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Retriever2800
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Anti leukemia activity (L1210) of 6-mercaptopurine and its metallo complexes in mice.
Six-mercaptopurine in the free form and complexed with Pt, Pd, or Bi metals was used at various dosage levels to treat L1210 leukemia in mice. Anticarcinogenic activity was shown by six-mercaptopurine and the Pd and Bi complexes, inactivity by the Pt complex, and toxicity by the highest dosage level of six-mercaptopurine.
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No pos
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No neg
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Retriever2801
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Isolation of Synthetic Antibodies Against BCL-2-Associated X Protein (BAX).
The BCL-2 protein family plays central roles in the mitochondrial pathway of cell apoptosis. The BCL-2-Associated X protein (BAX), along with other proapoptotic proteins, induces cell death in response to a variety of stress stimuli. Upon receipt of killing signals, cytosolic BAX is activated and translocates to mitochondria where it causes mitochondrial outer membrane permeabilization (MOMP) and initials a series of cellular events that eventually lead to cell destruction. Despite recent progress toward understanding the structure, function, and activation mechanism of BAX, detailed information about how cytosolic BAX can be inhibited is still limited. Here we describe a method of selecting synthetic antibody fragments (Fabs) against BAX using phage display. Synthetic antibodies discovered from the selection have been used as structural probes to gain novel mechanistic details on BAX inhibition. This synthetic antibody selection method could be potentially applied to other BCL-2 proteins.
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No pos
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No neg
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Retriever2802
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How to avoid taking the boards but save face.
The author present several options for other psychiatrists who wish to avoid taking board examinations and still save face. Although the author states that none of these worked for him, he wishes to present his suggestions to others in the field.
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No pos
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No neg
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Retriever2803
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Magnetic field gradient system for nuclear magnetic resonance microimaging.
In this study we present an orthogonal magnetic field gradient system for nuclear magnetic resonance (NMR) microimaging applications. The construction details are given for a prototype assembly for proton microscopy inside a 50-mm vertical bore magnet, which is designed to fit into a commercial 300-MHz NMR probe. This system has been used to acquire images of the human spinal cord in vitro. Its performance has been evaluated and compared to that predicted by computer simulation.
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No pos
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No neg
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Retriever2804
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Surgical resection of intracranial cavernous hemangioma located at uncommon location: Clinical presentation and management.
Background
Intracranial cavernous hemangiomas (CHs) usually originate from the cerebral and cerebellar hemispheres, while the clinical features and optimum treatment of CHs that originate from atypical locations remain unclear.
Methods
We conducted a retrospective analysis of CHs that originated from the sellar, suprasellar, or parasellar region, the ventricular system, the cerebral falx, or the meninges in patients who underwent surgery from 2009 to 2019 in our department.
Results
In our study, fourteen patients with pathologically confirmed CHs in uncommon locations (UCHs) were enrolled; 5 were located at the sellar or parasellar region, 3 at the suprasellar region, 3 at the ventricular system, 2 at the cerebral falx, and 1 originated from parietal meninges. The most common symptoms were headache and dizziness (10/14); however, none presented with seizures. All UCHs located in the ventricular systems and 2 of the 3 UCHs located in the suprasellar region manifested as hemorrhagic lesions and shared similar radiological features compared with axial CHs; other locations of UCHs did not have a "popcorn" appearance on T2-weighted image. Nine patients achieved GTR, 2 achieved STR, and 3 achieved PR. Four out of five patients who received incomplete resection underwent adjuvant gamma-knife radiosurgery. During the average follow-up of 71.1 ± 43.3 months, no patient died and one patient encountered recurrence and de novo formation of midbrain CH. Most patients had an excellent KPS score of 90-100 (9 of 14) or a good KPS score of 80 (1 of 14).
Conclusion
We suggest that surgery is the optimum therapeutic method for UCHs located at the ventricular system, dura mater, and cerebral falx. Stereotactic radiosurgery plays an important role in the treatment of UCHs located at the sellar or parasellar region and remnant UCHs. Favorable outcomes and lesion control could be achieved by surgery.
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No pos
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No neg
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Retriever2805
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Uterine cervical cancer associated with obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome: A case report and review of the literature.
•Cervical cancer occurring in patients with OHVIRA syndrome is very rare.•This case reports on HPV-negative adenocarcinoma located in the nonvisible cervix.•Colposcopy and imaging are essential for cervical cancer with uterine malformation.•In OHVIRA syndrome, cervical malignancies may be overlooked.
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No pos
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No neg
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Retriever2806
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Influence of serotonin on calcium transport in rat liver mitochondria.
It was shown in experiments in vitro that serotonin, depending on the concentration, has different effects on calcium transport in rat liver mitochondria. In a concentration of 10(-6) M it increases the ability of the mitochondria to bind calcium; in a higher concentration (10(-4) M) serotonin accelerates the release of calcium from the mitochondria. The effect of serotonin is detected at a calcium concentration in sucrose medium of the order of 10(-4) M and is not observed when the mitochondria are incubated in a complete reaction medium.
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No pos
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No neg
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Retriever2807
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Dual-wavelength excitation of mucosal autofluorescence for precise detection of diminutive colonic adenomas.
BACKGROUND
The mucosal layer of the colon contains metabolism-related fluorophores, such as reduced nicotinamide adenine dinucleotide (NADH), which might have the potential to serve as biomarkers for detecting neoplasia.
OBJECTIVE
To examine NADH fluorescence in human colonic adenoma while eliminating the effect of hemoglobin absorption and to develop a novel imaging technique for precise detection of adenomas.
DESIGN
Cross-sectional study.
PATIENTS AND INTERVENTIONS
A total of 66 endoscopically resected colonic polyps were investigated. After serial acquisition of autofluorescence images between 450 and 490 nm illuminated with dual-wavelength excitation at 365 nm (F(365ex)) and 405 nm (F(405ex)) on cross sections of the samples, ratio images were created by dividing F(365ex) by F(405ex). The excitation-emission wavelength combinations in F(365ex) and F(405ex) were optimized for NADH fluorescence and reference fluorescence.
MAIN OUTCOME MEASUREMENTS
The F(365ex)/F(405ex) ratio in the tumorous (T) and normal (N) mucosa.
RESULTS
F(365ex)/F(405ex) ratio images showed a 1.81- and 1.12-fold higher signal intensity in the adenomas and hyperplastic polyps, respectively, than in the adjacent normal mucosa. The ratio between signal intensities in tumorous mucosa and normal mucosa in F(365ex)/F(405ex) ratio images for tubular adenomas was significantly higher than that for hyperplastic polyps. The signal intensity in F(365ex)/F(405ex) ratio images was not correlated with the hemoglobin concentration index evaluated by reflection images at 550 nm and 610 nm. Diminutive adenomas (<5 mm) and large adenomas were well discriminated in F(365ex)/F(405ex) ratio images.
LIMITATIONS
Ex vivo experiment.
CONCLUSIONS
These results suggest that the precise measurement of NADH fluorescence intensity together with eliminating the influence of blood hemoglobin concentration serves as a method for visualizing colonic adenomas and that the dual-wavelength excitation method is a promising technique applicable to endoscopic detection of early colonic adenomas.
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No pos
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No neg
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Retriever2808
|
Relationship between oral poor hygiene and broken teeth with oral tongue squamous cell carcinoma.
Previous studies on etiology of squamous cell carcinoma (SCC) of the tongue have reported results with respect to long term exposure to cigarette smoking and alcohol abuse. The aim of this study was to investigate risk factors for SCC of the tongue in a set of patients with minimum exposure to cigarette smoking and alcohol. Sixty four cases with diagnosis of oral tongue SCC were reviewed in this study. The patients underwent surgical management at the educational and therapeutic centers, Imam and Buali Hospitals (Hamedan, Iran) between the dates of January 1990 and December 2006. Eighty five percent of patients were older than 40 years of age. Most of patients had poor oral hygiene, dental decay and halitosis. It appears that poor oral hygiene and nutritional deficiency can be considered as risk factors for the SCC of the tongue in west of Iran.
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No pos
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No neg
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Retriever2809
|
Dual Trigger Compared with Human Chorionic Gonadotropin Alone and Effects on Clinical Outcome of Intracytoplasmic Sperm Injection.
BACKGROUND
This study compared outcomes of the standard 6000 IU human chorionic gonadotropin (hCG) trigger with a dual trigger comprised of 6000 IU hCG and 1 mg leuprolide acetate for final oocyte maturation in an intracytoplasmic sperm injection (ICSI) cycle. By convention, ICSI was performed in most cases at the clinic.
MATERIALS AND METHODS
In this retrospective study, a total of 50 women were included in each arm. Participants were matched for age, indication and number of prior assisted reproduction technology (ART) cycles. Women at risk for ovarian hyperstimulation syndrome (OHSS) were excluded. A flexible gonadotropin releasing hormone (GnRH) antagonist protocol was used and final oocyte maturation was triggered when two leading follicles were >17 mm. Distribution of variables was evaluated visually with histograms. Continuous variables were defined by mean (standard deviation) or median (25th-75th percentile) depending on distribution characteristics. Categorical variables were defined by numbers and percentages. Continuous variables were compared between the groups with the t test or Mann-Whitney U test as appropriate. Categorical variables were compared by the chi-square test and its derivatives as appropriate. A two-sided P<0.05 indicated statistical significance.
RESULTS
Both groups had similar antral follicle counts, median parity (0) and number of previous failed cycles (0). The median number of oocytes (8 vs. 7), metaphase-two oocytes (6 vs. 5.5), blastocysts (1 vs. 1), clinical pregnancy rates (CPR) (28% vs. 22%), ongoing pregnancy rates (OPR) (22% vs. 20%) and pregnancy rate per transfer (53.3% vs 53.8%) were similar between the dual trigger and hCG only groups, respectively.
CONCLUSION
Dual trigger for oocyte maturation stimulation failed to improve the ICSI outcome.
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No pos
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No neg
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Retriever2810
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Self-limited oxygen exchange kinetics at SnO2 surfaces.
The oxygen exchange at SnO(2) surfaces strongly depends on surface termination, which is affected by the oxygen chemical potential. At low oxygen chemical potential, the surface adopts its reduced termination which allows oxygen exchange, while exchange is suppressed by the stoichiometric surface termination.
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No pos
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No neg
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Retriever2811
|
Brain energy metabolism in angiotensin-induced acute hypertension in rats.
In order to study if rapid elevation of blood pressure is associated with cerebral ischemia, anesthetized (70% N2O) and artificially ventilated rats were subjected to angiotensin-induced hypertension. After a 5 min hypertensive period, cerebral cortex tissue was frozen in situ for subsequent measurements of labile glycolytic metabolites, ammonia, and organic phosphates. The degree of hypertension induced, which gave evidence of blood-brain barrier damage in 7 of 8 rats, did not affect the tissue concentrations of labile metabolites. It is concluded that ischemia does not contribute to the barrier damage, nor is it likely to be the cause of the clinical symptoms that may occur in conscious rats in the same experimental model.
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No pos
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No neg
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Retriever2812
|
Adaptational responses in dynamic stability during disturbed walking in the elderly.
The purpose of this study was to examine the age-related predictive and feedback adaptive locomotor improvements in the components of dynamic stability control during disturbed walking. Thirteen old (62-74 yrs) and ten young (23-30 yrs) male subjects performed a gait protocol on a gangway, which included one covered element. By exchanging this element, the subjects walked either solely over hard surface or experienced a perturbation of the gait on the soft surface element. The gait protocol consisted of a baseline on hard surface and an adaptation phase with 19 trials on soft or hard (2nd, 8th and 19th) surface. The investigation of dynamic stability was made by using the margin of stability (MS), which was calculated as the difference between the base of support and the extrapolated center of mass (CM). Horizontal velocity of CM and its vertical projection in anterior-posterior direction as well as the eigenfrequency of an inverted pendulum generate the extrapolated CM. As a result of the first unexpected disturbance, MS was decreased in the step following the perturbation compared to baselines in both age-groups. This decrease was higher for the old participants compared to the young ones, indicating a more unstable position in the step after the perturbation for the elderly. In the following adaptation phase, MS returned to baseline values in both age-groups. In the hard trial after the first unexpected perturbation, both age-groups increased MS at touchdown of the disturbed leg compared to baseline, reflecting fast predictive adjustments. Our findings show that the well-known age-related biological impairments did not inhibit the adaptive improvements in the components of dynamic stability in the elderly. However, the feedback corrections after the first unexpected perturbation were less effective for the elderly. This may increase the risk of falling.
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No pos
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No neg
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Retriever2813
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Sulfaguanidine nanofiltration active layer towards anti-adhesive and antimicrobial attributes for desalination and dye removal.
A novel sulfaguanidine (SG)-modified polyamide thin-film composite (TFC) nanofiltration (NF) membrane was constructed by the strategy referred to as co-solvent assisted interfacial polymerization (CASIP), which involves the respective interfacial polymerization (IP) of piperazine (PIP) and SG with trimesoyl chloride (TMC) on porous polysulfone (PSf) supports. CASIP enables the formation of a defect-free thin dense active layer and favors higher water permeance up to 79.0 L m-2 h-1 with rejection above 98.3% for Na2SO4. The resulting PA membrane also demonstrates a high flux recovery ratio of nearly 98.9% to bovine serum albumin protein after being cleaned. More importantly, the current membrane shows excellent anti-adhesive and antimicrobial performances against Gram-negative Escherichia coli, Gram-positive Bacillus pumilus LDS.33 and Aspergillus parasiticus JFS. This promises great potential application of the PA membrane for practical water/wastewater treatment. The prospect of using the co-solvent mediated SG-modified layer as a next-generation anti-fouling/antimicrobial membrane is very encouraging.
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No pos
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No neg
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Retriever2814
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Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine.
N -Glycolylneuraminic acid (Neu5Gc), an abundant sialic acid in animal glycoconjugates, is formed by the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. The amount of Neu5Gc relative to other sialic acids is highly dependent on the species, tissue and developmental stage. Although the activity of the hydroxylase is a key factor in controlling Neu5Gc incorporation in adult animals, little is known about the regulation of hydroxylase expression and the role of this enzyme in determining changes in Neu5Gc during development. Using pig small intestine as a model system, the appearance of total sialic acid and the regulation of Neu5Gc biosynthesis during development were studied in various regions of this tissue. The amount of total sialic acid and Neu5Gc declined markedly in 2 weeks after birth. Although in subsequent developmental phases there were no positional differences in total sialic acid, a significant proximal-to-distal increase in Neu5Gc was detected. In all cases, a good correlation between the amount of Neu5Gc, the activity of the hydroxylase and the level of hydroxylase mRNA was observed. However, Western-blot analysis revealed considerable accumulation of less active enzyme in the post partum period, which persisted until adulthood. No evidence for cytosolic factors influencing the hydroxylase activity or for the formation of truncated enzyme was found, raising the possibility that other regulatory mechanisms are involved. The relevance of these results in the formation of Neu5Gc as a receptor for certain pig enteric pathogens is also discussed.
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No pos
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No neg
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Retriever2815
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Effect of the weakly acidic uncoupler 2,4-dinitrophenol and dimethyl sulfoxide on the coordination of Mg2+ with ATP. Possible mechanism of activation of the isolated F1-ATPase by 2,4-dinitrophenol.
The exchange rate constants between Mg2(+)-free and Mg2(+)-bound ATP were determined under various conditions by line shape analysis of the 31P-NMR spectrum based on the exchange reaction, and the thermodynamic parameters of this exchange reaction were determined from the temperature dependence of its rate constants. Analysis of the activation enthalpy change delta H showed that Mg2+ is coordinated with the beta- and gamma-phosphoryl groups of ATP asymmetrically, being in closer proximity to the beta-phosphoryl group. The weakly acidic uncoupler 2,4-dinitrophenol increased this asymmetric coordination of Mg2+, and this effect was enhanced by the further addition of dimethyl sulfoxide. The hydrolysis of ATP in aqueous solution correlated well with the degree of asymmetry of Mg2+ coordination. Thus, this asymmetric coordination specifically weakens the O-P gamma bond at which specific cleavage of ATP catalyzed by most ATPases takes place in the presence of Mg2+. In this paper, the mechanism of activation of isolated ATPase (F1-ATPase) by 2,4-dinitrophenol, and that of ATP synthesis by isolated F1-ATPase in the presence of dimethyl sulfoxide are considered on the basis of these results. The essential role of the OH group of Ser-174 of the beta-subunit of F1-ATPase in ATP hydrolysis is also discussed.
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No pos
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No neg
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Retriever2816
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Determinants of inequalities in the quality of Brazilian diet: trends in 12-year population-based study (2003-2015).
BACKGROUND
Recent studies have explored the influence of socioeconomic inequalities on the diet quality. However, there is lack of evidence regarding the level of inequalities in dietary quality and its main contributing factors from population-based follow-up studies. The primary objective of this study was to investigate the level and the determinants of inequalities in diet quality in a representative sample of adolescents, adults and older adults resident in São Paulo, Brazil.
METHODS
Data from the Health Survey of São Paulo (ISA-Capital) were analyzed for 2003 (n = 2398), 2008 (n = 1662) and 2015 (n = 1742) surveys. Information on food consumption was obtained through 24-h dietary recall, and diet quality was assessed based on the Revised Brazilian Healthy Eating Index (BHEI-R). The descriptive variables were compared using 95% confidence interval. The scores of BHEI-R and its components were compared across age groups and year. The association between socioeconomic inequalities and diet quality was based on the estimation of concentration index.
RESULTS
We observed that the BHEI-R scores gradually improved over 12-years, with older adults showing the greatest improvement. The increase in overall population score was observed for total fruits, whole fruits, whole grains, oils and sodium. The main contributor to socioeconomic inequality in diet quality in 2003 was ethnic group, and in 2008 and 2015, it was per capita household income; age was a persistent factor of inequality in the population over the years. Concentration indices indicated that lower income individuals had higher BHEI-R scores in 2003; however, there was a shift in favor of higher income individuals in 2008 and 2015.
CONCLUSIONS
Changes in the patterns of determination of inequalities according to age, ethnic group or income during the period analyzed show the existence of ongoing process of contribution of demographic and socioeconomic factors in the diet quality of individuals in a large urban center.
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No pos
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No neg
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Retriever2817
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Melanoma Early Detection: Big Data, Bigger Picture.
Innovative technologies, including novel communication and imaging tools, are affecting dermatology in profound ways. A burning question for the field is whether we will retrospectively react to innovations or proactively leverage them to benefit precision medicine. Early detection of melanoma is a dermatologic area particularly poised to benefit from such innovation. This session of the Montagna Symposium on Biology of Skin focused on provocative, potentially disruptive advances, including crowdsourcing of patient advocacy efforts, rigorous experimental design of public education campaigns, research with mobile phone applications, advanced skin imaging technologies, and the emergence of artificial intelligence as a diagnostic supplement.
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No pos
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No neg
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Retriever2818
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Human infections caused by thiamine- or menadione-requiring Staphylococcus aureus.
Stable dwarf forms of Staphylococcus aureus have been identified in clinical specimens as the sole or predominant isolate in eight cases. These organisms have been shown to be menadione or thiamine dependent, i.e., cultivation in the presence of one of these agents has permitted growth of colonies which appear typical of S. aureus. In vitro resistance to aminoglycosides was overcome by cultivation in the presence of menadione or thiamine. Menadione- or thiamine-requiring S. aureus can be considered as causative agents in severe human infections. Special care must be taken if they are to be identified in pathological specimens. Their antibiotic sensitivity testing should be done comparatively on supplemented and nonsupplemented media.
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No pos
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No neg
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Retriever2819
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Structure and composition of the Shigella flexneri "needle complex", a part of its type III secreton.
Type III secretion systems (TTSSs or secretons), essential virulence determinants of many Gram-negative bacteria, serve to translocate proteins directly from the bacteria into the host cytoplasm. Electron microscopy (EM) indicates that the TTSSs of Shigella flexneri are composed of: (1) an external needle; (2) a transmembrane domain; and (3) a cytoplasmic bulb. EM analysis of purified and negatively stained parts 1, 2 and a portion of 3 of the TTSS, together termed the "needle complex" (NC), produced an average image at 17 A resolution in which a base, an outer ring and a needle, inserted through the ring into the base, could be discerned. This analysis and cryoEM images of NCs indicated that the needle and base contain a central 2-3 nm canal. Five major NC components, MxiD, MxiG, MxiJ, MxiH and MxiI, were identified by N-terminal sequencing. MxiG and MxiJ are predicted to be inner membrane proteins and presumably form the base. MxiD is predicted to be an outer membrane protein and to form the outer ring. MxiH and MxiI are small hydrophilic proteins. Mutants lacking either of these proteins formed needleless secretons and were unable to secrete Ipa proteins. As MxiH was present in NCs in large molar excess, we propose that it is the major needle component. MxiI may cap at the external needle tip.
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No pos
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No neg
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Retriever2820
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No Need for Templates in the Auditory Enhancement Effect.
The audibility of a target tone in a multitone background masker is enhanced by the presentation of a precursor sound consisting of the masker alone. There is evidence that precursor-induced neural adaptation plays a role in this perceptual enhancement. However, the precursor may also be strategically used by listeners as a spectral template of the following masker to better segregate it from the target. In the present study, we tested this hypothesis by measuring the audibility of a target tone in a multitone masker after the presentation of precursors which, in some conditions, were made dissimilar to the masker by gating their components asynchronously. The precursor and the following sound were presented either to the same ear or to opposite ears. In either case, we found no significant difference in the amount of enhancement produced by synchronous and asynchronous precursors. In a second experiment, listeners had to judge whether a synchronous multitone complex contained exactly the same tones as a preceding precursor complex or had one tone less. In this experiment, listeners performed significantly better with synchronous than with asynchronous precursors, showing that asynchronous precursors were poorer perceptual templates of the synchronous multitone complexes. Overall, our findings indicate that precursor-induced auditory enhancement cannot be fully explained by the strategic use of the precursor as a template of the following masker. Our results are consistent with an explanation of enhancement based on selective neural adaptation taking place at a central locus of the auditory system.
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No pos
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No neg
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Retriever2821
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Microembolic signals detected with transcranial doppler sonography differ between symptomatic and asymptomatic middle cerebral artery stenoses in Northeast China.
Although microembolus monitoring has been widely used for ischemic cerebrovascular disease, the clinical significance of microembolic signal (MES) in asymptomatic middle cerebral artery (MCA) stenosis remains unclear. We aim to investigate the frequency of MES and the value of MES in predicting ischemic stroke secondary to asymptomatic MCA stenosis. From June 2011 to December 2012, microembolus monitoring was performed in 83 asymptomatic and 126 symptomatic subjects. By comparing the demographics and risk factors between the symptomatic and asymptomatic subjects, we found that the ratio of male sexuality and smoking history differed (101/126 vs 43/83, and 88/126 vs 38/83, respectively, p<0.01). The frequency of MES was significantly higher in the symptomatic group than in the asymptomatic group (49/126 vs 2/108, p<0.01). Specifically, the frequency of MES in the symptomatic and asymptomatic groups with mild stenosis, moderate stenosis, severe stenosis and occlusion groups was 4/18 (22.22%) vs 0/30 (0), 13/31 (41.94%) vs 1/28 (3.57%), 30/62 (48.39%) vs 1/39 (2.56%), 2/15 (13.33%) vs 0/11 (0), respectively. Except for the occlusive group, the frequency of MES is correlated with stenosis degree and symptom. Two patients in the asymptomatic group were found positive for MES, and the MES number was 1 for both. During the one-year follow-up, neither of them developed ischemic stroke. In conclusion, MES detected with TCD differs between symptomatic and asymptomatic MCA stenoses. Due to the low frequency, the value of MES as a predictor of subsequent ischemic stroke in patients with asymptomatic MCA stenosis might be limited.
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No pos
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No neg
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Retriever2822
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Intestinal Lipolysis Mitigates Nonalcoholic Fatty Liver Disease: New Roles for Carboxylesterase 2c in the Intestine.
The most important argument of this study is that modulation of intestinal lipid metabolism by enhancing intestinal Ces2c expression has the potential to affect hepatic and systemic lipid metabolism, regulating the development of NAFLD and systemic insulin resistance.
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No pos
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No neg
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Retriever2823
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Studies on the PR toxin of Penicillium roqueforti.
A mycotoxin, confirmed by chemical, physical and spectroscopic data as the PR toxin described by Ru-Dong Wei and coll. (15) has been isolated from culture filtrates of Penicillium roqueforti Thom. Factors affecting the toxin and mycelium production, acute and chronic toxicity in experimental animals and the frequency of toxinogenesis of 21 isolates of P. roqueforti (including a brown mutant) isolated from different materials, foods especially, were also studied. An hypothesis on the absence of PR toxin in cheeses fermented with P. roqueforti is also advanced.
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No pos
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No neg
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Retriever2824
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Attentional selection in the processing of hierarchical patterns: an ERP study.
The current study aimed to investigate the effect of attentional selection of distinctive local elements on the processing of hierarchically organized patterns. Event-related brain potentials (ERPs) were recorded from subjects during identifications of global or local shapes of hierarchical patterns where either all local elements were identical (homogeneous stimulus) or a local element closest to fixation was distinguished by color from others (pop-out stimulus). One group of subjects was presented with the homogeneous stimuli and required to identify global or local shapes in separate blocks of trials. The other group was presented with the pop-out stimuli and asked to attend to the unique local item in the local task. A global precedence effect was observed in behavioral data. ERPs showed enlarged posterior P1 and N2 amplitudes in the local relative to global conditions. Top-down attention to the pop-out item resulted in increased frontal/central N2 amplitudes in the local condition but eliminated the temporal/occipital N2 enhancement in the local relative to global conditions. Top-down attention to the pop-out item also increased local-to-global interference in reaction times and frontal N2 latencies. The results suggest that a frontal mechanism is involved in directing top-down attention to a specific local item whereas a temporal/occipital mechanism is engaged in an attentional filtering process in the identification of local shapes in hierarchical analysis.
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No pos
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No neg
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Retriever2825
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Malignant gastroparesis: pathogenesis and management of an underrecognized disorder.
Gastroparesis is a disorder of the stomach caused by delayed gastric emptying in the absence of mechanical obstruction. Symptoms of gastroparesis include nausea, vomiting, early satiety, bloating, and abdominal discomfort. Gastroparesis has been described as a complication of several malignancies, including gastric, pancreatic, gallbladder, esophageal, and lung cancers, as well as leiomyosarcoma. The prevalence of malignant gastroparesis (MG) is unknown, and this entity is widely underrecognized and undertreated. Diabetes mellitus is the most common identifiable cause of benign gastroparesis, ie, gastroparesis occurring in the absence of an underlying malignant pathology. In the setting of malignancy, gastroparesis may result from the cancer itself or may be a complication of its treatment with such modalities as surgery, radiation therapy, or chemotherapy. Coexisting conditions, including diabetes, hypothyroidism, and neurologic diseases, may further exacerbate MG. The pathogenesis of MG is not clearly understood at present. However, mechanisms suggested in the literature include postvagotomy syndrome, malignant infiltration of the autonomic nervous system, and paraneoplastic dysmotility with autoantibody-mediated destruction of the enteric nervous system (the interstitial cells of Cajal, also called the intrinsic pacemaker of the gastrointestinal tract, or the myenteric plexus). Appropriate treatment of MG may help to avoid serious consequences, such as cancer cachexia, intolerance of oral anticancer agents, dehydration, and hospitalization. In this article, we will describe our institutional experience with MG and will provide a concise review of the literature. Guidelines for management will be suggested.
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No pos
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No neg
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Retriever2826
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Dynamic contrast-enhanced MRI of the prostate with high spatiotemporal resolution using compressed sensing, parallel imaging, and continuous golden-angle radial sampling: preliminary experience.
PURPOSE
To demonstrate dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate with both high spatial and temporal resolution via a combination of golden-angle radial k-space sampling, compressed sensing, and parallel-imaging reconstruction (GRASP), and to compare image quality and lesion depiction between GRASP and conventional DCE in prostate cancer patients.
MATERIALS AND METHODS
Twenty prostate cancer patients underwent two 3T prostate MRI examinations on separate dates, one using standard DCE (spatial resolution 3.0 × 1.9 × 1.9 mm, temporal resolution 5.5 sec) and the other using GRASP (spatial resolution 3.0 × 1.1 × 1.1 mm, temporal resolution 2.3 sec). Two radiologists assessed measures of image quality and dominant lesion size. The experienced reader recorded differences in contrast arrival times between the dominant lesion and benign prostate.
RESULTS
Compared with standard DCE, GRASP demonstrated significantly better clarity of the capsule, peripheral/transition zone boundary, urethra, and periprostatic vessels; image sharpness; and lesion conspicuity for both readers (P < 0.001-0.020). GRASP showed improved interreader correlation for lesion size (GRASP: r = 0.691-0.824, standard: r = 0.495-0.542). In 8/20 cases, only GRASP showed earlier contrast arrival in tumor than benign; in no case did only standard DCE show earlier contrast arrival in tumor.
CONCLUSION
High spatiotemporal resolution prostate DCE is possible with GRASP, which has the potential to improve image quality and lesion depiction as compared with standard DCE.
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No pos
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No neg
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Retriever2827
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Is haptic feedback necessary to microsurgical suturing? Comparative study of 9/0 and 10/0 knot tying operated by 24 surgeons.
Robotically assisted telemanipulators are often criticised for their lack of direct haptic feedback. However, robotically assisted microsurgical sutures have already been achieved successfully. The aim of this study was to demonstrate that haptic feedback is not necessary in microsurgery. Our series included 24 surgeons of whom 14 were micro-surgeons. Each of them had to tighten a 9/0 and a 10/0 pre-tied nylon thread until getting the sensation of optimal knot tying. The procedure was performed four times, with open and closed eyes. The quality of knot tying was evaluated (fully tied, fairly or incompletely tied, or broken thread). The results obtained with the eyes open were significantly better. Neither the material size, nor the surgeon's expertise was shown to have an impact on knot tying quality. Our results demonstrate the uselessness of haptic feedback in microsurgery.
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No pos
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No neg
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Retriever2828
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Rapid stromal remodeling by short-term VEGFR2 inhibition increases chemotherapy delivery in esophagogastric adenocarcinoma.
Anti-angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit is limited, urging the improvement of combination therapies. We aimed to clarify the effects of vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration of drugs in esophagogastric adenocarcinoma (EAC). Patient-derived xenograft (PDX) models of EAC were subjected to long-term and short-term treatment with anti-VEGFR2 therapy followed by chemotherapy injection or multi-agent dynamic contrast-enhanced (DCE-) MRI and vascular casting. Long-term anti-VEGFR2-treated tumors showed a relatively lower flow and vessel density resulting in reduced chemotherapy uptake. On the contrary, short-term VEGFR2 targeting resulted in relatively higher flow, rapid vasodilation, and improved chemotherapy delivery. Assessment of the extracellular matrix (ECM) revealed that short-term anti-angiogenic treatment drastically remodels the tumor stroma by inducing nitric oxide synthesis and hyaluronan degradation, thereby dilating the vasculature and improving intratumoral chemotherapy delivery. These previously unrecognized beneficial effects could not be maintained by long-term VEGFR2 inhibition. As the identified mechanisms are targetable, they offer direct options to enhance the treatment efficacy of anti-angiogenic therapy combined with chemotherapy in EAC patients.
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No pos
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No neg
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Retriever2829
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Temporal Assessment of Prognostic Factors in Patients With Pancreatic Ductal Adenocarcinoma Undergoing Neoadjuvant Treatment and Resection.
BACKGROUND
The clinicopathologic factors associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC) during the different phases of neoadjuvant treatment (NT)-at diagnosis, restaging, or postoperatively-remain unclear.
METHODS
Data of patients with PDAC who underwent pancreatic resection after NT between 2008 and 2018 were retrospectively collected. Clinicopathologic characteristics and outcomes were compared stratified by resection margin status. Three multivariable regression models (at diagnosis, restaging, and postoperatively) were constructed to assess the temporal impact of different prognostic factors on all-cause survival (ACS) and disease-free survival (DFS).
RESULTS
All patients were diagnosed with a nonmetastatic PDAC and were appropriate candidates for NT according to the current National Comprehensive Cancer Network guidelines. From a total of 83 patients, 57 (68.7%) had a negative resection margin >1 mm (R0), whereas 26 patients (31.3%) had a positive resection margin (R1). At diagnosis, planned procedure (P = 0.017) and CA19-9 >100 U/mL (P = 0.047) were independent prognostic factors of decreased ACS. At restaging, planned procedure (P = 0.017), FOLFIRINOX (P = 0.026), and tumor size >30 mm (P = 0.030) were independent prognostic factors for increased and decreased ACS, respectively. Postoperatively, R0 was an independent prognostic factor for improved ACS (P = 0.005) and DFS (P = 0.002), whereas adjuvant therapy (P = 0.006) was associated with increased ACS. Lymph node involvement (P = 0.019) was associated with decreased DFS.
CONCLUSIONS
At diagnosis, restaging, and postoperatively, different, relevant clinicopathologic factors significantly impact the survival of patients with nonmetastatic PDAC undergoing NT. An R0 resection remains the most important prognostic factor and therefore should be the primary goal of surgical treatment in the neoadjuvant setting.
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No pos
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No neg
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Retriever2830
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RANK/RANKL Acts as a Protective Factor by Targeting Cholangiocytes in Primary Biliary Cholangitis.
BACKGROUND
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the highly selective autoimmune injury of small intrahepatic bile ducts. Studies reported that the cholangiocytes from PBC patients expressed significantly higher levels of both receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL. However, the accurate role of RANK/RANKL axis in PBC remains unclear.
METHODS
Forty patients with PBC were enrolled according to the inclusion criteria. The biochemical parameters (alkaline phosphatase, ALP; gamma-glutamyltransferase, GGT; alanine aminotransferase, ALT; aspartate transaminase, AST; total bilirubin, TB) were collected at baseline and followed-up after 6 months of treatment with ursodeoxycholic acid (UDCA, 15 mg/kg d). Stages of PBC were diagnosed based on liver biopsy histopathology according to Nakanuma's criteria. RANK expression in hepatic tissues was detected by immunohistochemistry. The cellular immunofluorescence method was used to locate the distribution of RANK in the human intrahepatic biliary epithelial cells (HIBECs) cultured in vitro. HIBECs were treated with RANKL at a concentration of 100 ng/ml or transfected with RANK-overexpressing lentivirus (LV-RANK). CCK-8 assay and cell cycle assay were used to detect the cell proliferation. Real-time PCR was used to detect the expression of IL-6, E-cadherin, VCAM, ICAM-1, TNF-α, and CD80.
RESULTS
RANK expression in liver biopsies from early PBC patients (stage I + stage II) was significantly lower than that from advanced PBC patients (stage III + stage IV) (1.7 ± 0.63 vs. 2.3 ± 0.45 scores, P < 0.05). High-RANK patients seemed to have better response to UDCA than low-RANK patients (88.9% vs. 40.9%, P < 0.05). The baseline biochemical parameters between the two groups were comparable. The decline percentages of ALP and GGT after UDCA treatment were more obvious in high-RANK patients than those in low-RANK patients (53.90% ± 9.82% vs. 23.93% ± 6.24%, P < 0.05; 74.11% ± 7.18% vs. 48.00% ± 8.17%, P < 0.05, respectively). HIBECs proliferation was significantly inhibited after treatment of RANKL or transfection with LV-RANK. Increased expression of IL-6 and E-cadherin was observed in HIBECs treated with RANKL or LV-RANK.
CONCLUSION
The overall hepatic RANK expression was associated with disease severity and biochemical response in PBC patients. Activation of RANK/RANKL signaling pathway inhibited cholangiocytes proliferation in vitro. Our study suggested that RANK/RANKL pathway might be a potential target of immunotherapy of PBC based on its involvement in the occurrence and development of the disease.
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No pos
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No neg
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Retriever2831
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Apoptotic pathways mobilized in microglia and neurones as a consequence of chromogranin A-induced microglial activation.
Senile plaques of Alzheimer's brain are characterized by activated microglia and immunoreactivity for the peptide chromogranin A. We have investigated the mechanisms by which chromogranin A activates microglia, producing modulators of neuronal survival. Primary cultures of rat brain-derived microglia display a reactive phenotype within 24 h of exposure to 10 nM chromogranin A, culminating in microglial death via apoptotic mechanisms mediated by interleukin-1beta converting enzyme. The signalling cascade initiated by chromogranin A triggers nitric oxide production followed by enhanced microglial glutamate release, inhibition of which prevents microglial death. The plasma membrane carrier inhibitor aminoadipate and the type II/III metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-sulphonophenylglycine are equally protective. A significant amount of the released glutamate occurs from bafilomycin-sensitive stores, suggesting a vesicular mode of release. Inhibition of this component of release affords significant microglial protection. Conditioned medium from activated microglia kills cerebellar granule cells by inducing caspase-3-dependent neuronal apoptosis. Brain-derived neurotrophic factor is partially neuroprotective, as are ionotropic glutamate receptor antagonists, and, when combined with boiling of conditioned medium, full protection is achieved; nitric oxide synthase inhibitors are ineffective.
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No pos
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No neg
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Retriever2832
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[Ultrasound screening in pregnancy: evidence and maternity care reality].
Since 1980 maternity care in Germany has included ultrasound screening. The aim of this review is (1) to assess the benefit of ultrasound screening on the basis of randomised, controlled trials in accordance with the criteria of evidence-based medicine, (2) to examine current screening practice and the quality of German maternity care in everyday clinical practice, and (3) to indicate priorities for further screening developments. We reviewed Cochrane reviews, health technology assessment reports and relevant individual studies. The three essential effects that may be achieved by ultrasound screening include: (1) earlier detection of multiple pregnancies, (2) better dating of pregnancy and reduction in induced labour by 40%, and (3) more frequent and earlier detection of foetal malformations including the option for an abortion. Yet, early detection does not increase the rate of successful pregnancies. The effects mentioned are only incompletely achieved with standard maternity care in Germany. For example, there is no evidence for an essential reduction of the frequency with which labour is induced. Detection rates in routine preventive care are markedly lower than described for trial conditions. Only multiple pregnancies can be identified more or less completely; detecting other target diagnoses remains unsatisfactory: placenta praevia 57% (without signs of bleeding 14%), postmaturity 46%, malformations 30-40% and intrauterine growth retardation 30%. Also, high rates of false positive findings can be observed that might lead to follow-up examinations and unnecessary treatment procedures. Quality of maternity screening is low and is not subjected to substantial quality assurance. We suggest the following priority measures: (1) to improve the quality of screening by modifying the previous three-step concept with the aim of promoting accessibility of highly qualified examiners for all pregnant women, (2) to strengthen quality assurance, (3) to assist the pregnant woman with her informed decision by offering independent and non-directional counselling concerning the advantages and disadvantages of screening and (4) to focus maternity care on effective interventions according to the criteria of evidence-based medicine.
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No pos
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No neg
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Retriever2833
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Survival of Implants in Immediate Extraction Sockets of Anterior Teeth: Early Clinical Results.
BACKGROUND
The aims and objectives of this study were placement of implants in freshly extracted sockets of anterior teeth and to evaluate the implant stability, peri-implant radiolucency and gingival inflammation around implant over a short period of 30 months.
MATERIALS AND METHODS
A total of 12 patients (8 male and 4 female), ranging in the age from 20 to 50 years, from March 2007 to June 2007, were evaluated for immediate implant placement into 22 fresh extraction sockets. Only maxillary and mandibular anterior teeth/roots (central incisors, lateral incisors and canines) were considered for replacement with implants. One piece implant with integrated abutment and integrated surface, non-submerged, threaded and tapered at apical 5 mm, sand-blasted and acid etched surfaced implants (HI-TEC TRX-OP Implants of Life Care Company) were used.
RESULTS
The mobility was not present in any of the implants at all the follow up visits. There were 2 implants at 6 month, 1 implant at 12 month, 1 implant at 18 month visits, showing peri-implant radiolucency at some sites at bone to implant contact site. Severe gingival inflammation was not observed in any of the implant site. At every follow-up visit, every implant met the criteria of success and none was found to be failed over a 30 months duration i.e. 100% success rate was achieved by implants in immediate extraction socket.
CONCLUSION
The success rate of implant survival in this study was found 100%. These implants have fulfilled all the criteria of implant success and based on the defined criteria, the success rate of implants placed in immediate extraction sockets of anterior teeth compared favorably with the conventional implants. The early results of the present study showed that high survival rates with the implants in immediate extraction sockets can be achieved.
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No pos
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No neg
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Retriever2834
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Aesthetic Penile Augmentation Procedures: A Comprehensive and Current Perspective.
PURPOSE OF REVIEW
Some men experience small penis syndrome (SPS), a body dysmorphic disorder in which a patient believes their penis to be small even when it is clinically average. As cosmetic surgery becomes more widely accepted, management of SPS may present a challenge for urologists. We aim to provide an updated review of aesthetic penile augmentation procedures.
RECENT FINDINGS
Augmentation procedures range from invasive to noninvasive. Surgical solutions include grafts and flaps, suspensory ligament release, and suprapubic lipectomy. Minimally invasive solutions include injections of fillers (hyaluronic acid, polylactic acid, and polymethyl methacrylate). Noninvasive solutions include external devices such as vacuum pumps and traction devices. In the current climate, aesthetic penile augmentation is becoming a desirable option for many patients but remains clinically controversial. Our review summarizes recent and relevant studies and demonstrates the need for further research and consensus on penile augmentation procedures.
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No pos
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No neg
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Retriever2835
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Development and Application of a Work-process Classification.
Occupational exposures are related to work processes carried out by the individual worker. A classification of the work processes was developed on the basis of analyses of several databases. Work-process data were collected in a sample of Danish employees. An unambiguous, exhaustive work-process classification was developed where the work process was defined as the transformation of a work object into a product. A test showed that at least 85% of free-text data on occupational injuries contained work-process data. To illustrate applications of the classification, work-process data were used to define highly exposed and unexposed job groups. This classification may be useful for (for example) major general surveys to supplement the exposure information that job and industry classifications yield.
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No pos
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No neg
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Retriever2836
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Consumers' attitudes towards GM Free products in a European Region. The case of the Prefecture of Drama-Kavala-Xanthi in Greece.
This study aims to identify the factors that affect consumers purchasing behaviour towards food products that are free from Genetic Modified Organism (GM Free) in a European Region and more precisely in the Prefecture of Drama-Kavala-Xanthi. Field interviews conducted in a random selected sample consisted of 337 consumers in the cities of Drama, Kavala, Xanthi, in November and December of 2009. Principal components analysis (PCA) was conducted in order to identify the factors that affect people in preferring consuming products that are GM Free. The factors that influence people in the study area to buy GM Free products are: (a) products' certification as GM Free or organic products, (b) interest about the protection of the environment and nutrition value, (c) marketing issues, and (d) price and quality. Furthermore, cluster and discriminant analysis identified two groups of consumers: (a) those are influenced by the product price, quality and marketing aspects and (b) those are interested in product's certification and environmental protection. Non parametric statistical bivariate techniques were performed to profile the identified groups of consumers regarding their personal characteristics and some other factors affecting their buying behaviour.
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No pos
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No neg
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Retriever2837
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[Management of neurourological patients during the COVID-19 pandemic.]
To report the recommendations of an expert panel to reorganize Neurourology units and to prioritize examinations and both conservative and surgical treatments during the COVID-19 pandemic. MATERIALS AND METHODS: Non-systematic review of the literature and national experts' opinion summarizing the recommendations in the diagnosis, management, and follow-up of neurourological patients during the COVID-19 pandemic. A modified nominal group technique was used due to extraordinary meeting and mobility restrictions during COVID-19 pandemic. RESULTS: Neurourological patients have special physiological and pathological characteristics that make them more vulnerable to SARS-CoV-2 infection. For prioritization purposes, they encompass in Functional Urology patients and their management is considered non-urgentor delayable with no specific deadline of recovery from normality. However, it is important to identify individual situations jeopardising the upper urinary tract, urinary retention or predisposing to urinary infections/sepsis. A classification is provided prioritizing conservative/outpatient management and the surgical treatment of the events occurring in neurourological patients during the COVID-19 pandemic. CONCLUSIONS: In neurourological patients we can find exceptional clinical situations in which a delayed treatment could develop irreversible changes in the upper urinary tract, advocating a more urgent treatment inspecific scenarios.
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No pos
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No neg
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Retriever2838
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Efficient Video Watermarking Algorithm Based on Convolutional Neural Networks with Entropy-Based Information Mapper.
This paper presents a method for the transparent, robust, and highly capacitive watermarking of video signals using an information mapper. The proposed architecture is based on the use of deep neural networks to embed the watermark in the luminance channel in the YUV color space. An information mapper was used to enable the transformation of a multi-bit binary signature of varying capacitance reflecting the entropy measure of the system into a watermark embedded in the signal frame. To confirm the effectiveness of the method, tests were carried out for video frames with a resolution of 256 × 256 pixels, with a watermark capacity of 4 to 16,384 bits. Transparency metrics (SSIM and PSNR) and a robustness metric-the bit error rate (BER)-were used to assess the performance of the algorithms.
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No pos
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No neg
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Retriever2839
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Lipid Species Dependent Vesicles Clustering Caused by alpha-Synuclein as Revealed by Single-Vesicle Imaging with Total Internal Reflection Fluorescence Microscopy.
Single-molecule methods have been applied to study the mechanisms of many bio-physical systems that occur on the nanometer scale. To probe the dynamics of the such systems including vesicle docking, tethering, fusion, trafficking, protein-membrane interactions, etc., and to obtain reproducible experimental data; proper methodology and framework are crucial. Here, we address this need by developing a protocol for immobilization of vesicles composed of synthetic lipids and measurement using total internal reflection fluorescence (TIRF) microscopy. Furthermore, we demonstrate applications including vesicle clustering mediated by proteins such as alpha-Synuclein (αSyn) and the influence of external ions by using TIRF microscopy. Moreover, we use this method to quantify the dependence of lipid composition and charge on vesicle clustering mediated by αSyn which is based on the methods previously reported.
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No pos
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No neg
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Retriever2840
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[A comparative study of efficacy and safety of torin and zoloft].
Zoloft (sertraline) is an original antidepressant of "Pfizer", torin is a generic form of sertraline of Veropharm. An aim of the study was to compare clinical effectiveness and tolerability of original and generic drugs. Forty patients with moderate and severe depression without psychotic symptoms have been studied: 20 of them were treated with torin and 20 with zoloft. Patient's state has been assessed during 7 weeks (1 week--wash out and 6 week--active therapy) clinically and using the Hamilton and CGI scales on 7th, 14th, 21st, 28th and 42nd days. The clinical equivalence of torin and the original drug demonstrated. Torin had a distinct thymoanaleptic effect, the primary action of which addresses anxious affect. This drug was soft as well as zoloft.
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No pos
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No neg
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Retriever2841
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Fermentative polyhydroxybutyrate production from a novel feedstock derived from bakery waste.
In this study, Halomonas boliviensis was cultivated on bakery waste hydrolysate and seawater in batch and fed-batch cultures for polyhydroxybutyrate (PHB) production. Results demonstrated that bakery waste hydrolysate and seawater could be efficiently utilized by Halomonas boliviensis while PHB contents between 10 and 30% (w/w) were obtained. Furthermore, three methods for bakery waste hydrolysis were investigated for feedstock preparation. These include: (1) use of crude enzyme extracts from Aspergillus awamori, (2) Aspergillus awamori solid mashes, and (3) commercial glucoamylase. In the first method, the resultant free amino nitrogen (FAN) concentration in hydrolysates was 150 and 250 mg L(-1) after 20 hours at enzyme-to-solid ratios of 6.9 and 13.1 U g(-1), respectively. In both cases, the final glucose concentration was around 130-150 g L(-1). In the second method, the resultant FAN and glucose concentrations were 250 mg L(-1) and 150 g L(-1), respectively. In the third method, highest glucose and lowest FAN concentrations of 170-200 g L(-1) and 100 mg L(-1), respectively, were obtained in hydrolysates after only 5 hours. The present work has generated promising information contributing to the sustainable production of bioplastic using bakery waste hydrolysate.
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No pos
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No neg
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Retriever2842
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Inhibition of human T-cell leukemia virus type 2 Rex function by truncated forms of Rex encoded in alternatively spliced mRNAs.
Three mRNA species encoding the x-III open reading frame are expressed in human T-cell leukemia virus type 2 (HTLV-2)-infected cells. An mRNA composed of exons 1, 2, and 3 produces the essential posttranscriptional regulator Rex; shorter 1-3 and 1-B mRNAs encode a family of x-III proteins of unknown function that represent truncated forms of Rex. This report presents an analysis of the functional interactions between Rex and the x-III proteins, results of which suggest a role for the x-III proteins as negative regulators of Rex function. Cotransfection assays demonstrated that the x-III proteins were able to inhibit the ability of Rex to activate the expression of a Rex-dependent mRNA. Analysis of intracellular compartmentalization in actinomycin D-treated cells showed that coexpression of the x-III proteins resulted in the sequestration of Rex into the nuclear compartment. Subcellular fractionation studies showed that Rex was preferentially localized in the cytoplasmic or nuclear fraction depending on its phosphorylation status and that coexpression of Rex with the x-III proteins changed the phosphorylation pattern of Rex and the intracellular distribution of the x-III proteins. In vitro protein binding assays demonstrated the formation of Rex-Rex homomultimeric complexes; however, mixed Rex/x-III multimers were not detected. These findings indicated a correlation between phosphorylation and intracellular trafficking of Rex and suggested that the mechanism underlying the inhibitory effects of the x-III proteins might result from an interference with these processes.
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No pos
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No neg
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Retriever2843
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Involvement of reactive oxygen species and nitric oxide in gastric ischemia-reperfusion injury in rats: protective effect of tetrahydrobiopterin.
The purpose of this study was to examine whether tetrahydrobiopterin (BH4), a cofactor of nitric oxide (NO) synthase, attenuates gastric ischemia-reperfusion injury induced by clamping of the celiac artery. Gastric injury was assessed by a formation of gastric mucosal erosions. The gastric injury was observed at 30 and 60 min after reperfusion following 30-min ischemia and was reduced by superoxide dismutase (SOD), catalase, or NO synthase inhibitors. Therefore, reactive oxygen species (ROS) and NO seem to be implicated in the ischemia-reperfusion injury. Treatment with BH4 reduced the ischemia-reperfusion injury. Pretreatment with sepiapterin, a precursor of BH4, also reduced the ischemia-reperfusion injury with an increase in BH4 content in serum and stomach. Both the increase in BH4 content and the protective effect of sepiapterin were prevented of pretreatment with N-acetylserotonin, an inhibitor of BH4 synthesis. These results suggest that the increase in BH4 content may protect against gastric ischemia-reperfusion injury via reduction of ROS and/or NO toxicity. BH4 might be useful as a therapeutic agent for gastric ischemia-reperfusion injury.
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No pos
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No neg
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Retriever2844
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Structures of the N-linked carbohydrate of ascorbic acid oxidase from zucchini.
The N-glycan moiety of ascorbic acid oxidase from zucchini (Cucurbita pepo) has been described to be a core-pentasaccharide with a xylose [D'Andrea et al. (1988) Glycoconjugate J 5:151-7]. Ascorbic acid oxidase is sometimes used to characterize antibodies directed against carbohydrate determinants on plant glycoproteins. To prevent misinterpretations of immunological data, the structure of the N-glycan of ascorbic acid oxidase has been reinvestigated. The oligosaccharides were released by almond N-glycosidase and analysed as their pyridylamino derivatives by 2D-HPLC and exoglycosidase digestions. The main structure resembled the typical complex plant N-glycan consisting of a core-pentasaccharide decorated with xylose and 3-linked fucose. The other abundant species lacked the fucose residue. Small amounts of these glycans carried a GlcNAc residue on the 6-arm. Therefore, ascorbic acid oxidase will not only react with antibodies directed against the xylosylated region but also with those binding to N-glycans with 3-linked fucose.
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No pos
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No neg
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Retriever2845
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Response of melatonin receptor MT1 in spleen of a tropical Indian rodent, Funambulus pennanti, to natural solar insolation and different photoperiodic conditions.
We analyzed the effect of natural solar insolation and artificial photoperiodic conditions on melatonin MT1 receptor expression of a tropical rodent, Funambulus pennanti. Melatonin mediates reproductive and circadian responses and regulates the production of a large number of cytokines, including interleukin-2 (IL-2), via modulation of MT1 receptor expression. Maximum pineal activity, resulting in high melatonin level, low melatonin receptor expression, and increased splenic mass, was noted in the winter months, while an opposite effect was noted during the summer months. Further, constant light exposure mimicked an "enhanced summer"-like condition with significant hyposplenia, and an opposite effect was observed with constant dark exposure with significant splenomegaly in F. pennanti. In the annual study, a slight increase in melatonin level was noted during the monsoon period, when the duration of photoperiod was the same but the amount of solar insolation and direct radiation decreased. The present study found that not only the duration of natural sunlight (i.e., photoperiod) but the intensity of sunlight expressed by solar insolation affects the circulatory level of melatonin and melatonin receptor expression in this wild tropical rodent. An increase in the circulatory level of melatonin induced a decrease in its receptor subtype MT1 expression in splenic cells, both at the transcriptional and translational levels, thus reflecting autoregulatory down-regulation of melatonin receptors. Therefore, in our animal model, F. pennanti melatonin may be suggested as a molecular messenger of photoperiodic signals (duration and intensity) directly acting via MT1 receptor regulation to adapt the immune system of animals residing in the tropical zone.
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No pos
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No neg
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Retriever2846
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Colopexy as a treatment for rectal prolapse in dogs and cats: a retrospective study of 14 cases.
Colopexy was evaluated as a treatment for recurrent rectal prolapse in eight dogs and six cats. Cases included in the study were from two institutions; the University of Pennsylvania School of Veterinary Medicine and the University of Tennessee College of Veterinary Medicine. Two different colopexy techniques were used: A simple suture technique was used in two cats and four dogs (University of Pennsylvania), and an incisional technique was used in four cats and four dogs (University of Tennessee). Rectal prolapse had not recurred in any of the 14 animals at the time of follow-up. Incisional dehiscence occurred in two animals and in one instance may have been related to the colopexy procedure. Infection at the colopexy site, secondary to suture penetration of the colonic lumen, is a potential complication of this procedure. Colopexy, using either surgical technique described here, was effective in preventing recurrent rectal prolapse.
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No pos
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No neg
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Retriever2847
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A sum rule for Inelastic Electron Tunneling Spectroscopy: an ab initio study of a donor (TTF) and acceptors (TCNE, TCNQ and DCNQI) parallelly oriented on Cu(100).
We performed first-principles simulations of Inelastic Electron Tunneling Spectroscopy (IETS) for horizontally lying individual molecules that form popular donor-acceptor pairs (the TTF donor and its possible partner acceptors TCNE, TCNQ and DCNQI) on Cu(100). We find that the highest frequency C-H stretching modes are highly active for the (electron-rich) donor molecule but inactive for the (electron-poor) acceptors. We explain this contrasting response by the spatial extension of sp(3) rehybridization upon adsorption: the donor molecule entirely deforms into sp(3) while the acceptors rehybridize only at their outer ends leaving the central spacer unaffected. The sp(3)-induced buckling permits in-plane vibration modes to overlap with the π-type tunneling states and hence to be detected in IETS. In addition, the IET-spectra of a family of cyano-group acceptors, TCNE, TCNQ and DCNQI, show a recurring pattern of signals from vibrations involving their common CN outer ends plus a set of compound-dependent signals arising from the spacing moiety. The IET-response of individual chemical groups thus adds up for these flat-lying acceptor molecules, evidencing a sum rule that may facilitate their identification.
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No pos
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No neg
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Retriever2848
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Reverse relationship between malignancy and cyclic AMP-dependent protein kinase activity in Yoshida rat ascites hepatomas.
Rat ascites hepatoma (AH) cells (10(6) cells/head) inoculated intraperitoneally into rats had host-killing ability (malignancy) in the order AH66F > AH44 > AH13 > AH7974 > AH109A > AH66 > AH130. The life span of the rats after inoculation closely correlated with the activity of cyclic AMP-dependent protein kinase (protein kinase A) in the tumor cells but not the activity of Ca2+/phospholipid-dependent protein kinase (protein kinase C). N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinoline-sulfonamide (H-87), a potent, selective inhibitor of protein kinase A, inhibited in vitro growth of these hepatoma cells with a similar potency and, intraperitoneally injected, prolonged the lives of rats bearing less malignant AH66 cells (with high protein kinase A activity) but did not affect the life span of rats bearing highly malignant AH66F cells (with low protein kinase A activity). On the other hand N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), an inhibitor of protein kinase C, inhibited AH66F cells more than AH66 cells, but did not influence the life span of rats bearing either hepatoma. From these results it is deduced that protein kinase A may be important in the regulation of malignancy and in vivo proliferation of AH cells.
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No pos
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No neg
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Retriever2849
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Pre-clinical investigations of multi-path propagation in transcranial Doppler ultrasound flow phantom.
There are various practical situations in medical applications when pre-clinical investigations must be performed using a simulation environment or test bench prior to human studies. One example is the analysis of propagation channels in Transcanial Doppler (TCD) ultrasound (US), a signal processing challenge requiring the analysis of data from US waves scattered in three dimensions (3D). When examining the effects of scatterers in such channels, it is common to use a data acquisition test bench and a Doppler flow phantom. Such medical phantoms are frequently required to verify image and signal processing systems, and are often used to support algorithm development for a wide range of imaging and blood flow assessments. In this paper we describe a TCD simulation environment for the acquisition, investigation and pre-clinical data analysis of multi-path propagation in TCD US systems. This is demonstrated by comparing the anticipated theoretical and simulation channel statistics with the measured acoustic characteristics in terms of the probability distribution and autocorrelation functions.
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No pos
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No neg
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Retriever2850
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Psychological pain and previous suicide attempts in young adults: Results with the Portuguese version of the Psychache Scale.
OBJECTIVES
In this study, we tested whether the unbearable pain scale of the Psychache Scale provides value for the statistical prediction of a previous suicide attempt; we evaluated whether psychological pain has incremental value in the statistical prediction of a previous suicide attempt relative to the reporting of having had a psychiatric diagnosis, and we established a cut-score for the Psychache Scale.
METHOD
Two samples participated: a sample consisting of 1,460 young adults and a sample of 628 Portuguese community adults.
RESULTS AND CONCLUSIONS
Results demonstrated that unbearable pain is not a stronger predictor of a previous suicide attempt than is the bearable pain score of the Psychache Scale; that the total score of the Psychache scale provides an additional statistically significant contribution to the statistical prediction of a previous suicide attempt relative to the reporting of having had a psychiatric diagnosis.
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No pos
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No neg
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Retriever2851
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Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers.
Purpose
The purpose of this study was to profile protein expression liquid vitreous biopsies from patients with uveal melanoma (UM) using mass spectrometry to identify prognostic biomarkers, signaling pathways, and therapeutic targets.
Methods
Vitreous biopsies were collected from two cohorts in a pilot study: comparative control eyes with epiretinal membranes (ERM; n = 3) and test eyes with UM (n = 8). Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Identified proteins were compared to data from a targeted multiplex ELISA proteomics platform.
Results
A total of 69 significantly elevated proteins were detected in the UM vitreous, including LYVE-1. LC-MS/MS identified 62 significantly upregulated proteins in UM vitreous that were not previously identified by ELISA. Analysis of differential protein expression by tumor molecular classification (gene expression profiling [GEP] and preferentially expressed antigen in melanoma [PRAME]) further identified proteins that correlated with these classifications. Patients with high-risk GEP tumors displayed elevated vitreous expression of HGFR (fold-change [FC] = 2.66E + 03, P value = 0.003) and PYGL (FC = 1.02E + 04, P = 1.72E-08). Patients with PRAME positive tumors displayed elevated vitreous expression of ENPP-2 (FC = 3.21, P = 0.04), NEO1 (FC = 2.65E + 03, P = 0.002), and LRP1 (FC = 5.59E + 02, P value = 0.01). IGF regulatory effectors were highly represented (P value = 1.74E-16). Cross-platform analysis validated seven proteins identified by ELISA and LC-MS/MS.
Conclusions
Proteomic analysis of liquid biopsies may provide prognostic information supporting gene expression of tumor biopsies. The use of multiple protein detection platforms in the same patient samples increases the sensitivity of candidate biomarker detection and allows for precise characterization of the vitreous proteome.
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No pos
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No neg
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Retriever2852
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Insights into the pathogenesis of enteropathogenic E. coli using an improved intestinal enterocyte model.
Enteropathogenic E. coli (EPEC) is a human pathogen that targets the small intestine, causing severe and often fatal diarrhoea in infants. A defining feature of EPEC disease is the loss (effacement) of absorptive microvilli (MV) from the surface of small intestinal enterocytes. Much of our understanding of EPEC pathogenesis is derived from studies using cell lines such as Caco-2 - the most extensively used small intestinal model. However, previous work has revealed fundamental differences between Caco-2 cells and in vivo differentiated enterocytes in relation to MV effacement. This, and the high heterogeneity and low transfection efficiency of the Caco-2 cell line prompted the isolation of several sub-clones (NCL-1-12) to identify a more tractable and improved in vivo-like cell model. Along with established Caco-2 clones (TC-7, BBE1), sub-clones were assessed for growth rate, apical surface morphology, epithelial barrier function and transfection efficiency. TC-7 cells provided the best all-round clone and exhibited highest levels of ectopic gene expression following cell polarisation. Novel alterations in EGFP-labelled mitochondria, that were not previously documented in non-polarised cell types, highlighted the potential of the TC-7 model for defining dynamic enterocyte-specific changes during infection. Crucially, the TC-7 cell line also mimicked ex vivo derived enterocytes with regard to MV effacement, enabling a better dissection of the process. Effacement activity caused by the EPEC protein Map in the Caco-2 but not ex vivo model, was linked to a defect in suppressing its Cdc42-dependent functionality. MV effacement activity of the EPEC protein EspF in the TC-7 model was dependent on its N-WASP binding motif, which is also shown to play an essential role in epithelial barrier dysfunction. Together, this study highlights the many advantages of using TC-7 cells as a small intestinal model to study host-pathogen interactions.
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No pos
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No neg
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Retriever2853
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Internal right atrial cardioversion of chronic atrial fibrillation: effects of low-energy biphasic shocks.
This study evaluates the efficacy and safety of internal right atrial cardioversion of atrial fibrillation using a defibrillation right atrial catheter and 2 thoracic patches with low-energy biphasic shocks.
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No pos
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No neg
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Retriever2854
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Novel metabolic drugs and blood pressure: implications for the treatment of obese hypertensive patients?
Hypertension and obesity often coexist, exposing patients to cardiovascular and metabolic risks, particularly type 2 diabetes mellitus. Moreover, obesity may render hypertensive patients treatment resistant. We review how drugs recently approved for obesity or type 2 diabetes mellitus treatment affect blood pressure. The weight-reducing drug lorcaserin induces modest reductions in body weight while slightly improving blood pressure. The fixed low-dose topiramate/phentermine combinations elicit larger reductions in body weight and blood pressure. Concomitant improvements in glucose metabolism, adiposity, and blood pressure differentiate the first clinically available SGLT2 inhibitor dapagliflozin from other oral antidiabetic drugs. Yet, the mechanisms through which metabolic drugs affect blood pressure and their interaction with antihypertensive drugs are poorly understood. Blood pressure-lowering effects of metabolic drugs could be exploited in the clinical management of obese hypertensive patients with and without type 2 diabetes mellitus, particularly in patients with difficult to control arterial hypertension.
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No pos
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No neg
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Retriever2855
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FUS-mediated alternative splicing in the nervous system: consequences for ALS and FTLD.
Mutations in fused in sarcoma (FUS) in a subset of patients with amyotrophic lateral sclerosis (ALS) linked this DNA/RNA-binding protein to neurodegeneration. Most of the mutations disrupt the nuclear localization signal which strongly suggests a loss-of-function pathomechanism, supported by cytoplasmic inclusions. FUS-positive neuronal cytoplasmic inclusions are also found in a subset of patients with frontotemporal lobar degeneration (FTLD). Here, we discuss recent data on the role of alternative splicing in FUS-mediated pathology in the central nervous system. Several groups have shown that FUS binds broadly to many transcripts in the brain and have also identified a plethora of putative splice targets; however, only ABLIM1, BRAF, Ewing sarcoma protein R1 (EWSR1), microtubule-associated protein tau (MAPT), NgCAM cell adhesion molecule (NRCAM), and netrin G1 (NTNG1) have been identified in at least three of four studies. Gene ontology analysis of all putative targets unanimously suggests a role in axon growth and cytoskeletal organization, consistent with the altered morphology of dendritic spines and axonal growth cones reported upon loss of FUS. Among the axonal targets, MAPT/tau and NTNG1 have been further validated in biochemical studies. The next challenge will be to confirm changes of FUS-mediated alternative splicing in patients and define their precise role in the pathophysiology of ALS and FTLD.
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No pos
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No neg
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Retriever2856
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Pathogenicity of the fungus, Verticillium lecanii, to the green peach aphid, Myzus persicae (Hom.: Aphididae).
Pathogenicity of the hyphomycete, Verticillium lecanii (DAOM 198499), was investigated to aphid, Myzus persicae under laboratory conditions. Analysis of lethal effect of six various concentrations 0, 10(4), 10(5), 10(6), 10(7) and 10(8) conidia/ml of V. lecanii against third nymphal stage of M. persicae, indicated significant mortality on aphids. Mean comparisons showed that there was significant difference between treatments. Three days after treatment, aphid mortality observed and after 12 days minimal mortality was 17.77 in control and maximum was 100 percent related to 10(7) and 10(8) conidia/ml. LC50 and LT50 values were estimated by probit analysis and life test. LC50 value for aphid mortality was 1.4 x 10(4) conidia/ml, LT50 values for concentrations 10(4), 10(6), 10(6), 10(7) and 10(8) conidla/ml was 10, 10, 9, 8 and 6 days, respectively. In this experiment, net reproduction rate of aphid's (R0) decreased significantly when concentration increased. These observations showed that V. lecanii (DAOM 198499) can be an active biological agent against aphids.
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No pos
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No neg
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Retriever2857
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[Genomic Analysis-Based Treatment for Cancer of Unknown Primary].
Progress in genomic analysis are expected to improve the treatment outcome of cancers of unknown primary(CUP). We conducted a randomized phase Ⅱ trial of carboplatin plus paclitaxel versus site-specific therapy based on gene expression profiling(GEP)in patients with CUP. A phase Ⅱ trial was conducted in patients with CUP to evaluate the feasibility of site- specific therapy based on NGS-based primary site prediction from GEPs, including irGEP. We proposed the possibility of treatment with immune checkpoint inhibitors for CUP patients. Based on the results, a physician-led clinical trial of nivolumab for CUP was conducted with favorable results.
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No pos
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No neg
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Retriever2858
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The contribution of list length to the absence of the primacy effect in word recall in dementia of the Alzheimer type.
It has repeatedly been demonstrated that patients with dementia of the Alzheimer type (DAT) show an absence of the primacy effect when asked to recall a list of items. The results of the present study show that the absence of the primacy effect in DAT patients is related to list length but probably in a way that is qualitatively not specific since it follows the same pattern as in normal ageing. It is also demonstrated that DAT patients differ in learning style. It is suggested that this indicates a reduced capacity to maintain controlled processing.
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No pos
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No neg
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Retriever2859
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Novel verbal fluency scores and structural brain imaging for prediction of cognitive outcome in mild cognitive impairment.
INTRODUCTION
The objective of this study was to assess the utility of novel verbal fluency scores for predicting conversion from mild cognitive impairment (MCI) to clinical Alzheimer's disease (AD).
METHOD
Verbal fluency lists (animals, vegetables, F, A, and S) from 107 MCI patients and 51 cognitively normal controls were transcribed into electronic text files and automatically scored with traditional raw scores and five types of novel scores computed using methods from machine learning and natural language processing. Additional scores were derived from structural MRI scans: region of interest measures of hippocampal and ventricular volumes and gray matter scores derived from performing ICA on measures of cortical thickness. Over 4 years of follow-up, 24 MCI patients converted to AD. Using conversion as the outcome variable, ensemble classifiers were constructed by training classifiers on the individual groups of scores and then entering predictions from the primary classifiers into regularized logistic regression models. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) was measured for classifiers trained with five groups of available variables.
RESULTS
Classifiers trained with novel scores outperformed those trained with raw scores (AUC 0.872 vs 0.735; P < .05 by DeLong test). Addition of structural brain measurements did not improve performance based on novel scores alone.
CONCLUSION
The brevity and cost profile of verbal fluency tasks recommends their use for clinical decision making. The word lists generated are a rich source of information for predicting outcomes in MCI. Further work is needed to assess the utility of verbal fluency for early AD.
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No pos
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No neg
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Retriever2860
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Fabrication of patterned cell co-cultures on albumin-based substrate: applications for microfluidic devices.
A surface coated with cross-linked albumin film resists the adhesion of cells, and subsequent exposure to UV irradiation or electrostatic adsorption of a cationic polymer switches the surface from non-adherent to adherent. Taking advantage of this unique property of cross-linked albumin, the authors fabricated patterned cell co-cultures with desired patterns and cell types. In this scheme, the cell-adherent region was initially created in the cell-non-adhesive albumin substrate, on which a first cell type was attached. Subsequently, the remaining region was also changed to adherent for the attachment of secondary cells in the same manner, thereby allowing distinctly localized co-cultures. As a proof of concept demonstration of the feasibility of this approach, a patterned co-culture of Neuro-2a cells with L929 cells was successfully prepared on the substrate. Furthermore, combining this technique with a microfluidic technique, a micropatterned co-culture of PA6 cells with 3T3 fibroblasts was created inside microfluidic devices. This approach could potentially be a useful tool for fundamental investigations of cell-cell interactions and for tissue engineering applications.
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No pos
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No neg
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Retriever2861
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In silico evaluation of the mechanical stimulation effect on the regenerative rehabilitation for the articular cartilage local defects.
Osteoarthritis is one of the most severe diseases of the human musculoskeletal system, and therefore, for many years, special attention has been paid to the search for effective methods of its treatment. However, even the most modern methods only in a limited number of cases in the early or intermediate stages of osteoarthritis lead to positive treatment results. In the later stages of development, osteoarthritis is practically incurable and most often ends with disability or the need for joint replacement for a large number of people. One of the main reasons hindering the development of osteoarthritis treatment methods is the peculiarities of articular cartilage, in which there is practically no vascular network and tissue homeostasis is carried out mainly due to the diffusion of nutrients present in the synovial fluid. In modern medicine, for the treatment of osteoarthritis, tissue engineering strategies have been developed based on the implantation of scaffolds populated with chondrogenic cells into the area of the defect. In vitro studies have established that these cells are highly mechanosensitive and, under the influence of mechanical stimuli of a certain type and intensity, their ability to proliferate and chondrogenesis increases. This property can be used to improve the efficiency of regenerative rehabilitation technologies based on the synergistic combination of cellular technologies, tissue engineering strategies, and mechanical tissue stimulation. In this work, using a regenerative rehabilitation mathematical model of local articular cartilage defects, numerical experiments were performed, the results of which indicate that the micro-and macro environment of the restored tissue, which changes during mechanical stimulation, has a significant effect on the formation of the extracellular matrix, and, consequently, cartilage tissue generally. The results obtained can be used to plan strategies for mechanical stimulation, based on the analysis of the results of cell proliferation experimental assessment after each stimulation procedure in vivo.
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No pos
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No neg
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Retriever2862
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Relationship between native papillary muscle T1 time and severity of functional mitral regurgitation in patients with non-ischemic dilated cardiomyopathy.
BACKGROUND
Functional mitral regurgitation is one of the severe complications of non-ischemic dilated cardiomyopathy (DCM). Non-contrast native T1 mapping has emerged as a non-invasive method to evaluate myocardial fibrosis. We sought to evaluate the potential relationship between papillary muscle T1 time and mitral regurgitation in DCM patients.
METHODS
Forty DCM patients (55 ± 13 years) and 20 healthy adult control subjects (54 ± 13 years) were studied. Native T1 mapping was performed using a slice interleaved T1 mapping sequence (STONE) which enables acquisition of 5 slices in the short-axis plane within a 90 s free-breathing scan. We measured papillary muscle diameter, length and shortening. DCM patients were allocated into 2 groups based on the presence or absence of functional mitral regurgitation.
RESULTS
Papillary muscle T1 time was significantly elevated in DCM patients with mitral regurgitation (n = 22) in comparison to those without mitral regurgitation (n = 18) (anterior papillary muscle: 1127 ± 36 msec vs 1063 ± 16 msec, p < 0.05; posterior papillary muscle: 1124 ± 30 msec vs 1062 ± 19 msec, p < 0.05), but LV T1 time was similar (1129 ± 38 msec vs 1134 ± 58 msec, p = 0.93). Multivariate linear regression analysis showed that papillary muscle native T1 time (β = 0.10, 95 % CI: 0.05-0.17, p < 0.05) is significantly correlated with mitral regurgitant fraction. Elevated papillary muscle T1 time was associated with larger diameter, longer length and decreased papillary muscle shortening (all p values <0.05).
CONCLUSIONS
In DCM, papillary muscle native T1 time is significantly elevated and related to mitral regurgitant fraction.
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No pos
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No neg
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Retriever2863
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Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate tuberculosis infection and disease in children of high endemic areas?
BACKGROUND
Diagnosis of childhood tuberculosis (TB) is difficult in high TB burden settings. Interferon-gamma-induced protein 10 (IP10) has been suggested as a marker of TB infection and disease, but its ability to differentiate the two conditions remains uncertain.
OBJECTIVES
To describe Interferon-gamma (INFγ) and IP10 expression in children with TB infection and disease and controls to assess their potential to differentiate latent and active TB.
METHODS
This was a cross sectional study of 322 1-15 years old children with symptoms of TB (28 confirmed, 136 probable and 131 unlikely TB), 335 children in contact with adults with pulmonary TB and 156 community controls in Southern Ethiopia. The Tuberculin Skin Test (TST) and Quantiferon-In-Tube (QFT-IT) were performed. INFγ and IP10 were measured in plasma supernatants.
RESULTS AND INTERPRETATION
Children with confirmed and probable TB and contacts were more likely to have TST+ (78.6%, 59.3% and 54.1%, respectively) than children with unlikely TB (28.7%) and controls (12.8%) (p<0.001). Children with confirmed TB (59.3%) and contacts (44.7%) were more likely to have INFγ+ than children with probable (37.6%) or unlikely TB (28.1%) and controls (13.1%) (p<0.001). IP10 concentrations were higher in INFγ+ children independently of TST (p<0.001). There was no difference between IP10 concentrations of children with confirmed TB and contacts (p = 0.8) and children with and without HIV (p>0.1). INFγ and IP10 can identify children with TB infection and disease, but cannot differentiate between the two conditions. HIV status did not affect the expression of IP10.
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No pos
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No neg
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Retriever2864
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Peginterferon plus Ribavirin for chronic hepatitis C in opiate addicts on methadone/buprenorphine maintenance therapy.
BACKGROUND
In developed countries hepatitis C is prevalently transmitted by intravenous drug users (IDUs). The problems associated with management of HCV hepatitis in these patients have, in the past, discouraged treatment.
AIM
To evaluate efficacy, safety and tolerability of a standard Peginterferon (Peg-IFN) alpha-2b or alpha-2a plus Ribavirin treatment in IDUs who were receiving methadone or buprenorphine.
METHODS
A multi-centre prospective observational study performed from September 2003 to September 2006 in Central Italy (Umbria and Marches regions). A shared care model of HCV management was used which integrated a multidimensional, multidisciplinary approach.
RESULTS
Sixty-five subjects were evaluated and 52 satisfied inclusion criteria. Forty-five completed treatment (25 with Peg-IFN alpha-2b, 20 with Peg-IFN alpha-2a), a total of 37 showed a biochemical/virological response at the end of treatment (ITT 71.1%), 26 had a sustained virological response (ITT 50%; 38.4% of cases genotype 1-4, 61.6% genotype 3-2).
CONCLUSIONS
The results indicate that patients on maintenance treatment with methadone/buprenorphine can be treated for HCV. The success rate was fairly good; tolerability and side effects were similar to those reported in non-IDU patients. Close cooperation with specialists in drug addiction and psychiatrists is however essential for success.
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No pos
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No neg
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Retriever2865
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[The epidural administration of steroids and local anesthetics as the basis for the pathogenetic therapy of a radicular pain syndrome in the stages of its development].
The efficacy of epidural administration of a steroid drug kenalog combined with low-dose 1% lidocaine solution was assessed in 26 patients with discal hernias at various stages of the radicular pain syndrome. Registration of paired H-reflex helped define the neurophysiological criteria objectively indicating cure and normalization of the reduced activities of inhibitory structures of the spinal segmentary system as a result of therapy in patients with the radicular syndrome. The efficacy of this method ranges between 57.3 and 100% and depends on the disease duration, therefore it is preferable at the early stages of the disease (up to 4-6 months). Failure of therapy after 3 successive epidural blockings at 6-7-day intervals may be considered as an indication to surgery.
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No pos
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No neg
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Retriever2866
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Gel-bound resealed red cell membranes: a new type of semi-artificial organ.
A novel type of semi-artificial organ is described, which uses resealed enzyme fille red cell ghosts bound to a matrix as an active metabolizing system. The stability and the selectivity of the system is discussed with enclosed glutaminase and urease as examples.
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No pos
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No neg
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Retriever2867
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Characterization of Bordetella holmesii isolates from patients with pertussis-like illness in The Netherlands.
Bordetella holmesii is a recently described human pathogen mainly isolated from blood. However, in the US and Canada, B. holmesii has also been cultured from the nasopharynx of patients with pertussis-like symptoms. To the best of our knowledge, respiratory isolates from Europe have not been characterized. Here, we report the isolation and characterization of B. holmesii from Dutch patients with pertussis-like illness. Species determination was confirmed by 16S rRNA gene sequencing and detection by PCR of IS481 and bhoE, a gene not found in Bordetella pertussis but present in B. holmesii. Comparative genomic hybridization (CGH) with microarrays revealed that the Dutch isolates formed a cluster distinct from isolates from the US and UK suggesting a distinct population or an epidemiological relationship between the Dutch isolates. All isolates contained a locus involved in iron uptake, previously suggested to originate from B. pertussis. The causes for the apparent increase in the isolation of B. holmesii are discussed.
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No pos
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No neg
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Retriever2868
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Fluid-bed coater modifications and study of their influence on the coating process of pellets.
OBJECTIVE
In this study, different modifications of bottom spray fluid-bed coater with draft tube inserted were characterized and evaluated.
MATERIALS AND METHODS
After coating the neutral pellets with polymeric solution comprising coloring agent pellet batches were characterized for coating variation, yield and degree of agglomeration.
RESULTS
Funnel-shaped distribution plate was found to improve process yield and decrease the degree of agglomeration at selected values of process parameters, whereas coating uniformity was worse in all cases when compared to conventional Wurster chamber. Results of the coating chamber with the swirl airflow generator indicate more uniform deposition of the coating material and in some cases an improved process yield and decreased formation of agglomerates when compared to conventional Wurster chamber. In series of experiments using Wurster chamber, having tangentially oriented air intake slots, which enabled introduction of air above the distribution plate, coating layer was more uniformly deposited on the pellet cores and formation of agglomerates was lower compared to the results obtained in a conventional Wurster coating chamber.
CONCLUSION
Modifications of Wurster coating process by introducing swirling air motion within the draft tube or by introduction of air above the distribution plate have at selected values of process parameters resulted in reduced per-particle coating variation, degree of agglomeration and improved process yield.
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No pos
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No neg
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Retriever2869
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Mechanisms of protein adhesion on surface films of hydrophobin.
Hydrophobins are adhesive proteins produced by filamentous fungi. They are in many cases secreted into the medium and adsorb readily to a number of different surfaces. They fulfill many different tasks such as the formation of various coatings and mediating adhesion of fungi to surfaces. The mechanism of how hydrophobins adhere and how they mediate fungal adhesion is of interest both from the point of view of fungal biology and for various biotechnical immobilization applications. It has been shown that hydrophobins typically form a monomolecular layer on solid substrates. We are especially interested in how a surface layer of hydrophobin can mediate the adhesion of a second layer of another protein. In this work we systematically studied how proteins adsorb onto hydrophobins that are bound as monomolecular layers on nonpolar surfaces. We found that several types of proteins readily adsorb onto hydrophobins, but only under defined conditions of pH and ionic strength. The binding conditions were also highly dependent on the adhering protein. By studying solution conditions such as pH and ionic strength, we conclude that the surface adhesion is due to selective Coulombic charge interactions. We conclude that hydrophobins can transform a nonpolar surface into one that efficiently recruits other proteins by charge interactions.
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No pos
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No neg
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Retriever2870
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Insulin-like growth factor II inhibits glucose-induced insulin exocytosis.
We have investigated the effect of IGF-II on glucose-induced insulin release in the pancreatic beta-cell. Introduction of IGF-II during perifusion of the cells with 20 mM glucose abolished glucose-induced insulin release. Concomitant addition of IGF-II with 20 mM glucose caused a complete inhibition of insulin release. In addition, IGF-II inhibited Ca(2+)-induced insulin release from electropermeabilized pancreatic beta-cells. IGF-II had no effect on K(+)-or tolbutamide-induced insulin release. However, IGF-II could suppress K(+)-stimulated insulin release when cells were pretreated with the protein phosphatase inhibitor okadaic acid. The inhibitory effect of IGF-II on insulin release was not associated with significant changes in membrane potential, activity of the voltage-gated L-type Ca(2+)-channel or cytoplasmic free Ca2+ concentration. Pretreatment of the cells with pertussis toxin or the phorbol ester TPA abolished the inhibitory action of IGF-II on insulin release. Hence, the molecular mechanism whereby activation of the IGF-II/M6P receptor by IGF-II inhibits glucose-stimulated insulin exocytosis in the pancreatic beta-cell involves pertussis toxin-sensitive G proteins and is dependent on PKC activity.
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No pos
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No neg
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Retriever2871
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Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia.
STUDY OBJECTIVES
To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients.
DESIGN
Adults (18-64 y) with chronic primary insomnia (DSM-IV) were randomly assigned to one of four sequences of 1 mg, 3 mg, and 6 mg of doxepin, and placebo in a crossover study. Treatment periods consisted of 2 polysomnographic assessment nights with a 5-day or 12-day drug-free interval between periods. Efficacy was assessed using polysomnography (PSG) and patient-reported measures. Safety analyses included measures of residual sedation and adverse events.
MEASUREMENTS AND RESULTS
Sixty-seven patients were randomized. Wake time during sleep, the a priori defined primary endpoint, was statistically significantly improved at the doxepin 3 mg and 6 mg doses versus placebo. All three doses had statistically significant improvements versus placebo for PSG-defined wake after sleep onset, total sleep time, and overall sleep efficiency (SE). SE in the final third-of-the-night also demonstrated statistically significant improvement at all doses. The doxepin 6 mg dose significantly reduced subjective latency to sleep onset. All three doxepin doses had a safety profile comparable to placebo. There were no statistically significant differences in next-day residual sedation, and sleep architecture was generally clinically preserved.
CONCLUSIONS
In adults with primary insomnia, doxepin 1 mg, 3 mg, and 6 mg was well-tolerated and produced improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. The side-effect profile was comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is efficacious in improving the sleep of patients with chronic primary insomnia.
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No pos
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No neg
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Retriever2872
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GDF11 expression in the adult rat central nervous system.
Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), is a member of the transforming growth factor β (TGF-β) superfamily. Although GDF11 plays pivotal roles during development, including anterior/posterior patterning, formation of the kidney, stomach, spleen and endocrine pancreas, little information is available for GDF11 expression in the adult central nervous system (CNS). We, thus, investigated GDF11 expression in the adult rat CNS using immunohistochemistry. GDF11 was intensely expressed in most neurons and their axons. Furthermore, we found that astrocytes and ependymal cells also express GDF11 protein. These data indicate that GDF11 is widely expressed throughout the adult CNS, and its abundant expression in the adult brain strongly supports the idea that GDF11 plays important roles in the adult brain.
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No pos
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No neg
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Retriever2873
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The potential prognostic role of cardiovascular autonomic failure in α-synucleinopathies.
Cardiovascular autonomic failure is the second most common dysautonomic feature of α-synucleinopathies and has significant impact on daily activities and quality of life. Here we provide a systematic review of cardiovascular autonomic failure in α-synucleinopathies, emphasizing its impact on cognitive functions and disease outcomes. Articles spanning the period between January 1985 and April 2012 were identified from the PubMed database using a keyword-based search. Epidemiological studies highlight the negative prognostic effect of cardiovascular autonomic failure on cardiovascular and cerebrovascular outcomes and overall mortality in all α-synucleinopathies. Altered cerebral perfusion, vascular pressure stress, and related disruption of the blood-brain barrier may also contribute to the white matter hyperintensities and cognitive dysfunction frequently found in patients affected by neurocardiovascular instability. These findings support the hypothesis that cardiovascular autonomic failure may play a negative prognostic role in α-synucleinopathies and suggest that precocious screening and therapeutic management of cardiovascular autonomic failure may positively impact disease course.
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No pos
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No neg
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Retriever2874
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Insight into the conformational dynamics of specific regions of porcine pancreatic phospholipase A2 from a time-resolved fluorescence study of a genetically inserted single tryptophan residue.
The effects of Ca2+ and substrate analogue binding on the conformational dynamics of porcine pancreas phospholipase A2 (PLA2) in different regions was explored by combining site-directed mutagenesis and time-resolved fluorescence measurements. The single tryptophan residue (Trp-3) of the wild-type protein (W3), in the alpha-helix A, was replaced by a phenylalanine residue (W3F), whereafter Trp was substituted either for leucine-31 (W31), located in the calcium binding loop, or for phenylalanine-94 (W94), located at the "back side" of the enzyme. Furthermore, mutants lacking the 62-66 sequence were constructed with the Trp at position 3 (delta W3) or 31 (delta W31). The total fluorescence intensity decays of Trp in each protein, in the protein-calcium and the protein-calcium-substrate analogue complexes, analyzed by the maximum entropy method (MEM) can be interpreted as distributions of separated lifetime classes. In the case of the W94 mutant, a major short-lived excited-state population (tau approximately 50 ps) is observed, probably deactivated by the interaction with two proximate disulfide bridges via a radiationless process. For the four other mutants, the respective barycenters of the four lifetime classes display comparable values, but the amplitude distributions are different for Trp-3 and Trp-31. The rotational mobility of the Trp residue varies along the peptide chain. Trp-3 experiences only a fast hindered motion. Trp-31 is sensitive to an additional local flexibility that is absent in the N-terminal part of the protein. The largest wobbling angle is observed at position 94. No effect of calcium binding occurs on the lifetime distribution of the Trp-3 and Trp-94 residues. Their mobilities are not affected. In contrast, calcium binding displays a strong influence on the excited-state population distribution of Trp-31. A major population decaying with the longest lifetime is selected in the W31 protein and contributes to approximately 50% of the decay. The local flexibility and the amplitude of motion of Trp-31 is wider in the protein-calcium complex than in the unliganded protein. Binding of the monomeric substrate analogue n-dodecylphosphocholine (C12PN) in the presence of calcium slightly affects the Trp-3 excited-state population distribution and its mobility. Trp-31 is more sensitive to this binding. In particular, a more restricted rotation of the Trp-31 residue and a decrease of the peptide local flexibility as protein-calcium complexes are observed in both the W31 and delta W31 mutants.(ABSTRACT TRUNCATED AT 400 WORDS)
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No pos
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No neg
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Retriever2875
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Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells in postmenopausal women.
Cytokines, such as interleukin-1 (IL-1) and tumor necrosis factors (TNF), produced by cells of the monocyte-macrophage lineage in the local bone microenvironment, are potentially important local regulators of bone turnover. To investigate whether the protective effects of estrogen against postmenopausal bone loss may be mediated by inhibition of cytokine release, we studied the effects of 17 beta-estradiol, dihydrotestosterone, and hydrocortisone on TNF release from human peripheral blood mononuclear cells (PBMC) in vitro. In unstimulated cells derived from eight postmenopausal women, seven of whom had osteoporotic vertebral fractures, 17 beta-estradiol inhibited TNF release in a dose-dependent manner between 10(-6) and 10(-12) M but had no consistent effect on cells derived from men or premenopausal women. Dihydrotestosterone in concentrations of up to 10(-6) M had no effect on TNF release in any patient group, whereas hydrocortisone at 10(-6) M was a potent inhibitor of TNF release in all groups. Since TNF is a potent stimulator of bone resorption, the inhibitory effect of estrogen on TNF release may be part of the mechanism by which it exerts a protective effect on the skeleton in postmenopausal women. These observations may also be relevant in other inflammatory diseases of connective tissue, such as rheumatoid arthritis, in which disease activity may fluctuate as estrogen levels change--during the menstrual cycle, in pregnancy, and after the menopause.
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No pos
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No neg
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Retriever2876
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Tracheal aspirates in long-term mechanically ventilated patients. A human model of gram-negative infection and airway inflammation.
It is well known that patients requiring long-term mechanical ventilation and tracheostomy have nearly universal airway colonization with Gram-negative organisms. However, useful parameters to objectively describe the airway inflammation associated with airway instrumentation and colonization have not been well define. In our respiratory care unit, patients who are medically stable except for ventilator dependence are readily available for longitudinal assessment of airway secretions and therefore provide a unique population for studying airway inflammation and infection. To quantitate production of respiratory secretions, we instituted a uniform protocol of suctioning over a 6-h period. Further, we devised a method of dilution and homogenization of tracheal aspirates that permits reproducible intrasample total cell counts (coefficient of variation, 4.6%). With these techniques, patients were then studied serially over a 4- to 7-week period. Total cell count, inflammatory cell differential, and two indices of airway inflammation, human neutrophil elastase (HLE) and soluble-intercellular adhesion molecule-1 (sICAM-1) studied in the sol phase of secretions were monitored. The mean total cell count was 42.2 x 10(6) cells per gram of secretions when patients were clinically stable and not receiving antibiotics. The average differential was neutrophils 69.9%, macrophages 26.9%, and lymphocytes 2.8%. Mean active HLE was 35.6 micrograms/mL and mean sICAM-1 was 83 ng/mL. Six patients during the period of observation received intravenous oral or aerosolized antibiotics for tracheobronchitis. A threefold drop in volume of secretions was measured (p < 0.018). The total cell count and percent neutrophils decreased from 76.4 x 10(6)/g of sputum to 54.9 x 10(6) and 72.2 to 54.9%, respectively. While these changes were not statistically significant, the absolute number of airway neutrophils over the 6 h decreased sevenfold (p < 0.014). Similarly sICAM-1 burden (micrograms per 6-h period) also decreased significantly (p < 0.034). These patients provide a unique human model for future studies specifically designed to assess the effect of novel modalities of anti-inflammatory and antimicrobial agents on respiratory secretions.
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No pos
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No neg
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Retriever2877
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Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats.
A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate the dynamic role of hippocampal and striatal acetylcholine (ACh) efflux across acquisition of a nonmatching-to-position (NMTP) T-maze task. Changes in ACh efflux were measured in rats at different time points in the acquisition curve of the task (early=day 1, middle=day 5, and late=day 10). Overall, the control group had higher accuracy scores than the PTD group in the latter sessions of NMTP training. During the three microdialysis sampling points, all animals displayed significant increases in ACh efflux in both hippocampus and striatum, while performing the task. However, on day 10, the PTD group showed a significant behavioral impairment that paralleled their blunted hippocampal--but not striatal--ACh efflux during maze training. The results support selective diencephalic-hippocampal dysfunction in the PTD model. This diencephalic-hippocampal interaction appears to be critical for successful episodic and spatial learning/memory.
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No pos
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No neg
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Retriever2878
|
Dental Follicle Cells Participate in Tooth Eruption via the RUNX2-MiR-31-SATB2 Loop.
Cleidocranial dysplasia (CCD) is characterized by the runt-related transcription factor 2 (RUNX2) mutation, which results in delayed tooth eruption due to disturbed functions of dental follicle. Accumulating evidence has revealed a key regulatory circuit, including RUNX2, miR-31, and special AT-rich binding protein 2 (SATB2) acting in concert in mesenchymal stem cell homeostasis and functions. However, whether such a regulatory loop works in dental follicle cells (DFCs) remains unknown. Herein, we investigated the roles of RUNX2-miR-31-SATB2 in DFCs from patients with CCD (DFCs-CCD) to advance our understanding regarding physical tooth eruption. We identified a novel mutation on exon 5 (c.634T>G, p.T212P) in RUNX2 via exome sequencing in the CCD patient with typical clinical presentations. Compared with DFCs from healthy donors, DFCs-CCD displayed significantly lower osteogenic, osteoclast-inductive, and matrix-degrading capacities and had lower RUNX2 (a transcriptional inhibitor of miR-31), higher miR-31, and downregulated SATB2. Lower ratios of RANKL/OPG and RANKL/RANK, as well as decreased expression of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 2 (MMP2), would lead to inactivation of osteoclasts and suppression of bone matrix remodeling in DFCs-CCD. Furthermore, the roles of the RUNX2-miR-31-SATB2 loop in DFCs-CCD were revealed by endogenous miR-31 knockdown, which resulted in increased SATB2 and RUNX2, as well as osteoclast-inductive and matrix degradation capacities. Conversely, SATB2, RUNX2, MMP9, MMP2, and osteoclast-inductive factors expression declined upon ectopic miR-31 overexpression in normal DFCs. Importantly, neonatal mice with in vivo siRUNX2 delivery exhibited less activated osteoclasts around dental follicles and delayed tooth eruption. Together, these results suggest that RUNX2 mutation/haploinsufficiency disturbs osteoclast-inductive signaling in DFCs, which may be responsible for delayed tooth eruption in CCD patients. Manipulation of the RUNX2-miR-31-SATB2 loop may be a potential way to facilitate tooth eruption in CCD patients.
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No pos
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No neg
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Retriever2879
|
Concurrent crack and powder cocaine users from Sao Paulo: do they represent a different group?
BACKGROUND
Cocaine abuse is a serious and socially damaging illegal drug problem. Different routes of administration are associated with a specific progression of use, different degrees of abuse liability, propensity for dependence and treatment response. There have been relatively few studies comparing different cocaine users groups and no studies into the characterization of the group of individuals reporting concurrent use of powder cocaine and crack cocaine.
METHODS
Six hundred and ninety-nine cocaine users were assessed during the period August 1997 to October 1998 in one outpatient and six inpatient clinics located in the São Paulo, Brazil. Patients were interviewed using a structured questionnaire schedule in Portuguese, designed specifically for the Brazilian population. The statistical analyses were performed using either ANOVA or a chi-squared test and focusing on their preferred form of use/route of administration and other variables.
RESULTS
For 83% of the variables tested in this study, the Dual Users subgroup (using both powder and crack cocaine) demonstrated statistical differences from the single drug user subgroups. Those differences include the initiation of cocaine, the abuse of other illicit drugs, and rates of criminal history.
CONCLUSION
These data suggest cocaine-dependent individuals who report use of both powder and crack cocaine are an at least partially, distinct subgroup. However, further studies will be necessary to confirm this and to determine if they also show a different treatment response.
|
No pos
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No neg
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Retriever2880
|
Exercise increases the frequency of circulating hematopoietic progenitor cells, but reduces hematopoietic colony-forming capacity.
Circulating hematopoietic progenitor cells (CPCs) may be triggered by physical exercise and/or normobaric hypoxia from the bone marrow. The aim of the study was to investigate the influence of physical exercise and normobaric hypoxia on CPC number and functionality in the peripheral blood as well as the involvement of oxidative stress parameters as possibly active agents. Ten healthy male subjects (25.3±4.4 years) underwent a standardized cycle incremental exercise test protocol (40 W+20 W/min) under either normoxic (FiO2 ∼0.21) or hypoxic conditions (FiO2<0.15, equals 3,500 m, 3 h xposure) within a time span of at least 1 week. Blood was drawn from the cubital vein before and 10, 30, 60, and 120 min after exercise. The number of CPCs in the peripheral blood was analyzed by flow cytometry (CD34/CD45-positive cells). The functionality of cells present was addressed by secondary colony-forming unit-granulocyte macrophage (CFU-GM) assays. To determine a possible correlation between the mobilization of CPCs and reactive oxygen species, parameters for oxidative stress such as malondialdehyde (MDA) and myeloperoxidase (MPO) were obtained. Data showed a significant increase of CPC release under normoxic as well as hypoxic conditions after 10 min of recovery (P<0.01). Most interestingly, although CD34+/CD45dim cells increased in number, the proliferative capacity of CPCs decreased significantly 10 min after cessation of exercise (P<0.05). A positive correlation between CPCs and MDA/MPO levels turned out to be significant for both normoxic and hypoxic conditions (P<0.05/P<0.01). Hypoxia did not provoke an additional effect. Although the CPC frequency increased, the functionality of CPCs decreased significantly after exercise, possibly due to the influence of increased oxidative stress levels.
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No pos
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No neg
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Retriever2881
|
[Leadership and CETREMI].
Según la Real Academia Española, el término «líder» significa «persona que dirige u orienta a un grupo, que reconoce su autoridad». Es importante este término ya que es muy ambiguo, porque no reconoce el nivel moral o la empatía que puede ejercer una persona en determinado grupo al reconocerlo como líder, y no solo con la autoridad que este puede ejercer en el mismo, siendo este último concepto algo muy común en el mundo anglosajón, denominándose líder a alguien que tiene un puesto de autoridad, lo cual se puede confundir con lo que conocemos como «jefe».
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No pos
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No neg
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Retriever2882
|
Exposure to sublethal levels of PCB-126 impacts fuel metabolism and swimming performance in rainbow trout.
Polychlorinated biphenyls (PCBs) are recognized physiological stressors to fish which over time may impair individual performance and perhaps fitness by inducing changes that could have population-level consequences. PCB-126 (3,3',4,4',5-pentachlorobiphenyl) accumulates in lipids and can subsequently be released into the bloodstream during periods of high activity that involve the mobilization of stored fuels to meet with increasing energy demands. The goal of this study was to determine if a sublethal exposure to PCB-126 altered the content of tissue energy supplies (carbohydrates, proteins, amino acids, triglycerides) and impaired swimming performance as well as oxygen consumption in rainbow trout (Oncorhynchus mykiss). Trout were injected intraperitoneally with a single Low (100μgkg(-1)) or High (400μgkg(-1)) dose of PCB-126 then swimming performance and metabolic rates from 1 to 9days post-injection were compared to Control (non-dosed) fish. Liver ethoxyresorufin-O-deethylase (EROD) activity was assessed as an indication of PCB-126 intoxication while plasma and white muscle tissue metabolites were analyzed as an index of physiological disturbance. Swimming performance, assessed using two successive modified critical swimming speed (Ucrit) tests, was highest for fish in the High PCB-126 treatment; however, their initial condition factor (K) was also higher, largely due to their greater body mass. Trout in the High and Low PCB-126 treatments exhibited impaired recovery following intense exercise as they swam comparatively poorly when provided a second challenge. PCB-exposed fish exhibited reduced spleen somatic indices as well as muscle glucose and glycogen contents; whereas plasma cortisol and glucose levels were elevated, indicating higher metabolic costs during recovery and muscle restoration. Overall, this research provides insights into the sublethal effects of a toxic organic compound on swimming performance in trout.
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No pos
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No neg
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Retriever2883
|
Symptoms of patients with myasthenia gravis receiving treatment.
The symptoms of myasthenia gravis (MG) are often simply classified as excessive fatigue rather than evaluated as different signs of disease progression. The purpose of this study was to evaluate the medical symptoms of patients with MG who had been under treatment for many years. Patients diagnosed with MG were compared to healthy controls. A survey questionnaire was used and differences were evaluated using non-parametric statistics. Health care givers should be aware of these differences in order to facilitate early appropriate treatment, to decrease disability, and to increase the quality of life.
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No pos
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No neg
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Retriever2884
|
Neural-like computing with populations of superparamagnetic basis functions.
In neuroscience, population coding theory demonstrates that neural assemblies can achieve fault-tolerant information processing. Mapped to nanoelectronics, this strategy could allow for reliable computing with scaled-down, noisy, imperfect devices. Doing so requires that the population components form a set of basis functions in terms of their response functions to inputs, offering a physical substrate for computing. Such a population can be implemented with CMOS technology, but the corresponding circuits have high area or energy requirements. Here, we show that nanoscale magnetic tunnel junctions can instead be assembled to meet these requirements. We demonstrate experimentally that a population of nine junctions can implement a basis set of functions, providing the data to achieve, for example, the generation of cursive letters. We design hybrid magnetic-CMOS systems based on interlinked populations of junctions and show that they can learn to realize non-linear variability-resilient transformations with a low imprint area and low power.
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No pos
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No neg
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Retriever2885
|
Fabrication of paper-based microfluidic devices using a 3D printer and a commercially-available wax filament.
In this work, we developed an alternative manufacturing paper-based microfluidics method through 3D printing and wax filament. Microfluidic paper-based analytical devices (μPADs) are low-cost and easy-to-manufacture tools used for various chemical and biological analyses and studies. Paper-based microfluidics with wax has been limited as the manufacturers have discontinued most wax printing equipment. We aim to develop a low-cost and accessible manufacturing method that can replace conventional wax-on paper-based microfluidic manufacturing methods. Using highly available commercial 3D printing technology and wax filament, we could create hydrophobic wax barriers on the surface of different paper types. The properties and limits of this manufacturing method were characterized. Moreover, using this paper-based microfluidic manufacturing method, we were able to measure dopamine electrochemically using μPAD as a passive flow-based method in concentrations as low as 1 nM using injections as small as 15 μL.
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No pos
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No neg
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Retriever2886
|
Nurse practitioner education: greater demand, reduced training opportunities.
PURPOSE
To document the factors that are increasing the tension between nurse practitioner (NP) educational programs and the clinical training sites needed for NP students.
DATA SOURCES
Literature and the faculty experiences garnered over years of placing NP students for clinical training.
CONCLUSIONS
Several conditions converge to create a situation where sites are increasingly reluctant to precept NP students. The underlying dynamics are diverse and include factors related to the electronic health record, productivity expectations, and the increasing demand for sites as a result of increasing NP enrollments and competing healthcare provider programs.
IMPLICATIONS FOR PRACTICE
The nursing community should approach this issue strategically and devise an action and policy agenda to support NP training, including federal monies to support NP training in a design that parallels the Graduate Medical Education; recognition of NPs as licensed professionals in advanced training; and identification of meaningful incentives for NP preceptors.
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No pos
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No neg
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Retriever2887
|
Genetic control of hepatic apoB-100 secretion in human apoB transgenic mouse strains.
Plasma apolipoprotein B (apoB) levels vary widely in the general population and elevated plasma levels of apoB are associated with higher risk for atherosclerotic coronary heart disease. Determination of genetic factors regulating population variance of plasma apoB levels is complicated by the genetic heterogeneity of human populations. Using a congenic human apoB transgenic mouse strain in the C57BL/6 background (B6 HuBTg), we assessed genetic effects on the variance of plasma apoB, and on hepatic apoB-100 secretion rates. Six inbred mouse strains were crossed with the B6 HuBTg strain. Mean plasma apoB levels in the parental B6 HuBTg strain were 95 +/- 14 mg/dl. F1 human apoB transgenic offspring displayed plasma human apoB levels ranging from 60 to 105 mg/dl. In three F1 strains, the BALB/B6, C3H/B6 and 129/B6 strains, markedly lower plasma apoB levels (61 +/- 11, 64 +/- 5, and 67 +/- 8 mg/dl) were due to lower apoB-100 secretion rates. Human apoB mRNA levels in these three F1 strains were similar to those of the parental B6 strain suggesting that the mechanism for varying apoB secretion rates is most likely not transcriptional. In summary, we have identified three inbred mouse strains possessing polymorphic alleles which, when crossed with the B6 strain, lower plasma apoB levels and apoB-100 secretion in their F1 offspring. These mouse strains provide a powerful tool for genetic analysis of factors regulating apoB-100 secretion and hence plasma apoB levels.
|
No pos
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No neg
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Retriever2888
|
[Choice of surgical procedure and management of postoperative incision for anal fistula].
Anal fistula is a common disease in general surgery. It is difficult to heal without intervention and surgical treatment is the major treatment. Method of surgical treatment and management of postoperative incision are based on features and classifications of anal fistula. Choosing the appropriate approach in accordance with specific conditions of patients can obtain effective healing and proper protection against anal sphincter, along with the improvement of life quality. Comprehensive evaluation on methods of surgical treatment and managements of postoperative incision for anal fistula is presented in this paper.
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No pos
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No neg
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Retriever2889
|
Successful pregnancy outcomes following liver transplantation is predicted by renal function.
Liver transplantation (LT) is a successful treatment for both acute liver failure and end-stage liver disease. The number of women of reproductive age undergoing LT is increasing. Pregnancy outcomes are favorable, but there is still a lack of prognostic markers. We aimed to identify factors predictive of adverse pregnancy outcomes in LT recipients. An analysis of all pregnancies occurring in LT recipients from 1989 to 2016 at King's College Hospital was performed. Clinical data of 162 conceptions in 93 women were reviewed. Descriptive and regression analyses were done to examine associations between laboratory markers and hepatological scores with pregnancy outcomes of live birth and preterm birth. Median age at LT was 23 years (range, 1-41 years), with a median age at conception of 30 years (range, 18-47 years). The live birth rate was 75% (n = 121). Of live births, 35% (n = 39/110 available) were delivered preterm. Preconception creatinine levels were higher in patients who had a preterm birth (85 versus 74 μmol/L; P = 0.008), with a preconception estimated glomerular filtration rate (eGFR) <90 mL/minute significantly associated with preterm delivery (P = 0.04). Progressive decline in eGFR predicted outcome, with gestational length declining with increasing chronic kidney disease (CKD) stage: CKD 0-1 = 39 weeks (median), CKD 2 = 37 weeks, and CKD 3 = 35 weeks. The risk of preterm birth was greatest in women with an eGFR <60 mL/minute (P = 0.004). Moreover, hypertension-related complications during pregnancy, such as gestational hypertension, preeclampsia, or eclampsia, were also associated with prematurity (P = 0.01). Women taking steroid-based immunosuppression had an increased risk of infection during pregnancy or postpartum (15% versus 4%; P = 0.02). In conclusion, although the majority of women have a successful pregnancy outcome after LT, preconception renal function predicts pregnancy outcome and steroids increase risk of infection during pregnancy or postpartum. Liver Transplantation 24 606-615 2018 AASLD.
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No pos
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No neg
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Retriever2890
|
Phasic relations in 90 degree abduction-adduction of the arm: the ARIMA representation.
Myoelectric signals (MES's) from the medial deltoid, posterior deltoid and medial trapezius were analyzed during 90 degree abduction-adduction cycles of arm movement. Two healthy males were utilized as subjects. The MES's records were divided into sub-sections of 50 ms of duration, and each segment was described by a suitable model. The models were based on autoregressive integrated moving average (ARIMA) processes. Several distinct phases were discerned within a given movement cycle, each phase being associated with a distinct type of ARIMA process. Phasic relations among the three muscles were then revealed. A simple test was suggested to detect the onset of muscle activity in real-time situations.
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No pos
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No neg
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Retriever2891
|
Human studies on the bioavailability of a quaternary ammonium compounds, tiemonium iodide and tiemonium methosulphate.
Five volunteers were administered capsules containing 14C-labelled tiemonium iodide and 4 volunteers received capsules of 14C-labelled tiemonium methosulphate. Serum, urine and faecal levels of tiemonium were measured. The percentage of the dose absorbed was determined after a further labelled intravenous injection into 3 of the volunteers. The drug appeared to be poorly absorved, as expected for quaternary ammonium compounds, but there was no difference in the bioavailability of these two tiemonium salts.
|
No pos
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No neg
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Retriever2892
|
S⋅⋅⋅Sn Tetrel Bonds in the Activation of Peroxisome Proliferator-Activated Receptors (PPARs) by Organotin Molecules.
In this study, a PDB (Protein Data Bank) analysis and theoretical calculations (PBE0-D3/def2-TZVP level of theory) were combined to analyze the impact of S⋅⋅⋅Sn tetrel-bonding interactions in the activation mechanism of peroxisome proliferator-activated receptors (PPARs) by two organotin derivatives, triphenyltin (TPT) and tributyltin (TBT). The presence of a covalently bonded CYS285 to the organotin molecule was found to be key to enhance the σ-hole-donor ability of the tin atom, thus strengthening the tetrel-bonding interaction with a sulfur atom belonging to a vicinal methionine residue (MET364).
|
No pos
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No neg
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Retriever2893
|
Non-coding RNAs and Cardiac Aging.
Aging is an important risk factor for cardiovascular diseases. Aging increasing the morbidity and mortality in cardiovascular disease patients. With the society is aging rapidly in the world, medical burden of aging-related cardiovascular diseases increasing drastically. Hence, it is urgent to explore the underlying mechanism and treatment of cardiac aging. Noncoding RNAs (ncRNAs, including microRNAs, long noncoding RNAs and circular RNAs) have been reported to be involved in many pathological processes, including cell proliferation, cell death differentiation, hypertrophy and aging in wide variety of cells and tissues. In this chapter, we will summarize the physiology and molecular mechanisms of cardiac aging. Then, the recent research advances of ncRNAs in cardiac aging will be provided. The lessons learned from ncRNAs and cardiac aging studies would bring new insights into the regulatory mechanisms ncRNAs as well as treatment of aging-related cardiovascular diseases.
|
No pos
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No neg
|
Retriever2894
|
Hyperthyroidism induced by secondary carcinoma in the thyroid.
A young women presenting with hyperthyroidism proved to have diffuse infiltration of the thyroid with carcinoma probably from a primary breast adenocarcinoma. The gland was diffusely infiltrated with tumour although the thyroid follicles were intact. Blood thyroid hormone levels were raised but thyroid uptake of iodine was undetectable. It is suggested that the tumour released a locally active agent which stimulated hormone release but not iodine uptake, the latter being very low due to suppression of TSH.
|
No pos
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No neg
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Retriever2895
|
Lessons learned from simultaneous face and bilateral hand allotransplantation.
UNLABELLED
The performance of simultaneous vascularized composite allotransplantation procedures on patients requiring both the face and bilateral hands remains controversial. The authors present their separate institutional experiences with this challenging procedure in the interests of dispelling misconceptions regarding this intervention and forwarding their understanding of the issues related to concomitant vascularized composite allotransplantation.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, V.
|
No pos
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No neg
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Retriever2896
|
[Primary prevention of cervical cancer].
Cervical cancer is a global public health problem related to infection by human papilloma virus. Countries with organized programs for detection and treatment of precancerous lesions and cervical cancer prevent 80% of cases; however, prevention-based cytology, colposcopy and treatment of injuries is effective but still expensive, invasive and nonspecific, especially in developing countries. The goal of primary prevention through immunization against human papillomavirus is with the use of quadrivalent vaccine genotypes 6, 11, 16 and 18 and bivalent genotypes 16 and 18, which are produced using recombinant technology. These are effective in patients without prior exposure to viral genotypes, mainly when they have not initiated sexual activity. Recommended ages are 9 to 13 years and vaccine is administered through school health centers or community centers who promote informational campaigns and dissemination aimed at parents who request this. Screening programs for cervical cancer are limited and only oncogenic virus immunization will reduce their frequency, saving the lives of hundreds of women worldwide.
|
No pos
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No neg
|
Retriever2897
|
Relationship between serum ferritin, erythrocyte protoporphyrin and transferrin saturation in Mauritanian free living children.
Serum ferritin, serum iron, total iron-binding capacity (TIBC) and erythrocyte protoporphyrin were measured in a group of 69 children (6.4 +/- 3.6 years) living in a rural area of Mauritania. The predictive value of low serum ferritin was calculated for each iron parameter. A serum ferritin value above 12 micrograms/l was present in 50.2% of children with abnormal serum iron, in 59.0% of those with abnormal TIBC, in 60.3% of those with abnormal transferrin saturation and in 60.0% of those with abnormal erythrocyte protoporphyrin. The percentages varied from 88.0 to 94.8% for a predictive value of serum ferritin of less than 50 micrograms/l. Nearly 35% of children had biochemical evidence of iron deficiency, i.e. 2 abnormal independent iron parameters or more, including serum ferritin of less than 12 micrograms/l. Nearly 32% had probable iron deficiency, i.e. 2 abnormal independent iron parameters, with a serum ferritin value between 13 and 50 micrograms/l.
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No pos
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No neg
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Retriever2898
|
Experience with 208 resections for intraductal papillary mucinous neoplasm of the pancreas.
HYPOTHESIS
Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized disease of the pancreas. We report our experience with pancreatic resection for IPMN.
DESIGN
Retrospective review from 1992 through 2005 with additional independent histopathologic confirmation.
SETTING
Mayo Clinic Rochester, a tertiary care center.
PATIENTS
All patients who underwent primary resection for pancreatic IPMN.
MAIN OUTCOME MEASURES
Disease-specific operative outcomes, survival, and recurrence patterns.
RESULTS
Of 208 patients (mean age, 66 years) with IPMN of the pancreas, 168 underwent partial pancreatectomy, and 40 underwent total pancreatectomy; 88 were classified as having adenoma, 38 as having borderline neoplasm, 19 as having carcinoma in situ, and 63 as having invasive carcinoma. The prevalence of a malignant neoplasm was 64% in patients with main duct IPMN compared with 18% in patients with branch duct IPMN. Re-resection of the initial pancreatic margin was necessary in 21% of patients. Final negative margins were achieved in 89% of patients. Five-year survival with noninvasive IPMN was 94%. Patients with invasive IPMN had a similar 5-year survival compared with a matched cohort with ductal adenocarcinoma (31% vs 24%; P = .26). In patients with invasive IPMN, 58% experienced disease recurrence. In patients with noninvasive IPMN, 10% experienced disease recurrence after partial pancreatectomy and 0% experienced disease recurrence after total pancreatectomy.
CONCLUSIONS
Patients with main duct IPMN or high-risk branch duct IPMN should be considered for targeted pancreatectomy. Invasive IPMN behaves as aggressively as ductal adenocarcinoma, but resection seems to provide the only potential for cure. Even with negative resection margins, the pancreatic remnant harbors a risk of recurrence and, thus, careful long-term surveillance is warranted.
|
No pos
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No neg
|
Retriever2899
|
Oxidative stress in patients with unstable angina.
The aim of this study was to determine whether oxidative stress occurs in unstable angina. Thirty patients with unstable angina class B (Braunwald classification) were prospectively studied. Control groups consisted of 23 patients presenting with stable angina and of 21 age-matched healthy volunteers. Upon admission and every 8 h for 24 h, blood samples were drawn for the determination of plasma malondialdehyde (MDA) levels, Se-glutathione peroxidase (GPX) activity, erythrocyte reduced glutathione (GSH) concentrations, erythrocyte GPX and superoxide dismutase (SOD) activities. Coronary angiograms were performed within 4 days of admission in 26 out of the 30 patients included in the study. Nine of these 30 patients were subsequently identified as presenting a non-Q wave myocardial infarction and were separately examined. On admission, only plasma MDA levels and erythrocyte GSH concentrations differed among groups. Plasma MDA levels of patients presenting with unstable angina (P < 0.01) and acute myocardial infarction (P < 0.05) were higher than those of patients with stable angina and of normal volunteers, whereas there was no difference in these parameters between unstable angina and non-Q wave myocardial infarction groups. Erythrocyte GSH concentration was lower in all patient groups as compared to normal subjects. ANOVA for repeated measures showed no difference between admission and subsequent levels for all parameters. Finally, no difference was observed for any of the parameters when anti-ischaemic or anti-aggregant treatment before admission, or the number of affected vessels on coronary angiograms, were considered. We conclude that an oxidative stress can be evidenced in patients with unstable angina or acute myocardial infarction.
|
No pos
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No neg
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