Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8

PurposeManagement of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire.Materials and methods171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4–6 weeks, and at 2–3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as ‘vulnerable’, 11–14 as ‘intermediate’, and >14 as ‘fit’. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes.ResultsMedian follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were ‘vulnerable’, 37% were ‘intermediate’, and 12% were ‘fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001).ConclusionThe G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.     

Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists.

The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications.     

The effect of papaine on the time course of the end-plate current

Papaine is known to detach cholinesterases from the synaptic cleft. It could be expected that this would result in an increase of the amplitude and half-time of the end-plate current. Thus, the effect of papaine on the end-plate current should be similar to the effect of anticholinesterase methanesulfonyl-fluoride.The end-plate current was recorded in frog skeletal muscle at various levels of membrane potential, before and after papaine was added to the bath.The effect of papaine was an increase of the half-time of the end-plate current, similarly as after treatment of the muscle by methanesulfonylfluoride.It seems that both papaine and methanesulfonyl-fluoride have a similar mechanism of action. In either experimental condition hydrolysis of transmitter is decreased or abolished, which results in an increase of the half-time of the end-plate current.This work was supported by the Research Community of Slovenia     

Changes in dielectric properties at 460 kHz of kidney and fat during heating: importance for radio-frequency thermal therapy

We have developed a system to measure the changes due to heating to high temperatures in the dielectric properties of tissues in the radio-frequency range. A two-electrode arrangement was connected to a low-frequency impedance analyser and used to measure the dielectric properties of ex vivo porcine kidney and fat at 460 kHz. This frequency was selected as it is the most commonly used for radio-frequency thermal therapy of renal tumours. Tissue samples were heated to target temperatures between 48 and 78 degrees C in a hot water bath and changes in dielectric properties were measured during 30 min of heating and 15 min of cooling. Results suggest a time-temperature dependence of dielectric properties, with two separate components: one a reversible, temperature-dependent effect and the other a permanent effect due to structural events (e.g. protein coagulation, fat melting) that occur in tissues during heating. We calculated temperature coefficients of 1.3 +/- 0.1% degrees C(-1) for kidney permittivity and 1.6% degrees C(-1) for kidney conductivity, 0.9 +/- 0.1% degrees C(-1) for fat permittivity and 1.7 +/- 0.1% degrees C(-1) for fat conductivity. An Arrhenius model was employed to determine the first-order kinetic rates for the irreversible changes in dielectric properties. The following Arrhenius parameters were determined: an activation energy of 57 +/- 5 kcal mol(-1) and a frequency factor of (6 +/- 1) x 10(34) s(-1) for conductivity of kidney, an activation energy of 48 +/- 2 kcal mol(-1) and a frequency factor of 6 x 10(28) s(-1) for permittivity of kidney. A similar analysis led to an activation energy of 31 +/- 4 kcal mol(-1) and a frequency factor of (4.43 +/- 1) x 10(16) s(-1) for conductivity of fat, and an activation energy of 40 +/- 4 kcal mol(-1) and a frequency factor of 4 x 10(22) s(-1) for permittivity of fat. Structural events occurring during heating at different target temperatures as determined by histological analyses were correlated with the changes in the measured dielectric properties.     

Design of Green Silver Nanoparticles Based on Primula Officinalis Extract for Textile Preservation

The present study aims to bring an addition to biomass resources valorization for environmental-friendly synthesis of nanoparticles. Thus, the green synthesis of silver nanoparticles (AgNPs) was performed, using a novel and effective reducing agent, Primula officinalis extract. The synthesis was optimized by monitoring the characteristic absorption bands, using UV–Vis spectroscopy, and by evaluating the size and physical stability. The phenolic consumption was established using Folin-Ciocâlteu method (1.40 ± 0.42 mg, representing ~5% from the total amount of poly--phenols) and the antioxidant activity was evaluated using chemiluminescence and TEAC methods. The optimum ratio extract to Ag ions was 1:3, for which the AgNPs presented a zeta potential value of −29.3 ± 1.2 mV and particles size of 5–30 nm. For characterization, EDS and XRD techniques were used, along with microscopy techniques (TEM). The AgNPs dispersions were applied on natural textile samples (cotton and wool), as a novel antimicrobial treatment for textile preservation. The treated fabrics were further characterized in terms of chromatic parameters and antimicrobial effect against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Penicillium hirsutum strains. The high percentages of bacterial reduction, >99%, revealed that the AgNPs produced are a good candidate for textiles preservation against microbial degradation.     

Control of Dielectric and Mechanical Properties of Styrenic Block Copolymer by Graphite Incorporation

The structure–property relationship of dielectric elastomers, as well as the methods of improving the control of this relationship, has been widely studied over the last few years, including in some of our previous works. In this paper, we study the control, improvement, and correlation, for a significant range of temperatures, of the mechanical and dielectric properties of polystyrene-b-(ethylene-co-butylene)-b-styrene (SEBS) and maleic-anhydride-grafted SEBS (SEBS-MA) by using graphite (G) as filler in various concentrations. The aim is to analyze the suitability of these composites for converting electrical energy into mechanical energy or vice versa. The dielectric spectroscopy analysis performed in the frequency range of 10 to 1 MHz and at temperatures between 27 and 77 °C emphasized an exponential increase in real permittivity with G concentration, a low level of dielectric losses (≈10⁻³), as well as the stability of dielectric losses with temperature for high G content. These results correlate well with the increase in mechanical stiffness with an increase in G content for both SEBS/G and SEBS-MA/G composites. The activation energies for the dielectric relaxation processes detected in SEBS/G and SEBS-MA/G composites were also determined and discussed in connection with the mechanical, thermal, and structural properties resulting from thermogravimetric analysis, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses.     

Co-Microencapsulation of Anthocyanins from Cornelian Cherry (Cornus mas L.) Fruits and Lactic Acid Bacteria into Antioxidant and Anti-Proliferative Derivative Powders

Driven by the modern lifestyle, the consumers are interested in healthier and balanced diets, including both probiotics and natural antioxidants. The beneficial health effects of probiotics are mainly due to their capacity of modulating the human intestinal microbiota, although achieving at least a 6 log of viable cells at the targeted site is still challenging. Therefore, in this study, an attempt to improve the bioaccessibility of Lacticaseibacillus casei (L. casei) 431^® through a co-microencapsulation by complex coacervation and freeze-drying, using an extract from Cornelian cherry and two biopolymeric matrices, whey protein isolates and casein (WPI-CN) and inulin (WPI-I), was studied. The powders showed a comparable anthocyanin content of around 32.00 mg cyanidin-3-rutinoside (C3R)/g dry matter (DM) and a microbial load of about 10 Log CFU/g DM. A high stability of the lactic acid bacteria was assessed throughout 90 days of storage, whereas the anthocyanins’ degradation during storage followed a first order kinetic model, allowing the estimation of a half-time of 66.88 ± 1.67 days for WPI-CN and 83.60 ± 2.46 days for WPI-I. The in vitro digestion showed a high stability of anthocyanins in the simulated gastric juice, whereas the release in the simulated intestinal juice was favored in the variant with inulin (up to 38%). The use of casein permitted to obtain finer spherosomes, with smaller diameters, whereas a double encapsulation was obvious in both variants, thus explaining the high resistance in the gastric environment. The anti-proliferative effect against the human colon cancer cell line (HT-29) was also demonstrated. No cytotoxicity has been found for the concentrations between 1 and 25 μg/mL for the WPI-I variant, whereas a cell proliferation effect was observed at low concentrations of 1–5 μg/mL.     

Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production

Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals.