Exploring the Combined Action of Adding Pertuzumab to Branded Trastuzumab versus Trastuzumab Biosimilars for Treating HER2+ Breast Cancer.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

Comparison of the influence of alcohol and cannabis on the dynamics of the accommodative response.

PURPOSE: To assess and compare the changes produced by the two most commonly used substances, alcohol and cannabis, on accommodation dynamics. METHODS: A total of 38 young participants (19 females) were enrolled in the study. They were assigned to two groups: a cannabis group (N = 19) and an alcohol group. Participants in the cannabis group underwent two randomized sessions: a baseline session and a session after smoking a cigarette. Participants in the alcohol group underwent three randomized sessions: a baseline session, a session after the intake of 300 ml of red wine (Alcohol 1), and other after the ingestion of 450 ml of wine (Alcohol 2). For the accommodation assessment, the open-field autorefractor WAM-5500 was used. RESULTS: The decrease of the mean velocity of the accommodative response produced by Alcohol 2 condition was significantly greater than that observed for Alcohol 1 and Cannabis (p = 0.046). The direction of the accommodation (near-distance and distance-near) had no effect on the deterioration of the accommodation dynamics following substance use. The target distance had a significant effect on the decrease of the mean velocity following substance use (p = 0.002). The decrease of the amplitude of the accommodative response was associated with a decrease of the peak velocity (p = 0.004) and the increase of the accommodative lag (p < 0.001). CONCLUSIONS: A moderate-high dose of alcohol impairs accommodation dynamics to a greater extent that lower dose of alcohol or smoked cannabis. The deterioration of the accommodation mean speed was higher for a shorter target distance.

Self-Regulation of Driving Behavior Under the Influence of Cannabis: The Role of Driving Complexity and Driver Vision.

OBJECTIVE: This study analyzed the self-regulation behaviors of drivers under the influence of cannabis and its relationship with road complexity and some driver traits, including visual deterioration. BACKGROUND: Cannabis is the illicit drug most often detected in drivers; its use results in significant negative effects in terms of visual function. Self-regulation behaviors involve the mechanisms used by drivers to maintain or reduce the risk resulting from different circumstances or the driving environment. METHODS: Thirty-one young, occasional cannabis users were assessed both in a baseline session and after smoking cannabis. We evaluated the visual function (visual acuity and contrast sensitivity) and driver self-regulation variables of both longitudinal and lateral control as the speed adaptation and standard deviation of lateral position (SDLP). RESULTS: Visual function was significantly impaired after cannabis use. Recreational cannabis use did not result in self-regulation, although some road features such as curved roads did determine self-regulation. Male participants adopted mean faster driving speeds with respect to the speed limit. Driver age also determined better lateral control with lower SDLPs. In addition, visual impairment resulting from cannabis use (contrast sensitivity) was linked with self-regulation by changes in longitudinal and lateral control. CONCLUSION: Contrast sensitivity could be a good indicator of individual visual status to help determine how drivers self-regulate their driving both in normal conditions and while under the influence of cannabis. APPLICATION: The findings provide new insights about driver self-regulation under cannabis effects and are useful for policy making and awareness campaigns.

Suppression of tomato wilt by cell-free supernatants of Acinetobacter baumannii isolates from wild cacao from the Colombian Amazon.

Tomato vascular wilt caused by Fusarium oxysporum f. sp. lycopersici (Fol) is one of the most limiting diseases of this crop. The use of fungicides and varieties resistant to the pathogen has not provided adequate control of the disease. In this study, siderophore-producing bacteria isolated from wild cocoa trees from the Colombian Amazon were characterized to identify prominent strategies for plant protection. The isolates were taxonomically classified into five different genera. Eight of the fourteen were identified as bacteria of the Acinetobacter baumannii complex. Isolates CBIO024, CBIO086, CBIO117, CBIO123, and CBIO159 belonging to this complex showed the highest efficiency in siderophore synthesis, producing these molecules in a range of 91-129 µmol/L deferoxamine mesylate equivalents. A reduction in disease severity of up to 45% was obtained when plants were pretreated with CBIO117 siderophore-rich cell-free supernatant (SodSid). Regarding the mechanism of action that caused antagonistic activity against Fol, it was found that plants infected only with Fol and plants pretreated with SodSid CBIO117 and infected with Fol showed higher levels of PR1 and ERF1 gene expression than control plants. In contrast, MYC2 gene expression was not induced by the SodSid CBIO117 application. However, it was upregulated in plants infected with Fol and plants pretreated with SodSid CBIO117 and infected with the pathogen. In addition to the disease suppression exerted by SodSid CBIO117, the results suggest that the mechanism underlying this effect is related to an induction of systemic defense through the salicylic acid, ethylene, and priming defense via the jasmonic acid pathway.

Assessing the influence of cannabis and alcohol use on different visual functions: A comparative study.

This study aimed to assess and compare the influence of alcohol intake and cannabis smoking on different visual functions. A total of 64 young and healthy volunteers took part in the study. All undertook several randomised experimental sessions in which different visual functions, namely distance stereopsis, retinal straylight, visual discrimination capacity, and contrast sensitivity, were tested. Cannabis smokers (N = 30) took a baseline session and a session after smoking a cannabis cigarette, whereas alcohol users (N = 34) underwent a baseline session, a session after a low alcohol intake (Alcohol 1), and a session after a moderate to high alcohol intake (Alcohol 2). All visual functions were impaired by cannabis and alcohol use, particularly for the Cannabis and Alcohol 2 groups. The deterioration of all visual variables was higher for the Alcohol 2 than for the Alcohol 1 and Cannabis groups, except for retinal straylight, the deterioration of which was equal for the Cannabis group, and distant stereopsis, which was more impaired for the Cannabis group. The Alcohol 2 group experienced the most impairing conditions, although very similar to the cannabis group, and that factors other than the experimental conditions, such as sex and age, also influenced these visual changes. Alcohol and cannabis use clearly impair vision. The deterioration caused by cannabis is similar to, but slightly lower than, that produced by a moderate to high alcohol intake, with the experimental conditions, sex and age all having an impact on the variability of visual deterioration.

Effect of interocular differences on binocular visual performance after inducing forward scattering.

PURPOSE: To assess binocular visual performance by means of binocular summation on visual function after inducing monocular forward scattering, and to study the influence of interocular differences on ocular parameters. METHODS: Seven young healthy subjects were recruited. Four Bangerter foils and five fog filters were used to induce monocular forward scattering. To analyse the impact of the scatter, visual acuity, contrast sensitivity, visual discrimination capacity and distance stereoacuity were measured binocularly with the filter placed over the dominant eye. Additionally, interocular differences were calculated for four ocular parameters: the Objective Scatter Index (OSI), Strehl ratio (SR), modulation transfer function cut-off (MTF cut off) and straylight (log[s]). Binocular summation was determined for these visual functions. RESULTS: A statistically significant deterioration in visual acuity, contrast sensitivity and stereoacuity was seen for all of the filter conditions with respect to the natural state (baseline), with the largest change being recorded for the Bangerter foils. Similarly, the interocular difference for the three retinal image quality parameters (OSI, SR and MTF cut-off) and log(s) increased significantly for the Bangerter foil condition, but not for the fog filters (except log(s)). Binocular summation declined gradually with the Bangerter foils, but not for the fog filters. Statistically significant correlations were found, that is, the greater the interocular differences, the lower the binocular summation of the visual functions and the greater the distance stereoacuity. CONCLUSION: Increased forward scattering in the dominant eye resulted in interocular differences, which reduced the overall binocular visual performance, including the binocular summation of several visual functions and distance stereoacuity. The results suggest that marked interocular differences in ocular parameters should be avoided in cases of ocular pathology, amblyopia and emmetropisation procedures (such as refractive surgery) or a monovision correction for presbyopia.

Changes in accommodation dynamics after alcohol consumption, for two different doses.

PURPOSE: The purpose of this work was to evaluate possible changes in accommodation dynamics caused by the intake of different doses of alcohol. METHODS: A total of 20 emmetropic subjects took part in the study. This involved a baseline session, a session after consuming 300 ml of red wine, and another after consuming 450 ml of the same wine. The accommodation dynamics were characterized for two target vergences (2.5D and 5.0D) using the Grand Seiko WAM-5500 autorefractor, which provided the accommodation and disaccommodation variables. The accommodative facility was measured using flippers of ± 2.00 D. RESULTS: The mean accommodation velocities and velocity peaks were significantly lower after consuming alcohol for the higher intake, particularly for 5.0D (p < 0.05). The response time was significantly higher only for the high-intake condition for 5.0D (p < 0.05). The accommodative microfluctuations were significantly higher for both target vergences for the high-intake condition (p < 0.05). The accommodative facility was significantly impaired in both intake conditions (p < 0.05). The breath alcohol content (BrAC) was correlated with the deterioration of some variables: the accommodative facility (ρ = 0.490), and the velocity peak for 2.5D (ρ = 0.349) and 5.0D (ρ = 0.387). CONCLUSIONS: Alcohol intake affects accommodation dynamics, causing deterioration in the mean velocity, velocity peak, response time, accommodative microfluctuations, and accommodative facility, especially for the target vergence of 5.0D and high alcohol dosages.

Dynamics of the accommodative response after smoking cannabis.

PURPOSE: Cannabis is the most widely consumed illicit drug worldwide. It has been suggested that cannabis could generate blurred vision during reading tasks. The goal of this study was to objectively assess the acute effects of smoking cannabis on the dynamics of ocular accommodation. The influence of other factors, including target distance and the direction of accommodation, as well as personal characteristics, were also analysed. METHODS: Nineteen young people who were occasional cannabis users participated in the study (mean age 22.53 [3.12] years). Their usage profiles were evaluated by means of the Cannabis Use Disorders Identification Test-revised (CUDIT-r). The dynamics of the accommodative response were evaluated using an open-field auto refractor (Grand Seiko WAM-5500). The participants completed two different experimental sessions, one week apart, and in random order (baseline session and after smoking cannabis). During these sessions, the amplitude of the response (D), mean velocity (D/s), peak velocity (D/s), response time (s), accommodative lag (D) and accommodation variability (D) were measured. RESULTS: The results indicated that cannabis use had a significant main effect on the mean accommodation/disaccommodation velocity (F1,13  = 7.21; p = 0.02; ηp2  = 0.396). Cannabis consumption also interacted significantly with other factors. Response time showed a significant two-way interaction between condition × target distance (F1,13  = 11.71; p = 0.005; ηp2  = 0.474) and condition × accommodation direction (F1,13  = 8.71; p = 0.01; ηp2  = 0.401). For mean velocity, two-way interactions were found between condition × age (F1,13  = 6.03; p = 0.03; ηp2  = 0.354), condition × CUDIT-r score (F1,13  = 6.03; p = 0.03; ηp2  = 0.356) and condition × target distance (F1,13  = 7.20; p = 0.02; ηp2  = 0.396). CONCLUSIONS: These findings suggest that cannabis use can alter the accommodation process, although further studies should be carried out to explore the role of attention deficits. According to these results, certain daily activities that depend on an accurate accommodative function may be affected by cannabis use.

Effect of Decentration on the Optical Quality of Two Intraocular Lenses.

PURPOSE: To analyze the effect of decentration on the optical quality of two diffractive-refractive intraocular lenses, a bifocal and a trifocal, when displaced laterally (horizontal direction) from the center. METHODS: The AT LISA 809M IOL (+3.75 D add) with two main foci and the AT LISA tri 839MP intraocular lens with three main foci (Carl Zeiss Meditec AG, Jena, Germany) were analyzed. The optical quality of the intraocular lenses was measured with the PMTF (power and modulation transfer function [MTF] measurement for refractive and diffractive intraocular lenses) optical bench (Lambda-X, Nivelles, Belgium). The optical quality of the lenses was evaluated by the MTF at different object vergences, the average modulation in the range of frequencies from 0 to 100 cycles/mm, and the through-focus MTF curves. All measures were recorded when the intraocular lenses were centered and decentered for 3.0- and 4.5-mm apertures. The Strehl ratio and the percentage of energy allocated at each focus at the centered position were also obtained. RESULTS: Our results showed a lower optical quality with increasing decentration. The MTFs for the diffractive-refractive intraocular lenses decreased when the intraocular lenses were decentered. Also, the relative percentages of light energy allocated at each object vergence, for both intraocular lenses, agreed well with theoretical specifications and were consistent with the overall design of each lens. CONCLUSIONS: The optical quality of these diffractive-refractive multifocal intraocular lenses was slightly reduced when the induced decentration was less than 0.4 mm. For a decentration of 0.4 mm, the maximum difference in average modulation values was about 18% compared to the centered position.

Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells.

We have previously reported a novel method for the production of tumour-antigen-presenting cells (referred to as TAPCells) that are currently being used in cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as TRIMEL) as an antigen provider and activation factor. It was recently demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune responses resulting in improved long-term survival of stage IV melanoma patients. Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is an important requirement for an effective anti-tumour immunization. This mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7), which is up-regulated on mature DCs. Using flow cytometry and immunohistochemistry, we investigated if TRIMEL was capable of inducing the expression of the CCR7 on TAPCells and enhancing their migration in vitro, as well as their in vivo relocation to lymph nodes in an ectopic xenograft animal model. Our results confirmed that TRIMEL induces a phenotypic maturation and increases the expression of surface CCR7 on melanoma patient-derived DCs, and also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated that TAPCells could migrate in vivo from the injection site into the draining lymph nodes. This work contributes to an increased understanding of the biology of DCs produced ex vivo allowing the design of new strategies for effective DC-based vaccines for treating aggressive melanomas.