Structure and phase transitions in niobium and tantalum derived nanoscale transition metal perovskites, Ba(Ti,MV)O3, M=Nb,Ta.

The prospect of creating ferroelectric or high permittivity nanomaterials provides motivation for investigating complex transition metal oxides of the form Ba(Ti, MV)O3, where M = Nb or Ta. Solid state processing typically produces mixtures of crystalline phases, rarely beyond minimally doped Nb/Ta. Using a modified sol-gel method, we prepared single phase nanocrystals of Ba(Ti, M)O3. Compositional and elemental analysis puts the empirical formulas close to BaTi0.5Nb0.5O3-δ and BaTi0.5Ta0.5O3-δ. For both materials, a reversible temperature dependent phase transition (non-centrosymmetric to symmetric) is observed in the Raman spectrum in the region 533-583 K (260-310 °C); for Ba(Ti, Nb)O3, the onset is at 543 K (270 °C); and for Ba(Ti, Ta)O3, the onset is at 533 K (260 °C), which are comparable with 390-393 K (117-120 °C) for bulk BaTiO3. The crystal structure was resolved by examination of the powder x-ray diffraction and atomic pair distribution function (PDF) analysis of synchrotron total scattering data. It was postulated whether the structure adopted at the nanoscale was single or double perovskite. Double perovskites (A2B'B″O6) are characterized by the type and extent of cation ordering, which gives rise to higher symmetry crystal structures. PDF analysis was used to examine all likely candidate structures and to look for evidence of higher symmetry. The feasible phase space that evolves includes the ordered double perovskite structure Ba2(Ti, MV)O6 (M = Nb, Ta) Fm-3m, a disordered cubic structure, as a suitable high temperature analog, Ba(Ti, MV)O3Pm-3m, and an orthorhombic Ba(Ti, MV)O3Amm2, a room temperature structure that presents an unusually high level of lattice displacement, possibly due to octahedral tilting, and indication of a highly polarized crystal.

Incidence and risk factors for non-cardiac syncope in a cohort of patients addressing an accredited Arterial Hypertension Center: the Innocent Study.

BACKGROUND: Hypotensive susceptibility in hypertensive patients could facilitate orthostatic hypotension, syncope and fall. The aim of this study was to identify incidence, clinical form, complications and risk factors for non-cardiac syncope in a cohort of hypertensive patients. METHODS: This is an observational, case-controlled, retrospective study carried out on 168 patients, evaluated at the Hypertension Center of the University Hospital of Parma (Italy). Based on the presence of episodes of syncope during the six months prior to enrolment, we identified cases and controls and then we compared them to personal data, comorbidities, current drug regimens, presence of orthostatic hypotension, office and ambulatory blood pressure monitoring (ABPM) blood pressure (BP) values. RESULTS: In patients with previous syncopal episodes (29.8% of total), we more frequently found female gender, comorbidities associated with autonomic dysfunction, diuretics and non-CV drugs potentially associated with hypotension in their current drug regimen, orthostatic hypotension and lower office and ABPM BP values. CONCLUSIONS: To identify hypertensive patients at higher risk for syncope and falls, physicians should focus on comorbidities and current drug regimens, systematically perform an active standing test to identify orthostatic hypotension, employ ABPM to compare BP values with the pre-established target and highlight systolic BP drops and abnormalities suggesting concomitant autonomic dysfunction. The modulation of antihypertensive therapy is an effective tool to counteract the risk of non-cardiac syncope, with possible trauma or other negative influences.

Starter protein content and supplemental soybean oil or hydrogenated palm fatty acids in Holstein dairy calves: growth performance, protozoa population, and nitrogen utilization efficiency.

The study hypothesized that a 24% protein starter diet supplemented with inert fat (palm fatty acids; PLFs) instead of triglyceride-rich soybean oil (SBO) would promote the growth of dairy calves. The effects of different protein contents (20 vs 24% CP) and fat sources (SBO vs PLF at 2.5% DM) on growth, digestibility, blood metabolites, rumen protozoa and urinary nitrogen in dairy calves were investigated. A total of 52 female dairy calves (mean age 3 days and BW 40.7 kg) were allocated to the following treatments in a completely randomized design: (1) 20% CP starter diet supplemented with SBO (20CP-SBO), (2) 20% CP starter diet supplemented with PLF (20CP-PLF), (3) 24% CP starter diet supplemented with SBO (24CP-SBO), and (4) 24% CP starter diet supplemented with PLF (24CP-PLF). Calves were weaned on day 53, and the study ended on day 73. The 24CP diets enhanced starter feed intake, average daily gain (ADG), withers height, hip width, organic matter (OM) digestibility, and preweaning blood glucose compared to the 20CP diets. In contrast, SBO supplementation reduced feed intake, ADG, withers height, OM and CP digestibility, and pre- and postweaning blood glucose and beta-hydroxybutyrate levels, while increasing preweaning aspartate aminotransferase, compared to PLF. SBO supplementation led to lower urinary excretion of purine derivatives and microbial protein synthesis postweaning, and a reduction in protozoa population both pre- and postweaning. Calves fed PLF had higher starter intake than those fed SBO, regardless of the diet being 20CP or 24CP. Calves fed the 24CP-PLF diet had the highest ADG, while calves fed the 20CP-SBO diet had the lowest ADG. Calves fed the 20CP-SBO diet had lower feed efficiency than calves fed the other diets during the preweaning period and throughout the experimental period. Calves fed the 24CP-PLF diet had higher hip heights at weaning and on day 73 than calves fed the other diets. Calves fed the 20CP-SBO diet had lower neutral detergent fiber digestibility than calves fed the other diets. Calves fed the 24CP-SBO diet had higher postweaning blood urea nitrogen concentration than calves fed the other diets. Feeding the 20CP-SBO diet to dairy calves decreased urinary allantoin excretion and rumen microbial protein synthesis but increased urinary nitrogen excretion during the preweaning period. Our results suggest that PLF is more suitable than SBO in calf diets, especially when calves fed 24% CP, possibly due to improved nutrient digestibility.

Prevalence and Mortality Rates of Acute Kidney Injury among Critically Ill Patients: A Retrospective Study.

Acute kidney injury (AKI) poses a significant challenge in critically ill patients. To determine the prevalence, risk factors, and mortality rate of AKI among nonsurgical critically ill patients in Jordan University Hospital, we conducted a retrospective study using a consecutive sampling method, including 457 nonsurgical critically ill patients admitted to the medical intensive care unit (MICU) from January to June 2021. The mean age was 63.8 ± 18 years, with 196 (42.8%) developing AKI during their stay in the MICU. Among AKI nonsurgical patients, pulmonary diseases (n = 52; 34.5%) emerged as the primary cause for admission, exhibiting the highest prevalence, followed by sepsis (n = 40; 20.4%). Furthermore, we found that older age (adjusted OR (AOR): 1.04; 95% confidence interval (CI): 1.04-1.06; p = 0.003), preadmission use of diuretics (AOR: 2.12; 95% CI: 1.06-4.25; p = 0.03), use of ventilators (2.19; 95% CI: 1.12-2.29; p = 0.02), and vasopressor use during MICU stay (AOR: 4.25; 95% CI: 2.1308.47; p = 0.001) were observed to have higher mortality rates. Prior utilization of statins before admission exhibited a significant association with reduced mortality rate (AOR: 0.42; 95% CI: 0.2-0.85; p = 0.02). Finally, AKI was associated with a higher mortality rate during MICU stay (AOR: 2.44; 95% CI: 1.07-5.56; p = 0.03). The prevalence of AKI among nonsurgical patients during MICU stay is higher than what has been reported previously in the literature, which highlights the nuanced importance of identifying more factors contributing to AKI in developing countries, and hence providing preventive measures and adhering to global strategies are recommended.

Development of 225Ac Production from Low Isotopic Dilution 229Th.

The promise of 225Ac targeted alpha therapies has been on the horizon for the last two decades. TerraPower Isotopes are uniquely suited to produce clinically relevant quantities of 225Ac through the decay of 229Th. Herein, a rapid processing scheme to isolate radionuclidic and radioisotopically pure 225Ac in good yield (98%) produced from 229Th that contains significant quantities of 228Th activity is described. The characterization of each step of the process is presented along with the detailed characterization of the resulting 225Ac isotopic starting material that will support the cancer research and development efforts.

Investigation of Chelating Agents for the Removal of Thorium from Human Teeth upon Nuclear Contamination.

Thorium-232 (232Th) is a radioactive heavy metal that is of increasing interest as a source of nuclear energy. However, upon nuclear incidents, the ingestion or inhalation of Th in major quantities can contribute to chemical and radiological health problems, including accumulation in the bone tissue and an increased risk of developing pancreatic, lung, and hematopoietic cancers. The major mineral component of the bone is hydroxyapatite (HAP)─also the major mineral component of the teeth. As such, the teeth are the first site of exposure upon oral ingestion of Th-contaminated materials, and Th can pose a potential risk to teeth development. In essence, in the case of human contamination, it is critical to identify effective chelating agents capable of removing Th. Using a batch study methodology, this present work investigates the uptake and the removal of Th from synthetic HAP and from teeth samples by diethylenetriamine pentaacetate (DTPA), ethylenediaminetetraacetic acid (EDTA), and other promising chelating agents. Th uptake over synthetic HAP exceeds 98% at physiological pH with <1 min of contact time and uptake exceeds 90% across the entire pH range. Regarding teeth, over 1 mg Th uptaken per gram of tooth is observed after 24 h. The overall effectiveness of chelating agents for the removal of Th from is as follows: DTPA > EDTA > NaF/mouthwash/3,4,3-LI(1,2-HOPO); this trend was observed both in synthetic HAP and Th-impregnated teeth samples.

Learning to reason over scene graphs: a case study of finetuning GPT-2 into a robot language model for grounded task planning.

Long-horizon task planning is essential for the development of intelligent assistive and service robots. In this work, we investigate the applicability of a smaller class of large language models (LLMs), specifically GPT-2, in robotic task planning by learning to decompose tasks into subgoal specifications for a planner to execute sequentially. Our method grounds the input of the LLM on the domain that is represented as a scene graph, enabling it to translate human requests into executable robot plans, thereby learning to reason over long-horizon tasks, as encountered in the ALFRED benchmark. We compare our approach with classical planning and baseline methods to examine the applicability and generalizability of LLM-based planners. Our findings suggest that the knowledge stored in an LLM can be effectively grounded to perform long-horizon task planning, demonstrating the promising potential for the future application of neuro-symbolic planning methods in robotics.

A Survey of Neck Pain among Dentists of the Lebanese Community.

Results: The majority of participants were between the ages of 25 and 35, and the gender distribution of the demographic distribution was comparable. The prevalence of pain was 86.8% (97/342 dentists). NDI analysis showed that 65.7% had mild disability, 12.8% have a moderate disability, and 1% had severe disability. Bivariate analysis showed that pain was affected by age (p=0.013), orthodontist practices (p=0.031), regular exercise (p < 0.001), using vibrating instruments (p < 0.001), cervical flexion for better vision while working (p < 0.001), knowledge, and experience about ergonomic posture (p < 0.005). Multivariate analysis showed four predictors for pain: age (p=0.017), performing stretching exercises after finishing clinical practice (p=0.022), orthodontist specialty (p=0.029), and performing cervical flexion for better vision while working (p=0.004). Conclusion: This study showed that through the application of some strategies such as stretching, exercising, and being careful in using vibrating instruments, the dentist may be able to relieve the pain.

Effects of arginine and guanidinoacetic acid with or without phenylalanine on ascites susceptibility in cold-stressed broilers fed canola meal-based diet.

In order to evaluate the effects of ARG sources (arginine [ARG] and Guanidinoacetic acid [GAA]) and phenylalanine (PHE) supplementation on performance, susceptibility to ascites, intestinal morphology, and nutrient digestibility in the cold-stressed broilers fed a canola meal (CM)-based diet, a 2×2 factorial experiment with four treatments was conducted. The dietary treatments included CM-based diet + 2.57 g/kg ARG, CM-based diet + 2.57 g/kg ARG + 1.5 g/kg PHE, CM-based diet + 1.8 g/kg GAA and CM-based diet + 1.8 g/kg GAA + 1.5 g/kg PHE. The corn-CM diet without supplementation was used as a negative control (NC) group in the fifth treatment that excluded the factorial arrangement. The results showed that adding ARG to diets without PHE supplement increased (p < 0.05) feed intake. Also, birds fed diets containing ARG had higher (p < 0.05) body weight gain (BWG) compared to those fed GAA added diets. Supplementation of PHE improved (p < 0.05) the FCR compared to groups fed diets without added PHE. Further, ARG addition increased (p < 0.05) plasma nitric oxide (NO) concentration, carcass, breast and leg yields, duodenal, jejunal, and ileal villus height (VH) to crypt depth (CD, and dry matter digestibility, while decreasing (p < 0.05) ascites mortality and right ventricle (RV) to total ventricle (TV) ratio compared to GAA added groups. Supplementation of PHE also declined susceptibility to ascites by reducing (p < 0.01) RV to TV ratio while increasing (p < 0.05) plasma NO level. The digestibility of ether extract also increased (p < 0.05) in broilers fed GAA supplemented diets versus those fed ARG added diets. The findings suggested that ARG may improve BWG and lower ascites incidence in broilers fed a diet based on CM under cold stress because of its antihypertensive effects. Moreover, the findings of this study demonstrated the importance of including PHE formulation in ARG-deficient diets to attenuate the adverse effects of cold stress on broilers. It was also concluded that GAA could be efficaciously used in cold-stressed broilers fed an ARG-deficient diet.

Neck and Musculoskeletal Pain Among Dentists: A Review of the Literature.

Musculoskeletal disorders (MSD), notably neck pain, are important occupational health issues in the field of dentistry. Many studies were done worldwide to gather data about neck and back pain. They used different characteristics and risk factors. Other studies aimed to determine only the prevalence of neck and back problems among dentists. We aim to review the literature for research about the optimal factors to be assessed and the proper measures to be installed by dentists to prevent cervical pain and to be taught and shared with dental students. Such an aim requires a thorough review of the current condition. This is a brief review of the literature to shed light on the latest news on this topic. Research using keywords such as dentistry, neck pain, neck pain index, occupational pain, and dental specialties were used to skim the literature for related topics. Publications are considered based on their relevance to the topic. Topics related to other professions and pain induced by illnesses other than occupational factors are not included. The final conclusion shows that no final results were conducted regarding the optimal characteristics that the dentists should be using. Therefore, we recommend a study with an aim to determine the optimal factors to be used by dentists to prevent cervical pain and to be taught to dental students.

Sc-HOPO: A Potential Construct for Use in Radioscandium-Based Radiopharmaceuticals.

Three isotopes of scandium─43Sc, 44Sc, and 47Sc─have attracted increasing attention as potential candidates for use in imaging and therapy, respectively, as well as for possible theranostic use as an elementally matched pair. Here, we present the octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO), an effective chelator for hard cations, as a potential ligand for use in radioscandium constructs with simple radiolabeling under mild conditions. HOPO forms a 1:1 Sc-HOPO complex that was fully characterized, both experimentally and theoretically. [47Sc]Sc-HOPO exhibited good stability in chemical and biological challenges over 7 days. In healthy mice, [43,47Sc]Sc-HOPO cleared the body rapidly with no signs of demetalation. HOPO is a strong candidate for use in radioscandium-based radiopharmaceuticals.

Capacitive and Resistive Electric Transfer Therapy: A Comparison of Operating Methods in Non-specific Chronic Low Back Pain.

Capacitive and resistive electric transfer (TECAR) modes of therapy use radiant energy to generate endogenous heat and are used for musculoskeletal disorders for their analgesic, decontracting, and elasticizing properties. While the capacitive mode is supposed to interact with soft tissues, the resistive mode interacts more with hard tissues. This study aims to investigate whether the successive order of the two modes during their application could make a difference concerning the outcome. The study included 40 patients affected by chronic non-specific low back pain. Patients were assessed using algometry, before and immediately after the therapeutic intervention, and thermal imaging, before, immediately after, and then 30 and 60 min after the intervention. Each patient had two TECAR interventions on different days of a total of 20 min each, with a resistive followed by capacitive mode and conversely, capacitive followed by resistive mode. The capacitive mode alternated with the resistive mode by 10 min during either intervention. Results showed that the effects consisting of temporary increases in the superficial temperature of the lower back and pressure pain threshold were alike for both interventions. We conclude that TECAR therapy reduces low back pain regardless of the operative mode adopted, with only an insignificant advantage when starting the sequence from the resistive application.

Quantum Medicine: A Role of Extremely Low-Frequency Magnetic Fields in the Management of Chronic Pain.

Extremely low-frequency electromagnetic field (ELF-MF) therapy is a promising treatment for chronic pain, given its ability to interact with body homeostasis using water-mediated transmission mechanisms typical of quantum medicine. The present study aims to assess the effects of ELF-MF therapy on chronic pain in 49 patients suffering from various musculoskeletal disorders. The therapy was applied through a Quec Phisis setup generating the electromagnetic field as the ion cyclotronic resonance. Patients underwent eight therapy sessions of 45 min each performed every other day. The bioimpedance assessment was based on the comparison of the height-adjusted body resistance (R/h) and reactance (Xc/h) measured during the first and last sessions of eight-session treatment. Pain perception was quantified using the standard visual-analog scale. We found significant increases in both R/h and Xc/h parameters of body bioimpedance after electromagnetic therapy corresponding with reductions in pain perception. We conclude that the ELF-MF therapy can restore the body's state of health and thus seems a valid therapeutic approach for the treatment of musculoskeletal-derived pain.

New phthalimide analog ameliorates CCl4 induced hepatic injury in mice via reducing ROS formation, inflammation, and apoptosis.

The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4 mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms.

Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)-Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru-IM (1), a water-soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA-MB-231) and African (HCC-1806) ancestry (including IC50 values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell-line panel screen). 1 was previously found highly efficacious in MDA-MB-231 cells and xenografts, with little systemic toxicity and preferential accumulation in the tumor. We observe a similar profile for this compound in the two cell lines studied, which includes high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties. Cytokine M-CSF, involved in the PI3/AKT pathway, shows protein expression inhibition with exposure to 1. We also demonstrate a p53 independent mechanism of action.

Powerful anti-inflammatory action of luteolin: Potential increase with IL-38.

Luteolin belongs to the flavone family originally present in some fruits and vegetables, including olives, which decrease intracellular levels of reactive oxygen species (ROS) following the activation of various stimuli. Luteolin inhibits inflammation, a complex process involving immune cells that accumulate at the site of infectious or non-infectious injury, with alteration of the endothelium leading to recruitment of leukocytes. Cytokines have been widely reported to act as immune system mediators, and IL-1 family members evolved to assist in host defense against infections. Interleukin (IL)-1 and Toll-like receptor (TLR) are involved in the innate immunity in almost all living organisms. After being synthesized, IL-1 induces numerous inflammatory mediators including itself, other pro-inflammatory cytokines/chemokines, and arachidonic acid products, which contribute to the pathogenesis of immune diseases. Among the 11 members of the IL-1 family, there are two new cytokines that suppress inflammation, IL-37 and IL-38. IL-38 binds IL-36 receptor (IL-1R6) and inhibits several pro-inflammatory cytokines, including IL-6, through c-Jun N-terminal kinase (JNK) induction and reducing AP1 and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity, alleviating inflammatory diseases. Therefore, since luteolin, IL-37 and IL-38 are all anti-inflammatory molecules with different signaling pathways, it is pertinent to recommend the combination of luteolin with these anti-inflammatory cytokines in inflammation.

Uptake and Removal of Uranium by and from Human Teeth.

Uranium-238 (238U), a long-lived radiometal, is widespread in the environment because of both naturally occurring processes and anthropogenic processes. The ingestion or inhalation of large amounts of U is a major threat to humans, and its toxicity is considered mostly chemical rather than radiological. Therefore, a way to remove uranium ingested by humans from uranium-contaminated water or from the air is critically needed. This study investigated the uranium uptake by hydroxyapatite (HAP), a compound found in human bone and teeth. The uptake of U by teeth is a result of U transport as dissolved uranyl (UO22+) in contaminated water, and U adsorption has been linked to delays in both tooth eruption and development. In this present work, the influence of pH, contact time, initial U concentration, and buffer solution on the uptake and removal of U in synthetic HAP was investigated and modeled. The influence of pH (pH of human saliva, 6.7-7.4) on the uptake of uranyl was negligible. Furthermore, the kinetics were extremely fast; in one second of exposure, 98% of uranyl was uptaken by HAP. The uptake followed pseudo-second-order kinetics and a Freundlich isotherm model. A 0.2 M sodium carbonate solution removed all the uranyl from HAP after 1 h. Another series of in vitro tests were performed with real teeth as targets. We found that, for a 50 mg/L U in PBS solution adjusted to physiological pH, ∼35% of the uranyl was uptaken by the tooth after 1 h, following pseudo-first-order kinetics. Among several washing solutions tested, a commercially available carbonate, as well as a commercially available fluoride solution, enabled removal of all the uranyl taken up by the teeth.

Manual Pressure Release and Low-Grade Electrical Peripheral Receptor Stimulation in Nonspecific Low Back Pain: A Randomized Controlled Trial.

Chronic nonspecific low back pain is a frequent clinical condition affecting the general population and influencing disability level and quality of life. We performed a single-blinded, randomized, and controlled study to compare the effectiveness of manual pressure release (MPR) and electrical neuromodulation (ENM) treatments in the management of chronic low back pain. There were 20 patients with chronic low back pain randomly assigned to 6 treatment sessions with either technique. Both groups were treated for 2 days a week for 3 weeks. Myofascial trigger points (MTrPs) were identified and skin conductance, pressure-pain threshold, postural changes, and the Oswestry Disability Index were assessed before and after each treatment session, along with the protocol-end data compared against the baseline data in each group. We found an outstanding and about equal deactivation of MTrPs from pre- to post-treatment in both groups, reducing disability in patients with chronic low back pain. The study highlights the ENM as a reliable tool for the evaluation of MTrPs, given a high agreement with the MPR. The effect on the neuromuscular condition of treating the "key trigger points" found in this study advances the knowledge of medical rehabilitation.

ImmunoPET Imaging of Pancreatic Tumors with 89Zr-Labeled Gold Nanoparticle-Antibody Conjugates.

PURPOSE: Targeted delivery in vivo remains an immense roadblock for the translation of nanomaterials into the clinic. The greatest obstacle is the mononuclear phagocyte system (MPS), which sequesters foreign substances from general circulation and causes accumulation in organs such as the liver and spleen. The purpose of this study was to determine whether attaching an active targeting antibody, 5B1, to the surface of gold nanoparticles and using clodronate liposomes to deplete liver and splenic macrophages could help to minimize uptake by MPS organs, increase targeted delivery to CA19.9-positive pancreatic tumors, and enhance pancreatic tumor delineation. PROCEDURES: To produce the antibody-gold nanoparticle conjugate (Ab-AuNP), the Ab was conjugated to p-isothiocyanatobenzyl-desferrioxamine (p-SCN-DFO) and subsequently conjugated to NHS-activated gold nanoparticles. The Ab-AuNP was characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Modified Lindmo assay was performed to assess binding affinity and internalization potential in vitro. The Ab-AuNP was radiolabeled with 89Zr and injected into CA19.9-positive BxPc-3 pancreatic orthotopic tumor-bearing mice pretreated with or without clodronate liposomes for PET imaging and biodistribution studies. Inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis was used to confirm delivery of gold nanoparticles to BxPc-3 pancreatic subcutaneous xenografts. RESULTS: Mice pretreated with clodronate liposomes in an orthotopic setting demonstrated decreased liver uptake at early time points (12.2 ± 2.3 % ID/g vs. 22.8 ± 3.8 % ID/g at 24 h) and increased tumor uptake at 120 h (13.8 ± 8.0 % ID/g vs. 6.0 ± 1.2 % ID/g). This allowed for delineation of orthotopic pancreatic xenografts in significantly more mice treated with clodronate (6/6) than in mice not treated with clodronate (2/6) or mice injected with gold nanoparticles labeled with a nonspecific antibody (0/5). CONCLUSIONS: The combination of clodronate liposomes and an active targeting antibody on the surface of gold nanoparticles allowed for PET/CT imaging of subcutaneous and orthotopic pancreatic xenografts in mice.

Comparison of Methods for Surface Modification of Barium Titanate Nanoparticles for Aqueous Dispersibility: Toward Biomedical Utilization of Perovskite Oxides.

Colloidal perovskite barium titanate (BaTiO3, or BT) nanoparticles (NPs), conventionally used for applications in electronics, can also be considered for their potential as biocompatible computed tomography (CT) contrast agents. NPs of BT produced by traditional solid-state methods tend to have broad size distributions and poor dispersibility in aqueous media. Furthermore, uncoated BT NPs can be cytotoxic because of leaching of the heavy metal ion, Ba2+. Here, we present and compare three approaches for surface modification of BT NPs (8 nm) synthesized by the gel collection method to improve their aqueous stability and dispersibility. The first approach produced citrate-capped BT NPs that exhibited extremely high aqueous dispersibility (up to 50 mg/mL) and a small hydrodynamic size (11 nm). Although the high dispersibility was found to be pH-dependent, such aqueous stability sufficiently enabled a feasibility analysis of BT NPs as CT contrast agents. The second approach, a core/shell design, aimed to encapsulate BT nanoaggregates with a silica layer using a modified Stöber method. A cluster of 7-20 NPs coated with a thick layer (20-100 nm) of SiO2 was routinely observed, producing larger NPs in the 100-200 nm range. A third approach was developed using a reverse-microemulsion method to encapsulate a single BT core within a thin (10 nm) silica layer, with an overall particle size of 29 nm. The -OH groups on the silica layer readily enabled surface PEGylation, allowing the NPs to remain highly stable in saline solutions. We report that the silica-coated BT NPs in both methods exhibited a low level of Ba2+ leaching (≤3% of total barium in NPs) in phosphate-buffered saline for 48 h compared to the unmodified BT NPs (14.4%).