Heterogeneous physical phantom for I-125 dose measurements and dose-to-medium determination.

PURPOSE: In this paper we present a further step in the implementation of a physical phantom designed to generate sets of "true" independent reference data as requested by TG-186, intending to address and mitigate the scarcity of experimental studies on brachytherapy (BT) validation in heterogeneous media. To achieve this, we incorporated well-known heterogeneous materials into the phantom in order to perform measurements of 125I dose distribution. The work aims to experimentally validate Monte Carlo (MC) calculations based on MBDCA and determine the conversion factors from LiF response to absorbed dose in different media, using cavity theory. METHODS AND MATERIALS: The physical phantom was adjusted to incorporate tissue equivalent materials, such as: adipose tissue, bone, breast and lung with varying thickness. MC calculations were performed using MCNP6.2 code to calculate the absorbed dose in the LiF and the dose conversion factors (DCF). RESULTS: The proposed heterogeneous phantom associated with the experimental procedure carried out in this work yielded accurate dose data that enabled the conversion of the LiF responses into absorbed dose to medium. The results showed a maximum uncertainty of 6.92 % (k = 1), which may be considered excellent for dosimetry with low-energy BT sources. CONCLUSIONS: The presented heterogeneous phantom achieves the required precision in dose evaluations due to its easy reproducibility in the experimental setup. The obtained results support the dose conversion methodology for all evaluated media. The experimental validation of the DCF in different media holds great significance for clinical procedures, as it can be applied to other tissues, including water, which remains a widely utilized reference medium in clinical practice.

A versatile physical phantom design and construction for I-125 dose measurements and dose-to-medium determination.

PURPOSE: In this paper we present a phantom designed to provide conditions to generate set of "true" independent reference data as requested by TG-186, and mitigating the scarcity of experimental studies on brachytherapy validation. It was used to perform accurate experimental measurements of dose of 125I brachytherapy seeds using LiF dosimeters, with the objective of experimentally validating Monte Carlo (MC) calculations with model-based dose calculation algorithm (MBDCA). In addition, this work intends to evaluate a methodology to convert the experimental values from LiF into dose in the medium. METHODS AND MATERIALS: The proposed PMMA physical phantom features cavities to insert a LiF dosimeter and a 125I seed, adjusted in different configurations with variable thickness. Monte Carlo calculations performed with MCNP6.2 code were used to score the absorbed dose in the LiF and the dose conversion parameters. A sensitivity analysis was done to verify the source of possible uncertainties and quantify their impact on the results. RESULTS: The proposed phantom and experimental procedure developed in this work provided precise dose data within 5.68% uncertainty (k = 1). The achieved precision made it possible to convert the LiF responses into absorbed dose to medium and to validate the dose conversion factor methodology. CONCLUSIONS: The proposed phantom is simple both in design and as in its composition, thus achieving the demanded precision in dose evaluations due to its easy reproducibility of experimental setup. The results derived from the phantom measurements support the dose conversion methodology. The phantom and the experimental procedure developed here can be applied for other materials and radiation sources.

Secukinumab on Refractory Lupus Nephritis.

Lupus nephritis (LN) is the most frequent severe organ manifestation of systemic lupus erythematosus (SLE). About 30% of patients are refractory to treatment. The authors report a case of treatment of LN with interleukin-17-targeted therapy, demonstrating its possible benefit, after reports of T helper 17 cell involvement in SLE pathogenesis. We present the case of a childbearing age woman with SLE, who developed refractory LN despite all the indicated therapeutic options. During follow up, infection with human papillomavirus was detected, a possible trigger, and the following management was based on this discovery. We currently know that cytokines play a major role in tissue damage and interleukin-17 (IL-17) seems to be a fundamental key in SLE and LN, having shown its expression in renal glomeruli and urinary sediment. Thus, it was decided to start treatment with an anti-IL-17A antibody, secukinumab. After starting secukinumab, clinical and biological features improved and complete renal response was achieved.

Valganciclovir in an HIV-infected patient with Castleman's disease / Valganciclovir en un paciente infectado por VIH con enfermedad de Castleman

No disponible

Bioaccessibility and bioavailability of iron in biofortified germinated cowpea.

BACKGROUND: Cowpea (Vigna unguiculata L. Walph) is predominantly consumed in the North and Northeast regions of Brazil, and its biofortification with iron seeks to reduce the high prevalence of iron deficiency anemia in these regions. It is commonly eaten cooked; however, in the germinated form, it can improve nutritional quality by reducing the antinutritional factors and consequently improving the bioavailability of elements. The present study aimed to determine the physico-chemical characteristics, bioaccessibility and bioavailability of iron in biofortified germinated cowpea. RESULTS: There was no statistical difference between the germinated and cooked beans with regard to centesimal composition. Germinated beans had phytates and tannins similar to cooked beans. The phytate-iron molar ratio for all groups did not present a statistical difference (cooking 3.58 and 3.41; germinated 3.94 and 3.51), nor did the parameters evaluating in vivo iron bioavailability. Total phenolics was higher in the germinated group (cooking 0.56 and 0.64; Germinated 2.05 and 2.45 mg gallic acid kg-1 ). In vitro bioaccessibility of iron of germinated beans presented higher values (P ≤ 0.05) compared to cooked beans. There was higher expression of divalent metal transporter-1 in biofortified and germinated beans. CONCLUSION: The iron bioavailability from the biofortified and germinated beans was comparable to ferrous sulfate. Germination can be considered as an alternative and efficient method for consuming cowpea, presenting good iron bioaccessibility and bioavailability. © 2019 Society of Chemical Industry.

Cadmium Bioavailability, Uptake, Toxicity and Detoxification in Soil-Plant System.

This review summarizes the findings of the most recent studies, published from 2000 to 2016, which focus on the biogeochemical behavior of Cd in soil-plant systems and its impact on the ecosystem. For animals and people not subjected to a Cd-contaminated environment, consumption of Cd contaminated food (vegetables, cereals, pulses and legumes) is the main source of Cd exposure. As Cd does not have any known biological function, and can further cause serious deleterious effects both in plants and mammalian consumers, cycling of Cd within the soil-plant system is of high global relevance.The main source of Cd in soil is that which originates as emissions from various industrial processes. Within soil, Cd occurs in various chemical forms which differ greatly with respect to their lability and phytoavailability. Cadmium has a high phytoaccumulation index because of its low adsorption coefficient and high soil-plant mobility and thereby may enter the food chain. Plant uptake of Cd is believed to occur mainly via roots by specific and non-specific transporters of essential nutrients, as no Cd-specific transporter has yet been identified. Within plants, Cd causes phytotoxicity by decreasing nutrient uptake, inhibiting photosynthesis, plant growth and respiration, inducing lipid peroxidation and altering the antioxidant system and functioning of membranes. Plants tackle Cd toxicity via different defense strategies such as decreased Cd uptake or sequestration into vacuoles. In addition, various antioxidants combat Cd-induced overproduction of ROS. Other mechanisms involve the induction of phytochelatins, glutathione and salicylic acid.

Collision-kerma conversion between dose-to-tissue and dose-to-water by photon energy-fluence corrections in low-energy brachytherapy.

The AAPM TG-43 brachytherapy dosimetry formalism, introduced in 1995, has become a standard for brachytherapy dosimetry worldwide; it implicitly assumes that charged-particle equilibrium (CPE) exists for the determination of absorbed dose to water at different locations, except in the vicinity of the source capsule. Subsequent dosimetry developments, based on Monte Carlo calculations or analytical solutions of transport equations, do not rely on the CPE assumption and determine directly the dose to different tissues. At the time of relating dose to tissue and dose to water, or vice versa, it is usually assumed that the photon fluence in water and in tissues are practically identical, so that the absorbed dose in the two media can be related by their ratio of mass energy-absorption coefficients. In this work, an efficient way to correlate absorbed dose to water and absorbed dose to tissue in brachytherapy calculations at clinically relevant distances for low-energy photon emitting seeds is proposed. A correction is introduced that is based on the ratio of the water-to-tissue photon energy-fluences. State-of-the art Monte Carlo calculations are used to score photon fluence differential in energy in water and in various human tissues (muscle, adipose and bone), which in all cases include a realistic modelling of low-energy brachytherapy sources in order to benchmark the formalism proposed. The energy-fluence based corrections given in this work are able to correlate absorbed dose to tissue and absorbed dose to water with an accuracy better than 0.5% in the most critical cases (e.g. bone tissue).

Monte Carlo studies on water and LiF cavity properties for dose-reporting quantities when using x-ray and brachytherapy sources.

Model-based dose calculation algorithms (MBDCAs) are the current tools to estimate dose in brachytherapy, which takes into account heterogeneous medium, therefore, departing from water-based formalism (TG-43). One aspect associated to MBCDA is the choice of dose specification medium since it offers two possibilities to report dose: (a) dose to medium in medium, D m,m; and (b) dose to water in medium, D w,m. The discussion about the preferable quantity to be reported is underway. The dose conversion factors, DCF, between dose to water in medium, D w,m, and dose to medium in medium, D m,m, is based on cavity theory and can be obtained using different approaches. When experimental dose verification is desired using, for example, thermoluminescent LiF dosimeters, as in in vivo dose measurements, a third quantity is obtained, which is the dose to LiF in medium, D LiF,m. In this case, DCF to convert from D LiF,m to D w,m or D m,m is necessary. The objective of this study is to estimate DCFs using different approaches, present in the literature, quantifying the differences between them. Also, dose in water and LiF cavities in different tissue media and respective conversion factors to be able to convert LiF-based dose measured values into dose in water or tissue were obtained. Simple cylindrical phantoms composed by different tissue equivalent materials (bone, lung, water and adipose) are modelled. The phantoms contain a radiation source and a cavity with 0.002 69 cm3 in size, which is a typical volume of a disc type LiF dosimeter. Three x-rays qualities with average energies ranging from 47 to 250 keV, and three brachytherapy sources, 60Co, 192Ir and 137Cs, are considered. Different cavity theory approaches for DCF calculations and different cavity/medium combinations have been considered in this study. DCF values for water/bone and LiF/bone cases have strong dependence with energy increasing as the photon energy increases. DCF values also increase with energy for LiF/lung and water/lung cases but, they are much less dependent of energy. For LiF/adipose, water/adipose and LiF/water cases, the DCF values are also dependent of photon energy but, decreases as the energy increases. Maximum difference of 12% has been found compared to values in literature.

Validation of a new standardized test method for the freshwater amphipod Hyalella azteca: Determining the chronic effects of silver in sediment.

Environment Canada has developed a new 42-d sediment toxicity test method that includes a reproduction test endpoint with the freshwater amphipod Hyalella azteca. Because of concerns that existing standard methodologies, whereby adults are transferred to a water-only exposure before release of their first brood at day 28, will lead to internal contaminant depuration and loss of sensitivity, the Environment Canada methodology conducts the entire exposure in sediment. To demonstrate applicability of the method for assessing the toxicity of chemical-spiked sediment, H. azteca were exposed for 42 d to sediment amended with silver nitrate (AgNO3 ). Mortality was significantly higher at the highest sediment concentration of Ag (2088 mg/kg dry wt); however, there was no significant reduction in biomass or reproduction as a result of Ag exposure despite significant bioaccumulation. Based on Ag measurements and speciation modeling, the principle route of Ag exposure was likely through the ingestion of complexed colloidal or particulate Ag. The techniques used to recover young amphipods from sediment were critical, and although this effort can be labor intensive (20-45 min/replicate), the technicians demonstrated 91% recovery in blind trials. For the first time, Environment Canada will require laboratories to report their recovery proficiency for the 42-d test-without this information, data will not be accepted. Overall, the reproduction test will be more applicable when only a few chemical concentrations need to be evaluated in laboratory-amended sediments or for field-collected contaminated site assessments (i.e., contaminated site vs reference site comparisons). Environ Toxicol Chem 2016;35:2430-2438. © 2016 SETAC.

Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection.

Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free 'click' chemistry on an anti-fouling surface molecular architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 µL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers.

Scalable DNA-Based Magnetic Nanoparticle Agglutination Assay for Bacterial Detection in Patient Samples.

We demonstrate a nanoparticle-based assay for the detection of bacteria causing urinary tract infections in patient samples with a total assay time of 4 h. This time is significantly shorter than the current gold standard, plate culture, which can take several days depending on the pathogen. The assay is based on padlock probe recognition followed by two cycles of rolling circle amplification (RCA) to form DNA coils corresponding to the target bacterial DNA. The readout of the RCA products is based on optomagnetic measurements of the specific agglutination of DNA-bound magnetic nanoparticles (MNPs) using low-cost optoelectronic components from Blu-ray drives. We implement a detection approach, which relies on the monomerization of the RCA products, the use of the monomers to link and agglutinate two populations of MNPs functionalized with universal nontarget specific detection probes and on the introduction of a magnetic incubation scheme. This enables multiplex detection of Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa at clinically relevant concentrations, demonstrating a factor of 30 improvement in sensitivity compared to previous MNP-based detection schemes. Thanks to the universal probes, the same set of functionalized MNPs can be used to read out products from a multitude of RCA targets, making the approach truly scalable for parallel detection of multiple bacteria in a future integrated point of care molecular diagnostics system.

Quantification of rolling circle amplified DNA using magnetic nanobeads and a Blu-ray optical pick-up unit.

We present the first implementation of a Blu-ray optical pickup unit (OPU) for the high-performance low-cost readout of a homogeneous assay in a multichamber microfluidic disc with a chamber thickness of 600 µm. The assay relies on optical measurements of the dynamics of magnetic nanobeads in an oscillating magnetic field applied along the light propagation direction. The laser light provided by the OPU is transmitted through the sample chamber and reflected back onto the photo detector array of the OPU via a mirror. Spectra of the 2nd harmonic photo detector signal vs. the frequency of the applied magnetic field show a characteristic peak due to freely rotating magnetic nanobeads. Beads bound to ~1 µm coils of DNA formed off-chip by padlock probe recognition and rolling circle amplification show a different dynamics and the intensity of the characteristic peak decreases. We have determined the optimum magnetic bead concentration to 0.1mg/mL and have measured the response vs. concentration of DNA coils formed from Escherichia Coli. We have found a limit of detection of 10 pM and a dynamic range of about two orders of magnitude, which is comparable to the performance obtained using costly and bulky laboratory equipment. The presented device leverages on the advanced but low-cost technology of Blu-ray OPUs to provide a low-cost and high-performance magnetic bead-based readout of homogeneous bioassays. The device is highly flexible and we have demonstrated its use on microfluidic chambers in a disc with a thickness compatible with current optical media mass-production facilities.

Novel readout method for molecular diagnostic assays based on optical measurements of magnetic nanobead dynamics.

We demonstrate detection of DNA coils formed from a Vibrio cholerae DNA target at picomolar concentrations using a novel optomagnetic approach exploiting the dynamic behavior and optical anisotropy of magnetic nanobead (MNB) assemblies. We establish that the complex second harmonic optical transmission spectra of MNB suspensions measured upon application of a weak uniaxial AC magnetic field correlate well with the rotation dynamics of the individual MNBs. Adding a target analyte to the solution leads to the formation of permanent MNB clusters, namely, to the suppression of the dynamic MNB behavior. We prove that the optical transmission spectra are highly sensitive to the formation of permanent MNB clusters and, thereby to the target analyte concentration. As a specific clinically relevant diagnostic case, we detect DNA coils formed via padlock probe recognition and isothermal rolling circle amplification and benchmark against a commercial equipment. The results demonstrate the fast optomagnetic readout of rolling circle products from bacterial DNA utilizing the dynamic properties of MNBs in a miniaturized and low-cost platform requiring only a transparent window in the chip.

Validation of a structured interview for telephone assessment of the modified Rankin Scale in Brazilian stroke patients.

BACKGROUND: The modified Rankin Scale (mRS) is a commonly used scale to assess the functional outcome after stroke. Several studies on mRS showed good reliability, feasibility, and interrater agreement of this scale using a face-to-face assessment. However, telephone assessment is a more time-efficient way to obtain an mRS grade than a face-to-face interview. The aim of this study was to validate the telephone assessment of mRS among the Portuguese using a structured interview in a sample of Brazilian stroke patients. METHODS: We evaluated 50 stroke outpatients twice. The first interview was face-to-face and the second was made by telephone and the time between the two assessments ranged between 7 and 14 days. Four certified raters evaluated the patients using a structured interview based on a questionnaire previously published in the literature. Raters were blinded for the Rankin score given by the other rater. For both assessments, the rater could also interview a caregiver if necessary. RESULTS: The patients' mean age was 62.8 ± 14.7, mean number of years of study 5.2 ± 3.4, 52% were males, 55.2% of patients needed a caregiver's help to answer the questions. The majority of caregivers were female (85%), mean age 49.1 ± 15, and mean number of years of study 8.3 ± 3.4. Perfect agreement between the telephone and face-to-face assessments was obtained for 27 (54%) patients, corresponding to an unweighted Kappa of 0.44 (95% CI 0.27-0.61) and a weighted Kappa of 0.89. The median of telephone assessment mRS was 3.5 (interquartile range = 2-4) and of face-to-face assessment was 4 (interquartile range = 2-5). There was no difference between the two assessments (Wilcoxon test, p = 0.35). CONCLUSIONS: Despite the low education level of our sample, the telephone assessment of functional impairment of stroke patients using a translated and culturally adapted Brazilian Portuguese version of the mRS showed good validity and reliability. Therefore, the telephone assessment of mRS can be used in clinical practice and scientific studies in Brazil.

A medical image-based graphical platform -- features, applications and relevance for brachytherapy.

PURPOSE: Brachytherapy dose calculation is commonly performed using the Task Group-No 43 Report-Updated protocol (TG-43U1) formalism. Recently, a more accurate approach has been proposed that can handle tissue composition, tissue density, body shape, applicator geometry, and dose reporting either in media or water. Some model-based dose calculation algorithms are based on Monte Carlo (MC) simulations. This work presents a software platform capable of processing medical images and treatment plans, and preparing the required input data for MC simulations. METHODS AND MATERIALS: The A Medical Image-based Graphical platfOrm-Brachytherapy module (AMIGOBrachy) is a user interface, coupled to the MCNP6 MC code, for absorbed dose calculations. The AMIGOBrachy was first validated in water for a high-dose-rate (192)Ir source. Next, dose distributions were validated in uniform phantoms consisting of different materials. Finally, dose distributions were obtained in patient geometries. Results were compared against a treatment planning system including a linear Boltzmann transport equation (LBTE) solver capable of handling nonwater heterogeneities. RESULTS: The TG-43U1 source parameters are in good agreement with literature with more than 90% of anisotropy values within 1%. No significant dependence on the tissue composition was observed comparing MC results against an LBTE solver. Clinical cases showed differences up to 25%, when comparing MC results against TG-43U1. About 92% of the voxels exhibited dose differences lower than 2% when comparing MC results against an LBTE solver. CONCLUSION: The AMIGOBrachy can improve the accuracy of the TG-43U1 dose calculation by using a more accurate MC dose calculation algorithm. The AMIGOBrachy can be incorporated in clinical practice via a user-friendly graphical interface.

Lead toxicity to Lemna minor predicted using a metal speciation chemistry approach.

In the present study, predictive measures for Pb toxicity and Lemna minor were developed from bioassays with 7 surface waters having varied chemistries (0.5-12.5 mg/L dissolved organic carbon, pH of 5.4-8.3, and water hardness of 8-266 mg/L CaCO3 ). As expected based on water quality, 10%, 20%, and 50% inhibitory concentration (IC10, IC20, and IC50, respectively) values expressed as percent net root elongation (%NRE) varied widely (e.g., IC20s ranging from 306 nM to >6920 nM total dissolved Pb), with unbounded values limited by Pb solubility. In considering chemical speciation, %NRE variability was better explained when both Pb hydroxides and the free lead ion were defined as bioavailable (i.e., f{OH} ) and colloidal Fe(III)(OH)3 precipitates were permitted to form and sorb metals (using FeOx as the binding phase). Although cause and effect could not be established because of covariance with alkalinity (p = 0.08), water hardness correlated strongly (r(2) = 0.998, p < 0.0001) with the concentration of total Pb in true solution ([Pb]T_True solution ). Using these correlations as the basis for predictions (i.e., [Pb]T_True solution vs water hardness and %NRE vs f{OH} ), IC20 and IC50 values produced were within a factor of 2.9 times and 2.2 times those measured, respectively. The results provide much needed effect data for L. minor and highlight the importance of chemical speciation in Pb-based risk assessments for aquatic macrophytes.

Defying standard criteria for digital replantation: A case series.

INTRODUCTION: There is much controversy regarding the current indications and contraindications for digital replantation. PRESENTATION OF CASE: Three patients with absolute contraindications for digital replantation according to classical criteria are presented (Case 1: multilevel amputation of the hand and fingers; Case 3: avulsion of the thumb; Case 4: index amputation proximal to the insertion of the flexor digitorum superficialis). In addition a patient with a very distal digital amputation (Case 2), whose indication for replantation is controversial is also presented. In all cases, the patients were replanted and showed good functional and aesthetical results. DISCUSSION: Most authors advocate that the classical indications for replantation have been validated by experience, are predicated on the potential for long-term function, and should be followed in most if not all cases. However, some surgeons have been adopting a more liberal attitude with good results. CONCLUSION: The clinical cases presented in this paper suggest that the standard criteria for digital replantation should not be followed rigidly but instead should be regarded as a general guide.

Copper toxicity to Lemna minor modelled using humic acid as a surrogate for the plant root.

Humic acids are chemically analogous to plant root cell walls in that their surface sites are principally comprised of carboxylic and phenolic acids which bind both metals and protons. Based on this analogy, we developed a biotic-ligand type of model to predict Cu toxicity to Lemna minor, using particulate humic acid (HA(part)) of the Windermere Humic Aqueous Model (WHAM), and 7d static-renewal exposures with five surface waters and one nutrient media which varied in DOC (1-10 mg L(-1)), pH (6.9-8.7), and water hardness (35-236 mg equivalent CaCO(3)L(-1)). Although the range of waters tested resulted in a 36-fold variation in 50% inhibitory concentration (IC50) values, the calculated concentration of Cu bound to HA(part) using this framework was highly correlated with pooled percent net root elongation (%NRE) (R(2)=0.95). Ten and fifty percent IC values based on [Cu-HA(part)] were additionally within a factor of ±1.5 and ±1.4, respectively, inclusive of 95% confidence limits. This model construct, which defines the free metal ion and the first hydrolysis product (but not metal carbonate complexes) as being bioavailable, provides an alternative means of defining the binding surface in bioavailability models, whereby a heterogeneous mixture of ligands collectively influence root-metal sorption and toxicity.

Avaliação da qualidade de vida em pacientes com infertilidade / Evaluation of quality of life in patients with infertility

Trata de um estudo transversal controlado, não intervencionista, realizado no ambulatório de infertilidade no Hospital Fêmina. Foram selecionadas pacientes provenientes do ambulatório de planejamento familiar que estavam buscando ligadura tubária. A escolha do grupo se deu por serem pacientes com prole já constituída, que estão buscando a esterilização, configurando, portanto num momento de vida oposto às pacientes com infertilidade. Foram incluídas pacientes com diagnóstico de infertilidade e pacientes que consultavam para a realização de ligadura tubária, com idade variando entre 19 e 45 anos. 67 pacientes aceitaram participar do estudo. Este estudo não demonstrou diferença na avaliação da qualidade de vida entre o grupo de infertilidade e o grupo controle. Pode-se concluir que as populações estudadas não apresentam diferenças quanto à qualidade de vida, depressão e ansiedade (AU)