Search

Background: Potential risk associated with low‐dose radiation exposures is often expressed using the effective dose (E) quantity. Other risk‐related quantities have been proposed as alternatives. The recently introduced risk index (RI) shares similarities with E but expands the metric to incorporate medical imaging‐appropriate risks factors including patient‐specific size, age, and sex. Purpose: The aim of this work is to examine the RI metric for quantifying stochastic radiation risk and demonstrate its applications in nuclear imaging. The advantages in this improved metric may help the field progress toward stratified risk consideration in the course of patient management, improve efforts for procedure optimization, and support an evolution in the science of radiation risk assessment. Methods: In this study we describe, implement, and calculate RI for various diagnostic nuclear imaging scenarios using reference biokinetics published in ICRP Publication 128 for commonly utilized radiopharmaceuticals. All absorbed dose, E and RI calculations were performed using the freely available MIRDcalc nuclear medicine dosimetry software; the organ specific risk parameters used in the software are also benchmarked in this text. The resulting RI and E values are compared and various trends in RI values identified. Results: E and RI coefficients were calculated for 3016 use cases. Notably RI values vary depending on patient characteristics. Overall, across the population, global trends in RI values can be identified. In general, RI values were 2.15 times higher for females than males, due to higher risk coefficients and activities being distributed in smaller reference masses. The pediatric patients showed higher RIs than adults, as younger patients generally receive higher absorbed doses per administered activity, and are more radiosensitive, and have a longer projected lifespan at risk. A compendium of E and RI values is also provided in table format to serve as a reference for the community. Conclusions: RI is a rational quantity that could be used for justification, risk communication and protocol optimization in medical imaging. It has some advantages when compared to the long‐utilized E value with respect to personalization, since accounts for patient size, age, sex, and natural incidence of cancer risk. [ABSTRACT FROM AUTHOR]

It is urgent yet challenging to develop new environmentally friendly and cost-effective sources of energy. Molecular solar thermal (MOST) systems for energy capture and storage are a promising option. With this in mind, we have prepared a new water-soluble (pH > 6) norbornadiene derivative (HNBD1) whose MOST properties are reported here. HNBD1 shows a better matching to the solar spectrum compared to unmodified norbornadiene, with an onset absorbance of λonset = 364 nm. The corresponding quadricyclane photoisomer (HQC1) is quantitatively generated through the light irradiation of HNBD1. In an alkaline aqueous solution, the MOST system consists of the NBD1−/QC1− pair of deprotonated species. QC1− is very stable toward thermal back-conversion to NBD1−; it is absolutely stable at 298 K for three months and shows a marked resistance to temperature increase (half-life t½ = 587 h at 371 K). Yet, it rapidly (t½ = 11 min) releases the stored energy in the presence of the Co(II) porphyrin catalyst Co-TPPC (ΔHstorage = 65(2) kJ∙mol−1). Under the explored conditions, Co-TPPC maintains its catalytic activity for at least 200 turnovers. These results are very promising for the creation of MOST systems that work in water, a very interesting solvent for environmental sustainability, and offer a strong incentive to continue research towards this goal. [ABSTRACT FROM AUTHOR]

This work presents a comparative study of two continuous flow reaction systems for the synthesis of propylene carbonate (PC) from CO2 and propylene oxide (PO). The reaction systems in continuous flow consist of a flow tubular reactor and a Robinson-Mahoney (RM) isothermal packed bed reactor in homogeneous regime. The formulation of the synthesized catalyst had KI as the active phase on a support of aluminum oxy-hydroxide, activated carbon, sodium dihydrogen sulfate, nitric acid and poly (vinyl alcohol); the mixture of materials was spheronized to improve its mechanical and workability properties. The results revealed that the reaction followed a catalyst deactivation pattern, since the yield under heterogeneous regime dropped for both reaction systems after the first 4 h of operation; however, the overall performance of the RM reactor, determined by Total Dynamic Performance (TDP) measurements, turned out to be 5 times higher than that of the tubular reactor. The RM reactor was then used in a mixed heterogeneous/homogeneous operation, thus keeping a sustained yield and selectivity of about 90 and 84%, respectively, for the total evaluation time (50 h) after adjusting to homogeneous regime. The mixed operation proposal using the RM reactor ensured the correct distribution of reagents and catalyst, along with the additional benefits of using a three-phase reactor system. In addition, the continuous flow operation allowed to maintain high performance and selectivity rates, enabling to continue the next stages of the scaling-up process. [ABSTRACT FROM AUTHOR]

Na+/K+-ATPase is an essential transmembrane enzyme found in all mammalian cells with critical functions for cell ion homeostasis. The inhibition of this enzyme by several cardiotonic steroids (CTS) has been associated with the cytotoxic effect on cancer cell lines of phytochemicals such as ouabain and digitoxin. This study evaluated the inhibitory capacity of cardenolides calotropin and corotoxigenin 3-O-glucopyranoside (C3OG) from Asclepias subulata over the Na+/K+-ATPase activity in vitro and silico. The inhibitory assays showed that calotropin and C3OG decreased the Na+/K+-ATPase activity with IC50 values of 0.27 and 0.87 mM, respectively. Furthermore, the molecules presented an uncompetitive inhibition on Na+/K+-ATPase activity, with Ki values of 0.2 mMto calotropin and 0.5 mMto C3OG. Furthermore, the molecular modeling indicated that calotropin and C3OG might interact with the Thr797 and Gln111 residues, considered essential to the interaction with the Na+/K+-ATPase. Besides, these cardenolides can interact with amino acid residues such as Phe783, Leu125, and Ala323, to establish hydrophobic interactions on the binding site. Considering the results, these provide novel evidence about the mechanism of action of cardenolides from A. subulata, proposing that C3OG is a novel cardenolide that deserves further consideration for in vitro cellular antiproliferative assays and in vivo studies as an anticancer molecule. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37–0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p = 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR = 100%, n = 8; complete response 62.5%) compared to chemotherapy (OR = 33.3%, n = 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is a multifocal low-grade vascular neoplasm that can affect the skin, mucus membranes, visceral organs, and lymph nodes. KS can also affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis. In this review, the manifestations of ocular KS are discussed along with theories for pathogenesis, common risk factors, and management options. KS is caused by the oncogenic human herpesvirus 8 (HHV8). Immunosuppression in patients with HIV and AIDS contributes to the development of KS but conjunctival and ocular adnexal KS lesions are now uncommon in the era of anti-retroviral therapy. A high index of suspicion is required to diagnose ocular KS as these lesions can be mistaken for alternative entities. Prompt diagnosis can reduce significant morbidity and mortality by prompting a multidisciplinary systemic evaluation, particularly in immunosuppressed individuals. While surgical excision, cryotherapy, intralesional or systemic chemotherapy, and radiation are all viable treatment options, ongoing research to identify novel therapies and molecular treatment targets will help expand the armamentarium of therapeutics available for this disease. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to quantitatively compare five commercial dosimetric software platforms based on the analysis of clinical datasets of patients who benefited from peptide receptor radionuclide therapy (PRRT) with 177Lu‐DOTATATE (LUTATHERA®). Methods: The dosimetric analysis was performed on two patients during two cycles of PRRT with 177Lu. Single photon emission computed tomography/computed tomography images were acquired at 4, 24, 72, and 192 h post injection. Reconstructed images were generated using Dosimetry Toolkit® (DTK) from Xeleris™ and HybridRecon‐Oncology version_1.3_Dicom (HROD) from HERMES. Reconstructed images using DTK were analyzed using the same software to calculate time‐integrated activity coefficients (TIAC), and mean absorbed doses were estimated using OLINDA/EXM V1.0 with mass correction. Reconstructed images from HROD were uploaded into PLANET® OncoDose from DOSIsoft, STRATOS from Phillips, Hybrid Dosimetry Module™ from HERMES, and SurePlan™ MRT from MIM. Organ masses, TIACs, and mean absorbed doses were calculated from each application using their recommendations. Results: The majority of organ mass estimates varied by <9.5% between all platforms. The highest variability for TIAC results between platforms was seen for the kidneys (28.2%) for the two patients and the two treatment cycles. Relative standard deviations in mean absorbed doses were slightly higher compared with those observed for TIAC, but remained of the same order of magnitude between all platforms. Conclusions: When applying a similar processing approach, results obtained were of the same order of magnitude regardless of the platforms used. However, the comparison of the performances of currently available platforms is still difficult as they do not all address the same parts of the dosimetric analysis workflow. In addition, the way in which data are handled in each part of the chain from data acquisition to absorbed doses may be different, which complicates the comparison exercise. Therefore, the dissemination of commercial solutions for absorbed dose calculation calls for the development of tools and standards allowing for the comparison of the performances between dosimetric software platforms. [ABSTRACT FROM AUTHOR]

This article presents a 5-GS/s 12-b passive-sampling $8\times $ -interleaved hybrid analog-to-digital converter (ADC) that achieves a low-frequency SFDR/SNDR of 75.2/62.4 dB and a Nyquist SFDR/SNDR of 65.4/58.5 dB. A significant power reduction while attaining a bandwidth in excess of 6 GHz and a high spectral purity are enabled by: 1) an on-chip terminated very fast settling buffer-less input front end; 2) an on-chip clock chain with as low as 11-fs added jitter; 3) an asynchronous three-stage pipelined-successive approximation register (SAR) sub-ADC; and 4) on-chip co-designed analog–digital calibrations deal with sub-ADC and time-interleaving (TI) artifacts to achieve the desired spectral performance levels. The 28-nm bulk CMOS prototype chip occupies a total area of 4.56 mm2 with a core area of 1.76 mm2 and consumes 158.6 mW from a 1-V supply, leading to the Nyquist figure of merits of Schreier (FoMS) and Walden (FoMW) of 160.5 dB and 46.1 fJ/conversion step, respectively. [ABSTRACT FROM AUTHOR]

In the last decades, the numerical studies on hemodynamics have become a valuable explorative scientific tool. The very first studies were done over idealized geometries, but as numerical methods and the power of computers have become more affordable, the studies tend to be patient specific. We apply the study to the numerical analysis of tumor‐targeting during liver radioembolization (RE). RE is a treatment for liver cancer, and is performed by injecting radiolabeled microspheres via a catheter placed in the hepatic artery. The objective of the procedure is to maximize the release of radiolabeled microspheres into the tumor and avoid a healthy tissue damage. Idealized virtual arteries can serve as a generalist approach that permits to separately analyze the effect of a variable in the microsphere distribution with respect to others. However, it is important to use proper physiological boundary conditions (BCs). It is not obvious, the need to account for the effect of tortuosity when using an idealized virtual artery. We study the use of idealized geometry of a hepatic artery as a valid research tool, exploring the importance of using realistic spiral‐flow inflow BC. By using a literature‐based cancer scenario, we vary two parameters to analyze the microsphere distribution through the outlets of the geometry. The parameters varied are the type of microspheres injected and the microsphere injection velocity. The results with realistic inlet velocity profile showed that the particle distribution in the liver segments is not affected by the analyzed injection velocity values neither by the particle density. Novelty Statement In this article, we assessed the use of idealized geometries as a valid research tool and applied the use of an idealized geometry to the case of an idealized hepatic artery to study the particle‐hemodynamics during radioembolization (RE). We studied three different inflow boundary conditions (BCs) to assess the usefulness of the geometry, two types of particle injection velocities and two types of commercially available microspheres for RE treatment. In recent years, the advent in computational resources allowed for more detailed patient‐specific geometry generation and discretization and hemodynamics simulations. However, general studies based on idealized geometries can be performed in order to provide medical doctors with some basic and general guidelines when using a given catheter for a given cancer scenario. Moreover, using an idealized geometry can be a reasonable approach which allows us to isolate a given parameter and control other parameters, so that parameters can be independently assessed. Even though an idealized geometry does not match any patient's geometry, the use of an idealized geometry can be valid when drawing general conclusions that may be useful in patient‐specific cases. However, we believe that even if an idealized hepatic artery geometry is used for the study, it is necessary to account for the upstream and downstream tortuosity of vessels through the BCs. In this work, we highlighted the need of modeling the tortuosity of upstream and downstream vasculatures through the BCs. [ABSTRACT FROM AUTHOR]

During the iodoetherification of chiral and conformationally restricted 3-butenyl carbinols to give 2,5-disubstituted THFs, the presence of an ester in the side chain exerts a profound effect on the chemo- and diastereoselectivity of the reaction. When submitted to standard iodoetherification conditions, ester-containing substrates gave diastereomeric mixtures of THFs, together with variable amounts of iodohydrins. Conversely, when the ester group was reduced to an alcohol or ether, the corresponding trans-THFs were obtained more quickly, with complete diastereoselectivity and without contamination by the iodohydrin. In this paper, the mechanistic details of the iodoetherification of protected 3-butenyl carbinols are revealed. The results show that the carbonyl group decreases the nucleophilicity of the acetonide oxygen atoms, and stabilizes the reactants by a carbonyl-iodonium through-space interaction. Additionally, it promotes the formation of a stable seven-membered-ring carboxonium intermediate, causing an increase in the activation barriers and a decrease in the reaction diastereoselectivity compared to the non-ester analogues. [ABSTRACT FROM AUTHOR]

Three water-soluble Ru(II) chiral heteroleptic coordination compounds [Ru(en)(pdto)]Cl2 (1), [Ru(gly)(pdto)]Cl (2), and [Ru(acac)(pdto)]Cl (3), where pdto = 2,2′-[1,2-ethanediylbis-(sulfanediyl-2,1-ethanediyl)]dipyridine, en = ethylendiamine, gly = glycinate, and acac = acetylacetonate, have been synthezised and fully characterized. The crystal structures of compounds 1-3 are described. The IC50 values for compounds 1-3 are within nanomolar range (14, 12, and 6 nM, respectively). The cytotoxicity for human peripheral blood lymphocytes is extremely low (>100 μM). Selectivity indexes for Ru(II) compounds are in the range 700-1300. Trophozoites exposed to Ru(II) compounds die through an apoptotic pathway triggered by ROS production. The orally administration to infected mice induces a total elimination of the parasite charge in mice faeces 1-2-fold faster than metronidazole. Besides, all compounds inhibit the trophozoite proliferation in amoebic liver abscess induced in hamster. All our results lead us to propose these compounds as promising candidates as antiparasitic agents. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most commonly diagnosed dementia, where signs of neuroinflammation and oxidative stress are prominent. In this study we intend to further characterize the roles of the antioxidant, anti-inflammatory, and heavy metal binding protein, metallothionein-1 (MT-1), by crossing Mt1 overexpressing mice with a well-known mouse model of AD, Tg2576 mice, which express the human amyloid-β protein precursor (hAβPP) with the Swedish K670N/M671L mutations. Mt1 overexpression increased overall perinatal survival, but did not affect significantly hAβPP-induced mortality and weight loss in adult mice. Amyloid plaque burden in ∼14-month-old mice was increased by Mt1 overexpression in the hippocampus but not the cortex. Despite full length hAβPP levels and amyloid plaques being increased by Mt1 overexpression in the hippocampus of both sexes, oligomeric and monomeric forms of Aβ, which may contribute more to toxicity, were decreased in the hippocampus of females and increased in males. Several behavioral traits such as exploration, anxiety, and learning were altered in Tg2576 mice to various degrees depending on the age and the sex. Mt1 overexpression ameliorated the effects of hAβPP on exploration in young females, and potentiated those on anxiety in old males, and seemed to improve the rate of spatial learning (Morris water maze) and the learning elicited by a classical conditioning procedure (eye-blink test). These results clearly suggest that MT-1 may be involved in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Although glycogen is the only carbohydrate reserve of the brain, its overall contribution to brain functions remains unclear. It has been proposed that glycogen participates in the preservation of such functions during hypoxia. Several reports also describe a relationship between brain glycogen and susceptibility to epilepsy. To address these issues, we used our brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse to study the functional consequences of glycogen depletion in the brain under hypoxic conditions and susceptibility to epilepsy. GYS1Nestin-KO mice presented significantly different power spectra of hippocampal local field potentials (LFPs) than controls under hypoxic conditions. In addition, they showed greater excitability than controls for paired-pulse facilitation evoked at the hippocampal CA3-CA1 synapse during experimentally induced hypoxia, thereby suggesting a compensatory switch to presynaptic mechanisms. Furthermore, GYS1Nestin-KO mice showed greater susceptibility to hippocampal seizures and myoclonus following the administration of kainate and/or a brief train stimulation of Schaffer collaterals. We conclude that brain glycogen could play a protective role both in hypoxic situations and in the prevention of brain seizures. [ABSTRACT FROM AUTHOR]

A simple and inexpensive solution-based method to grow functional and continuous nano-crystalline CdS thin films is demonstrated. The resulting CdS films are used to fabricate n-type thin film transistors (TFTs) with field effect mobility as high as ∼0.55 cm2 V−1 s−1, a threshold voltage (VT) of ∼8.4 V, and an on/off current ratio of 106. This method utilizes a solid-state reaction at low temperature that eliminates the need for nanoparticle synthesis to fabricate the semiconducting layer in the TFTs. The method also promotes efficient usage of the chemical precursors, which further reduces the cost of the process. This is a promising method that could be easily implemented in a manufacturable process such as roll-to-roll. [ABSTRACT FROM AUTHOR]

The cerebellum in transgenic mice expressing pseudorabies virus immediate-early protein IE180 (TgIE96) was substantially diminished in size, and its histoarchitecture was severely disorganized, resulting in severe ataxia. TgIE96 mice can therefore be used as an experimental model to study the involvement of cerebellar circuits in different learning tasks. The performance of three-month-old TgIE96 mice was studied in various behavioral tests, including associative learning (classical eyeblink conditioning), object recognition, spatial orientation (water maze), startle response and prepulse inhibition, and passive avoidance, and compared with that of wild-type mice. Wild-type and TgIE96 mice presented similar reflexively evoked eyeblinks, and acquired classical conditioned eyelid responses with similar learning curves for both trace and delay conditioning paradigms. The two groups of mice also had similar performances during the object recognition test. However, they showed significant differences for the other three tests included in this study. Although both groups of animals were capable of swimming, TgIE96 mice failed to learn the water maze task during the allowed time. The startle response to a severe tone was similar in both control and TgIE96 mice, but the latter were unable to produce a significant prepulse inhibition. TgIE96 mice also presented evident deficits for the proper accomplishment of a passive avoidance test. These results suggest that the cerebellum is not indispensable for the performance of classical eyeblink conditioning and for object recognition tasks, but seems to be necessary for the proper performance of water maze, prepulse inhibition, and passive avoidance tests. [ABSTRACT FROM AUTHOR]