg grating sensors are suitable for accurate real-time monitoring of small internal strains of biomaterials, e.g., due to polymerization shrinkage and hydroscopic expansion. Detailed data on polymerization shrinkage and water sorption behavior of different dental materials can be used to optimize the mechanical properties of dental composite materials and to improve the longevity of a dental restoration. | 18,762,334 |
Age-related changes in multi-finger interactions in adults during maximum voluntary finger force production tasks. | This study aimed to continue our characterization of finger strength and multi-finger interactions across the lifespan to include those in their 60s and older. Building on our previous study of children, we examined young and elderly adults during isometric finger flexion and extension tasks. Sixteen young and 16 elderly, gender-matched participants produced maximum force using either a single finger or all four fingers in flexion and extension. The maximum voluntary finger force (MVF), the percentage contributions of individual finger forces to the sum of individual finger forces during four-finger MVF task (force sharing), and the non-task finger forces during a task finger MVF task (force enslaving), were computed as dependent variables. Force enslaving during finger extension was greater than during flexion in both young and elderly groups. The flexion-extension difference was greater in the elderly than the young adult group. The greater independency in flexion may result from more frequent use of finger flexion in everyday manipulation tasks. The non-task fingers closer to a task finger produced greater enslaving force than non-task fingers farther from the task finger. The force sharing pattern was not different between age groups. Our findings suggest that finger strength decreases over the aging process, finger independency for flexion increases throughout development, and force sharing pattern remains constant across the lifespan. | 18,762,348 |
Manufacturing process of reproduction plate by nonmetallic materials reclaimed from pulverized printed circuit boards. | The aim of this study was to present a new method for resource utilization of nonmetallic materials reclaimed from pulverized waste printed circuit boards. A reproduction nonmetallic plate (RNMP) was prepared by adding resin paste, glass fiber and additives into nonmetallic materials using self-made hot-press former. Principle of manufacturing process and effects of mould temperature and moulding time on the mechanical properties of RNMP were studied. The results showed that when moulding pressure was fixed at 6 MPa, the optimum conditions for the RNMP were as follows: 140/135 degrees C for top/bottom mould temperature, 5 min for moulding time. The maximum content of nonmetallic materials in RNMP was up to 40 wt%. When nonmetallic material content was 20 wt%, the RNMP moulded at optimum conditions had excellent mechanical properties, with impact strength of 5.8 kJ/m(2) and flexural strength of 65.1 MPa. | 18,762,372 |
Quinolone-resistance in Salmonella is associated with decreased mRNA expression of virulence genes invA and avrA, growth and intracellular invasion and survival. | A variety of environmental factors, such as oxygen, pH, osmolarity and antimicrobial agents, modulate the expression of Salmonella pathogenicity islands (SPI) genes. This study investigated SPI-1 gene expression and the pathogenicity of quinolone-resistant Salmonella. mRNA expression levels of the invA and avrA genes, located in SPI-1, in quinolone-susceptible and quinolone-resistant Salmonella strains were determined using real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Twenty-five quinolone-resistant Salmonella mutants were derived from quinolone-susceptible strains by multiple-passage selection through increasing concentrations of ciprofloxacin in vitro, while an additional 15 strains were quinolone-resistant Salmonella clinical isolates. Sequence analysis showed no gene deletion or point mutations of nine SPI-1 genes (including invA and avrA) occurred in either the selected or clinical quinolone-resistant strains, while a single gyrA point mutation (S83F) was observed in all 40 quinolone-resistant strains. The mRNA expression levels of invA and avrA were significantly decreased (P<0.005) in quinolone-resistant strains (clinically acquired or experimentally selected in vitro), compared to the quinolone-susceptible strains. The resistant strains also had a slower growth rate combined with decreased epithelial cell invasion and intracellular replication in epithelial cells and macrophages. The results suggest that quinolone-resistance may be associated with lower virulence and pathogenicity than in quinolone-susceptible strains. | 18,762,392 |
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