ABSTRACT
Organometallic molecules are promising for molecular electronic devices due to their potential to improve electrical conductance through access to complex orbital covalency that is not available to light-element organic molecules. However, studies of the formation of organometallic monolayers and their charge transport properties are scarce. Here, we report the cluster formation and charge transport properties of gold-triarylbismuthane-gold molecular junctions. We found that triarylbismuthane molecules with -CN anchoring groups form clusters during the creation of self-assembled submonolayers. This clustering is attributed to strong interactions between the bismuth (Bi) center and the nitrogen atom in the -CN group of adjacent molecules. Examination of the influence of -NH2 and -CN anchoring groups on junction conductance revealed that, despite a stronger binding energy between the -NH2 group and gold, the conductance per molecular unit (i.e., molecule for the -NH2 group and cluster for the -CN group) is higher with the -CN anchoring group. Further analysis showed that an increase in the number of -CN groups from one to three within the junctions leads to a decrease in conductance while increasing the size of the cluster. This demonstrates the significant effects of different anchoring groups and the impact of varying the number of -CN groups on both the charge transport and cluster formation. This study highlights the importance of selecting the appropriate anchoring group in the design of molecular junctions. Additionally, controlling the size and formation of clusters can be a strategic approach to engineering charge transport in molecular junctions.
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Background Diabetes mellitus and cancer are two associated chronic diseases. Despite being a widely researched topic, the underlying mechanisms of this association remain unclear. One of the poorly explored topics regarding diabetes and cancer is the relation between the age of cancer onset and diabetes mellitus status; therefore, this research exposes the difference in the age of cancer diagnosis in both groups. Methods We conducted a retrospective study by reviewing the clinical files on a secondary care hospital's database. Files from first-time consultations of patients over 18 diagnosed using a histopathological report were included. The present study aimed to determine whether there is a difference in age at the onset of cancer in diabetic and non-diabetic individuals. Moreover, we calculated the average BMI at the onset for both populations. Results Our study included 8,741 patients; 1,551 (17.8%) were diabetic, and 7,190 (82.2%) were non-diabetic. From 28 types of cancer, 27 showed a difference in the age at the onset of cancer when diabetic and non-diabetic subjects were compared. This difference is significant as it suggests a potential link between diabetes and cancer, which could have implications for early detection and prevention strategies. Out of the 27 types, 17 showed statistical significance with p-values ranging from 0.048 to <0.0001 considering a 95% CI. Among those, the most significant types of cancer were breast, cervical, lung, ovarian, rectal, thyroid, and sarcoma, reporting p-values <0.0001. The mean age at onset of cancer in diabetic and non-diabetic populations was 62.7 years (SD ± 3.9) and 55.3 years (SD ± 7.9), respectively, showing a difference of 7.4 years in both groups. The BMI was statistically significant in patients with breast (p = 0.006), endometrial (p = 0.007), head and neck (p=0.014), and thyroid (p = 0.022) cancer types. Conclusion The data offer a critical view of the relationship between cancer and diabetes. Since virtually no one has produced a similar report, there is a broad field for researching the causal factors implicated in the pathway of diabetic and non-diabetic individuals who develop cancer. Research regarding metformin, diabetic neuropathy, and other possible causes must be addressed to determine whether they are involved in this process.
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Physics-based modeling methods have the potential to investigate the mechanical factors associated with knee osteoarthritis (OA) and predict the future radiographic condition of the joint. However, it remains unclear what level of detail is optimal in these methods to achieve accurate prediction results in cohort studies. In this work, we extended a template-based finite element (FE) method to include the lateral and medial compartments of the tibiofemoral joint and simulated the mechanical responses of 97 knees under three conditions of gait loading. Furthermore, the effects of variations in cartilage thickness and failure equation on predicted cartilage degeneration were investigated. Our results showed that using neural network-based estimations of peak knee loading provided classification performances of 0.70 (AUC, p < 0.05) in distinguishing between knees that developed severe OA or mild OA and knees that did not develop OA eight years after a healthy radiographic baseline. However, FE models incorporating subject-specific femoral and tibial cartilage thickness did not improve this classification performance, suggesting there exists an optimal point between personalized loading and geometry for discrimination purposes. In summary, we proposed a modeling framework that streamlines the rapid generation of individualized knee models achieving promising classification performance while avoiding motion capture and cartilage image segmentation.
Subject(s)
Finite Element Analysis , Knee Joint , Neural Networks, Computer , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/classification , Female , Male , Middle Aged , Knee Joint/diagnostic imaging , Knee Joint/physiopathology , Aged , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/physiopathology , Models, Biological , Weight-Bearing , Gait/physiologyABSTRACT
Azobenzenes are fascinating molecular machines that can reversibly transform between two isomeric forms by an external stimulus. Diazocine, a type of bridged azobenzene, has been shown to possess enhanced photoexcitation properties. Due to the distortion caused by the ethyl bridge in the E-isomer, the Z-form becomes the thermodynamically stable configuration. Despite a comprehensive understanding of its photophysical properties, there is still much to learn about the behavior of diazocine on a metal surface. Here we show the operando photoswitching of diazocine molecules deposited directly on a Au(111) surface using scanning tunneling microscopy. Molecules were shown to aggregate into disordered islands with edge sites being susceptible to photon-induced movement. A few molecules were shown to undergo directional movement under UV irradiation with the motion reversed under blue light exposure. These findings contribute new insight into the activity of single and ensemble molecular systems toward purposefully guided motion.
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Guadua angustifolia is a bamboo species that has been used in construction since it is an excellent sustainable material. However, it creeps under sustained loading, modifying the structural behavior of culms and joints. Thus, this study was aimed at describing the creep behavior of Guadua on the transverse plane. To this end, 60 Guadua rings were submitted to a diametric compression load by means of steel blocks, while the diametric displacement was measured over time. In tests conducted for up to 90 days, the displacements did not reach a stationary value. A high degree of deformation over time was measured, which was about 2-3 times that reported for bamboo creep under axial bending. The data were successfully fitted to a generalized Maxwell model and a Burgers model. Model parameters were not significantly different when being fitted at 30, 50, 60, and 90 days, suggesting that parameters of viscoelastic models to represent bamboo creep on the transverse plane can be captured with tests lasting 30 days. Eleven rings failed at a stress level of 3.64 MPa (Coefficient of variation CV = 0.22) and a strain level of 0.0373 (CV = 0.20) which are 39% lower and 78% higher than the failure stress and strain, respectively, obtained in static control tests. The substantial creep on the transverse plane indicates that the stiffness and capacity of some types of bamboo joints may be drastically reduced over time. Fitted parameters may be used in theoretical models to assess the performance of bamboo elements and joints under transverse loading over time.
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We sought to explore the intrafamilial communication and cascade genetic testing (CGT) experiences of patients with hereditary cancer from diverse, medically underserved populations and their relatives. Participants included patients receiving oncology care at an urban, safety net hospital in Texas or comprehensive cancer center in Alabama and their first-degree relatives. In-depth semi-structured qualitative interviews were completed wherein patients shared their experiences with genetic counseling (GC), genetic testing (GT), and communicating their results to relatives. Relatives shared their experiences receiving information from the patient and considering CGT. Interviews were transcribed, coded, and themes were identified. Of 25 participating patients, most recalled key aspects of GC and their GT results. Most (80%) patients shared their results with relatives, but only some relatives underwent CGT; patients reported low perceived susceptibility to hereditary cancer as a common barrier to CGT for their relatives. Of 16 participating relatives, most reported feeling distress upon learning the patient's GT results. Relatives were fearful of learning their own CGT results but identified prevention and early detection as CGT benefits. Interviews identified opportunities during family communication to improve relatives' perceived susceptibility to hereditary cancer. Tailored resources may support patients and relatives experiencing distress and fear during GT. PREVENTION RELEVANCE: This study of intrafamilial communication and cascade genetic testing experiences of patients with hereditary cancer and their relatives from diverse, medically underserved populations identified relatives' perceived susceptibility to hereditary cancer risks, distress, and fear as frequent reactions and barriers to testing. These results may inform future hereditary cancer prevention efforts.
Subject(s)
Medically Underserved Area , Neoplasms , Humans , Genetic Testing , Communication , Genetic Counseling , Neoplasms/diagnosis , Neoplasms/genetics , Genetic Predisposition to DiseaseABSTRACT
Photochromic molecules can undergo a reversible conversion between two isomeric forms upon exposure to external stimuli such as electromagnetic radiation. A significant physical transformation accompanying the photoisomerization process defines them as photoswitches, with potential applications in various molecular electronic devices. As such, a detailed understanding of the photoisomerization process on surfaces and the influence of the local chemical environment on switching efficiency is essential. Herein, we use scanning tunneling microscopy to observe the photoisomerization of 4-(phenylazo)benzoic acid (PABA) assembled on Au(111) in kinetically constrained metastable states guided by pulse deposition. Photoswitching is observed at low molecular density and is absent in tight-packed islands. Furthermore, switching events were noted in PABA molecules coadsorbed in a host octanethiol monolayer, suggesting an influence of the surrounding chemical environment on photoswitching efficiency.
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Computational models can be used to predict the onset and progression of knee osteoarthritis. Ensuring the transferability of these approaches among computational frameworks is urgent for their reliability. In this work, we assessed the transferability of a template-based modeling strategy, based on the finite element (FE) method, by implementing it on two different FE softwares and comparing their results and conclusions. For that, we simulated the knee joint cartilage biomechanics of 154 knees using healthy baseline conditions and predicted the degeneration that occurred after 8 years of follow-up. For comparisons, we grouped the knees using their Kellgren-Lawrence grade at the 8-year follow-up time and the simulated volume of cartilage tissue that exceeded age-dependent thresholds of maximum principal stress. We considered the medial compartment of the knee in the FE models and used ABAQUS and FEBio FE softwares for simulations. The two FE softwares detected different volumes of overstressed tissue in corresponding knee samples (p < 0.01). However, both programs correctly distinguished between the joints that remained healthy and those that developed severe osteoarthritis after the follow-up (AUC = 0.73). These results indicate that different software implementations of a template-based modeling method similarly classify future knee osteoarthritis grades, motivating further evaluations using simpler cartilage constitutive models and additional studies on the reproducibility of these modeling strategies.
Subject(s)
Cartilage, Articular , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/diagnosis , Reproducibility of Results , Knee Joint , Biomechanical Phenomena , Magnetic Resonance Imaging/methodsABSTRACT
We developed a novel knee joint model in FEBio to simulate walking. Knee cartilage was modeled using a fibril-reinforced biphasic (FRB) formulation with depth-wise collagen architecture and split-lines to account for cartilage structure. Under axial compression, the knee model with FRB cartilage yielded contact pressures, similar to reported experimental data. Furthermore, gait analysis with FRB cartilage simulated spatial and temporal trends in cartilage fluid pressures, stresses, and strains, comparable to those of a fibril-reinforced poroviscoelastic (FRPVE) material in Abaqus. This knee joint model in FEBio could be used for further studies of knee disorders using physiologically relevant loading.
Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Cartilage, Articular/physiology , Finite Element Analysis , Knee Joint/physiology , Gait/physiology , Stress, Mechanical , Models, Biological , Biomechanical PhenomenaABSTRACT
Festuca arundinacea Schreb. is a widely used type of forage due to its great ecological breadth and adaptability. An agricultural intervention that improves the selenium content in cultivated plants has been defined as bio-fortification, a complementary strategy to improve human and non-human animals' nutrition. The advancement of science has led to an increased number of studies based on nanotechnologies, such as the development of nanoparticles (NPs) and their application in crop plants. Studies show that NPs have different physicochemical properties compared to bulk materials. The objectives of this study were (1) to determine the behavior of F. arundinacea Schreb. plants cultivated with Se nanoparticles, (2) to identify the specific behavior of the agronomic and productive variables of the F. arundinacea Schreb. plants, and (3) to quantify the production and quality of the forage produced from the plant (the bioactive compounds' concentrations, antioxidant activity, and the concentration of selenium). Three different treatments of SeNPs were established (0, 1.5, 3.0, and 4.5 mg/mL). The effects of a foliar fertilization with SeNPs on the morphological parameters such as the root size, plant height, and biomass production were recorded, as well as the effects on the physicochemical parameters such as the crude protein (CP), lipids (L), crude fiber (CF), neutral detergent fiber (NDF), acid detergent fiber (ADF), carbohydrates (CH), the content of total phenols, total flavonoids, tannins, quantification of selenium and antioxidant activity 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2,2-diphenyl-1-picrylhydrazyl (DPPH). Significant differences (p < 0.05) were found between treatments in all the response variables. The best results were obtained with foliar application treatments with 3.0 and 4.5 mg/mL with respect to the root size (12.79 and 15.59 cm) and plant height (26.18 and 29.34 cm). The F. arundinacea Schreb. plants fertilized with 4.5 mg/L had selenium contents of 0.3215, 0.3191, and 0.3218 mg/Kg MS; total phenols of 249.56, 280.02, and 274 mg EAG/100 g DM; and total flavonoids of 63.56, 64.96, and 61.16 mg QE/100 g DM. The foliar biofortified treatment with a concentration of 4.5 mg/mL Se NPs had the highest antioxidant capacities (284.26, 278.35, and 289.96 mg/AAE/100 g).
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The aim of this review is to know the current status of sarcopenia in people living with acquired immunodeficiency virus, as well as predictors, prevalence, and associated factors. Searches were done in PubMed, Scielo, and ScienceDirect databases (January 2010 to August 2021), using predefined search terms. Prevalence, intervention, and meta-analysis studies investigating sarcopenia or muscle mass and function in people living with Human immunodeficiency virus (PLHIV) were selected. We identified reports of high prevalence and increased risk for sarcopenia due to factors such as prolonged exposure to antiretroviral drugs, lack of physical activity, central obesity, drug use, and other sociodemographic factors, as well as disease duration. HIV should be considered a risk factor for sarcopenia, and evaluation of sarcopenia should be included as part of the comprehensive medical care of PLHIV. Forceful actions are required to prevent muscle weakness, especially in stages before old age with actions aimed at preserving strength and function.
Subject(s)
HIV Infections , Sarcopenia , Humans , HIV , HIV Infections/complications , HIV Infections/drug therapy , Obesity , Prevalence , Risk Factors , Sarcopenia/complications , Sarcopenia/epidemiologyABSTRACT
Self-assembled islands of 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin (2HTFPP) on Au(111) contain two bistable molecular species that differ by shifted electronic energy levels. Interactions with the underlying gold herringbone reconstruction and neighboring 2HTFPP molecules cause approximately 60% of molecules to have shifted electronic energy levels. We observed the packing density decrease from 0.64 ± 0.04 molecules per nm2 to 0.38 ± 0.03 molecules per nm2 after annealing to 200 °C. The molecules with shifted electronic energy levels show longer-range hexagonal packing or are adjacent to molecular vacancies, indicating that molecule-molecule and molecule-substrate interactions contribute to the shifted energies. Multilayers of porphyrins do not exhibit the same shifting of electronic energy levels which strongly suggests that molecule-substrate interactions play a critical role in stabilization of two electronic species of 2HTFPP on Au(111).
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Activated Cdc42-associated kinase (ACK) is an oncogenic nonreceptor tyrosine kinase associated with poor prognosis in several human cancers. ACK promotes proliferation, in part by contributing to the activation of Akt, the major effector of class 1A phosphoinositide 3-kinases (PI3Ks), which transduce signals via membrane phosphoinositol lipids. We now show that ACK also interacts with other key components of class 1A PI3K signaling, the PI3K regulatory subunits. We demonstrate ACK binds to all five PI3K regulatory subunit isoforms and directly phosphorylates p85α, p85ß, p50α, and p55α on Tyr607 (or analogous residues). We found that phosphorylation of p85ß promotes cell proliferation in HEK293T cells. We demonstrate that ACK interacts with p85α exclusively in nuclear-enriched cell fractions, where p85α phosphorylated at Tyr607 (pTyr607) also resides, and identify an interaction between pTyr607 and the N-terminal SH2 domain that supports dimerization of the regulatory subunits. We infer from this that ACK targets p110-independent p85 and further postulate that these regulatory subunit dimers undertake novel nuclear functions underpinning ACK activity. We conclude that these dimers represent a previously undescribed mode of regulation for the class1A PI3K regulatory subunits and potentially reveal additional avenues for therapeutic intervention.
Subject(s)
Phosphatidylinositol 3-Kinases , Protein-Tyrosine Kinases , Cell Nucleus/enzymology , HEK293 Cells , Humans , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Protein Multimerization , Protein-Tyrosine Kinases/metabolism , Signal TransductionABSTRACT
We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12-70 years, Australia: 16-73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away. We call this approach a 'rolling weights' model. In The Netherlands, the estimated effect of the PGS was relatively similar from age 12 to age 41, and decreased from age 41-70. In Australia, there was a peak in the effect of the PGS around age 40 years. These results are a first indication from a molecular genetics perspective that genetic influences on aggressive behavior that are expressed in childhood continue to play a role later in life.
Subject(s)
Aggression , Multifactorial Inheritance , Adolescent , Adult , Aged , Australia , Child , Humans , Middle Aged , Netherlands , Risk Factors , Young AdultABSTRACT
BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. OBJECTIVE: Report the results of the first years (2017-2019) of the Mexican FH registry. METHODS: There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations. RESULTS: To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033). CONCLUSION: The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.
Subject(s)
Hyperlipoproteinemia Type II , Adult , Humans , Middle AgedABSTRACT
Convection-enhanced delivery is a technique to bypass the blood-brain barrier and deliver therapeutic drugs into the brain tissue. However, animal investigations and preliminary clinical trials have reported reduced efficacy to transport the infused drug in specific zones, attributed mainly to backflow, in which an annular gap is formed outside the catheter and the fluid preferentially flows toward the surface of the brain rather than through the tissue in front of the cannula tip. In this study, a three-dimensional human brain finite element model of backflow was developed to study the influence of anatomical structures during flow-controlled infusions. Predictions of backflow length were compared under the influence of ventricular pressure and the distance between the cannula and the ventricles. Simulations with zero relative ventricle pressure displayed similar backflow length predictions for larger cannula-ventricle distances. In addition, infusions near the ventricles revealed smaller backflow length and the liquid was observed to escape to the longitudinal fissure and ventricular cavities. Simulations with larger cannula-ventricle distances and nonzero relative ventricular pressure showed an increase of fluid flow through the tissue and away from the ventricles. These results reveal the importance of considering both the subject-specific anatomical details and the nonlinear effects in models focused on analyzing current and potential treatment options associated with convection-enhanced delivery optimization for future clinical trials.
Subject(s)
Brain , Drug Delivery Systems , Animals , Catheters , Finite Element Analysis , Humans , Nonlinear DynamicsABSTRACT
Introduction: The hepatic steatosis of the nonalcoholic origin or NAFLD is increasing at present, particularly in Western countries, parallel to the increase in obesity, constituting one of the most prevalent hepatic processes in the Western society. Melatonin has been successfully tested in experimental models in mice as a drug capable of reversing steatosis. The effect of melatonin on fat metabolism can be summarized as a decrease in lipid peroxidation and a decrease in oxidative stress, biochemical phenomena intimately related to fat deposition in the hepatocyte. There are hardly any studies in large animals. Objective: In this study, we investigate the effects of melatonin administered orally at a dose of 10 mg/kg/day to reverse established hepatic steatosis induced by a special diet in a porcine animal model. Materials and Methods: We analyze the parameters of oxidative stress: malondialdehyde (MDA), 4-hydroxyalkenals (4-HDA), and carbonyls, degree of fat infiltration (analyzed by direct vision by a pathologist and by means of a computer program of image treatment), and serological parameters of lipid metabolism and hepatic damage. These parameters were analyzed in animals to which hepatic steatosis was induced by means of dietary modifications. Results: We have not been able to demonstrate globally a beneficial effect of melatonin in the improvement or reversal of liver steatosis once established, induced by diet in a porcine animal model. However, we have found several signs of improvement at the histological level, at the level of lipid metabolism, and at the level of oxidative stress parameters. We have verified in our study that, in the histological analysis of the liver sample by means of the program image treatment (free of subjectivity) of the animals that continue with the diet, those that consume melatonin do not increase steatosis as much as those that do not consume it significantly (p=0.002). Regarding the parameters of oxidative stress, MDA modifies in a significant manner within the group of animals that continue with the diet and take melatonin (p=0.004). As for lipid metabolism, animals that maintain the steatotic diet and take melatonin lower total and LDL cholesterol levels and increase HDL levels, although these results do not acquire statistical significance. Conclusions: In this study, it has not been possible to demonstrate a beneficial effect of melatonin in the improvement or reversal of liver steatosis once established and induced by diet in the porcine model. It is true that signs of improvement have been found at the histological level, at the level of lipid metabolism, and at the level of oxidative stress phenomena, when comparing animals with established steatosis that are treated with melatonin with those who do not take it. This work is the first study conducted in a large animal model in which the effect of melatonin is studied as a treatment in the reversal of established hepatic steatosis.
Subject(s)
Antioxidants/pharmacology , Lipid Metabolism/drug effects , Melatonin/pharmacology , Non-alcoholic Fatty Liver Disease/drug therapy , Oxidative Stress/drug effects , Animals , Diet, High-Fat/adverse effects , Disease Models, Animal , Liver/metabolism , Non-alcoholic Fatty Liver Disease/etiology , SwineABSTRACT
PURPOSE: Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and disease-free survival (DFS) with SR and RS for different cancer types and simulate the plausibility of RS- and SR-induced antitumor immunity contributing to outcomes. MATERIALS AND METHODS: We analyzed a SEER data set of early-stage cancers treated with SR or RS. OS and DFS were calculated for cancers with sufficient numbers for statistical power (cancers of lung and bronchus, esophagus, rectum, cervix uteri, corpus uteri, and breast). We simulated the immunologic consequences of SR, RS, and radiotherapy alone in a mathematical model of tumor-immune interactions. RESULTS: RS improved OS for cancers with low 20-year survival rates (lung: hazard ratio [HR], 0.88; P = .046) and improved DFS for cancers with higher survival (breast: HR = 0.64; P < .001). For rectal cancer, with intermediate 20-year survival, RS improved both OS (HR = 0.89; P = .006) and DFS (HR = 0.86; P = .04). Model simulations suggested that RS could increase OS by eliminating cancer for a broader range of model parameters and radiotherapy-induced antitumor immunity compared with SR for selected parameter combinations. This could create an immune memory that may explain increased DFS after RS for certain cancers. CONCLUSION: Study results suggest plausibility that radiation to the bulk of the tumor could induce a more robust immune response and better harness the synergy of radiotherapy and antitumor immunity than postsurgical radiation to the tumor bed. This exploratory study provides motivation for prospective evaluation of immune activation of RS versus SR in controlled clinical studies.
Subject(s)
Immunity , Neoplasms/epidemiology , Neoplasms/immunology , Algorithms , Dose-Response Relationship, Radiation , Humans , Immunity/radiation effects , Models, Theoretical , Neoplasm Staging , Neoplasms/mortality , Neoplasms/therapy , Prognosis , Public Health Surveillance , Radiotherapy, Adjuvant/adverse effects , Radiotherapy, Adjuvant/methods , SEER Program , Surgical Procedures, Operative/adverse effects , Surgical Procedures, Operative/methods , Treatment OutcomeABSTRACT
One of the main assumptions of the standard electrokinetic model is that ions behave as point-like entities. In a previous work (López-García, et al., 2015) we removed this assumption and analyzed the influence of finite ionic size on the dielectric and electrokinetic properties of colloidal suspensions using both the Bikerman and the Carnahanâ»Starling equations for the steric interactions. It was shown that these interactions improved upon the standard model predictions so that the surface potential, electrophoretic mobility, and the conductivity and permittivity increment values were increased. In the present study, we extend our preceding works to systems made of three or more ionic species with different ionic sizes. Under these conditions, the Bikerman and Carnahanâ»Starling expressions cease to be valid since they were deduced for single-size spheres. Fortunately, the Carnahanâ»Starling expression has been extended to mixtures of spheres of unequal size, namely the "Boublikâ»Mansooriâ»Carnahanâ»Starlingâ»Leland" (BMCSL) equation of state, making it possible to analyze the most general case. It is shown that the BMCSL expression leads to results that differ qualitatively and quantitatively from the standard electrokinetic model.
ABSTRACT
The purpose of this study was to characterize mineral trioxide aggregates (MTA) enriched with iron disulfide (FeS2 ) nanostructures at different concentrations, and to investigate their storage modulus, radiopacity, setting time, pH, cytotoxicity, and antimicrobial activity. Iron disulfide nanostructures [with particle size of 0.357 ± 0.156 µm (mean ± SD)] at weight ratios of 0.2, 0.4, 0.6, 0.8, and 1.0 wt% were added to white MTA (wMTA). The radiopacity, rheological properties, setting time, and pH, as well as the cytotoxicity (assessed using the MTT assay) and antibacterial activity (assessed using the broth microdilution test) were determined for MTA/FeS2 nanostructures. The nanostructures did not modify the radiopacity values of wMTA (~6 mm of aluminium); however, they reduced the setting time from 18.2 ± 3.20 min to 13.7 ± 1.8 min, and the storage modulus was indicative of a good stiffness. Whereas the wMTA/FeS2 nanostructures did not induce cytotoxicity when in contact with human pulp cells (HPCs) and human gingival fibroblasts (HGFs), they showed bacteriostatic activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. Adding FeS2 nanostructures to MTA might be an option for improving the root canal sealing and antibacterial effects of wMTA in endodontic treatments.