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Retriever3000
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Management of crush syndrome.
Our experience in treating seven patients with severe crush injury of the lower limbs is described. They were brought to hospital 12 h after rescue and had no treatment until then. All seven developed acute renal failure due to myoglobinuria and dehydration. Five were anuric and three non-oliguric. All developed severe sepsis and two had also acute respiratory failure. No bleeding tendency was observed. They were treated along the following lines: early extensive fasciotomy and removal of dead tissues; early fluid challenge; early peritoneal dialysis and/or hemodialysis; high caloric, high protein nutrition; vigorous antibiotic therapy when infection was evident. There were no deaths in our patients. Our management and results are discussed and compared with those in the literature.
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No pos
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No neg
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Retriever3001
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[Uptake of gamma-aminobutyric acid by 3H-glial cells and synaptosomes of rat cerebral cortex under the influence of psychotropic substances].
Chlorpromazine was shown to inhibit non-competitively the 3H-GABA uptake both by the glial cells and synaptosomes; synaptosomal uptake was more sensitive to the inhibitor. Only the low-affinity GABA uptake in the glial cells was competitively inhibited by beta-alanine. On the whole, there was a correlation between the inhibition of GABA uptake by psychotropic drugs in the glial cells and in the synaptosomes. It is assumed that there existed two different systems of GABA uptake (of high and low affinity) in the nerve endings and glial cells.
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No pos
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No neg
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Retriever3002
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Conformal Hydrogel-Skin Coating on a Microfluidic Channel through Microstamping Transfer of the Masking Layer.
Poly(dimethylsiloxane) (PDMS) is used in microfluidics owing to its biocompatibility and simple fabrication. However, its intrinsic hydrophobicity and biofouling inhibit its microfluidic applications. Conformal hydrogel-skin coating for PDMS microchannels, involving the microstamping transfer of the masking layer, is reported herein. A selective uniform hydrogel layer with a thickness of ∼1 μm was coated in diverse PDMS microchannels with a resolution of ∼3 μm, maintaining its structure and hydrophilicity after 180 days (6 months). The wettability transition of PDMS was demonstrated through the switched emulsification in a flow-focusing device (water-in-oil [pristine PDMS] to oil-in-water [hydrophilic PDMS]). A one-step bead-based immunoassay was performed to detect the anti-severe acute respiratory syndrome coronavirus 2 IgG using a hydrogel-skin-coated point-of-care platform.
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No pos
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No neg
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Retriever3003
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The Padua Inventory: do revisions need revision?
The purpose of the present study was to examine the psychometric properties, factorial structure, and validity of the Padua Inventory-Washington State University Revision and of the Padua Inventory-Revised in a large sample of patients with obsessive-compulsive disorder (n = 228) and with anxiety disorders and/or depression (n = 213). The five-factor structures of both revisions were not replicated. A 24-item revision, referred to as the Padua Inventory-Palatine Revision (PI-PR), was developed on the basis of both theoretical and statistical considerations. The PI-PR assesses six subscales: Contamination and Washing, Checking, Numbers, Dressing and Grooming, Rumination, and Harming Obsessions and Impulses. The results demonstrate that the PI-PR is a brief, psychometrically sound, and valid measure for the assessment of a broad range of obsessive-compulsive symptoms, which has important advantages over both previous revisions.
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No pos
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No neg
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Retriever3004
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A plant virus manipulates the behavior of its whitefly vector to enhance its transmission efficiency and spread.
Plant viruses can produce direct and plant-mediated indirect effects on their insect vectors, modifying their life cycle, fitness and behavior. Viruses may benefit from such changes leading to enhanced transmission efficiency and spread. In our study, female adults of Bemisia tabaci were subjected to an acquisition access period of 72 h in Tomato yellow leaf curl virus (TYLCV)-infected and non-infected tomato plants to obtain viruliferous and non-viruliferous whiteflies, respectively. Insects that were exposed to virus-infected plants were checked by PCR to verify their viruliferous status. Results of the Ethovision video tracking bioassays indicated that TYLCV induced an arrestant behavior of B. tabaci, as viruliferous whitefly adults remained motionless for more time and moved slower than non-viruliferous whiteflies after their first contact with eggplant leaf discs. In fact, Electrical Penetration Graphs showed that TYLCV-viruliferous B. tabaci fed more often from phloem sieve elements and made a larger number of phloem contacts (increased number of E1, E2 and sustained E2 per insect, p<0.05) in eggplants than non-viruliferous whiteflies. Furthermore, the duration of the salivation phase in phloem sieve elements (E1) preceding sustained sap ingestion was longer in viruliferous than in non-viruliferous whiteflies (p<0.05). This particular probing behavior is known to significantly enhance the inoculation efficiency of TYLCV by B. tabaci. Our results show evidence that TYLCV directly manipulates the settling, probing and feeding behavior of its vector B. tabaci in a way that enhances virus transmission efficiency and spread. Furthermore, TYLCV-B. tabaci interactions are mutually beneficial to both the virus and its vector because B. tabaci feeds more efficiently after acquisition of TYLCV. This outcome has clear implications in the epidemiology and management of the TYLCV-B. tabaci complex.
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No pos
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No neg
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Retriever3005
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Sex-specific differences in the association between body mass index and brain aging in young adults: Findings from the human connectome project.
BACKGROUND
This report evaluated sex-specific differences in the association between brain aging and body mass index (BMI) in young adults using the publicly available data from the Human Connectome Project (HCP).
METHODS
Participants of HCP with available structural imaging and BMI data were included [n = 1112; mean age = 28.80 (SD = 3.70); mean BMI = 26.53 (SD = 5.20); males n = 507, females n = 605]. Predicted brain age was generated using raw T1-weighted MRI scan and a Gaussian Processes regression model. The difference (Δ aging) between brain age predicted by structural imaging and chronological age was computed. A linear regression model was used with Δ aging as the dependent variable, and sex, BMI, and BMI-by-sex interaction as independent variables of interest, and race, ethnicity, income, and education as covariates.
RESULTS
There was a significant BMI-by-sex interaction for Δ aging (p = 0.041). Higher BMI was associated with greater brain aging in both sexes. However, this association was substantially stronger in males (β = 0.215; SE = 0.050; p < 0.0001) than in females (β = 0.122; SE = 0.035; p = 0.0005).
CONCLUSION
We found evidence suggesting that higher BMI is associated with greater brain aging in adults. Furthermore, the association between higher BMI and greater brain aging was stronger in males than in females. Future studies are needed to explore the mechanistic pathways that link higher BMI to greater brain aging and whether weight-loss interventions, such as exercise, can reverse higher BMI-associated greater brain aging.
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No pos
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No neg
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Retriever3006
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[Pharmacological treatment of obsessive compulsive disorder in children/adolescents].
Obsessive compulsive disorder (OCD) is a frequent condition. First-choice psychopharmacological treatment includes SSRIs where the choice of drug depends on the occurrence of side effects. If remission is obtained, continued treatment is recommended for at minimum of one year. If only a partial or no response is obtained, augmentation treatment with atypical antipsychotics may be attempted. However, only few studies have examined the effect and side effects of augmentation treatment in children and adolescents. The aim was to provide a summary on the current knowledge on psychopharmacological treatment of children and adolescents with OCD.
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No pos
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No neg
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Retriever3007
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Development of Photoluminescent and Photochromic Polyester Nanocomposite Reinforced with Electrospun Glass Nanofibers.
A polyester resin was strengthened with electrospun glass nanofibers to create long-lasting photochromic and photoluminescent products, such as smart windows and concrete, as well as anti-counterfeiting patterns. A transparent glass@polyester (GLS@PET) sheet was created by physically immobilizing lanthanide-doped aluminate (LA) nanoparticles (NPs). The spectral analysis using the CIE Lab and luminescence revealed that the transparent GLS@PET samples turned green under ultraviolet light and greenish-yellow in the dark. The detected photochromism can be quickly reversed in the photoluminescent GLS@PET hybrids at low concentrations of LANPs. Conversely, the GLS@PET substrates with the highest phosphor concentrations exhibited sustained luminosity with slow reversibility. Transmission electron microscopic analysis (TEM) and scanning electron microscopy (SEM) were utilized to examine the morphological features of lanthanide-doped aluminate nanoparticles (LANPs) and glass nanofibers to display diameters of 7-15 nm and 90-140 nm, respectively. SEM, energy-dispersive X-ray spectroscopy (EDXA), and X-ray fluorescence (XRF) were used to analyze the luminous GLS@PET substrates for their morphology and elemental composition. The glass nanofibers were reinforced into the polyester resin as a roughening agent to improve its mechanical properties. Scratch resistance was found to be significantly increased in the created photoluminescent GLS@PET substrates when compared with the LANPs-free substrate. When excited at 368 nm, the observed photoluminescence spectra showed an emission peak at 518 nm. The results demonstrated improved hydrophobicity and UV blocking properties in the luminescent colorless GLS@PET hybrids.
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No pos
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No neg
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Retriever3008
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Immunohistochemistry in the pathologic diagnosis and management of thyroid neoplasms.
The use of immunohistochemistry cannot be underestimated in the everyday practice of thyroid pathology. It has evolved over the years beyond the traditional confirmation of thyroid origin to molecular profiling and the prediction of clinical behavior. In addition, immunohistochemistry has served to implement changes in the current thyroid tumor classification scheme. It is prudent to perform a panel of immunostains, and the immunoprofile should be interpreted in light of the cytologic and architectural features. Immunohistochemistry can also be easily performed in the limited cellularity specimen preparation generated from thyroid fine-needle aspiration and core biopsy; however, it will require laboratory validation of immunostains specific to these preparations to avoid diagnostic pitfalls. This review discusses the application of immunohistochemistry in thyroid pathology with a focus on limited cellularity preparations.
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No pos
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No neg
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Retriever3009
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The range of validity of the anomalous diffraction approximation to electromagnetic scattering by a sphere.
The ranges of refractive index and particle size over which the anomalous diffraction approximation is valid to within 15%, 50%O, and 100% are mapped. The approximation is found to have a broader range of applicability for the extinction efficiency than the Rayleigh-Gans approximation. The large range of validity explains the success of schemes for determining particle size distributions of spheres from extinction measurements based on analytic inversions of formulas containing the approximation.
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No pos
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No neg
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Retriever3010
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Blind deconvolution estimation of fluorescence measurements through quadratic programming.
Time-deconvolution of the instrument response from fluorescence lifetime imaging microscopy (FLIM) data is usually necessary for accurate fluorescence lifetime estimation. In many applications, however, the instrument response is not available. In such cases, a blind deconvolution approach is required. An iterative methodology is proposed to address the blind deconvolution problem departing from a dataset of FLIM measurements. A linear combination of a base conformed by Laguerre functions models the fluorescence impulse response of the sample at each spatial point in our formulation. Our blind deconvolution estimation (BDE) algorithm is formulated as a quadratic approximation problem, where the decision variables are the samples of the instrument response and the scaling coefficients of the basis functions. In the approximation cost function, there is a bilinear dependence on the decision variables. Hence, due to the nonlinear nature of the estimation process, an alternating least-squares scheme iteratively solves the approximation problem. Our proposal searches for the samples of the instrument response with a global perspective, and the scaling coefficients of the basis functions locally at each spatial point. First, the iterative methodology relies on a least-squares solution for the instrument response, and quadratic programming for the scaling coefficients applied just to a subset of the measured fluorescence decays to initially estimate the instrument response to speed up the convergence. After convergence, the final stage computes the fluorescence impulse response at all spatial points. A comprehensive validation stage considers synthetic and experimental FLIM datasets of ex vivo atherosclerotic plaques and human breast cancer cell samples that highlight the advantages of the proposed BDE algorithm under different noise and initial conditions in the iterative scheme and parameters of the proposal.
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No pos
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No neg
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Retriever3011
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Visualization of a DNA-PK/PARP1 complex.
The DNA-dependent protein kinase (DNA-PK) and Poly(ADP-ribose) polymerase-1 (PARP1) are critical enzymes that reduce genomic damage caused by DNA lesions. They are both activated by DNA strand breaks generated by physiological and environmental factors, and they have been shown to interact. Here, we report in vivo evidence that DNA-PK and PARP1 are equally necessary for rapid repair. We purified a DNA-PK/PARP1 complex loaded on DNA and performed electron microscopy and single particle analysis on its tetrameric and dimer-of-tetramers forms. By comparison with the DNA-PK holoenzyme and fitting crystallographic structures, we see that the PARP1 density is in close contact with the Ku subunit. Crucially, PARP1 binding elicits substantial conformational changes in the DNA-PK synaptic dimer assembly. Taken together, our data support a functional, in-pathway role for DNA-PK and PARP1 in double-strand break (DSB) repair. We also propose a NHEJ model where protein-protein interactions alter substantially the architecture of DNA-PK dimers at DSBs, to trigger subsequent interactions or enzymatic reactions.
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No pos
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No neg
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Retriever3012
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Electrochemical quartz crystal microbalance analysis of the oxygen reduction reaction on Pt-based electrodes. Part 2: adsorption of oxygen species and ClO4(-) anions on Pt and Pt-Co alloy in HClO4 solutions.
To gain deeper insight into the role of adsorbed oxygenated species in the O2 reduction reaction (ORR) kinetics on platinum and platinum-cobalt alloys for fuel cells, we carried out a series of measurements with the electrochemical quartz crystal microbalance (EQCM) and the rotating disk electrode (RDE) in acid solution. The effects of anion adsorption on the activities for the ORR were first assessed in HClO4 and HF electrolyte solutions at various concentrations. In our previous work (Part 1), we reported that the perchlorate anion adsorbs specifically on bulk-Pt, with a Frumkin-Temkin isotherm, that is, a linear relationship between Δm and log[HClO4]. Here, we find that the specific adsorption on the Pt-skin/Pt3Co alloy was significantly stronger than that on bulk-Pt, in line with its modified electronic properties. The kinetically controlled current density j(k) for the O2 reduction at the Pt-skin/Pt3Co-RDE was about 9 times larger than that of the bulk-Pt-RDE in 0.01 M HClO4 saturated with air, but the j(k) values on Pt-skin/Pt3Co decreased with increasing [HClO4] more steeply than in the case of Pt, due to the blocking of the active sites by the specifically adsorbed ClO4(-). We have detected reversible mass changes for one or more adsorbed oxygen-containing species (Ox = O2, O, OH, H2O) on the Pt-skin/Pt3Co-EQCM and Pt-EQCM in O2-saturated and He-purged 0.01 M HClO4 solutions, in which the specific adsorption of ClO4(-) anions was negligible. The coverages of oxygen species θ(Ox) on the Pt-skin/Pt3Co in the potential range from 0.86 to 0.96 V in the O2-saturated solution were found to be larger than those on pure Pt, providing strong evidence that the higher O2 reduction activity on the Pt3Co is correlated with higher θ(Ox), contrary to the conventional view.
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No pos
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No neg
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Retriever3013
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[Evaluation of the risk of acute poisoning with chemicals in inhabitants of Krakow in from 1983 to 1987].
In Kraków in 1983-1987 11,664 cases of acute poisoning by chemical substances were reported: 11,123 patients were hospitalized; 541 patients died before was given any medical intervention. Among those patients who were treated there were 9725 adult patients older than 14 years--hospitalized in Toxicological Department and 1398 children who were treated in the pediatric departments of many hospitals in Kraków. The cases of the poisoning due to suicidal attempt in the studied period mean 43% and during this time the decreasing tendency was evident (from 47.6% in 1983 to 34.4% in 1987). Narcotic and drug addicts covered only 2% of the whole material concerning the cases of the acute poisoning. Overall incidence rate of poisoning by chemical substances per 10,000 inhabitants of Kraków ranged from 33.9 in 1983 to 32.7 in 1987, and it was always higher in adult population (32.6 in 1983-35.0 in 1987) than in children (24.5 in 1983-23.4 in 1987). During the whole studied period and its successive years the most common poisoning was the poisoning due to: drugs (mean 50%), ethyl alcohol (mean 22%), and carbon monoxide (mean 18%). The highest incidence rate of the acute poisoning was presented to the hospital or clinic in January and October; on Mondays, Tuesdays, and Thursdays; between 12 p.m. and 12 a.m., whereas the lowest was noted during summer months; on Sunday; between 4 a.m. and 8 a.m. Our studies gave us a real picture of the poisons the population in Kraków is exposed to; and total mortality rate amounts 0.8%, yet being calculated on the base of clinical studies goes up to 5.4% when forensic data are taken into account.
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No pos
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No neg
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Retriever3014
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A case of an interstitial tandem direct duplication of long arm of chromosome 4: 46, XY, dup (4) (q25q31.3) de novo.
We report a 4 2/12-year-old Japanese boy with a de novo direct tandem dup (4) (q25q31.3). The major clinical picture includes postnatal growth and psychomotor retardation, thick eye-lashes, a cleft lip, and large and prominent helix and antitragus. He did not have any hearing deficit. His eyegrounds were normal. There was no organ malformations including brain, kidney, liver, pancreas, gallbladder, urinary bladder, stomach, and heart. Routine hematological tests, blood chemistry including thyroid hormones, and urinalysis including urinary screening tests for congenital metabolic disorders showed normal results. He showed an electroencephalographic abnormality which could have resulted from mild aseptic meningitis at 2 months. Our case supports the idea that the association of thumb and renal deformities in duplication 4q syndrome is related to the region 4q22-q23 as many researchers have already pointed out.
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No pos
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No neg
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Retriever3015
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Alpha-band activity in parietofrontal cortex predicts future availability of vibrotactile feedback in prosthesis use.
Prosthesis disuse and abandonment is an ongoing issue in upper-limb amputation. In addition to lost structural and motor function, amputation also results in decreased task-specific sensory information. One proposed remedy is augmenting somatosensory information using vibrotactile feedback to provide tactile feedback of grasping objects. While the role of frontal and parietal areas in motor tasks is well established, the neural and kinematic effects of this augmented vibrotactile feedback remain in question. In this study, we sought to understand the neurobehavioral effects of providing augmented feedback during a reach-grasp-transport task. Ten persons with sound limbs performed a motor task while wearing a prosthesis simulator with and without vibrotactile feedback. We hypothesized that providing vibrotactile feedback during prosthesis use would increase activity in frontal and parietal areas and improve grasp-related behavior. Results show that anticipation of upcoming vibrotactile feedback may be encoded in motor and parietal areas during the reach-to-grasp phase of the task. While grasp aperture is unaffected by vibrotactile feedback, the availability of vibrotactile feedback does lead to a reduction in velocity during object transport. These results help shed light on how engineered feedback is utilized by prostheses users and provide methodologies for further assessment in advanced prosthetics research.
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No pos
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No neg
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Retriever3016
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End-to-end application of model-informed drug development for ertugliflozin, a novel sodium-glucose cotransporter 2 inhibitor.
Model-informed drug development (MIDD) is critical in all stages of the drug-development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end-to-end development of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose-response relationships, (2) dose-response modeling and model-based meta-analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose-proportionality and the impact of uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically-based PK modeling to assess the risk of UGT-mediated drug-drug interactions. These end-to-end MIDD approaches for ertugliflozin facilitated decision making, resulted in time/cost savings, and supported registration and labeling.
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No pos
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No neg
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Retriever3017
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Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines.
Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.
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No pos
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No neg
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Retriever3018
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Prescription Patterns and Patient Care Practices in Two Tertiary Hospitals in South-South Nigeria.
BACKGROUND
Inappropriate use of medicines still characterize all levels of healthcare, with important public health implications. Available evidence indicate that irrational use of medicines can lead to poor therapeutic outcomes, adverse drug reactions, and thus increase morbidity and mortality rates. This study assessed the prescription pattern, patient and health care facility indicators in two tertiary health facilities in Nigeria.
METHODS
A cross-sectional survey of 1800 prescriptions and 600 patients' encounters was conducted at the General Outpatient Departments of the University of Benin and Delta State University Teaching Hospitals using the WHO drug use indicators. Data from 12-month prescription sheets as well as patient interviews were entered into standard indicator forms and analyzed according to WHO guidelines.
RESULTS
Overall, the average number of drugs per encounter was 2.8 ± 1.6. The percentage of generic prescription was 49.6%, while percentage of encounters with antibiotics, antimalarial and injections were 27.4%, 23.2% and 12.4% respectively. Prescription of medicines listed in the Essential Medicines List was 66.6%, even though no copy was available at the consulting rooms. Average consulting and dispensing time were 15.3 minutes and 136 seconds respectively. Percentage of medicines actually dispensed was 86.2% while 98.7% of medicines were adequately labelled.
CONCLUSION
Gaps still exist in the rational use of medicines in Nigeria. There needs to be sustained interventional schemes with capacity for monitoring and evaluation to detect inappropriate drug use patterns and prevent the undesirable consequences of irrational use of medicines.
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No pos
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No neg
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Retriever3019
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[Indoor air quality in schools].
Indoor air quality in schools has received particular attention over the past several years. Children are considered as one of the most sensitive groups to atmospheric pollution because their bodies are actively growing and they breathe higher volumes of air relative to their body weights than adults do. They also spend more time in school or group structures (preschools, day nurseries) than in any indoor environments other than the home. The analysis of children's exposure to air pollution at school requires the identification of the main pollutant sources present in these educational institutions. Both a strong contribution of outdoor pollution and a very specific pollution bound to school activities such as the use of paints, markers, glues, and manufactured ink eraser pens, exist. The ventilation in school buildings also plays an important role in air quality. A higher air exchange may improve thermal comfort and air quality. The cause of indoor air pollution is a combinatory effect of physical, chemical, and biological factors, and the adequacy of ventilation in the environment. Several pollutants have been reported to exist in classrooms such as bacteria, molds, volatile organic compounds, persistent organic pollutants and microparticles. There is a correlation between the concentrations of the pollutants and onset of health problems in schoolchildren. We observe predominantly respiratory symptoms as well as a prevalence of respiratory diseases such as asthma and allergies. This study shows that poor indoor air quality affects children's health.
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No pos
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No neg
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Retriever3020
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Comparative study of visual pathways in owls (Aves: Strigiformes).
Although they are usually regarded as nocturnal, owls exhibit a wide range of activity patterns, from strictly nocturnal, to crepuscular or cathemeral, to diurnal. Several studies have shown that these differences in the activity pattern are reflected in differences in eye morphology and retinal organization. Despite the evidence that differences in activity pattern among owl species are reflected in the peripheral visual system, there has been no attempt to correlate these differences with changes in the visual regions in the brain. In this study, we compare the relative size of nuclei in the main visual pathways in nine species of owl that exhibit a wide range of activity patterns. We found marked differences in the relative size of all visual structures among the species studied, both in the tectofugal and the thalamofugal pathway, as well in other retinorecipient nuclei, including the nucleus lentiformis mesencephali, the nucleus of the basal optic root and the nucleus geniculatus lateralis, pars ventralis. We show that the barn owl (Tyto alba), a species widely used in the study of the integration of visual and auditory processing, has reduced visual pathways compared to strigid owls. Our results also suggest there could be a trade-off between the relative size of visual pathways and auditory pathways, similar to that reported in mammals. Finally, our results show that although there is no relationship between activity pattern and the relative size of either the tectofugal or the thalamofugal pathway, there is a positive correlation between the relative size of both visual pathways and the relative number of cells in the retinal ganglion layer.
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No pos
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No neg
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Retriever3021
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An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases.
Neuromuscular diseases (NMDs) are dysfunctions that involve skeletal muscle and cause incorrect communication between the nerves and muscles. The specific causes of NMDs are not well known, but most of them are caused by genetic mutations. NMDs are generally progressive and entail muscle weakness and fatigue. Muscular impairments can differ in onset, severity, prognosis, and phenotype. A multitude of possible injury sites can make diagnosis of NMDs difficult. Mitochondria are crucial for cellular homeostasis and are involved in various metabolic pathways; for this reason, their dysfunction can lead to the development of different pathologies, including NMDs. Most NMDs due to mitochondrial dysfunction have been associated with mutations of genes involved in mitochondrial biogenesis and metabolism. This review is focused on some mitochondrial routes such as the TCA cycle, OXPHOS, and β-oxidation, recently found to be altered in NMDs. Particular attention is given to the alterations found in some genes encoding mitochondrial carriers, proteins of the inner mitochondrial membrane able to exchange metabolites between mitochondria and the cytosol. Briefly, we discuss possible strategies used to diagnose NMDs and therapies able to promote patient outcome.
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No pos
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No neg
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Retriever3022
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Sonographic diagnosis of an unusual case of multilocular cystic nephroma mimicking polycystic kidney disease.
The following is a report of the unusual case of a multilocular cystic nephroma in an 8-year-old boy who was transferred to our unit with a palpable abdominal tumor. The patient suffered from thoracic pain and night sweating. The laboratory values were normal. Abdominal sonography showed a huge kidney tumor on the right side consisting of numerous small cysts transversed by irregular septa of variable thickness. The cysts had a diameter of 1 -5 mm; larger cysts of more than 1 cm in diameter were not able to be shown. In the center of the tumor a normal renal parenchyma was able to be shown. The tumor arose like a mushroom from the kidney. Color Doppler sonography showed good vascularity of the normal renal parenchyma while the tumor had only a few internal vessels. The tumor was surgically removed. The histologic diagnosis was cystic nephroma. Unusual features of this tumor were the small size of the numerous cysts similar to polycystic kidney disease and the mushroom-like growth of the tumor.
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No pos
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No neg
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Retriever3023
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Clinicopathological significance and impact on outcomes of the gene expression levels of IGF-1, IGF-2 and IGF-1R, IGFBP-3 in patients with colorectal cancer: Overexpression of the IGFBP-3 gene is an effective predictor of outcomes in patients with colorectal cancer.
The insulin-like growth factors (IGF) system is involved in tumor proliferation, invasion and metastasis in cancer. The current study investigated the association of IGF-1, IGF-2 and IGF-1 receptor (IGF-1R), IGF binding proteins type 3 (IGFBP-3) mRNA expression levels with clinicopathological characteristics and outcomes of 202 patients with untreated colorectal cancer (CRC). IGF-1, IGF-2, IGF-1R and IGFBP-3 mRNA expression levels were analyzed in surgical specimens of cancer tissues and adjacent normal mucosa cells using reverse transcription-quantitative polymerase chain reaction. The IGF-1R gene expression level was significantly higher in cancer tissue compared with adjacent normal mucosa. By contrast, IGF-1 gene expression levels were reduced in cancer tissue compared with normal mucosa. IGF-2 and IGFBP-3 gene expression levels did not differ significantly between cancer tissue and adjacent normal mucosa. As for the association of gene expression and clinicopathological characteristics, IGFBP-3 gene expression was significantly associated with lymph node metastasis. High IGFBP-3 gene expression was associated with poor 5-year overall survival compared with patients with low IGFBP-3 expression. Furthermore, IGFBP-3 gene expression was identified as an independent prognostic factor using multivariate analysis. Overexpression of the IGFBP-3 gene is considered an effective independent predictor of outcomes in patients with CRC.
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No pos
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No neg
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Retriever3024
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[Melanoma research in Hungary: promising results in a previously orphan tumor].
Melanoma research has a two decade history in Hungary and is based on three groups located at the National Institute of Oncology (NIO), the University of Debrecen (DU) and Semmelweis University (SU). Previously we have summarized the achievements of the NIO group in this Journal, now this paper summarizes the recent results of their collaborations. The research group of DU revealed several novel genetic alterations in the melanoma genome which might have clinical relevance as prognosticators or predictors in light of the novel target therapies. Data indicating unique, perhaps melanoma-specific epigenetic changes during progression might be even more important, identifying novel genes otherwise not detected as genetically altered ones. The research group in Budapest extensively used experimental human melanoma models and demonstrated the host sex as a key factor in progression due to the specific function of NK cells. Identification of functional glucocorticoid receptor in human melanoma might lead to therapeutic exploitation similar to certain leukemias. Studies on extracellular matrix revealed collagen XVII and CD44 splice variants as progression associated factors of melanoma. Since the double wild type genotype of melanoma is lacking effective therapy, data on the use of FGFR2, c-met or cannabinoid receptor as target can be important. On the other hand, experimental data on the antitumoral effects of heparin derivatives or bisphosphonate in melanoma models can also be encouraging.
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No pos
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No neg
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Retriever3025
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Aortic stiffness is increased in polymyalgia rheumatica and improves after steroid treatment.
BACKGROUND
Inflammatory rheumatic diseases have been associated with increased cardiovascular risk and arterial stiffness. Polymyalgia rheumatica (PMR), a disease which affects primarily older people, is characterised by a systemic inflammatory response but little is known about aortic involvement in PMR. A study was undertaken to investigate whether aortic stiffness is increased in PMR and whether it improves after steroid treatment.
METHODS
Thirty-nine patients with PMR (age 72 ± 8 years, 44% men, blood pressure (BP) 134/75 ± 16/9 mm Hg) and 39 age-, sex- and BP-matched control subjects underwent aortic pulse wave velocity (PWV) determination. Aortic augmentation as a measure of the impact of the reflection wave on central haemodynamics was also measured and corrected for heart rate. Twenty-nine of the patients were re-examined after 4 weeks of treatment with prednisone at a dose of 15 mg/day.
RESULTS
Aortic PWV was higher in patients with PMR than in control subjects (12.4 ± 4 vs 10.2 ± 2 m/s, p<0.01). Treatment was followed by a reduction in heart rate (from 78 ± 12 to 70 ± 10 beats/min, p<0.001) and no significant change in BP. Aortic PWV decreased after prednisone treatment (from 11.8 ± 3 to 10.5 ± 3 m/s, p=0.015), and the difference was independent of BP and heart rate changes. The change in aortic PWV had a direct correlation with percentage change in plasma C reactive protein (r=0.40, p=0.037). Treatment was also associated with a significant reduction in aortic augmentation index (from 34 ± 7% to 29 ± 8%, p=0.012).
CONCLUSIONS
Polymyalgia rheumatica is associated with increased aortic stiffness which may improve upon reduction of systemic inflammation induced by treatment with glucocorticoids.
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No pos
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No neg
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Retriever3026
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Validity of trunk extensor and flexor torque measurements using isokinetic dynamometry.
This study aimed to evaluate the validity and test-retest reliability of trunk muscle strength testing performed with a latest-generation isokinetic dynamometer. Eccentric, isometric, and concentric peak torque of the trunk flexor and extensor muscles was measured in 15 healthy subjects. Muscle cross sectional area (CSA) and surface electromyographic (EMG) activity were respectively correlated to peak torque and submaximal isometric torque for erector spinae and rectus abdominis muscles. Reliability of peak torque measurements was determined during test and retest sessions. Significant correlations were consistently observed between muscle CSA and peak torque for all contraction types (r=0.74-0.85; P<0.001) and between EMG activity and submaximal isometric torque (r ⩾ 0.99; P<0.05), for both extensor and flexor muscles. Intraclass correlation coefficients were comprised between 0.87 and 0.95, and standard errors of measurement were lower than 9% for all contraction modes. The mean difference in peak torque between test and retest ranged from -3.7% to 3.7% with no significant mean directional bias. Overall, our findings establish the validity of torque measurements using the tested trunk module. Also considering the excellent test-retest reliability of peak torque measurements, we conclude that this latest-generation isokinetic dynamometer could be used with confidence to evaluate trunk muscle function for clinical or athletic purposes.
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No pos
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No neg
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Retriever3027
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The evolution of social interactions changes predictions about interacting phenotypes.
In many traits involved in social interactions, such as courtship and aggression, the phenotype is an outcome of interactions between individuals. Such traits whose expression in an individual is partly determined by the phenotype of its social partner are called "interacting phenotypes." Quantitative genetic models suggested that interacting phenotypes can evolve much faster than nonsocial traits. Current models, however, consider the interaction between phenotypes of social partners as a fixed phenotypic response rule, represented by an interaction coefficient (ψ). Here, we extend existing theoretical models and incorporate the interaction coefficient as a trait that can evolve. We find that the evolution of the interaction coefficient can change qualitatively the predictions about the rate and direction of evolution of interacting phenotypes. We argue that it is crucial to determine whether and how the phenotypic response of an individual to its social partner can evolve to make accurate predictions about the evolution of traits involved in social interactions.
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No pos
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No neg
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Retriever3028
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A predictive model for the treatment approach to community-acquired pneumonia in patients needing ICU admission.
OBJECTIVE
To create a predictive model for the treatment approach to community-acquired pneumonia (CAP) in patients needing Intensive Care Unit (ICU) admission.
DESIGN
Multicenter prospective study.
SETTING
Twenty-six Spanish ICUs.
PATIENTS
One hundred seven patients with CAP, all of them with accurate etiological diagnosis, divided in three groups according to their etiology in typical (bacterial pneumonia), Legionella and other atypical (Mycoplasma, Chlamydia spp. and virus). For the multivariate analysis we grouped Legionella and other atypical etiologies in the same category.
METHODS
We recorded 34 variables including clinical characteristics, risk factors and radiographic pattern. We used a multivariate logistic regression analysis to find out a predictive model.
RESULTS
We have the complete data in 70 patients. Four variables: APACHE II, (categorized as a dummy variable) serum sodium and phosphorus and "length of symptoms" gave an accurate predictive model (c = 0.856). From the model we created a score that predicts typical pneumonia with a sensitivity of 90.2% and specificity 72.4%.
CONCLUSION
Our model is an attempt to help in the treatment approach to CAP in ICU patients based on a predictive model of basic clinical and laboratory information. Further studies, including larger numbers of patients, should validate and investigate the utility of this model in different clinical settings.
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No pos
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No neg
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Retriever3029
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Endoscopic third ventriculostomy for hydrocephalus: early and late efficacy in relation to aetiology.
OBJECTIVES
The aim of the study was to analyse the effectiveness and usefulness of treatment of hydrocephalus by Endoscopic Third Ventriculostomy (ETV). We sought to relate rates of failure to the cause of hydrocephalus, distinguishing between early and late outcome.
PATIENTS AND METHODS
Between September 1999 and April 2001, 30 patients underwent ETV. In 23 patients hydrocephalus was caused by an expansive mass (tumour). Three groups of patients were distinguished, according to the different aims of ETV. Thus in group T--ETV was carried out to eliminate hydrocephalus prior to the main surgery (53%), in C--ETV was the definite treatment of choice (30%), and in group P--ETV was a palliative treatment (17%). The results were assessed in the early postoperative period and in long term follow-up using clinical relief of symptoms, and radiological criteria (pre- and postoperative computed tomography and/or magnetic resonance scans).
RESULTS
In the early postoperative period ETV was rated to be effective by clinical criteria in 29 patients, and by radiological criteria in 27. According to late assessment the method was successful in 25 patients using clinical criteria, and in 21 using radiological criteria. There was no peri-operative mortality. A transient complication (wound CSF leak) occurred in two patients.
CONCLUSIONS
ETV is effective in well chosen patients in relieving symptoms of hydrocephalus. It is valuable before a definitive major operation to remove the cause of hydrocephalus, as a palliative treatment, and in itself as a method of definitive management when indications are correct.
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No pos
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No neg
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Retriever3030
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Evolving therapies for multiple sclerosis.
The introduction of immunomodulatory and immunosuppressive agents for treatment of multiple sclerosis (MS) has forever altered the natural course of this incurable and disabling neurodegenerative disorder. Despite early diagnosis of relapsing-remitting MS and early initiation of therapy, patients still experience breakthrough relapses and progression of their underlying MS pathology. The imperfect effectiveness, side effects, and toxicity of these agents, emphasize the necessity for development of more effective medications with less adverse events. This chapter presents readers with the most current information on the nature, mechanism(s) of action, and side effects of the most promising experimental agents currently under clinical trials. Some of the agents now at different stages of clinical trial have emerged as both safe and promising. The understanding of MS etiology will lead to the development of increasingly specific, safer, and effective treatments for MS by neuroscientists and neurologists.
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No pos
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No neg
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Retriever3031
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Prediction of properties of chiral compounds by molecular topology.
A common assumption in chemistry is that chiral behavior is associated with 3-D geometry. However, chiral information is related to symmetry, which allows the topological handling of chiral atoms by weighted graphs and the calculation of new descriptors that give a weight to the corresponding entry in the main diagonal of the topological matrix. In this study, it is demonstrated that, operating in this way, chiral topological indices are obtained that can differentiate the pharmacological activity between pairs of enantiomers. The 50% inhibitory concentration (IC50) values of the D2 dopamine receptor and the sigma receptor for a group of 3-hydroxy phenyl piperidines are specifically predicted. Moreover, the sedative character of a group of chiral barbiturates can be identified.
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No pos
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No neg
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Retriever3032
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Forelimb and hindlimb stepping by the anesthetized rat elicited by electrical stimulation of the pons and medulla.
This study determined the lower brainstem sites at which electrical stimulation elicits stepping movements of the forelimbs and hindlimbs. Rats (N = 45), anesthetized with nembutal, were fixed in a stereotaxic apparatus so that their limbs contacted a moving treadmill belt. Electrical stimulation (100 microA, 10-sec trains, 0.5-msec cathodal pulses, 50-Hz pulse frequency) was applied every 200 micron through 173 movable electrodes. Well coordinated quadrupedal stepping was elicited by stimulation at dorsal posterior mesencephalic sites including the inferior collicular commissure, the central gray, the nucleus cuneiformis and lateral aspects of the pedunculopontine tegmental nucleus. Caudal and ventral to this general region, sites supporting quadrupedal stepping appeared mainly in or near the spinal trigeminal nucleus. Stepping with only the forelimb and hindlimb contralateral to the stimulation site was associated with the corticospinal tract, the lateral pontis oralis, the lateral pontis caudalis and the ventral reticular nucleus of the medulla. Bilateral forelimb stepping was associated with the trigeminal system and the gigantocellular reticular nucleus. At the level of the rostral medulla, systems involved in bilateral forelimb stepping and contralateral hindlimb stepping appear to be located medially. Systems concerned with bilateral hindlimb stepping appear to be located laterally.
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No pos
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No neg
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Retriever3033
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[A retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer].
We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.
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No pos
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No neg
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Retriever3034
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Influence of environmental parameters on pentachlorophenol biotransformation in soil by Lentinula edodes and Phanerochaete chrysosporium.
The influences of temperature, soil moisture potential and initial pH on the biotransformation of pentachlorophenol (PCP) by the lignicolous fungi Lentinula edodes and Phanerochaete chrysosporium were examined. At 10 degrees C, L. edodes was more effective in degrading PCP (P < 0.05) than P. chrysosporium. At 15 degrees C similar results were obtained for the two fungi. The highest levels of degradation occurred for both fungi at 25 degrees C. With P. chrysosporium, the extent of PCP elimination was directly related to soil moisture content and optimal at approximately 47%. With L. edodes, in contrast, the process was inversely related to moisture content and maximal at 26%. The initial soil pH also had a marked influence, and pH 4.0 was optimal for both fungi.
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No pos
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No neg
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Retriever3035
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Nanosized concave pit/convex dot microarray for immunomodulatory osteogenesis and angiogenesis.
The immunomodulatory capability of biomaterials is of paramount importance for successful material-mediated bone regeneration. Particularly, the design of surface nano-topography can be leveraged to instruct immune reactions, yet the understanding of such "nano-morphology effect" is still very limited. Herein, highly ordered nano-concave pit (denoted as NCPit) and nano-convex dot (denoted as NCDot) microarrays with two different sizes were successfully constructed on a 316LSS surface via anodization and subsequently immersion-coating treatment, respectively. We, for the first time, comparatively investigated the interactions of NCPit and NCDot microarrays with RAW264.7 macrophages and their immunomodulatory impacts on osteogenesis and angiogenesis of human bone mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs). NCDot microarrays induced macrophages towards M2 polarization with the higher expression level of anti-inflammatory markers (IL-10 and CD 206) and the lower level of pro-inflammatory markers (TNF-α, IL-1β, IL-6 and CD 86) than those of the corresponding NCPit microarrays. During the process, the expressions of osteogenesis-related genes (Runx2, OPN and OCN) of hBMSCs, and angiogenesis-related genes (eNOS, HIF-1α, KDR and VEGF) of HUVECs were significantly upregulated by the NCDot microarray-modulating immune microenvironment of macrophages, and finally stimulated osteogenesis and angiogenesis. Thus, the prepared NCDot arrays were able to significantly promote osteo-/angiogenic activity by generating a more suitable immune microenvironment than NCPit arrays, offering substantial evidence for designing immunomodulatory biomaterials with specific microstructures and optimal bioactivity.
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No pos
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No neg
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Retriever3036
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New Ln-MOFs based on mixed organic ligands: synthesis, structure and efficient luminescence sensing of the Hg2+ ions in aqueous solutions.
In view of Hg2+ ion sensing by luminescence, a series of new, phenanthroline-decorated 3D lanthanide metal organic frameworks (Ln-MOFs) valorising an original combination of four different lanthanides and two organic ligands, i.e. thiobis(4-methylene-benzoic acid) (H2tmba) and 1,10-phenanthroline (phen), have been successfully synthesized, namely {[Ln4(tmba)6(phen)4]·m(H2O)(phen)} [Ln = Ce, m = 3 (1); Pr, m = 1 (2); Eu, m = 3 (3); and Tb, m = 3 (4)]. Compounds 1-4 were characterised by single-crystal X-ray diffraction, elemental and thermogravimetric analyses, and powder X-ray diffraction. The luminescence properties of complexes 3 and 4 were thoroughly investigated. It is herein proved that compound 3 sensitively and selectively acts as an excellent luminescent probe for the detection of Hg2+ ions in waters, with a detection limit of 1.00 μM. As additional assets, 3 displays superb stability over a wide pH range (3-12) of the aqueous media, as well as convenient recycling after completion of the detection experiments. The rationale for the observed luminescence quenching effect of mercury might be a strong interaction arising between Hg2+ ions and the carboxylate oxygen atoms of the tmba2- ligand. The results open new perspectives for applications in environmental remediation.
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No pos
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No neg
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Retriever3037
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Mother-infant bonding : A scientific fiction.
A study of the research on postpartum mother-infant bonding shows that results from poorly constructed research programs were published in major journals and became a part of hospital policy because the bonding concept was politically useful in the struggle between advocates of natural childbirth and managers of the medical model of birth. The concept was also uncritically accepted because it was consistent with a longstanding ideology of motherhood that sees women as the prime architects of their children's personalities.
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No pos
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No neg
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Retriever3038
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Fixed Dosing of Monoclonal Antibodies in Oncology.
Most monoclonal antibodies in oncology are administered in body-size-based dosing schedules. This is believed to correct for variability in both drug distribution and elimination between patients. However, monoclonal antibodies typically distribute to the blood plasma and extracellular fluids only, which increase less than proportionally with the increase in body weight. Elimination takes place via proteolytic catabolism, a nonspecific immunoglobulin G elimination pathway, and intracellular degradation after binding to the target. The latter is the primary route of elimination and is related to target expression levels rather than body size. Taken together, the minor effects of body size on distribution and elimination of monoclonal antibodies and their usually wide therapeutic window do not support body-size-based dosing. We evaluated effects of body weight on volume of distribution and clearance of monoclonal antibodies in oncology and show that a fixed dose for most of these drugs is justified based on pharmacokinetics. A survey of the savings after fixed dosing of monoclonal antibodies at our hospital showed that fixed dosing can reduce costs of health care, especially when pooling of preparations is not possible (which is often the case in smaller hospitals). In conclusion, based on pharmacokinetic parameters of monoclonal antibodies, there is a rationale for fixed dosing of these drugs in oncology. Therefore, we believe that fixed dosing is justified and can improve efficiency of the compounding. Moreover, drug spillage can be reduced and medication errors may become less likely.
IMPLICATIONS FOR PRACTICE
The currently available knowledge of elimination of monoclonal antibodies combined with the publicly available data from clinical trials and extensive population pharmacokinetic (PopPK) modeling justifies fixed dosing. Interpatient variation in exposure is comparable after body weight and fixed dosing and most monoclonal antibodies show relatively flat dose-response relationships. For monoclonal antibodies, this results in wide therapeutic windows and no reduced clinical efficacy after fixed dosing. Therefore, we believe that fixed dosing at a well-selected dose can increase medication safety and help in reduction of costs of health care without the loss of efficacy or safety margins.
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No pos
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No neg
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Retriever3039
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Schiff's base formation in the lens protein gamma-crystallin.
Uniquely among the soluble lens-specific proteins, gamma-crystallin is capable of binding the strongly chromophoric aldehyde retinal. A role for gamma-crystallin in protecting lens components from toxic aldehydes resulting from membrane oxidation is proposed and a molecular model of the probable interaction site is presented. The sequence of a tetrapeptide at this site is identical to that of the retinal binding site of bacteriorhodopsin.
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No pos
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No neg
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Retriever3040
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The contribution of genetic and environmental factors to quantitative variability of erythrocyte membrane proteins in primary hypotension.
Our previous studies have shown that, compared with healthy individuals, patients with primary arterial hypotension (PAH) have significant quantitative changes in erythrocyte membrane proteins. The purpose of the present study was to evaluate the contribution made by genetic and environmental factors to quantitative variation of erythrocyte membrane proteins in PAH. We studied 109 hypotensive patients, 124 normotensive subjects, 222 of their first-degree relatives and 24 twin pairs by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. The decomposition of total phenotypic variance of erythrocyte membrane proteins to genetic and environmental components was performed on the basis of correlations among first-degree relatives by the least squares method. The genetic dominance and shared environmental factors were found to influence the variability of cytoskeletal membrane proteins whose contents were changed in PAH. Furthermore, variations in alpha-spectrin, actin and anion exchanger in hypotensives were substantially influenced by major gene and maternal effects. Ankyrin 2.1 and actin content was under the control of common underlying genes. Variations in membrane-associated glutathione-S-transferase and tropomyosin were predominantly affected by polygenes. These findings suggest that the putative major genes with pleiotropic effects appear to be involved in the control of quantitative disorders of erythrocyte membrane proteins in primary hypotension.
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No pos
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No neg
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Retriever3041
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Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.
BACKGROUND
A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent.
OBJECTIVE
To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients.
METHODS
This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m2), obesity class I and II (BMI 30-39.9kg/m2), and obesity class III (BMI≥40 kg/m2) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated.
RESULTS
Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75).
CONCLUSIONS
Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.
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No pos
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No neg
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Retriever3042
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Hemodynamic impact of coronary stenosis using computed tomography: comparison between noninvasive fractional flow reserve and 3D fusion of coronary angiography with stress myocardial perfusion.
Vasodilator-stress CT perfusion imaging in addition to CT coronary angiography (CTCA) may provide a single-test alternative to nuclear stress testing, commonly used to assess hemodynamic significance of stenosis. Another alternative is fractional flow reserve (FFR) calculated from cardiac CT images. We studied the concordance between these two approaches and their relationship to outcomes. We prospectively studied 150 patients with chest pain, who underwent CTCA and regadenoson CT. CTCA images were interpreted for presence and severity of stenosis. Fused 3D displays of subendocardial X-ray attenuation with coronary arteries were created to detect stress perfusion defects (SPD) in each coronary territory. In patients with stenosis > 25%, CT-FFR was quantified. Significant stenosis was determined by: (1) combination of stenosis > 50% with an SPD, (2) CT-FFR ≤ 0.80. Patients were followed-up for 36 ± 25 months for death, myocardial infarction or revascularization. After excluding patients with normal arteries and technical/quality issues, in final analysis of 76 patients, CTCA depicted stenosis > 70% in 13/224 arteries, 50-70% in 24, and < 50% in 187. CT-FFR ≤ 0.80 was found in 41/224 arteries, and combination of SPD with > 50% stenosis in 31/224 arteries. Inter-technique agreement was 89%. Despite high incidence of abnormal CT-FFR (30/76 patients), only 7 patients experienced adverse outcomes; 6/7 also had SPDs. Only 1/9 patients with CT-FFR ≤ 0.80 but normal perfusion had an event. Fusion of CTCA and stress perfusion can help determine the hemodynamic impact of stenosis in one test, in good agreement with CT-FFR. Adding stress CT perfusion analysis may help risk-stratify patients with abnormal CT-FFR.
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No pos
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No neg
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Retriever3043
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C,O-bisglycosylapigenins from the leaves of Rhamnella inaequilatera.
From the leaves of Rhamnella inaequilatera, three flavone C,O-bisglycosides, rhamnellaflavosides A, B and C, were isolated and their structures were elucidated based on their spectral data and chemical evidence.
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No pos
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No neg
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Retriever3044
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Optical Imaging of Ventricular Action Potentials in a Torso Tank: A New Platform for Non-Invasive Electrocardiographic Imaging Validation.
Background: Non-invasive electrocardiographic imaging (ECGI) is a promising tool to provide high-resolution panoramic imaging of cardiac electrical activity noninvasively from body surface potential measurements. Current experimental methods for ECGI validation are limited to comparison with unipolar electrograms and the relatively low spatial resolution of cardiac mapping arrays. We aim to develop a novel experimental set up combining a human shaped torso tank with high-resolution optical mapping allowing the validation of ECGI reconstructions. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, with the left anterior descending artery (LAD) cannulated on a separate perfusion. Electrical signals were recorded from an 108-electrode epicardial sock and 128 electrodes embedded in the tank surface. Simultaneously, optical mapping of the heart was performed through the anterior surface of the tank. Recordings were made in sinus rhythm and ventricular pacing (n = 55), with activation and repolarization heterogeneities induced by perfusion of hot and cold solutions as well as Sotalol through the LAD. Fluoroscopy provided 3D cardiac and electrode geometries in the tank that were transformed to the 2D optical mapping window using an optimization algorithm. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGI and validated using optical activation and repolarization maps. Results: The transformation and alignment of the 3D geometries onto the 2D optical mapping window was good with an average correlation of 0.87 ± 0.10 and error of 7.7 ± 3.1 ms with activation derived from the sock. The difference in repolarization times were more substantial (error = 17.4 ± 3.7 ms) although the sock and optical repolarization patterns themselves were very similar (correlation = 0.83 ± 0.13). Validation of ECGI reconstructions revealed ECGI accurately captures the pattern of activation (correlation = 0.79 ± 0.11) and identified regions of late and/or early repolarization during different perfusions through LAD. ECGI also correctly demonstrated gradients in both activation and repolarization, although in some cases these were under or over-estimated or shifted slightly in space. Conclusion: A novel experimental setup has been developed, combining a human-shaped torso tank with optical mapping, which can be effectively used in the validation of ECGI techniques; including the reconstruction of activation and repolarization patterns and gradients.
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No pos
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No neg
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Retriever3045
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The pepR gene of Lactobacillus sakei is positively regulated by anaerobiosis at the transcriptional level.
Lactobacillus sakei is a lactic acid bacterium belonging to the natural flora of meat products. It constitutes the main flora of vacuum-packed meat and is largely used in western Europe as a starter for the manufacturing of fermented sausages. This species is able to grow both under aerobiosis and anaerobiosis. In many technological processes involving it, oxygen is scarce. The aim of this study was to identify the major proteins affected by growth under anaerobiosis. Using two-dimensional electrophoresis, we showed that one spot was 10-fold overexpressed when cells were grown under anaerobiosis. By N-terminal sequencing it was identified as a peptidase (PepR), and the pepR gene was cloned. Northern analysis revealed that pepR was expressed as a single 1.27-kb transcript induced under anaerobiosis. A mutant was constructed by single crossover in the pepR gene, and its growth and survival were not affected by anaerobiosis.
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No pos
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No neg
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Retriever3046
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Pulmonary resistance in cardiovascular context.
Comparison of the human cardiovascular system with arrangements of circulatory systems found in lower vertebrates and invertebrates allows appreciation of the functional elegance of our double circulation with systemic and pulmonary vascular trees served by a single looped and septated heart. In the pulmonary part of the circulation, consideration of the nature of alveolar microvessels in relation to the system as a whole may throw light on the pathophysiology of pulmonary regurgitation and pulmonary hypertension. Pulmonary microvessels impose remarkably little resistance to flow compared with the systemic. This may be attributed to their delicate, compliant structure, with tissue support on one side only, their respiratory walls remaining relatively free to expand in alveolar air. Low resistance may also depend on the branch pattern of alveolar capillaries, with almost immediate proximity between bifurcations and confluences in a uniquely dense, interconnected network. In the presence of free pulmonary regurgitation, pulmonary microvessels probably play a valve-like role, representing a low-resistance boundary or watershed between pulmonary arteries and veins. This microvascular watershed imposes little resistance to systolic forward flow, but in diastole, with venous pressures being kept low by function of the left heart, there is presumably little or no reversal of gradient to move blood back through the capillaries. The delicacy and potential vulnerability of alveolar capillaries to elevation of flow and pressure is likely, however, to go with a protective feedback circuit which, in abnormal circumstances, could contribute to development of arteriolar medial hypertrophy and pulmonary arterial hypertension.
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No pos
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No neg
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Retriever3047
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Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits.
Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t-PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
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No pos
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No neg
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Retriever3048
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Clinical isolation and functional characterization of cord blood CD133+ hematopoietic progenitor cells.
BACKGROUND
Human cord blood is a relevant source of CD133+ HPCs. Clinical-scale isolation of human umbilical cord blood (UCB) CD133+ HPCs using immunomagnetic microbeads and the CliniMACS clinical cell isolator is reported. CD133+ HPCs isolated after large-scale processing were functionally characterized.
STUDY DESIGN AND METHODS
Closed disposable sets were used to process nine different samples of RBC-reduced UCB nucleated cells. In-vitro hematopoietic assays and human xenografts in NOD/SCID mice were performed to assess the functional properties of isolated CD133+ cells. Different mixtures of human cytokines were tested for the ability to expand nascent CD133+ HPCs. Furthermore, freshly isolated CD133+ cells were conditioned in culture medium specifically tested to support in-vitro myogenesis or osteogenesis.
RESULTS
Isolation procedures yielded the recovery of an average of 2.53 x 10(6) CD133+ HPCs with a mean recovery of 96 percent (referred to as RBC-reduced samples) and a final sample purity of 82 percent. Purified CD133+ cells had high cloning efficiency, had relevant long-term activity, and were capable of repopulating irradiated NOD/SCID mice. In 10-day stroma-free cultures, a 2-fold and 8.3-fold expansion of colony-forming cells (CFCs) and extended long-term culture-initiating cells, respectively, was obtained. Freshly isolated CD133+ cells differentiated into large nucleated cells expressing either myosin D or osteopontin (as revealed by RT-PCR and immuno-cytochemistry), with a protein/mRNA expression comparable to or even higher than that observed in UCB CD133- nucleated cells in identical culture conditions.
CONCLUSION
Collectively, clinical-scale isolation of UCB CD133+ cells provides a relevant amount of primitive HPCs with high hematopoietic activity and in-vitro mesenchymal potential.
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No pos
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No neg
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Retriever3049
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Numerical study of the SNR and SAR of MRI coil arrays.
Coil arrays have become a very popular coil configuration for magnetic resonance imaging. This due to that, an image of a larger area can be obtained with uniform sensitivity and higher SNR as compared to standard MR volume coil. Ultra-fast procedures like parallel imaging and phased-array can take advantage of these properties. It is very important to understand the performance of this type of devices to take full advantage of these imaging schemes. Although, the study of the single and coil arrays pose a great challenge because of the mathematical theory involved, a simulation approach can be adopted to study various coil array configuration. The principal objective of this paper is to propose a simple method to study the performance of coil array. This method numerically simulates the electric field, magnetic field, signal-to-noise ratio and specific absorption rate of MRI coil arrays. A strip of squared-shaped coil array is proposed with three different configurations. To numerically compute the electric and magnetic fields, a commercial software tool based on the Finite-Element Method was used to solve the Maxwell's equations. Matrices were formed with the image entries of the electric and magnetic fields, and used to compute the signal-to-noise ratio and specific absorption rate of the coil array configurations. Results showed a good agreement with those reported in the literature. The visualization of the electromagnetic fields allows us to study the behavior of a particular coil array configuration.
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No pos
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No neg
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Retriever3050
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The Black-White Disparity in Preterm Birth: Race or Racism?
Policy Points Racism is an upstream determinant of health that influences health through many midstream and downstream factors. This Perspective traces multiple plausible causal pathways from racism to preterm birth. Although the article focuses on the Black-White disparity in preterm birth, a key population health indicator, it has implications for many other health outcomes. It is erroneous to assume by default that underlying biological differences explain racial disparities in health. Appropriate science-based policies are needed to address racial disparities in health; this will require addressing racism.
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No pos
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No neg
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Retriever3051
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[Outpatient monitoring of oesophageal pH with a catheter-free pH-meter (Bravo System). A Study of tolerance, safety and efficacy].
BACKGROUND AND OBJECTIVE
A new catheter-free outpatient oesophageal pH-meter system (Bravo) has recently been developed. The objective of this study is to test the tolerance, safety and efficacy of the system in the measurement of gastric-oesophageal reflux by comparing it with a conventional pH system.
PATIENTS AND METHOD
The study was performed on a control group consisting of 10 healthy volunteers (group 1) and in a group of 40 patients with symptoms of gastric-oesophageal reflux disease (groups 2 and 3). An upper digestive system endoscopy, oesophageal manometry and oesophageal pH measurements with a conventional system and/or with the Bravo catheter-free system, was performed on all patients. All patients who had both tests done (groups 1 and 2) filled in a questionnaire on any physical problems and changes in their daily activity.
RESULTS
The test tolerance was higher with the Bravo system in the 9 parameters studied. In the group of healthy volunteers (group 1), the median (range) of the total percentage of pH < 4 was 1.1% (0.5-3.1) with the conventional pH and 1.7% (0-3.4) with the Bravo. When comparing the patients with symptoms of gastric-oesophageal reflux disease (group 2) with those who had only one type of pH measurement made, the acid reflux was significantly higher in patients with Barrett's oesophagus than in the rest of the groups, with conventional pH as well as with the Bravo. If we analyse the patient group with disease due to gastric-oesophageal reflux with those on whom both techniques were used (group 3), 7 of the 10 patients had a pathological reflux that only showed up on measuring pH with the Bravo system.
CONCLUSIONS
Catheter-free pH measurements (Bravo) is better tolerated and with better satisfaction for the healthy volunteers and patients than with conventional PH, even, on occasions being more efficient for studying acid reflux due to the lower incidence of negative results.
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No pos
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No neg
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Retriever3052
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Time course of spinal doublecortin expression in developing rat and porcine spinal cord: implication in in vivo neural precursor grafting studies.
Expression of doublecortin (DCX), a 43-53 kDa microtubule binding protein, is frequently used as (i) an early neuronal marker to identify the stage of neuronal maturation of in vivo grafted neuronal precursors (NSCs), and (ii) a neuronal fate marker transiently expressed by immature neurons during development. Reliable identification of the origin of DCX-immunoreactive cells (i.e., host vs. graft) requires detailed spatial and temporal mapping of endogenous DCX expression at graft-targeted brain or spinal cord regions. Accordingly, in the present study, we analyzed (i) the time course of DCX expression in pre- and postnatal rat and porcine spinal cord, and (ii) the DCX expression in spinally grafted porcine-induced pluripotent stem cells (iPS)-derived NSCs and human embryonic stem cell (ES)-derived NSCs. In addition, complementary temporospatial GFAP expression study in porcine spinal cord was also performed. In 21-day-old rat fetuses, an intense DCX immunoreactivity distributed between the dorsal horn (DH) and ventral horn was seen and was still present in the DH neurons on postnatal day 20. In animals older than 8 weeks, no DCX immunoreactivity was seen at any spinal cord laminae. In contrast to rat, in porcine spinal cord (gestational period 113-114 days), DCX was only expressed during the pre-natal period (up to 100 days) but was no longer present in newborn piglets or in adult animals. Immunohistochemical analysis was confirmed with a comparable expression profile by western blot analysis. Contrary, the expression of porcine GFAP started within 70-80 days of the pre-natal period. Spinally grafted porcine iPS-NSCs and human ES-NSCs showed clear DCX expression at 3-4 weeks postgrafting. These data indicate that in spinal grafting studies which employ postnatal or adult porcine models, the expression of DCX can be used as a reliable marker of grafted neurons. In contrast, if grafted neurons are to be analyzed during the first 4 postnatal weeks in the rat spinal cord, additional markers or grafted cell-specific labeling techniques need to be employed to reliably identify grafted early postmitotic neurons and to differentiate the DCX expression from the neurons of the host.
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No pos
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No neg
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Retriever3053
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Sociality and the evolution of intelligence.
Two recently published studies provide important new data relevant to the evolution of human intelligence. Both studies of social behavior in baboons, Bergman et al. demonstrated that baboons use two criteria simultaneously to classify other troop members, and Silk et al. showed that highly social female baboons have higher reproductive success than less social females. Taken together, these studies provide strong evidence for the importance of social context in cognitive evolution.
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No pos
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No neg
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Retriever3054
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Clinical effects of submucosal middle turbinectomy for eosinophilic chronic rhinosinusitis.
OBJECTIVE
The preservation or resection of the middle turbinate (MT) during endoscopic sinus surgery (ESS) currently remains a matter of debate. The present study aimed to investigate the effects of submucosal middle turbinectomy (SMT) in ESS for eosinophilic chronic rhinosinusitis (ECRS).
METHODS
The study included 38 ECRS patients (63 sides) who had undergone full-house ESS with SMT and 20 ECRS patients (40 sides) without SMT as a control group. Post-operative middle turbinate lateralization (MTL), synechia formation, and the patency grade of the olfactory cleft (OC) were assessed as the primary outcomes 3 months after surgery. CT scans and the T&T test were performed on the SMT group 3 months after surgery and assessed as secondary outcomes.
RESULTS
MTL and synechia formation rates were slightly higher in the control group than in the SMT group (20% vs. 7.9%, p=0.072, 17.5% vs. 9.5%, p=0.235), although neither reached statistically significance. The mean patency score of OC was significantly better in the SMT group than in the control group (0.5±0.6 vs. 1.3±0.7, <0.001). CT findings and T&T test scores showed good improvements after SMT combined with ESS. No major adverse events occurred due to SMT.
CONCLUSION
We demonstrated the potential advantages of SMT for ECRS patients. This method may avoid physiological functional loss through its preservation of the mucosa and structure of the MT.
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No pos
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No neg
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Retriever3055
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[Expression of pi glutathione S-transferase in intestinal metaplasia and its relationship with Helicobacter pylori infection].
OBJECTIVE
To study the dynamic change of glutathione S- transferase pi (GST-pi) in normal gastric mucosa, gastric mucosa with intestinal metaplasia (IM) and gastric cancer and to investigate the relationship between human carcinogen detoxification system and the virulence of Helicobacter pylori(H.pylori) in the stage of IM.
METHODS
Two hundred and nineteen biopsy specimens of gastric mucosa, including 30 cases with normal gastric mucosa, 171 cases with IM and 18 cases with gastric cancer, were examined. The expression of GST-pi was detected by S-P immunohistochemical method. High-iron diamine /alcian blue pH2.5/periodic acid -Schiff (HID-ABpH 2.5-PAS) method was used to classify IM. H.pylori infection was confirmed or excluded by hematoxylin-eosin (HE) staining, of H.pylori-DNA PCR and ELISA. The 80 cases with H.pylori infection were treated by bismuthate + amoxicillin + metronidazole for three months and then biopsy specimens were taken again from the original sites.
RESULTS
The GST-pi expression rate was 69.6% in gastric mucosa with IM, significantly higher than that in gastric cancer (44.4%, P < 0.05) and that in normal gastric mucosa (0%, P <0.01). The GST-pi expression rate in IM II, IM III, and IM I decreased in sequence (83.3%, 71.1%, and 48.9%). The GST-pi expression rate in IM without H.pylori infection was 79.0%, significantly higher than that in IM with HP infection (64.2%, P <0.05). The positive rate of GST-pi expression in H.pylori eradicated group was 81.9%, significantly higher than that before H.pylori eradication (63.8%, P < 0.01). The GST-pi expression rate decreased from normal gastric mucous to IM and to gastric cancer, and from IM I -->II-->III too.
CONCLUSION
IM III with low or no expression of GST-pi is a high-risk condition of gastric cancer. The risk of gastric cancer increases when low or no expression of GST-pi is combined with H.pylori infection. The carcinogen detoxification role of GST-pi and the virulence of H.pylori might interact each other in the stage of intestinal metaplasia, the precancerous condition of gastric cancer.
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No pos
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No neg
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Retriever3056
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Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.
PURPOSE
Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities.
EXPERIMENTAL DESIGN
We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs.
RESULTS
These studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurrence. Analyses of clinical databases revealed significant association of this transcriptional profile with worse overall survival and upregulation at recurrence. Notably, gene expression analyses identified upregulation of TGFβ signaling, and more than one-hundred-fold increase in THY1 levels at recurrence. Furthermore, THY1-positive cells represented <10% of cells in treatment-naïve tumors, compared to 75-96% in recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples and determined that they were inherently resistant to chemoradiation in orthotopic models. Additionally, using image-guided biopsies from treatment-naïve human GBM, we conducted spatial transcriptomic analyses. This revealed rare THY1+ regions characterized by mesenchymal/stem-like gene expression, analogous to our recurrent mouse model, which co-localized with macrophages within the perivascular niche. We then inhibited TGFBRI activity in vivo which decreased mesenchymal/stem-like protein levels, including THY1, and restored sensitivity to TMZ/IR in recurrent tumors.
CONCLUSIONS
These findings reveal that GBM recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive, mesenchymal cells within the perivascular niche.
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No pos
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No neg
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Retriever3057
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Alternative psychotherapeutic practice among middle class Americans: I: Case studies and follow-up.
Historically, alternative psychotherapeutic procedures have florished worldwide in various inspirational, spiritualistic and shamanistic versions. However, few investigations have described these interventions in detail, or followed the clinical outcomes longitudinally. This present report is an ethnographic and clinical description of one particular American practitioner's alternative method as it is used with middle class clientele in several regions of the USA. Two case studies are presented in detail while nine individual cases are qualitatively reviewed with one month and one year treatment outcomes reported. A condensed ethnobiographical study of the practitioner's personal and professional life is included.
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No pos
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No neg
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Retriever3058
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Differences in contributory factors among hemicentral, central, and branch retinal vein occlusions.
Hemicentral retinal vein occlusion (HRVO) is an anatomic variant of central retinal vein occlusion (CRVO) and thus different from branch retinal vein occlusion (BRVO). Therefore, the risk factors for HRVO should be similar to those of CRVO and different from those of BRVO. To test this, the authors compared 15 demographic and clinical variables of 28 HRVO patients with those of 117 CRVO and 214 BRVO patients. Mean age of onset and sex ratio were not significantly different among the groups. Elevated erythrocyte sedimentation rate (ESR) (P = 0.019) and elevated intraocular pressure (IOP) (P = 0.025) were significantly more prevalent in the HRVO than the BRVO group. In addition, when the authors compared CRVO with BRVO, elevated ESR (P = 0.003), elevated IOP (P = 0.015), and positive purified protein derivative (PPD) (P = 0.003) were significantly more prevalent in the CRVO than the BRVO group, whereas hypertension (P = 0.03) and hyperopia (P = 0.008) were significantly more prevalent in the BRVO group. However, of the variables tested between HRVO and CRVO patients, no significant differences were found.
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No pos
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No neg
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Retriever3059
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Botulinum toxin A for treatment of sialorrhea in children: an effective, minimally invasive approach.
OBJECTIVES
To report (1) our experience with botulinum toxin A injections into the salivary glands of pediatric patients with sialorrhea, (2) the clinical outcomes of these interventions, and (3) the associated complication rates.
DESIGN
Retrospective cohort study.
SETTING
Urban pediatric hospital and pediatric rehabilitation center.
PATIENTS
Forty-five neurologically impaired children.
INTERVENTIONS
Patients received botulinum toxin A intrasalivary injections between January 2004 and May 2008 at the Hospital for Sick Children in Toronto, Ontario, Canada. All patients received sedation or general anesthesia for their botulinum toxin A injections, which were performed using ultrasonographic guidance.
MAIN OUTCOME MEASURES
Posttreatment assessments included the duration of effect, patient complications, saliva consistency, caregiver willingness to repeat the treatment, caregiver satisfaction with the treatment, and caregiver overall assessment of the child's posttreatment quality of life.
RESULTS
Forty-five subjects received a total of 91 botulinum toxin A treatments. The mean (SD) duration of effect was 4.6 (5.2) months. Duration of effect (log transformed) was significantly negatively associated with saliva quantity (P = .02), and there was a positive association with both increasing age and female sex, although neither reached statistical significance (P = .08 for each). Seven of the 24 documented complications were major, according to the Society of Interventional Radiology Classification System for Complications by Outcome scale. Thirty-six of the caregivers reported that this treatment improved the child's quality of life (80%).
CONCLUSION
Ultrasonographically guided botulinum toxin A injections into the salivary glands are safe and efficacious in the management of sialorrhea in children with neurologic disorders.
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No pos
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No neg
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Retriever3060
|
Patterns of care for glaucoma patients in Korea from 2002 to 2013 using the national health insurance service claims data.
Due to the rapidly increasing life-expectancy, the prevalence of glaucoma has increased steadily in recent years. We aimed to evaluate the patterns of care and primary treatment strategy patterns in Korea according to glaucoma subtypes to assess the quality of care for glaucoma patients.In this serial cross-sectional survey, the claims data from the Korean National Health Insurance Service was used to identify and group glaucoma patients into primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), other types of glaucoma, and ocular hypertension from 2002 to 2013. Records for outpatient visits, hospitalizations, drug prescriptions, admissions, and surgical interventions were used to determine the patterns of care and identify primary treatment strategies.Both the prevalence (0.11% in 2002 to 0.43% in 2013) and incidence rates (0.06% in 2003 to 0.11% in 2013) for glaucoma increased over time. The mean number of outpatient visits increased (4.9-6.0 visits per year), while the proportion of hospitalized patients (2.3-1.0% of patients) and duration of hospital stay (4.5-3.4 days among hospitalized patients) decreased between 2002 and 2013 for patients with POAG. The proportion of patients not being managed by medication or surgery decreased, with POAG and PACG patients receiving medications increasing from 70.9% and 59.2% in 2002 to 88.4% and 63.3% in 2013, respectively. Finally, while the proportion of trabeculectomy decreased (22.2% to 10.0% of surgical procedures in 2002 and 2013, respectively), more patients with PACG have received iridectomy (59.3% to 86.0% of surgical procedures in 2002 and 2013, respectively).Between 2002 and 2013, the pattern of care for both patients with POAG and PACG has shifted toward management by outpatient visits and intervention with anti-glaucoma medications in Korea.
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No pos
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No neg
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Retriever3061
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Anorexia in patients with cancer with special references on its association with early changes in food-intake behavior chemotherapeutic treatment and adjuvant enteral nutrition (review).
Anorexia defined as decreased appetite resulting in fatigue, change of body image and weight loss is stated to be fundamental to the syndrome of cancer cachexia. Weight loss is the most apparent symptom of anorexia and cachexia, and occurs quite frequently in patients with cancer. Interest in the pathogenetic mechanisms, is due to the strong association between weight loss and lower duality and quantity of life. This review discusses anorexia in the pathogenesis of cancer cachexia, particularly the effect of taste alterations and chemotherapy; and the long-term acceptability and effect of oral nutritional support and drug therapy.
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No pos
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No neg
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Retriever3062
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Pacbio sequencing of copper-tolerant Xanthomonas citri reveals presence of a chimeric plasmid structure and provides insights into reassortment and shuffling of transcription activator-like effectors among X. citri strains.
BACKGROUND
Xanthomonas citri, a causal agent of citrus canker, has been a well-studied model system due to recent availability of whole genome sequences of multiple strains from different geographical regions. Major limitations in our understanding of the evolution of pathogenicity factors in X. citri strains sequenced by short-read sequencing methods have been tracking plasmid reshuffling among strains due to inability to accurately assign reads to plasmids, and analyzing repeat regions among strains. X. citri harbors major pathogenicity determinants, including variable DNA-binding repeat region containing Transcription Activator-like Effectors (TALEs) on plasmids. The long-read sequencing method, PacBio, has allowed the ability to obtain complete and accurate sequences of TALEs in xanthomonads. We recently sequenced Xanthomonas citri str. Xc-03-1638-1-1, a copper tolerant A group strain isolated from grapefruit in 2003 from Argentina using PacBio RS II chemistry. We analyzed plasmid profiles, copy number and location of TALEs in complete genome sequences of X. citri strains.
RESULTS
We utilized the power of long reads obtained by PacBio sequencing to enable assembly of a complete genome sequence of strain Xc-03-1638-1-1, including sequences of two plasmids, 249 kb (plasmid harboring copper resistance genes) and 99 kb (pathogenicity plasmid containing TALEs). The pathogenicity plasmid in this strain is a hybrid plasmid containing four TALEs. Due to the intriguing nature of this pathogenicity plasmid with Tn3-like transposon association, repetitive elements and multiple putative sites for origins of replication, we might expect alternative structures of this plasmid in nature, illustrating the strong adaptive potential of X. citri strains. Analysis of the pathogenicity plasmid among completely sequenced X. citri strains, coupled with Southern hybridization of the pathogenicity plasmids, revealed clues to rearrangements of plasmids and resulting reshuffling of TALEs among strains.
CONCLUSIONS
We demonstrate in this study the importance of long-read sequencing for obtaining intact sequences of TALEs and plasmids, as well as for identifying rearrangement events including plasmid reshuffling. Rearrangement events, such as the hybrid plasmid in this case, could be a frequent phenomenon in the evolution of X. citri strains, although so far it is undetected due to the inability to obtain complete plasmid sequences with short-read sequencing methods.
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No pos
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No neg
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Retriever3063
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Naringenin suppresses Edwardsiella tarda infection in GAKS cells by NanA sialidase inhibition.
Edwardsiella tarda (E. tarda) is a gram-negative bacterium, which causes Edwardsiellosis in aquaculture. Previous studies indicate that E. tarda NanA sialidase plays crucial roles in infection through the desialylation of glycoproteins in fish cells. On the other hand, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, classic sialidase inhibitor, negatively regulates E. tarda infection of goldfish scale GAKS cells. Here, to development the suppression model of E. tarda infection for aquaculture application, the possibility of NanA inhibitory activities in citrus phytochemicals was evaluated as citrus extracts have widely been used as a supplement in fish diets for the improvement of meat quality. Some flavanones such as naringenin, hesperetin, hesperidin and naringin showed sialidase inhibitory activity toward recombinant NanA in vitro. Among them, naringenin showed the most potent inhibitory activity and its inhibitory pattern was non-competitive. Naringenin significantly suppressed E. tarda infection in GAKS cells at 200 and 400 μM without bactericidal effect on E. tarda. On the other hand, naringin, glycosylation form of naringenin, showed slight suppression of E. tarda infection toward GAKS cells, suggesting the glycosides on flavanone could be important for NanA inhibition. Fluorescence microscopy analysis verified that number of invading E. tarda in GAKS cells was declined by naringenin treatment. The present study exhibited the possibility of naringenin as an effective ingredient in fish diet for the inhibition of E. tarda infection.
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No pos
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No neg
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Retriever3064
|
Size distribution and maturation of newly replicated DNA through the S and G2 phases of Physarum polycephalum.
The size distribution of newly made DNA and the dynamics of size maturation of progeny DNA molecules were studied in the synchronous S and G2 phases of Physarum polycephalum. Pulse labeling of DNA and analysis of the products on alkaline sucrose gradients showed that synthesis of primary replication units (which will also be referred to as "Okazaki" fragments) occurred throughout the S period. Pulse and pulse-chase experiments revealed a distinct pattern of size maturation. An apparently linear increase in molecular weight of progeny DNA molecules during the first hour of the S phase occurred at a rate of approximately 4-5 X 10(5) daltons per min at 26 degrees C, corresponding to the joining of 6-8 Okazaki fragments. The resulting 35-45S (1.1-2.2 X 10(7) daltons) DNA molecules may correspond to the Physarum "replicon." The further size increases of the newly made DNA appear to occur in steps, possibly reflecting a clustering of isochronous replicons along the chromatide. These observations are discussed with regard to mechanisms of DNA replication and size maturation.
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No pos
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No neg
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Retriever3065
|
Effects of pH on light absorption properties of water-soluble organic compounds in particulate matter emitted from typical emission sources.
Water-soluble organic compounds (WSOC) have a significant impact on aerosol radiative forcing and climate change, and there is considerable uncertainty in predicting and mitigating their climate and environmental effects. Here, the effects of pH on the light absorption properties of WSOC in particulate matter from different typical emission sources and ambient aerosols were systematically investigated using UV-vis spectrophotometer. pH (2-10) had an important impact on the light absorption properties of WSOC. The absorption, aromaticity, and the light absorption capacity of WSOC increased significantly with increasing pH for all samples. The difference absorbance spectra (∆absorbance) showed that the change of light absorption properties with pH was related to the deprotonate of carboxyl and phenolic groups resonating with aromatic and conjugated systems, with the most likely structures being carboxylic acids and phenols. Coal combustion and summer samples exhibited much higher susceptibility of light absorption properties to pH variation (increased by 27.0% and 65.9% relative to the pH 2 level, respectively). Absorption indices of almost all samples were significantly correlated with pH, indicating that the light absorption properties of WSOC may be quantitatively related to pH. The pH-dependent light absorption properties may have profound implications for evaluating the climate impacts of aerosol WSOC such as radiative forcing.
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No pos
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No neg
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Retriever3066
|
Cell type-specific recognition of human metapneumoviruses (HMPVs) by retinoic acid-inducible gene I (RIG-I) and TLR7 and viral interference of RIG-I ligand recognition by HMPV-B1 phosphoprotein.
Human metapneumoviruses (HMPVs) are recently identified Paramyxoviridae that contribute to respiratory tract infections in children. No effective treatments or vaccines are available. Successful defense against virus infection relies on early detection by germ line-encoded pattern recognition receptors and activation of cytokine and type I IFN genes. Recently, the RNA helicase retinoic acid-inducible gene I (RIG-I) has been shown to sense HMPV. In this study, we investigated the abilities of two prototype strains of HMPV (A1 [NL\1\00] and B1 [NL\1\99]) to activate RIG-I and induce type I IFNs. Despite the abilities of both HMPV-A1 and HMPV-B1 to infect and replicate in cell lines and primary cells, only the HMPV-A1 strain triggered RIG-I to induce IFNA/B gene transcription. The failure of the HMPV-B1 strain to elicit type I IFN production was dependent on the B1 phosphoprotein, which specifically prevented RIG-I-mediated sensing of HMPV viral 5' triphosphate RNA. In contrast to most cell types, plasmacytoid dendritic cells displayed a unique ability to sense both HMPV-A1 and HMPV-B1 and in this case sensing was via TLR7 rather than RIG-I. Collectively, these data reveal differential mechanisms of sensing for two closely related viruses, which operate in cell type-specific manners.
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No pos
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No neg
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Retriever3067
|
Standalone hybrid PV/wind/diesel-electric generator system for a COVID-19 quarantine center.
This work is motivated by the need in overcoming the electricity crisis in Gaza, which is initiated due to political reasons and the spread of COVID-19. Building quarantine centers is one of the most important means used in combating the COVID-19, but connecting these centers to the electricity distribution network at the appropriate time is not always possible and increases the burden on the local utility company. This article proposed a hybrid off-grid energy system (HES) to effectively energize the quarantine COVID-19 center in Gaza economically and environmentally. To achieve this aim, the estimated load profile of the quarantine center is fed to the HOMER-Pro program. In addition, the various systems components are introduced to the program, then modeled, and optimized. The developed approach was tested using a real case study considering realistic input data. HOMER-Pro program is used to simulate and optimize the system design. The results revealed the potential of the HES to provide environment-friendly, cost-effective, and affordable electricity for the studied quarantine center, as compared to just the diesel generators system. For the considered case study, it is found that the PV-wind-diesel generators HES can cover the connected load with the lowest cost ($ 0.348/kWh) in comparison to other possible HES structures. Taking into consideration the price of harmful emissions, the wining system shows a reduction of 54.89% of the cost of energy (CoE) compared to other systems. For the considered case study, it is found that a combination of 150 kW PV, 200 kW wind, and two diesel generators with capacities of 500 and 250 kW can hold 100% of the electrical load required to keep the quarantine COVID-19 center in operation. The initial capital cost of this HES is $510,576 where the share of wind energy, solar PV, inverter, and diesel-electric generators are $320,000, $83,076, $25,000, and $82,500, respectively. The replacemen cost ($55,918) is due to diesel generators. The total operation and maintainance cost (O&M) is $268,737, that is, 25.6% for wind turbines, 1.2% for inverters, and 70.7% for diesel electric generators. The PV/wind/diesel generators HES generate 1,659,038 kWh of electricity. The total energy requirement of 1,442,553 kWh, which means a surplus of 212,553 kWh of energy/year. The total energy (kWh) is an integration of energy sources which are 427,276 (25.8%), 274,500 (16.5%), and 857,263 (57.7%), due to wind, solar and diesel generators respectively. The cost of yearly consumed fuel is $437,828.769. The payback period for the winning system is 1.8 years. Finally, it is proved that the developed approach gives a reasonable solution to the decision-makers to find a fast, economic and reliable solution to energize the quarantine centers.
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No pos
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No neg
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Retriever3068
|
ZIF-8 Nanoparticles Induce Behavior Abnormality and Brain Oxidative Stress in Adult Zebrafish (Danio rerio).
Zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) are typical metal-organic framework (MOF) materials and have been intensively studied for their potential application in drug delivery and environmental remediation. However, knowledge of their potential risks to health and the environment is still limited. Therefore, this study exposed female and male zebrafish to ZIF-8 NPs (0, 9.0, and 90 mg L-1) for four days. Subsequently, variations in their behavioral traits and brain oxidative stress levels were investigated. The behavioral assay showed that ZIF-8 NPs at 90 mg/L could significantly decrease the locomotor activity (i.e., hypoactivity) of both genders. After a ball falling stimulation, zebrafish exposed to ZIF-8 NPs (9.0 and 90 mg L-1) exhibited more freezing states (i.e., temporary cessations of movement), and males were more sensitive than females. Regardless of gender, ZIF-8 NPs exposure significantly reduced the SOD, CAT, and GST activities in the brain of zebrafish. Correlation analysis revealed that the brain oxidative stress induced by ZIF-8 NPs exposure might play an important role in their behavioral toxicity to zebrafish. These findings highlight the necessity for further assessment of the potential risks of MOF nanoparticles to aquatic species and the environment.
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No pos
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No neg
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Retriever3069
|
A Marxist view of medical care.
Marxist studies of medical care emphasize political power and economic dominance in capitalist society. Although historically the Marxist paradigm went into eclipse during the early twentieth century, the field has developed rapidly during recent years. The health system mirrors the society's class structure through control over health institutions, stratification of health workers, and limited occupational mobility into health professions. Monopoly capital is manifest in the growth of medical centers, financial penetration by large corporations, and the "medical-industrial complex." Health policy recommendations reflect different interest groups' political and economic goals. The state's intervention in health care generally protects the capitalist economic system and the private sector. Medical ideology helps maintain class structure and patterns of domination. Comparative international research analyzes the effects of imperialism, changes under socialism, and contradictions of health reform in capitalist societies. Historical materialist epidemiology focuses on economic cycles, social stress, illness-generating conditions of work, and sexism. Health praxis, the disciplined uniting of study and action, involves advocacy of "nonreformist reforms" and concrete types of political struggle.
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No pos
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No neg
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Retriever3070
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Development of the hair in the rat: in vivo and in transplanted tissue.
Differentiation of the hair was examined in the head skin of rat embryos aged from days 12.5 to 18.5 of gestation. In 12.5-day-old embryos, the skin consisted of single layered epidermis and underlying loose connective tissue. On day 17.5 of gestation, the epidermis appeared to have a two or three layered epithelium, and the subepidermal connective tissue gave rise to an overlying dense tissue, into which blood capillaries arose from the deeper layer. The epidermis showed partial thickenings, where basal cells were arranged perpendicular to the surface of the epidermis. Beneath the epidermal thickenings, a number of connective tissue cells appeared to have accumulated and occasionally were accompanied by blood capillaries. In sequential development of the skin, the thickenings protruded as cords to the underlying dermal tissue and formed hair follicles covered with a connective tissue sheath. Skin obtained from 12.5-day-old embryos was transplanted singly or with cerebral cortex into the third ventricle of adult male rats. Thirty days after the transplantation, hairs and sebaceous glands had developed from the grafted skin. Hair growth tended to be more prominent in the cotransplanted skin grafts. However, no nerve fibers immunoreactive for substance P or calcitonin gene-related peptide (CGRP) were found in the grafted skin, although these fibers appeared in the dermis at the end of gestation in vivo. These results showed that the skin of 12.5-day-old embryos was able to induce hair growth in the third ventricle without accompanying peripheral neuronal fibers or blood capillaries, although the effects of connective tissue cells could not be ruled out.
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No pos
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No neg
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Retriever3071
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The IVS4 + 4 A to T mutation of the fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients.
Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and a susceptibility to leukemia. There are at least 8 complementation groups (A through H). Extensive analyses of the FA group C gene FANCC in Western countries revealed that 10% to 15% of FA patients have mutations of this gene. The most common mutation is IVS4 + 4 A to T (IVS4), a splice mutation in intron 4, which has been found only in patients of Ashkenazi Jewish ancestry. When we screened 29 Japanese patients (20 unrelated patients and 4 families) using polymerase chain reaction-single strand conformation polymorphism, we found 8 unrelated patients homozygous for IVS4. This is apparently the first non-Ashkenazi-Jewish population for whom this mutation has been detected. The Ashkenazi Jewish patients homozygous for IVS4 have a severe phenotype, in comparison with other FA patients. Our analyses of Japanese patients indicate no significant difference between IVS4 homozygotes and other patients with regard to severity of a clinical phenotype. Thus, ethnic background may have a significant effect on a clinical phenotype in FA patients carrying the same mutation. (Blood. 2000;95:1493-1498)
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No pos
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No neg
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Retriever3072
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Gastrointestinal physiology and digestive disorders in sleep.
PURPOSE OF REVIEW
The dynamic interplay of the digestive system and sleep is an excellent example of brain-body interaction. New advances in measuring techniques provide an opportunity to evaluate physiology that is dependent upon the sleep/wake state or circadian rhythm and potentially differentiate between normal and pathological conditions.
RECENT FINDINGS
Sleep-related changes in gastrointestinal physiology create vulnerabilities to digestive issues such as reflux, whereas disorders such as duodenal ulcers raise the importance of circadian variations in digestive system function. Advances in the area of normal sleep physiology have furthered our understanding of the underlying cause of irritable bowel syndrome, and the mechanisms by which sleep disruption may aggravate inflammatory bowel disease. Additionally, important early work has shown that the treatment of digestive disorders such as reflux can improve sleep quality just as the improvement in sleep may aid in the treatment of digestive disorders.
SUMMARY
For the clinician, these forward steps in our knowledge mark the start of an era in which understanding the effects of the sleep/wake state and circadian rhythms on gastrointestinal physiology promise to yield novel diagnostic and therapeutic opportunities.
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No pos
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No neg
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Retriever3073
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Control of pharmaceutical properties of soybean trypsin inhibitor by conjugation with dextran. I: Synthesis and characterization.
The Kunitz-type soybean trypsin inhibitor (STI), a model protein, was conjugated with dextran (Mw, approximately 9900; STI-D), and its physicochemical and biochemical properties were studied to develop a novel delivery system for a protein drug. Conjugation was carried out using periodate oxidation, and cyanogen bromide, carbodiimide, cyanuric chloride, epichlorhydrin, and N-succiniimidyl-3-(2-pyridyldithio)propionate (SPDP) reagent methods. Dextran was conjugated to STI at a molar ratio of 1.5 to 4.6, but the degree of modification, as well as yield and contamination extent of unreacted STI and dextran, varied with the method of synthesis. Gel filtration and electrophoresis confirmed the covalent attachment of dextran to STI but also demonstrated the broad molecular weight distribution of the conjugates. The STI-D conjugate retained satisfactory activity, although the attachment partially reduced its inhibitory activity against trypsin. The periodate oxidation method seemed to be the best for the preparation of STI-D since it gave the conjugate with a high modification ratio (4.6 molecules per STI), high yield (95%), and satisfactory activity recovery (63%). Chemical modification of STI was also carried out with activated polyethylene glycol (PEG) for comparison. The STI-PEG conjugate was obtained in a satisfactory yield (96%) and modification degree (5.8 molecules per STI), but the remaining activity was considerably lower (34%). Thus, conjugation of protein with dextran by the periodate oxidation method is suggested to be preferable for preparing a protein-carrier system without significant diminution of its biological activity.
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No pos
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No neg
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Retriever3074
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Corrigendum: Eocene Podocarpium (Leguminosae) from South China and its biogeographic implications.
[This corrects the article DOI: 10.3389/fpls.2015.00938.].
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No pos
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No neg
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Retriever3075
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Medicines management.
I am moving from a hospital-based role to primary care where my patients will have a much broader range of conditions. What prescribing advice can you give me?
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No pos
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No neg
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Retriever3076
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Vanishing clams on an Iberian beach: local consequences and global implications of accelerating loss of shells to tourism.
Multi-decadal increase in shell removal by tourists, a process that may accelerate degradation of natural habitats, was quantified via two series of monthly surveys, conducted thirty years apart (1978-1981 and 2008-2010) in one small embayment on the Mediterranean coast of the Iberian Peninsula. Over the last three decades, the local tourist arrivals have increased almost three-fold (2.74), while the area has remained unaffected by urban encroachment and commercial fisheries. During the same time interval the abundance of mollusk shells along the shoreline decreased by a comparable factor (2.62) and was significantly and negatively correlated with tourist arrivals (r = -0.52). The strength of the correlation increased when data were restricted to months with high tourist arrivals (r = -0.72). In contrast, the maximum monthly wave energy (an indirect proxy for changes in rate of onshore shell transport) was not significantly correlated with shell abundance (r = 0.10). Similarly, rank dominance of common species, drilling predation intensity, and body size-frequency distribution patterns have all remained stable over recent decades. A four-fold increase in global tourist arrivals over the last 30 years may have induced a comparable worldwide acceleration in shell removal from marine shorelines, resulting in multiple, currently unquantifiable, habitat changes such as increased beach erosion, changes in calcium carbonate recycling, and declines in diversity and abundance of organisms, which are dependent on shell availability.
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No pos
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No neg
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Retriever3077
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Gut Microbiota and Metabolism in Different Stages of Life and Health.
In a very fascinating read, John Goodsir, a Scottish surgeon, describes how he isolated "vegetable organisms" from the "ejected fluid" from the stomach of his 19-year-old patient [...].
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No pos
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No neg
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Retriever3078
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A Systematic Review of Salt Reduction Initiatives Around the World: A Midterm Evaluation of Progress Towards the 2025 Global Non-Communicable Diseases Salt Reduction Target.
In 2013, the WHO recommended that all member states aim to reduce population salt intake by 30% by 2025. The year 2019 represents the midpoint, making it a critical time to assess countries' progress towards this target. This review aims to identify all national salt reduction initiatives around the world in 2019, and to quantify countries' progress in achieving the salt reduction target. Relevant data were identified through searches of peer-reviewed and gray literature, supplemented with responses from prefilled country questionnaires sent to known country leads of salt reduction or salt champions, WHO regional representatives, and international experts to request further information. Core characteristics of each country's strategy, including evaluations of program impact, were extracted and summarized. A total of 96 national salt reduction initiatives were identified, representing a 28% increase in the number reported in 2014. About 90% of the initiatives were multifaceted in approach, and 60% had a regulatory component. Approaches include interventions in settings (n= 74), food reformulation (n = 68), consumer education (n = 50), front-of-pack labeling (n = 48), and salt taxation (n = 5). Since 2014, there has been an increase in the number of countries implementing each of the approaches, except consumer education. Data on program impact were limited. There were 3 countries that reported a substantial decrease (>2 g/day), 9 that reported a moderate decrease (1-2 g/day), and 5 that reported a slight decrease (<1 g/day) in the mean salt intake over time, but none have yet met the targeted 30% relative reduction in salt intake from baseline. In summary, there has been an increase in the number of salt reduction initiatives around the world since 2014. More countries are now opting for structural or regulatory approaches. However, efforts must be urgently accelerated and replicated in other countries and more rigorous monitoring and evaluation of strategies is needed to achieve the salt reduction target.
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No pos
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No neg
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Retriever3079
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Redox effects and formation of gold nanoparticles for the nucleation of low thermal expansion phases from BaO/SrO/ZnO/SiO2 glasses.
Glasses in the system BaO/SrO/ZnO/SiO2 containing 0.01 and 0.1 mol% gold were used to study the formation of gold nanoparticles with the aim to use them as nucleation agents. In order to promote gold clustering, the glasses were additionally doped with 0.5 mol% Sb2O3. Depending on the heat treatment schedule, Au particle sizes were in the range from 6 to above 50 nm. In contrast to many other gold ruby glass systems, the clustering is completely prevented by the absence of antimony; then the glasses remain colorless. Surprisingly, at higher temperatures, a re-dissolution of gold clusters was also observed, which now allows the formulation of a more comprehensive model concerning the redox and clustering behavior. This growth model is completed by the fact that a high gold concentration enables the stabilization of much smaller Au clusters. Mie theory with the aid of quantum confined size-dependent dielectric functions was successfully used to describe the optical behavior of the gold nanoparticles also for sizes below 10 nm. These results were confirmed using high resolution scanning transmission electron microscopy, including energy dispersive X-ray spectroscopy. It could also be shown that small gold particles up to a size of 50 nm are not effective as nucleating agents.
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No pos
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No neg
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Retriever3080
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Effect of electromyographic biofeedback training on motor function of quadriceps femoris in patients with incomplete spinal cord injury: A randomized controlled trial.
BACKGROUND
Electromyographic biofeedback (EMG BF) training is an effective method of promoting motor learning and control in neurorehabilitation, but its effect on quadriceps femoris muscle in individuals with spinal cord injury (SCI) is unknown.
OBJECTIVE
The aim of the study was to investigate the therapeutic effect of EMG BF training on motor function of quadriceps femoris in patients with incomplete SCI.
METHODS
Thirty-three incomplete paraplegic patients with quadriceps femoris strength ranging grade 1 to grade 3 less than 6 months post-injury were enrolled. Control group (n = 16) received conventional physical therapy to enhance quadriceps femoris strength, while intervention group (n = 17) was treated with conventional physical therapy and EMG BF training. All received treatment once a day for 30 days. Surface electromyograph (sEMG), muscle strength and thigh circumference size were assessed to evaluate motor function of quadriceps femoris. Activities of daily living (ADL) was evaluated by Modified Barthel Index (MBI). All the measures evaluated three times in total.
RESULTS
Compared to the control group, intervention group significantly improved on sEMG values and strength of quadriceps femoris (PsEMG < 0.001, Pstrength < 0.05). sEMG values of quadriceps femoris increased earlier than strength of quadriceps femoris in intervention group (Prest = 0.07, Pactive = 0.031). There were no statistical differences in thigh circumference size and ADL scores between groups (Pthigh > 0.05, PADL = 0.423).
CONCLUSIONS
EMG BF training appeared to be a useful tool to enhance motor function of quadriceps femoris in patients with incomplete SCI. sEMG could quantify the changes of single muscle myodynamia precisely before visible or touchable changes occur.
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No pos
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No neg
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Retriever3081
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Pancreatic Polypeptide revisited: potential therapeutic effects in obesity-diabetes.
Pancreatic polypeptide (PP), a member of the neuropeptide Y (NPY) family of peptides, is a hormone secreted from the endocrine pancreas with established actions on appetite regulation. Thus, through activation of hypothalamic neuropeptide Y4 (NPY4R or Y4) receptors PP induces satiety in animals and humans, suggesting potential anti-obesity actions. In addition, despite being actively secreted from pancreatic islets and evidence of local Y4 receptor expression, PP mediated effects on the endocrine pancreas have not been fully elucidated. To date, it appears that PP possesses an acute insulinostatic effect, similar to the impact of other peptides from the NPY family. However, it is interesting that prolonged activation of pancreatic Y1 receptors leads to established benefits on beta-cell turnover, preservation of beta-cell identity and improved insulin secretory responsiveness. This may hint towards possible similar anti-diabetic actions of sustained Y4 receptor modulation, since the Y1 and Y4 receptors trigger comparable cell signalling pathways. In terms of exploiting the prospective therapeutic promise of PP, this is severely restricted by a short circulating half-life as is the case for many regulatory peptide hormones. It follows that long-acting, enzyme resistant, forms of PP will be required to determine viability of the Y4 receptor as an anti-obesity and -diabetes drug target. The current review aims to refocus interest on the biology of PP and highlight opportunities for therapeutic development.
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No pos
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No neg
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Retriever3082
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Is dieting advice from magazines helpful or harmful? Five-year associations with weight-control behaviors and psychological outcomes in adolescents.
OBJECTIVE
The purpose of this study was to evaluate the association between frequent reading of magazine articles about dieting/weight loss and weight-control behaviors and psychological outcomes 5 years later in a sample of adolescents.
PARTICIPANTS AND METHODS
Data are from Project EAT (Eating Among Teens), a 5-year longitudinal study of eating, activity, weight, and related variables in 2516 middle and high school students. In 1999 (time 1), participants completed surveys and had their height and weight measured. In 2004 (time 2), participants were resurveyed.
RESULTS
For female adolescents, the frequency of healthy, unhealthy, and extreme weight-control behaviors increased with increasing magazine reading after adjusting for time 1 weight-control behaviors, weight importance, BMI, and demographic covariates. The odds of engaging in unhealthy weight-control behaviors (such as fasting, skipping meals, and smoking more cigarettes) were twice as high for the most frequent readers compared with those who did not read magazine articles about dieting and weight loss. The odds of using extreme weight-control behaviors (such as vomiting or using laxatives) were 3 times higher in the highest frequency readers compared with those who did not read such magazines. There were no significant associations for either weight-control behaviors or psychological outcomes for male adolescents.
CONCLUSIONS
Frequent reading of magazine articles about dieting/weight loss strongly predicted unhealthy weight-control behaviors in adolescent girls, but not boys, 5 years later. Findings from this study, in conjunction with findings from previous studies, suggest a need for interventions aimed at reducing exposure to, and the importance placed on, media messages regarding dieting and weight loss.
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No pos
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No neg
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Retriever3083
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Postoperative hyperperfusion in a patient with a dural arteriovenous fistula with retrograde leptomeningeal venous drainage: case report.
OBJECTIVE AND IMPORTANCE
Hyperperfusion has been reported after carotid endarterectomy or stenting for stenosis of the internal carotid artery. Because few reports have examined postoperative hyperperfusion after treatment for dural arteriovenous fistulae (DAVFs), we present a case describing a patient who manifested this clinical entity.
CLINICAL PRESENTATION
The patient was a 63-year-old man with a DAVF in the left transverse sigmoid sinus with retrograde leptomeningeal venous drainage. He experienced slowly progressive disorientation lasting for several months. Preoperative single-photon emission computed tomography with (123)I-labeled N-isopropyl-p-iodoamphetamine revealed an area of hyperintensity on T2-weighted magnetic resonance imaging (MRI) scans that coincided with the hypoperfusion area; it was not increased after acetazolamide challenge. Complete DAVF obliteration was achieved by embolization, then sinus isolation. After treatment, he experienced frequent generalized convulsions that were terminated by 2-day barbiturate therapy.
INTERVENTION
On T2-weighted MRI scans obtained 3 days after surgery, the hyperintense area not only persisted but had expanded to the left parietal lobe. Moreover, a subcortical hyperintense lesion was recognized on T1-weighted MRI scans; this was considered to reflect cortical laminar necrosis. Single-photon emission computed tomography revealed hyperperfusion in the left parietal lobe; it changed to hypoperfusion a month after treatment.
CONCLUSION
In patients with DAVFs with preoperative findings of marked low perfusion and a poor perfusion reserve, postoperative study may reveal hyperperfusion on single-photon emission computed tomography or cortical laminar necrosis on MRI. This may be evidence of severe perfusion disturbance as a result of venous infarction. In these patients, careful blood pressure control and early treatment of seizures are important after DAVF treatment.
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No pos
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No neg
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Retriever3084
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Activated charcoal significantly reduces the amount of colchicine released from Gloriosa superba in simulated gastric and intestinal media.
BACKGROUND
Poisoning with Gloriosa superba, a plant containing colchicine, is common in Sri Lanka.
OBJECTIVES
This study was to estimate release of colchicine from 5 g of different parts of Gloriosa superba in simulated gastric and intestinal media, and examine the binding efficacy of activated charcoal (AC) to colchicine within this model.
METHODS
A USP dissolution apparatus-II was used to prepare samples for analysis of colchicine using HPLC.
RESULTS
Cumulative colchicine release from tuber in gastric media at 120 minutes was significantly higher (2883 μg/g) than in intestinal media (1015 μg/g) (p < .001). Mean ± SD cumulative colchicine concentration over 2 hours from tuber, leaves and trunk in gastric medium was 2883.15 ± 1295.63, 578.25 ± 366.26 and 345.60 ± 200.08 μg/g respectively and the release in intestinal media was 1014.75 ± 268.16, 347.40 ± 262.61 and 251.55 ± 285.72 μg/g respectively. Introduction of 50 g of AC into both media made colchicine undetectable (<0.1 μg/ml).
CONCLUSIONS
The tuber released the highest quantity of colchicine. The colchicine release and elapse time to achieve saturated, equilibrium dissolution mainly depends on physicochemical properties of plant part. Significant in vitro binding of colchicine to AC suggests that AC has a role in decontamination of patients presenting to hospital after ingestion of Gloriosa superba.
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No pos
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No neg
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Retriever3085
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Effects of multisystemic therapy through midlife: a 21.9-year follow-up to a randomized clinical trial with serious and violent juvenile offenders.
OBJECTIVE
Although current evidence suggests that the positive effects of multisystemic therapy (MST) on serious crime reach as far as young adulthood, the longer term impact of MST on criminal and noncriminal outcomes in midlife has not been evaluated. In the present study, the authors examined a broad range of criminal and civil court outcomes for serious and violent juvenile offenders who participated on average 21.9 (range = 18.3-23.8) years earlier in a clinical trial of MST (C. M. Borduin et al., 1995).
METHOD
Participants were 176 individuals who were originally randomized to MST or individual therapy (IT) during adolescence and averaged 3.9 arrests for felonies prior to treatment. Arrest, incarceration, and civil suit data were obtained in middle adulthood when participants were on average 37.3 years old.
RESULTS
Intent-to-treat analyses showed that felony recidivism rates were significantly lower for MST participants than for IT participants (34.8% vs. 54.8%, respectively) and that the frequency of misdemeanor offending was 5.0 times lower for MST participants. In addition, the odds of involvement in family-related civil suits during adulthood were twice as high for IT participants as for MST participants.
CONCLUSIONS
The present study represents the longest follow-up to date of an MST clinical trial and demonstrates that the positive impact of an evidence-based youth treatment such as MST can last well into adulthood. Implications of the authors' findings for policymakers and service providers are discussed.
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No pos
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No neg
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Retriever3086
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New approaches for cement-based prophylactic augmentation of the osteoporotic proximal femur provide enhanced reinforcement as predicted by non-linear finite element simulations.
BACKGROUND
High incidence and increased mortality related to secondary, contralateral proximal femoral fractures may justify invasive prophylactic augmentation that reinforces the osteoporotic proximal femur to reduce fracture risk. Bone cement-based approaches (femoroplasty) may deliver the required strengthening effect; however, the significant variation in the results of previous studies calls for a systematic analysis and optimization of this method. Our hypothesis was that efficient generalized augmentation strategies can be identified via computational optimization.
METHODS
This study investigated, by means of finite element analysis, the effect of cement location and volume on the biomechanical properties of fifteen proximal femora in sideways fall. Novel cement cloud locations were developed using the principles of bone remodeling and compared to the "single central" location that was previously reported to be optimal.
FINDINGS
The new augmentation strategies provided significantly greater biomechanical benefits compared to the "single central" cement location. Augmenting with approximately 12ml of cement in the newly identified location achieved increases of 11% in stiffness, 64% in yield force, 156% in yield energy and 59% in maximum force, on average, compared to the non-augmented state. The weaker bones experienced a greater biomechanical benefit from augmentation than stronger bones. The effect of cement volume on the biomechanical properties was approximately linear. Results of the "single central" model showed good agreement with previous experimental studies.
INTERPRETATION
These findings indicate enhanced potential of cement-based prophylactic augmentation using the newly developed cementing strategy. Future studies should determine the required level of strengthening and confirm these numerical results experimentally.
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No pos
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No neg
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Retriever3087
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Use of the external fixation apparatus for percutaneous insertion of pins in the distal one-third of the radius: an anatomic study.
OBJECTIVE
To assess the risk of soft-tissue injury during percutaneous placement of external fixation pins in the proximal radius.
DESIGN
An anatomic study with embalmed cadaver limbs.
SETTING
Hand and upper limb centre at a university-affiliated hospital.
INTERVENTIONS
Two 4-mm Hoffman half pins were percutaneously placed along the dorsoradial ridge of the radius, four finger breadths proximal to the radial styloid process.
MAIN OUTCOME MEASURES
Injuries to soft tissues including tendons, nerves and vessels were noted.
RESULTS
Nerve or tendon injuries occurred in 7 of 26 forearms. Three pins transfixed either the superficial branch of the radial nerve or lateral antebrachial cutaneous nerves. Tendon injuries included the brachioradialis in two forearms, the extensor carpi radialis brevis in three forearms, and the extensor carpi radialis longus and the abductor pollicis longus in one forearm each.
CONCLUSIONS
Percutaneous pin placement in the distal radius is unsafe. The authors recommend open pin placement for fractures of the distal radius.
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No pos
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No neg
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Retriever3088
|
Rapid and extensive uptake and activation of hydrophobic triphenylphosphonium cations within cells.
Mitochondria-targeted molecules comprising the lipophilic TPP (triphenylphosphonium) cation covalently linked to a hydrophobic bioactive moiety are used to modify and probe mitochondria in cells and in vivo. However, it is unclear how hydrophobicity affects the rate and extent of their uptake into mitochondria within cells, making it difficult to interpret experiments because their intracellular concentration in different compartments is uncertain. To address this issue, we compared the uptake into both isolated mitochondria and mitochondria within cells of two hydrophobic TPP derivatives, [3H]MitoQ (mitoquinone) and [3H]DecylTPP, with the more hydrophilic TPP cation [3H]TPMP (methyltriphenylphosphonium). Uptake of MitoQ by mitochondria and cells was described by the Nernst equation and was approximately 5-fold greater than that for TPMP, as a result of its greater binding within the mitochondrial matrix. DecylTPP was also taken up extensively by cells, indicating that increased hydrophobicity enhanced uptake. Both MitoQ and DecylTPP were taken up very rapidly into cells, reaching a steady state within 15 min, compared with approximately 8 h for TPMP. This far faster uptake was the result of the increased rate of passage of hydrophobic TPP molecules through the plasma membrane. Within cells MitoQ was predominantly located within mitochondria, where it was rapidly reduced to the ubiquinol form, consistent with its protective effects in cells and in vivo being due to the ubiquinol antioxidant. The strong influence of hydrophobicity on TPP cation uptake into mitochondria within cells facilitates the rational design of mitochondria-targeted compounds to report on and modify mitochondrial function in vivo.
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No pos
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No neg
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Retriever3089
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Multifractal Conductance Fluctuations in High-Mobility Graphene in the Integer Quantum Hall Regime.
We present the first experimental evidence for the multifractality of a transport property at a topological phase transition. In particular, we show that conductance fluctuations display multifractality at the integer quantum Hall plateau-to-plateau transitions in high-mobility mesoscopic graphene devices. The multifractality gets rapidly suppressed as the chemical potential moves away from these critical points. Our combination of experimental study and multifractal analysis provides a novel method for probing the criticality of wave functions at phase transitions in mesoscopic systems, and quantum criticality in several condensed-matter systems.
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No pos
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No neg
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Retriever3090
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N-terminal extension of canine glutamine synthetase created by splicing alters its enzymatic property.
It was found that an extra exon exists in the first intron of glutamine synthetase gene, generated by means of alternative splicing. Inclusion of this exon decreased the translation of glutamine synthetase (GS) in human, dog, and mouse. When translated in vitro with the canine GS transcript containing the exon, we obtained two different species of GS enzymes. Besides the known 45-kDa protein, the extended form of GS was identified with additional 40 amino acids on its N-terminal end. An upstream ATG in the extra exon served as a translation initiator for the long form of GS. When the long transcript was translated in vivo in animal cells, only the long GS was expressed. On the other hand, the long GS is less predominant relative to the short one in canine tissues including brain and liver. Subcellular fractionation of canine brain revealed that the long GS is present in all cellular compartments as is the short one, which is consistent with fluorescence microscopy data obtained with green fluorescent protein fused to GS. The short (SGS) and long (LGS) forms of canine GS were purified in Escherichia coli and shown to have similar Km values for l-glutamate and hydroxylamine. However, the Km values for ATP were slightly altered, 1.3 and 1.9 mm for the short and long GSs, respectively. The Kis for l-methionine-S-sulfoximine (MSOX), a highly potent ATP-dependent inactivator of GS, were considerably different such that the values are 0.067 and 0.124 mm for the short and long forms, respectively. When the intrinsic fluorescences of tryptophans were monitored upon bindings of chloride and metal ions without any effect on the oligomeric state, the pattern of quenching in LGS was significantly different from that of SGS. Taken together, the N-terminal extension in the long isoform of GS induces a conformational change of core enzyme, leading to a change in affinity to its substrates as well as in the effector-induced conformational alterations.
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No pos
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No neg
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Retriever3091
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Effect of pH on Au Nanorods in Ag Ion-Assisted Seed-Mediated Growth.
Au nanorods (NRs) with different aspect ratios were synthesized using a silver ion-assisted seed-mediated growth method through controlling the pH of solutions using hydrochloric acid to adjust the pH values of solutions. The Au NRs with longitudinal absorption peak range from 713 nm to 916 nm were fabricated by adjusting the concentrations of silver nitrate, hydrochloric acid, and cetyltrimethy-lammonium bromide in the growth solution. It was found that silver ions and hydrochloricacid were used together to systematically tune the shape and size of Au NRs. H+ ions other than Cl- ions play important role to govern the growth of Au NRs. Au NRs with a large aspect ratio and high yield can be synthesized in a relative high silver nitrate concentration and a low pH value. In optimal conditions, the Au NRs reveal an average diameter of 10 nm and length of 60 nm. Namely, the Au NRs became slender at a lower pH value and higher concentration of the AgNO₃ in the growth solution.
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No pos
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No neg
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Retriever3092
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Effectiveness of a Multicomponent Treatment for Fibromyalgia Based on Pain Neuroscience Education, Exercise Therapy, Psychological Support, and Nature Exposure (NAT-FM): A Pragmatic Randomized Controlled Trial.
A recent study (FIBROWALK has supported the effectiveness of a multicomponent treatment based on pain neuroscience education (PNE), exercise therapy (TE), cognitive behavioral therapy (CBT), and mindfulness in patients with fibromyalgia. The aim of the present RCT was: (a) to analyze the effectiveness of a 12-week multicomponent treatment (nature activity therapy for fibromyalgia, NAT-FM) based on the same therapeutic components described above plus nature exposure to maximize improvements in functional impairment (primary outcome), as well as pain, fatigue, anxiety-depression, physical functioning, positive and negative affect, self-esteem, and perceived stress (secondary outcomes), and kinesiophobia, pain catastrophizing thoughts, personal perceived competence, and cognitive emotion regulation (process variables) compared with treatment as usual (TAU); (b) to preliminarily assess the effects of the nature-based activities included (yoga, Nordic walking, nature photography, and Shinrin Yoku); and (c) to examine whether the positive effects of TAU + NAT-FM on primary and secondary outcomes at post-treatment were mediated through baseline to six-week changes in process variables. A total of 169 FM patients were randomized into two study arms: TAU + NAT-FM vs. TAU alone. Data were collected at baseline, at six-week of treatment, at post-treatment, and throughout treatment by ecological momentary assessment (EMA). Using an intention to treat (ITT) approach, linear mixed-effects models and mediational models through path analyses were computed. Overall, TAU + NAT-FM was significantly more effective than TAU at posttreatment for the primary and secondary outcomes evaluated, as well as for the process variables. Moderate-to-large effect sizes were achieved at six-weeks for functional impairment, anxiety, kinesiophobia, perceived competence, and positive reappraisal. The number needed to treat (NNT) was 3 (95%CI = 1.6-3.2). The nature activities yielded an improvement in affective valence, arousal, dominance, fatigue, pain, stress, and self-efficacy. Kinesiophobia and perceived competence were the mediators that could explain a significant part of the improvements obtained with TAU + NAT-FM treatment. TAU + NAT-FM is an effective co-adjuvant multicomponent treatment for improving FM-related symptoms.
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No pos
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No neg
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Retriever3093
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The supracostal approach for percutaneous nephrostolithotomy.
Sixty-nine patients underwent percutaneous nephrostolithotomy or ultrasonic lithotripsy through a nephrostomy tract placed over the 12th rib. All procedures were accomplished as a single stage in a standard operating room with patients under general anesthesia. With the exception of a single failed access the targeted calculus was removed in all instances. There were no episodes of postoperative pneumothorax or hydrothorax. One patient suffered delayed postoperative pneumonia and another patient had a delayed pleural effusion. The supracostal approach for percutaneous nephrostolithotomy is an important and safe modification of the traditional percutaneous approach to the kidney for an endourological procedure.
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No pos
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No neg
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Retriever3094
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Chromosome localization of three syntenic gene pairs in the American mink (Mustela vison).
Twenty eight American mink X Chinese hamster somatic cell hybrids were analysed for the expression of mink enzymes and for mink chromosomes. The results of this analysis made it possible to assign the genes for phosphoglucomutase-1 and phosphogluconate dehydrogenase to chromosome 2, those for lactate dehydrogenase A and glucose phosphate isomerase to chromosome 7, and those for lactate dehydrogenase B and triosephosphate isomerase to chromosome 9.
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No pos
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No neg
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Retriever3095
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Long-term muscle-derived cell culture: multipotency and susceptibility to cell death stimuli.
Improvement in the yield of adult organism stem cells, and the ability to manage their differentiation and survival potential are the major goals in their application in regenerative medicine and in the adult stem cell research. We have demonstrated that adult rabbit muscle-derived cell lines with an unlimited proliferative potential in vitro can differentiate into myogenic, osteogenic, adipogenic and neurogenic lineages. Studies of cell survival in vitro showed that differentiated cells, except neurogenic ones, are more resistant to apoptosis inducers compared to proliferating cells. Resistance to death signals correlated with the level of protein kinase AKT phosphorylation. Skeletal muscle-derived cell lines can be multipurpose tools in therapy. Enhanced resistance of differentiated cells to certain types of damage shows their potential for long-term survival and maintenance in an organism. This article was published online on 29 January 2013. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 6 March 2013.
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Retriever3096
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From doing to leading: PGY-1 to PGY-2 transition.
BACKGROUND
Clinical trainees experience several professional transitions throughout their career, which can be exciting, anxiety-provoking or both. The first to second post-graduate year (PGY) transition for residents (junior doctors) in North America involves assuming new roles such as team leader, clinical supervisor, and teacher, often with minimal preparation. We explored resident experiences and emotions during this transition, and obtained their strategies for navigating this transition, through the lens of Bridges' transition model. This model has three stages: (1) ending, losing and letting go, (2) the neutral zone and (3) the new beginning.
METHODS
We conducted one in-person focus group and subsequent one-on-one virtual semistructured interviews (due to COVID-19) of PGY-2 and PGY-3 residents who had previously undergone the transition. These sessions were recorded and transcribed, and thematic analysis was performed.
FINDINGS
Four residents participated in the focus group, and 14 participated in one-on-one interviews. We identified five key themes: (1) not just a cog in the wheel, (2) contributing to growth of near-peers, (3) being flexible and adaptive, (4) emulating resident role models and (5) relationships with attendings. Residents suggested a transitions-focused retreat, simulation training to lead clinical emergencies, supervised opportunities for PGY-1s to act as PGY-2s coached by senior residents, and pairing PGY-1s with senior residents to help prepare for the transition.
CONCLUSION
Professional transitions are both anxiety-provoking and exciting. Clinical trainees need preparation to successfully navigate multiple transitions. The Bridges' transition model could be useful in conceptualising transitions and planning curricula.
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Retriever3097
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Organizational control and the status of marketing in multihospital systems.
Research on organizational control and multihospital systems has focused on operational and performance characteristics. Little attention has been directed to the role of marketing as an operational strategy. This article examines the practice of marketing across interorganizational types and develops comparative profiles.
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Retriever3098
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Analytical and clinical validation of an amplicon-based next generation sequencing assay for ultrasensitive detection of circulating tumor DNA.
Next-generation sequencing of circulating tumor DNA presents a promising approach to cancer diagnostics, complementing conventional tissue-based diagnostic testing by enabling minimally invasive serial testing and broad genomic coverage through a simple blood draw to maximize therapeutic benefit to patients. LiquidHALLMARK® is an amplicon-based next-generation sequencing assay developed for the genomic profiling of plasma-derived cell-free DNA (cfDNA). The comprehensive 80-gene panel profiles point mutations, insertions/deletions, copy number alterations, and gene fusions, and further detects oncogenic viruses (Epstein-Barr virus (EBV) and hepatitis B virus (HBV)) and microsatellite instability (MSI). Here, the analytical and clinical validation of the assay is reported. Analytical validation using reference genetic materials demonstrated a sensitivity of 99.38% for point mutations and 95.83% for insertions/deletions at 0.1% variant allele frequency (VAF), and a sensitivity of 91.67% for gene fusions at 0.5% VAF. In non-cancer samples, a high specificity (≥99.9999% per-base) was observed. The limit of detection for copy number alterations, EBV, HBV, and MSI were also empirically determined. Orthogonal comparison of epidermal growth factor receptor (EGFR) variant calls made by LiquidHALLMARK and a reference allele-specific polymerase chain reaction (AS-PCR) method for 355 lung cancer specimens revealed an overall concordance of 93.80%, while external validation with cobas® EGFR Mutation Test v2 for 50 lung cancer specimens demonstrated an overall concordance of 84.00%, with a 100% concordance rate for EGFR variants above 0.4% VAF. Clinical application of LiquidHALLMARK in 1,592 consecutive patients demonstrated a high detection rate (74.8% circulating tumor DNA (ctDNA)-positive in cancer samples) and broad actionability (50.0% of cancer samples harboring alterations with biological evidence for actionability). Among ctDNA-positive lung cancers, 72.5% harbored at least one biomarker with a guideline-approved drug indication. These results establish the high sensitivity, specificity, accuracy, and precision of the LiquidHALLMARK assay and supports its clinical application for blood-based genomic testing.
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Retriever3099
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Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies.
Malignant primary brain tumors are characterized by a short median survival and an almost 100% tumor-related mortality. Despite the addition of new chemotherapy regimes, the overall survival has improved marginally, and radiotherapy is only transiently effective, illustrating the profound impact of treatment resistance on prognosis. Recent studies suggest that a small subpopulation of cancer stem cells (CSCs) has the capacity to repopulate tumors and drive malignant progression and mediate radio- and chemoresistance. This implies that future therapies should turn from the elimination of the rapidly dividing, but differentiated tumor cells, to specifically targeting the minority of tumor cells that repopulate the tumor. Although there exists some support for the CSC hypothesis, there remain many uncertainties regarding theoretical, technical, and interpretational aspects of the data supporting it. If correct, the CSC hypothesis could have profound implications for the way tumors are classified and treated. In this review of the literature, we provide original data and hypotheses supporting alternative explanations and outline some of the therapeutic implications that can be derived.
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