Chemotherapeutic responses in canine lymphoma models after treatment with the CHOP protocol

Includes bibliographical references.In both human and veterinary oncology, multi-drug resistance is a phenomenon where a cancer gains a cyto-protective effect against chemotherapeutics. Resistance is often witnessed when remitted cancers relapse and become untreatable. As an example, canine lymphomas are notorious for relapsing after treatment with the multi-drug CHOP protocol. While canonical drug efflux transporters have been implicated with the chemo-resistance phenotype, there are other transporters which might also contribute. Recent research has demonstrated that exposure to chemotherapeutics results in epigenetic changes to transporter gene expression; this could be a possible route for acquiring the resistance phenotype. What is still unknown, however, is a mechanistic understanding of the chemotherapy-transporter expression relationship. To address this void, we are focusing our research on three questions: 1) What are the temporal fluctuations in transporter expression following exposure to multi-drug regimens? 2) What patterns of epigenetic markers on transporter genes promote altered expression? 3) How does transporter expression correlate to protein levels in chemo-resistant lymphomas? We will address each of these questions using a panel of four chemo-sensitive canine lymphomas as our models, and the CHOP protocol as our drug regimen. We will expose the lymphomas to combinations of the CHOP protocol to mimic short- and long-term treatments, and monitor transporter expression via QT-PCR, and epigenetic changes via ChIP-assays. Additionally, protein levels will be monitored with LC-MS/MS methods to correlate expression with translation. We hypothesize that changes in transporter expression exhibit temporal and drug-dependent patterns

In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease.

BackgroundLiver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats.Hypothesis/objectivesTo determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.AnimalsEleven LD and 11 age-matched control cats.MethodsCase-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.ResultsThere was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P = .03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P < .002). Mirtazapine half-life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (-0.0022 min-1 , CI: -0.0050 to 0.00054 min-1 ) and cats without LD (0.01849 min-1 , CI: -0.025 to -0.012 min-1 ; P = .002).Conclusions and clinical importanceCats with LD might require less frequent administration of mirtazapine than normal cats

Calidad de vida y sobrecarga del cuidador informal de adultos hospitalizados de una institución de salud pública, Trujillo 2022

La investigación tuvo por objetivo determinar la relación que existe entre calidad de vida y sobrecarga del cuidador informal de adultos hospitalizados de una Institución de Salud Pública, Trujillo 2022. El tipo de investigación fue básica, diseño no experimental, descriptiva y correlacional; con una muestra de 100 participantes. La técnica utilizada fue la encuesta. Se aplicó el cuestionario de salud SF-36 y la escala de sobrecarga del cuidador de Zarit, adaptado por las autoras. Se obtuvo como resultados en relación a la calidad de vida, que el 60% de los cuidadores informales presentaron un nivel regular y el 65% de cuidadores informales percibieron sobrecarga intensa. Se concluyó que existe relación significativa moderada entre ambas variables de estudio porque muestra un coeficiente de correlación de -0.442 con un nivel de significancia menor a 0.05, aceptando que la H1 es verdadera

Multi-Scale Structural-aware Exposure Correction for Endoscopic Imaging

Endoscopy is the most widely used imaging technique for the diagnosis of cancerous lesions in hollow organs. However, endoscopic images are often affected by illumination artefacts: image parts may be over- or underexposed according to the light source pose and the tissue orientation. These artifacts have a strong negative impact on the performance of computer vision or AI-based diagnosis tools. Although endoscopic image enhancement methods are greatly required, little effort has been devoted to over- and under-exposition enhancement in real-time. This contribution presents an extension to the objective function of LMSPEC, a method originally introduced to enhance images from natural scenes. It is used here for the exposure correction in endoscopic imaging and the preservation of structural information. To the best of our knowledge, this contribution is the first one that addresses the enhancement of endoscopic images using deep learning (DL) methods. Tested on the Endo4IE dataset, the proposed implementation has yielded a significant improvement over LMSPEC reaching a SSIM increase of 4.40% and 4.21% for over- and underexposed images, respectively.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

Reduced structural flexibility of eplet amino acids in HLA proteins

International audienceThe proteins encoded in the HLA (Human Leukocyte Antigen) system are largely responsible for the compatibility in organ transplants. To date, the molecular determinants involved in recognizing HLA antigens by recipient antibodies are unknown. Here we explore flexibility as a potential determinant. For this purpose, we compare in terms of N-RMSF (Normalized Root Mean Square Fluctuation) amino acids labeled as confirmed eplets (regions defined around polymorphic amino acids) against amino acids that have not been reported as eplets. We found that eplet amino acids tend to be less flexible than non-eplet amino acids, which would indicate that the antibodies would have a preference for binding with less mobile regions

Expansion microscopy of zebrafish for neuroscience and developmental biology studies

Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses. Finally, ExM could resolve subsynaptic protein organization, such as ring-like structures composed of glycine receptors. Regarding development, we used ExM to characterize the shapes of nuclear invaginations and channels, and to visualize cytoskeletal proteins nearby. We detected nuclear invagination channels at late prophase and telophase, potentially suggesting roles for such channels in cell division. Thus, ExM of the larval and embryonic zebrafish may enable systematic studies of how molecular components are configured in multiple contexts of interest to neuroscience and developmental biology.National Institutes of Health (U.S.) (Grant 1R01EB024261)National Institutes of Health (U.S.) (Grant 1R01MH110932)National Institutes of Health (U.S.) (Grant 2R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS087950)National Institutes of Health (U.S.) (Grant 1U01MH106011

¿De qué hablamos cuando hablamos de comunicación comunitaria? Etnografía de un proceso desde la universidad

What do we talk about when we talk about community communication? Ethnography of a process from the university The research systematized the conceptualization of Community Communication developed by the Area of Community Communication (ACC) from 2004 to 2017, assuming that it is a concept in definition and that it is carried out in the practices themselves, with the participation of the intervening actors.A self-ethnography was carried out on ACC field projects with inmates from the penal unit, rural producers who work on food sovereignty, members of social organizations, and women who worked on gender violence and memory of the neighborhood in Paraná.The initial analytical categories were communication, community and intervention, adding after the category of university, process, dialogue, time, celebration and participation.In terms of context, we also analyze the place of Community Communication in other academic spaces of Social Communication of national universities and inquire about university extension policies that frame the practices.  La investigación sistematizó la conceptualización de la comunicación comunitaria desarrollada por el Área de Comunicación Comunitaria (ACC) de 2004 a 2017, suponiendo que se trata de un concepto en definición y que se realiza en las prácticas mismas, con la participación de los actores intervinientes. Se realizó una autoetnografía sobre los proyectos en terreno del ACC con internos de la unidad penal, productores rurales que trabajan la soberanía alimentaria, integrantes de organizaciones sociales y mujeres que trabajaron sobre violencia de género y memoria barrial en Paraná. Las categorías analíticas iniciales fueron comunicación, comunidad e intervención, agregándose luego universidad, proceso, diálogo, tiempo, celebración y participación. En términos de contexto, analizamos también el lugar de la comunicación comunitaria en otros espacios académicos de Comunicación Social de las universidades nacionales e indagamos sobre las políticas de extensión universitaria que enmarcan las prácticas. &nbsp

Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long‐Acting Intramuscular Injection in Real‐World People with HIV

Long‐acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real‐world reference percentile curves of cabotegravir concentrations, accounting for patient‐related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one‐compartment model with distinct first order‐absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady‐state of 8 months and an elimination half‐life of 4.6 weeks for long‐acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model‐based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4‐fold protein‐adjusted 90% inhibitory target concentration

Influences on gum feeding in primates

This chapter reviews the factors that may affect patterns of gum feeding by primates. These are then examined for mixed-species troops of saddleback (S. fuscicollis) and mustached (S. mystax) tamarins. An important distinction is made between gums produced by tree trunks and branches as a result of damage and those produced by seed pods as part of a dispersal strategy as these may be expected to differ in their biochemistry. Feeding on fruit and Parkia seed pod exudates was more prevalent in the morning whereas other exudates were eaten in the afternoon. This itinerary may represent a deliberate strategy to retain trunk gums in the gut overnight, thus maximising the potential for microbial fermentation of their β-linked oligosaccharides. Both types of exudates were eaten more in the dry than the wet season. Consumption was linked to seasonal changes in resource availability and not the tamarins’ reproductive status pro-viding no support for the suggestion that gums are eaten as a pri-mary calcium source in the later stages of gestation and lactation. The role of availability in determining patterns of consumption is further supported by the finding that dietary overlap for the trunk gums eaten was greater between species within mixed-species troops within years than it was within species between years. These data and those for pygmy marmosets (Cebuella pygmaea) suggest that patterns of primate gummivory may reflect the interaction of prefer-ence and availability for both those able to stimulate gum production and those not