Impact of shield location on staff and caregiver dose rates for I-131 radiopharmaceutical therapy patients.

The goal of this study is to investigate the effect of the location and width of a single lead shield on the dose rate of staff and caregivers in a hospital room with an I-131 patient. The best orientation of the patient and caregiver relative to the shield was determined based on minimizing staff and caregiver radiation dose rates. Shielded and unshielded dose rates were simulated using a Monte Carlo computer simulation and validated using real-world ionisation chamber measurements. Based on a radiation transport analysis using an adult voxel phantom published by the International Commission on Radiological Protection, placing the shield near the caregiver yielded the lowest dose rates. However, this strategy reduced the dose rate in only a tiny area of the room. Furthermore, positioning the shield near the patient in the caudal direction provided a modest dose rate reduction while shielding a large room area. Finally, increased shield width was associated with decreasing dose rates, but only a four-fold dose-rate reduction was observed for standard width shields. The recommendations of this case study may be considered as potential candidate room configurations where radiation dose rates are minimized, however these findings must be weighed against additional clinical, safety, and comfort considerations.

The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Nociceptive related microRNAs and their role in rheumatoid arthritis.

Rheumatoid Arthritis (RA) is an autoimmune disease with unknown etiology and a global incidence around 1%, a positive family history increases the risk of RA roughly three to five times. Pain is one of the first symptoms to appear in this disease. MicroRNAs (miRNAs) belong to the class of small non-coding RNAs; they regulate multiple cellular processes including embryonic development, cellular proliferation, differentiation and apoptosis among others. A great deal of evidence points to the employment of miRNAs as therapeutic targets and biomarkers for several pathologies. The main objective of this Review is to assess how miRNAs participate in the pathogenesis of RA. Two advanced searches were conducted in databases, one using "micro-RNA" and "rheumatoid arthritis" as key words, and another one with "micro-RNA", "pain" and "nociception". In this Review, we describe how six miRNAs: miR-16-5p, miR-23b-3b, miR-124-3p, miR-146a-5p, miR-155-5p and miR-223-3p, involved in the modulation and transmission of the nociceptive input are unregulated in RA patients. Key molecular pathways involved in nociception, inflammation and autoimmune responses, are regulated by these miRNAs; the NF-κB, TNF-α, interleukins and TLR4. By means of gene repression, the miRNAs here described modulate the nociceptive process as well as the autoimmune response that characterize this disease.

Production of Encecalin in Cell Cultures and Hairy Roots of Helianthella quinquenervis (Hook.) A. Gray.

Plant cell and organ cultures of Helianthella quinquenervis, a medicinal plant whose roots are used by the Tarahumara Indians of Chihuahua, Mexico, to relieve several ailments, were established to identify and quantify some chromenes with biological activity, such as encecalin, and to evaluate their potential for biotechnological production. Gas chromatography-mass spectrometry (GC-MS) analysis corroborated the presence of quantifiable amounts of encecalin in H. quinquenervis cell cultures (callus and cell suspensions). In addition, hairy roots were obtained through three transformation protocols (prick, 45-s sonication and co-culture), using wild type Agrobacterium rhizogenes A4. After three months, cocultivation achieved the highest percentage of transformation (66%), and a comparable production (FW) of encecalin (110 µg/g) than the sonication assay (120 µg/g), both giving far higher yields than the prick assay (19 µg/g). Stable integration of rolC and aux1 genes in the transformed roots was confirmed by polymerase chain reaction (PCR). Hairy roots from cocultivation (six months-old) accumulated as much as 1086 µg/g (FW) of encecalin, over three times higher than the cell suspension cultures. The production of encecalin varied with growth kinetics, being higher at the stationary phase. This is the first report of encecalin production in hairy roots of H. quinquenervis, demonstrating the potential for a future biotechnological production of chromenes.

Effect of ancymidol on cell wall metabolism in growing maize cells.

MAIN CONCLUSION: Ancymidol inhibits the incorporation of cellulose into cell walls of maize cell cultures in a gibberellin-independent manner, impairing cell growth; the reduction in the cellulose content is compensated with xylans. Ancymidol is a plant growth retardant which impairs gibberellin biosynthesis. It has been reported to inhibit cellulose synthesis by tobacco cells, based on its cell-malforming effects. To ascertain the putative role of ancymidol as a cellulose biosynthesis inhibitor, we conducted a biochemical study of its effect on cell growth and cell wall metabolism in maize cultured cells. Ancymidol concentrations ≤ 500 µM progressively reduced cell growth and induced globular cell shape without affecting cell viability. However, cell growth and viability were strongly reduced by ancymidol concentrations ≥ 1.5 mM. The I50 value for the effect of ancymidol on FW gain was 658 µM. A reversal of the inhibitory effects on cell growth was observed when 500 µM ancymidol-treated cultures were supplemented with 100 µM GA3. Ancymidol impaired the accumulation of cellulose in cell walls, as monitored by FTIR spectroscopy. Cells treated with 500 µM ancymidol showed a ~ 60% reduction in cellulose content, with no further change as the ancymidol concentration increased. Cellulose content was partially restored by 100 µM GA3. Radiolabeling experiments confirmed that ancymidol reduced the incorporation of [14C]glucose into α-cellulose and this reduction was not reverted by the simultaneous application of GA3. RT-PCR analysis indicated that the cellulose biosynthesis inhibition caused by ancymidol is not related to a downregulation of ZmCesA gene expression. Additionally, ancymidol treatment increased the incorporation of [3H]arabinose into a hemicellulose-enriched fraction, and up-regulated ZmIRX9 and ZmIRX10L gene expression, indicating an enhancement in the biosynthesis of arabinoxylans as a compensatory response to cellulose reduction.

Implications of biological factors on accumulation of persistent organic pollutants in Antarctic notothenioid fish.

In the present study, the possible associations between selected persistent organic pollutants (POPs) and biological factors were assessed in different tissues of two Antarctic notothenioid fish: Notothenia rossii (NOR) and Trematomus newnesi (TRN) collected at Potter Cove, King George Island/Isla 25 de Mayo, South Shetland Islands. Specifically, association patterns between biological factors (body size, lipid content, body condition) and POP concentrations (polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and metabolites, polybrominated diphenyl ethers (PBDEs), and hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), chlordanes (CHLs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs)), were explored by using two approaches: multivariate analyses (principal component analysis: PCA) and intraspecific correlations. Integrating results suggest that biological factors such as size, KI and tissue type seemed to be associated to selective accumulation of POPs for immature specimens of N. rossii, and KI and tissue type for mature specimens of T. newnesi. Each particular factor should be considered when choosing N. rossii or T. newnesi as sentinels for POPs pollution in Antarctic marine environments. Further, both nototheniids showed a selective accumulation pattern in their gonads of penta-chlorinated biphenyls (penta-CBs; 55.5 and 29ngg-1 lw for N. rossii and T. newnesi, respectively) and organochlorine pesticides such as DDTs (199 and 13.3ngg-1 lw, for N. rossii and T. newnesi respectively), and of polybrominated diphenyl ethers (PBDEs) in gills (97.2 and 22.1 for ngg-1 lw, for N. rossii and T. newnesi, respectively), highlighting the importance of these tissues in monitoring studies of pollution in fish. The current study expands the knowledge concerning the biological factors to be investigated when specific pollutants are monitored and supports the importance of tissue type for the selective accumulation of POPs in Antarctic fish. Additionally, a contribution to the scarce data on concentration of MeO-PBDEs in Antarctic marine organisms, particularly in the highly diverse perciform suborder Notothenioidei is provided.

Laser Spot Detection Based on Reaction Diffusion.

Center-location of a laser spot is a problem of interest when the laser is used for processing and performing measurements. Measurement quality depends on correctly determining the location of the laser spot. Hence, improving and proposing algorithms for the correct location of the spots are fundamental issues in laser-based measurements. In this paper we introduce a Reaction Diffusion (RD) system as the main computational framework for robustly finding laser spot centers. The method presented is compared with a conventional approach for locating laser spots, and the experimental results indicate that RD-based computation generates reliable and precise solutions. These results confirm the flexibility of the new computational paradigm based on RD systems for addressing problems that can be reduced to a set of geometric operations.

Levetiracetam as an antiepileptic, neuroprotective, and hyperalgesic drug.

The main purpose of this review was to expound upon the mechanism of action of Levetiracetam (LEV) as an antiepileptic, neuroprotective, and hyperalgesic drug. LEV is a second-generation anti-epileptic drug (AED) that is approved for clinical use as monotherapy and may also be used for adjunctive treatment of patients with seizures. Several researchers have recommended LEV as a treatment option in different diseases causing neuronal damage, and recently, LEV has been used as an antihyperalgesic drug. LEV exhibits favorable characteristics, including a low potential for interaction, a short elimination half-life, and has neither active metabolites nor major negative effects on cognition. This has generated many new research avenues for the utilization of this drug. However, the precise mechanism of action of LEV has not been fully elucidated. In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation index for studies evaluating the effects of LEV as an antiepileptic, neuroprotective, and hyperalgesic drug. A total of 32 studies related to the use of LEV suggested different mechanisms of action, such as binding to the synaptic vesicle glycoprotein 2A (SV2A) protein, inhibition of Ca2+ N-type channels, and its presence as a neuromodulator. These studies concluded that the pharmacodynamics of LEV should be viewed as a single pathway, and should not be based on specific molecular targets that depend on the physiological or pathological conditions prevalent at that time.

Gas bubble dynamics in soft materials.

Epstein and Plesset's seminal work on the rate of gas bubble dissolution and growth in a simple liquid is generalized to render it applicable to a gas bubble embedded in a soft elastic solid. Both the underlying diffusion equation and the expression for the gas bubble pressure were modified to allow for the non-zero shear modulus of the medium. The extension of the diffusion equation results in a trivial shift (by an additive constant) in the value of the diffusion coefficient, and does not change the form of the rate equations. But the use of a generalized Young-Laplace equation for the bubble pressure resulted in significant differences on the dynamics of bubble dissolution and growth, relative to an inviscid liquid medium. Depending on whether the salient parameters (solute concentration, initial bubble radius, surface tension, and shear modulus) lead to bubble growth or dissolution, the effect of allowing for a non-zero shear modulus in the generalized Young-Laplace equation is to speed up the rate of bubble growth, or to reduce the rate of bubble dissolution, respectively. The relation to previous work on visco-elastic materials is discussed, as is the connection of this work to the problem of Decompression Sickness (specifically, "the bends"). Examples of tissues to which our expressions can be applied are provided. Also, a new phenomenon is predicted whereby, for some parameter values, a bubble can be metastable and persist for long times, or it may grow, when embedded in a homogeneous under-saturated soft elastic medium.

Thermodynamic stability in elastic systems: Hard spheres embedded in a finite spherical elastic solid.

We determined the total system elastic Helmholtz free energy, under the constraints of constant temperature and volume, for systems comprised of one or more perfectly bonded hard spherical inclusions (i.e. "hard spheres") embedded in a finite spherical elastic solid. Dirichlet boundary conditions were applied both at the surface(s) of the hard spheres, and at the outer surface of the elastic solid. The boundary conditions at the surface of the spheres were used to describe the rigid displacements of the spheres, relative to their initial location(s) in the unstressed initial state. These displacements, together with the initial positions, provided the final shape of the strained elastic solid. The boundary conditions at the outer surface of the elastic medium were used to ensure constancy of the system volume. We determined the strain and stress tensors numerically, using a method that combines the Neuber-Papkovich spherical harmonic decomposition, the Schwartz alternating method, and Least-squares for determining the spherical harmonic expansion coefficients. The total system elastic Helmholtz free energy was determined by numerically integrating the elastic Helmholtz free energy density over the volume of the elastic solid, either by a quadrature, or a Monte Carlo method, or both. Depending on the initial position of the hard sphere(s) (or equivalently, the shape of the un-deformed stress-free elastic solid), and the displacements, either stationary or non-stationary Helmholtz free energy minima were found. The non-stationary minima, which involved the hard spheres nearly in contact with one another, corresponded to lower Helmholtz free energies, than did the stationary minima, for which the hard spheres were further away from one another.

Therapeutic treatment with fluoxetine using the chronic unpredictable stress model induces changes in neurotransmitters and circulating miRNAs in extracellular vesicles.

The most widely prescribed antidepressant, fluoxetine (FLX), is known for its antioxidant and anti-inflammatory effects when administered post-stress. Few studies have evaluated the effects of FLX treatment when chronic stress has induced deleterious effects in patients. Our objective was to evaluate FLX treatment (20 mg/kg/day, i.v.) once these effects are manifested, and the drug's relation to extracellular circulating microRNAs associated with inflammation, a hedonic response (sucrose intake), the forced swim test (FST), and corticosterone levels (CORT) and monoamine concentrations in limbic areas. A group of Wistar rats was divided into groups: Control; FLX; CUMS (for six weeks of exposure to chronic, unpredictable mild stress); and CUMS + FLX, a mixed group. After CUMS, the rats performed the FST, and serum levels of CORT and six microRNAs (miR-16, -21, -144, -155, -146a, -223) were analyzed, as were levels of dopamine, noradrenaline, and serotonin in the prefrontal cortex, hippocampus, and hypothalamus. CUMS reduced body weight, sucrose intake, and hippocampal noradrenaline levels, but increased CORT, immobility behavior on the FST, dopamine concentrations in the prefrontal cortex, and all miRNAs except miR-146a expression. Administering FLX during CUMS reduced CORT levels and immobility behavior on the FST and increased the expression of miR-16, -21, -146a, -223, and dopamine. FLX protects against the deleterious effects of stress by reducing CORT and has an antidepressant effect on the FST, with minimally-modified neurotransmitter levels. FLX increased the expression of miRNAs as part of the antidepressant effect. It also regulates both neuroinflammation and serotoninergic neurotransmission through miRNAs, such as the miR-16.

SUBSTANTIAL EXTERNAL DOSE RATE VARIABILITY OBSERVED IN A COHORT OF LU-177 PATIENTS INDEPENDENT OF BMI AND SEX.

External dose rates were measured 1 m away from 230 Lu-177 patients to characterise the variability in normalised dose rates as a function of administered activity, body mass index (BMI) and sex. The largest dose rate observed was 0.07 mSv/h associated with an administered activity of 7.2 GBq. Substantial variability was found in the distribution of the normalised dose rate associated that had an average of 0.0037 mSv/h per GBq and a 95% confidence interval of 0.0024-0.0058 mSv/h per GBq. Based on this study, estimating the patient dose rate based on the Lu-177 gamma exposure factor overestimates the dose rate by a factor of 2. A statistically significant inverse relationship was found between the patient dose rate and patient BMI and an empirically derived equation relating these two quantities was reported. On average, male patient dose rates were 3.5% lower than female dose rates, which may be attributed to the larger average BMI of the male patient group.

Infinite penetration of a projectile into a granular medium.

An object falling in a fluid reaches a terminal velocity when the drag force and its weight are balanced. Contrastingly, an object impacting into a granular medium rapidly dissipates all its energy and comes to rest always at a shallow depth. Here we study, experimentally and theoretically, the penetration dynamics of a projectile in a very long silo filled with expanded polystyrene particles. We discovered that, above a critical mass, the projectile reaches a terminal velocity and, therefore, an endless penetration.

Liquid chromatography time-of-flight mass spectrometry following sorptive microextraction for the determination of fungicide residues in wine.

This work evaluates the suitability of sorptive microextraction, using disposable silicone sorbents, and liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) for the determination of 15 fungicides in wine. Under optimized conditions, wine samples (10 mL) were diluted with the same volume of ultrapure water and poured in a glass vessel containing a magnetic stirrer and 4 g of sodium chloride. Extractions were performed at room temperature for 4 h, using an inexpensive silicone disk (12 µL volume) exposed directly to the sample. Thereafter, analytes were recovered with 0.2 mL of acetonitrile. The electrospray ionization (ESI) source was operated in the fast polarity switching mode obtaining, in the same injection, selective LC-MS records (extracted with a mass window of 10 ppm) of compounds rendering [M + H](+) and [M-H](-) ions. The method provided limits of quantification (LOQs) between 0.1 and 2.2 ng mL(-1), linear response ranges up to 500 ng mL(-1), relative recoveries from 75% to 117% and an inter-day variability below 15% for all analytes in red and white wine samples. The feasibility of in situ sample enrichment followed by delayed desorption and analysis is also assessed.

Success of medical therapy in a rare case of cecal ameboma.

INTRODUCTION: Colitis caused by Entamoeba histolytica (EH) is prevalent in developing countries. Clinical presentation ranges from mild diarrhoea episodes to dysentery and liver abscess. Ameboma, a complication caused by EH invasion of the intestinal wall, is a rare presentation of amebiasis, occurring approximately in 1.5% of cases. Because of its insidious and variable clinical presentation only few cases are diagnosed previous to surgical intervention. We report a 52 years old Mexican-mestizo female, presenting with a pain-less right lower quadrant abdominal mass and diagnosed of cecal ameboma prior to surgery by colonoscopy and histopathologic examination. The present case highlights the importance of early diagnosis and medical therapy with antiparasitic drugs in order to avoid complications that could lead these patients to unnecessary surgical management.

[Predicting very early rebleeding after acute variceal bleeding based in classification and regression tree analysis (CRTA).]. / Predicción de resangrado precoz en cirróticos con hemorragia variceal aguda. Función del análisis con árboles de clasificación y regresión (CART).

BACKGROUND: Variceal bleeding (VB) is the main cause of death among cirrhotic patients. About 30-50% of early rebleeding is encountered few days after the acute episode of VB. It is necessary to stratify patients with high risk of very early rebleeding (VER) for more aggressive therapies. However, there are few and incompletely understood prognostic models for this purpose. AIMS: To determine the risk factors associated with VER after an acute VB. Assessment and comparison of a novel prognostic model generated by Classification and Regression Tree Analysis (CART) with classic-used models (MELD and Child-Pugh [CP]). PATIENTS AND METHODS: Sixty consecutive cirrhotic patients with acute variceal bleeding. CART analysis, MELD and Child-Pugh scores were performed at admission. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the models. RESULTS: Very early rebleeding rate was 13%. Variables associated with VER were: serum albumin (p = 0.027), creatinine (p = 0.021) and transfused blood units in the first 24 hrs (p = 0.05). The area under the ROC for MELD, CHILD-Pugh and CART were 0.46, 0.50 and 0.82, respectively. The value of cut analyzed by CART for the significant variables were: 1) Albumin 2.85 mg/dL, 2) Packed red cells 2 units and 3) Creatinine 1.65 mg/dL the ABC-ROC. CONCLUSION: Serum albumin, creatinine and number of transfused blood units were associated with VER. A simple CART algorithm combining these variables allows an accurate predictive assessment of VER after acute variceal bleeding. Key words: cirrhosis, variceal bleeding, esophageal varices, prognosis, portal hypertension.

An explicitly multi-component arterial gas embolus dissolves much more slowly than its one-component approximation.

We worked out the growth and dissolution rates of an arterial gas embolism (AGE), to illustrate the evolution over time of its size and composition, and the time required for its total dissolution. We did this for a variety of breathing gases including air, pure oxygen, Nitrox and Heliox (each over a range of oxygen mole fractions), in order to assess how the breathing gas influenced the evolution of the AGE. The calculations were done by numerically integrating the underlying rate equations for explicitly multi-component AGEs, that contained a minimum of three (water, carbon dioxide and oxygen) and a maximum of five components (water, carbon dioxide, oxygen, nitrogen and helium). The rate equations were straight-forward extensions of those for a one-component gas bubble. They were derived by using the Young-Laplace equation and Dalton's law for the pressure in the AGE, the Laplace equation for the dissolved solute concentration gradients in solution, Henry's law for gas solubilities, and Fick's law for diffusion rates across the AGE/arterial blood interface. We found that the 1-component approximation, under which the contents of the AGE are approximated by its dominant component, greatly overestimates the dissolution rate and underestimates the total dissolution time of an AGE. This is because the 1-component approximation manifestly precludes equilibration between the AGE and arterial blood of the inspired volatile solutes (O2, N2, He) in arterial blood. Our calculations uncovered an important practical result, namely that the administration of Heliox, as an adjunct to recompression therapy for treating a suspected N2-rich AGE must be done with care. While Helium is useful for preventing nitrogen narcosis which can arise in aggressive recompression therapy wherein the N2 partial pressure can be quite high (e.g.∼5 atm), it also temporarily expands the AGE, beyond the expansion arising from the use of Oxygen-rich Nitrox. For less aggressive recompression therapy wherein nitrogen narcosis is not a significant concern, Oxygen-rich Nitrox is to be preferred, both because it does not temporarily expand the AGE as much as Heliox, and because it is much cheaper and more conservation-minded.

Diagnostic approach in suspected recurrent primary brain tumors using (18)FDG-PET/MRI, perfusion MRI, visual and quantitative analysis, and three dimensional stereotactic surface projections. First experience in Mexico.

UNLABELLED: Thirty patients with primary cerebral tumors WHO III and IV previously treated, undergoing evaluation for tumoral recurrence, they underwent (18)FDG-PET study, MRI and PMRI. PET uptake was determined by visual inspection and was quantified by use of standard uptake values, the ratio of tumor uptake to normal tissue and were z scored using automated voxel-based comparison. PMRI was quantified by use of ratios of cerebral blood volume (rCBV). The accuracies were determined by comparing imaging data with histologic findings and clinical follow up of up to 21 mo. RESULTS: Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy were 100 %, 82 %, 90 %, 100 % and 93 % respectively for the PET/MRI fusion and 68 %, 82 %, 87 %, 60 % and 73 % respectively for PMRI. There were two false positive cases for PET/MRI fusion that were confirmed by biopsy: chronic inflammation; and foreign body granulomas. The receiver operating characteristic (ROC) curve analysis showed statistically significant difference (p = 0.0225). CONCLUSIONS: (18)FDG SUVs, glucose uptake ratios and 3D stereotactic surface projections in brain tumors were not a reliable measure for evaluating recurrent tumors. PET/MRI fusion was more sensitive and accurate than PMRI for imaging recurrent primary brain tumors. The region of interest can be visually analyzed on the PET/MRI fusion images and described as recurrent tumor when any activity (lower, equal or greater than the contralateral cortex) is presented in the zone of hyperintensity seen on the post-gadolinium T1-weighted MRI.