Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy.

Infiltration of immunosuppressive cells into the breast tumor microenvironment (TME) is associated with suppressed effector T cell (Teff) responses, accelerated tumor growth, and poor clinical outcomes. Previous studies from our group and others identified infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) as critical contributors to immune dysfunction in the orthotopic claudin-low tumor model, limiting the efficacy of adoptive cellular therapy. However, approaches to target these cells in the TME are currently lacking. To overcome this barrier, polymeric micellular nanoparticles (PMNPs) were used for the co-delivery of small molecule drugs activating Toll-like receptors 7 and 8 (TLR7/8) and inhibiting PI3K delta (PI3Kδ). The immunomodulation of the TME by TLR7/8 agonist and PI3K inhibitor led to type 1 macrophage polarization, decreased MDSC accumulation and selectively decreased tissue-resident Tregs in the TME, while enhancing the T and B cell adaptive immune responses. PMNPs significantly enhanced the anti-tumor activity of local radiation therapy (RT) in mice bearing orthotopic claudin-low tumors compared to RT alone. Taken together, these data demonstrate that RT combined with a nanoformulated immunostimulant diminished the immunosuppressive TME resulting in tumor regression. These findings set the stage for clinical studies of this approach.

Judging emotion in natural images of crowds.

It has been suggested that humans use summary statistics such as the average of the emotion of individual faces when they rapidly judge group emotion. Previous studies have mainly used faces of actors posing basic emotions, and morphed versions of these faces, against a plain background. In the present study, photographs taken in real-world settings were used to investigate the influence of mean facial emotion, maximal facial emotion, and background context on judgments of group emotion, assessed using dimensional ratings of valence, arousal, and dominance. Background context explained a significant amount of unique variance in group ratings for each dimension. Mean emotion explained additional unique variance for valence ratings, whereas maximal emotion explained additional unique variance for arousal, with dominance showing more mixed results. Removing background context and disrupting the contextual and spatial relationship between faces by randomly replacing faces with ones from other images within the stimulus set increased reliance on mean emotion. However, under all conditions, the maximally arousing face continued to exert an influence on ratings of group arousal, in line with theoretical accounts arguing for a unique bottom-up effect of emotional arousal on attentional competition and postattentive perceptual processing. Together these findings suggest that individuals' reliance on average emotion when judging crowd scenes differs as a function of the dimension of affect. In addition, the presence of background context both directly impacts judgments of crowd emotion and modulates the relative influence of maximal versus mean emotion on these judgments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Occipital-temporal cortical tuning to semantic and affective features of natural images predicts associated behavioral responses.

In everyday life, people need to respond appropriately to many types of emotional stimuli. Here, we investigate whether human occipital-temporal cortex (OTC) shows co-representation of the semantic category and affective content of visual stimuli. We also explore whether OTC transformation of semantic and affective features extracts information of value for guiding behavior. Participants viewed 1620 emotional natural images while functional magnetic resonance imaging data were acquired. Using voxel-wise modeling we show widespread tuning to semantic and affective image features across OTC. The top three principal components underlying OTC voxel-wise responses to image features encoded stimulus animacy, stimulus arousal and interactions of animacy with stimulus valence and arousal. At low to moderate dimensionality, OTC tuning patterns predicted behavioral responses linked to each image better than regressors directly based on image features. This is consistent with OTC representing stimulus semantic category and affective content in a manner suited to guiding behavior.

Type II innate lymphoid cell plasticity contributes to impaired reconstitution after allogeneic hematopoietic stem cell transplantation.

Type II innate lymphoid cells (ILC2s) maintain homeostasis and barrier integrity in mucosal tissues. In both mice and humans, ILC2s poorly reconstitute after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Determining the mechanisms involved in their impaired reconstitution could improve transplant outcomes. By integrating single-cell chromatin and transcriptomic analyses of transplanted ILC2s, we identify a previously unreported population of converted ILC1-like cells in the mouse small intestine post-transplant. Exposure of ILC2s to proinflammatory cytokines resulted in a mixed ILC1-ILC2 phenotype but was able to convert only a small population of ILC2s to ILC1s, which were found post-transplant. Whereas ILC2s protected against acute graft-versus-host disease (aGVHD) mediated mortality, infusion of proinflammatory cytokine-exposed ILC2s accelerated aGvHD. Interestingly, murine ILC2 reconstitution post-HSCT is decreased in the presence of alloreactive T cells. Finally, peripheral blood cells from human patients with aGvHD have an altered ILC2-associated chromatin landscape compared to transplanted controls. These data demonstrate that following transplantation ILC2s convert to a pro-pathogenic population with an ILC1-like chromatin state and provide insights into the contribution of ILC plasticity to the impaired reconstitution of ILC2 cells, which is one of several potential mechanisms for the poor reconstitution of these important cells after allo-HSCT.

Hepatic transcript profiling in beef cattle: Effects of feeding endophyte-infected tall fescue seeds.

The objective of our study was to evaluate the effect of endophyte-infected tall fescue (E+) seeds intake on liver tissue transcriptome in growing Angus × Simmental steers and heifers through RNA-seq analysis. Normal weaned calves (~8 months old) received either endophyte-free tall fescue (E-; n = 3) or infected tall fescue (E+; n = 6) seeds for a 30-d period. The diet offered was ad libitum bermudagrass (Cynodon dactylon) hay combined with a nutritional supplement of 1.61 kg (DM basis) of E+ or E- tall fescue seeds, and 1.61 kg (DM basis) of energy/protein supplement pellets for a 30-d period. Dietary E+ tall fescue seeds were included in a rate of 20 µg of ergovaline/kg BW/day. Liver tissue was individually obtained through biopsy at d 30. After preparation and processing of the liver samples for RNA sequencing, we detected that several metabolic pathways were activated (i.e., upregulated) by the consumption of E+ tall fescue. Among them, oxidative phosphorylation, ribosome biogenesis, protein processing in endoplasmic reticulum and apoptosis, suggesting an active mechanism to cope against impairment in normal liver function. Interestingly, hepatic protein synthesis might increase due to E+ consumption. In addition, there was upregulation of "thermogenesis" KEGG pathway, showing a possible increase in energy expenditure in liver tissue due to consumption of E+ diet. Therefore, results from our study expand the current knowledge related to liver metabolism of growing beef cattle under tall fescue toxicosis.

Additive-manufactured paper-PMMA hybrid microfluidic chip for simultaneous monitoring of creatinine and pH in artificial urine.

Nowadays, kidney dysfunction is a common health issue due to the modernized lifestyle. Even though medications are commercially available to treat kidney diseases, early diagnosis is crucial and challenging. Clinically, measuring urine creatinine and pH has gained significant interest as a way to diagnose kidney diseases early. In the present work, we attempted to develop a low-cost, robust, accurate and naked-eye colorimetric method to determine both creatinine levels and pH variations in artificial urine samples using a simple 3D-printed hybrid microfluidic device. Creatinine was detected by the incorporation of the traditional Jaffe test onto the hybrid paper-PMMA microfluidic device and pH (4-8) was measured by a simple anthocyanin test. Notably, the tests were established without employing any sophisticated or costly instrument clusters. The developed 3D-printed microfluidic probe showed a limit of detection (LOD) of 0.04 mM for creatinine over a concentration range of 1-10 mM, with a regression coefficient (R2) of 0.995 in laboratory conditions. Interestingly, the experimental data obtained with artificial urine exhibited a wide linear range from 0.1 mM to 5 mM under different pH values ranging from 4 to 8 in the presence of matrices commonly found in urine samples other than proteins, indicating the potential use of this method in pre-clinical analysis. Since the wide linear range of urine creatinine in artificial urine samples falls well below the clinically relevant concentrations in humans (0.07-0.27 mM), the developed lab-on-chip device is further suitable for clinical evaluation with proper ethical clearance. This 3D-printed hybrid microfluidic colorimetry-based creatinine detection and pH indicator platform can be beneficial in the healthcare sector due to the on-site testing capability, cost-effectiveness, ease of use, robustness, and instrument-free approach.

UCP1 expression in human brown adipose tissue is inversely associated with cardiometabolic risk factors.

OBJECTIVE: Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is commonly used to quantify human BAT mass and activity. Detectable 18F-FDG uptake by BAT is associated with reduced prevalence of cardiometabolic disease. However, 18F-FDG uptake may not always be a reliable marker of BAT thermogenesis, for example, insulin resistance may reduce glucose uptake. Uncoupling protein 1 (UCP1) is the key thermogenic protein in BAT. Therefore, we hypothesised that UCP1 expression may be altered in individuals with cardiometabolic risk factors. METHODS: We quantified UCP1 expression as an alternative marker of thermogenic capacity in BAT and white adipose tissue (WAT) samples (n = 53) and in differentiated brown and white pre-adipocytes (n = 85). RESULTS: UCP1 expression in BAT, but not in WAT or brown/white differentiated pre-adipocytes, was reduced with increasing age, obesity, and adverse cardiometabolic risk factors such as fasting glucose, insulin, and blood pressure. However, UCP1 expression in BAT was preserved in obese subjects of <40 years of age. To determine if BAT activity was also preserved in vivo, we undertook a case-control study, performing 18F-FDG scanning during mild cold exposure in young (mean age ∼22 years) normal weight and obese volunteers. 18F-FDG uptake by BAT and BAT volume were similar between groups, despite increased insulin resistance. CONCLUSION: 18F-FDG uptake by BAT and UCP1 expression are preserved in young obese adults. Older subjects retain precursor cells with the capacity to form new thermogenic adipocytes. These data highlight the therapeutic potential of BAT mass expansion and activation in obesity.

Environmental impact of microplastics and potential health hazards.

Microscopic plastic (microplastic) pollutants threaten the earth's biodiversity and ecosystems. As a result of the progressive fragmentation of oversized plastic containers and products or manufacturing in small sizes, microplastics (particles of a diameter of 5 mm with no lower limit) are used in medicines, personal care products, and industry. The incidence of microplastics is found everywhere in the air, marine waters, land, and even food that humans and animals consume. One of the greatest concerns is the permanent damage that is created by plastic waste to our fragile ecosystem. The impossibility of the complete removal of all microplastic contamination from the oceans is one of the principal tasks of our governing body, research scientists, and individuals. Implementing the necessary measures to reduce the levels of plastic consumption is the only way to protect our environment. Cutting off the plastic flow is the key remedy to reducing waste and pollution, and such an approach could show immense significance. This review offers a comprehensive exploration of the various aspects of microplastics, encompassing their composition, types, properties, origins, health risks, and environmental impacts. Furthermore, it delves into strategies for comprehending the dynamics of microplastics within oceanic ecosystems, with a focus on averting their integration into every tier of the food chain.

Structural and biophysical analysis of cytochrome P450 2C9*14 and *27 variants in complex with losartan.

The human cytochrome P450 (CYP) 1, 2 and 3 families of enzymes are responsible for the biotransformation of a majority of the currently available pharmaceutical drugs. The highly polymorphic CYP2C9 predominantly metabolizes many drugs including anticoagulant S-warfarin, anti-hypertensive losartan, anti-diabetic tolbutamide, analgesic ibuprofen, etc. There are >80 single nucleotide changes identified in CYP2C9, many of which significantly alter the clearance of important drugs. Here we report the structural and biophysical analysis of two polymorphic variants, CYP2C9*14 (Arg125His) and CYP2C9*27 (Arg150Leu) complexed with losartan. The X-ray crystal structures of the CYP2C9*14 and *27 illustrate the binding of two losartan molecules, one in the active site near heme and another on the periphery. Both losartan molecules are bound in an identical conformation to that observed in the previously solved CYP2C9 wild-type complex, however, the number of losartan differs from the wild-type structure, which showed binding of three molecules. Additionally, isothermal titration calorimetry experiments reveal a lower binding affinity of losartan with *14 and *27 variants when compared to the wild-type. Overall, the results provide new insights into the effects of these genetic polymorphisms and suggests a possible mechanism contributing to reduced metabolic activity in patients carrying these alleles.

Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy.

Infiltration of immunosuppressive cells into the breast tumor microenvironment (TME) is associated with suppressed effector T cell (Teff) responses, accelerated tumor growth, and poor clinical outcomes. Previous studies from our group and others identified infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) as critical contributors to immune dysfunction in the orthotopic triple-negative breast cancer (TNBC) tumor model limiting the efficacy of adoptive cellular therapy. However, approaches to target these cells specifically in the TME are currently lacking. To overcome this barrier, polymeric micelles nanoparticles (PMNPs) were used for co-delivery of small molecule drugs activating Toll-like receptors 7 and 8 (TLR7/8) and inhibiting PI3K delta. The immunomodulation of the TME by TLR7/8 agonist and PI3K inhibitor altered macrophage polarization, reduced MDSC accumulation and selectively decreased tissue-resident Tregs in the TME, while enhancing the T and B cell adaptive immune response. PMNPs significantly enhanced the anti-tumor activity of local radiation therapy (RT) in mice bearing orthotopic TNBC tumors compared to RT alone. Taken together, these data demonstrate that RT combined with a nanoformulated immunostimulant restructured the TME and has promising potential for future translation combined with RT for patients with TNBC.

Disposable paper electrodes for detection of changes in dopamine concentrations in rat brain homogenates.

Dopamine, the main catecholamine neurotransmitter plays an important role in renal, cardiovascular, central nervous systems, and pathophysiological processes. The abnormal dopamine levels can result in neurological disorders such as Parkinson's, Alzheimer's, schizophrenia, acute anxiety, neuroblastoma and also contribute to cognitive dysfunctions. Given the widespread importance of dopamine concentration levels, it is imperative to develop sensors that are able to monitor dopamine. Herein, we have developed pre-anodized disposable paper electrode modified with 1-pyrenebutyric acid, for the selective and sensitive determination of dopamine. The sensor was characterized with Fourier transform infrared spectroscopy, Energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and electrochemical techniques for addressing the robust formation and electrochemical activity. The modified electrode exhibited excellent electrocatalytic activity towards dopamine without the common interference from ascorbic acid. The calibration plot for the dopamine sensor resulted linear range from 0.003 µM to 0.5 µM with a detection limit of 0.11 nM. The sensor's potential utility was tested by monitoring dopamine concentration changes in rat brain homogenates when subjected to neurotoxicity. The developed sensor was validated with gold-standard UV-Vis spectroscopy studies and computational studies were performed to understand the interaction between 1-pyrenebutyric acid and dopamine.

Toxoplasma gondii infection in people with schizophrenia is related to higher hair glucocorticoid levels.

Introduction: Toxoplasma gondii (TG) is a common protozoan parasite infecting approximately one third of the human population. Animal studies have shown that this parasite can manipulate its host behavior. Based on this, human studies have assessed if TG can be involved in mental health disorders associated with important behavioral modifications such as schizophrenia. However, results have been discrepant. Given that TG has a strong impact on fear and risk-taking processes in animal studies and that fear and risk-taking behaviors are associated with the human stress response, we tested whether glucocorticoid biomarkers (salivary and hair) differ in people with schizophrenia and controls as a function of TG status. Methods: We measured TG antibodies in blood samples, as well as salivary and hair glucocorticoid levels in 226 people with schizophrenia (19.9% women, mean age = 39 years old) and 129 healthy individuals (controls) (45.7% women, mean age = 41 years old). Results: The results showed that people with schizophrenia infected with TG presented significantly higher hair glucocorticoid concentrations than non-infected people with schizophrenia. This effect was not found in control participants. No effect was observed for salivary glucocorticoid levels. Additionally, there were no associations between TG infection and positive psychotic symptoms nor impulsivity. Discussion: These results show that people with schizophrenia present high levels of hair glucocorticoid levels only when they are infected with TG. Further studies performed in populations suffering from other mental health disorders are needed to determine if this effect is specific to schizophrenia, or whether it is generalized across mental health disorders.

Using the Operating Room Black Box to Assess Surgical Team Member Adaptation Under Uncertainty: An Observational Study.

OBJECTIVE: Identify how surgical team members uniquely contribute to teamwork and adapt their teamwork skills during instances of uncertainty. BACKGROUND: The importance of surgical teamwork in preventing patient harm is well documented. Yet, little is known about how key roles (nurse, anesthesiologist, surgeon, and medical trainee) uniquely contribute to teamwork during instances of uncertainty, particularly when adapting to and rectifying an intraoperative adverse event (IAE). METHODS: Audiovisual data of 23 laparoscopic cases from a large community teaching hospital were prospectively captured using OR Black Box. Human factors researchers retrospectively coded videos for teamwork skills (backup behavior, coordination, psychological safety, situation assessment, team decision-making, and leadership) by team role under 2 conditions of uncertainty: associated with an IAE versus no IAE. Surgeons identified IAEs. RESULTS: In all, 1015 instances of teamwork skills were observed. Nurses adapted to IAEs by expressing more backup behavior skills (5.3× increase; 13.9 instances/hour during an IAE vs 2.2 instances/hour when no IAE) while surgeons and medical trainees expressed more psychological safety skills (surgeons: 3.6× increase; 30.0 instances/hour vs 6.6 instances/hour and trainees: 6.6× increase; 31.2 instances/hour vs 4.1 instances/hour). All roles expressed fewer situation assessment skills during an IAE versus no IAE. CONCLUSIONS: OR Black Box enabled the assessment of critically important details about how team members uniquely contribute during instances of uncertainty. Some teamwork skills were amplified, while others dampened when dealing with IAEs. The knowledge of how each role contributes to teamwork and adapts to IAEs should be used to inform the design of tailored interventions to strengthen interprofessional teamwork.

The Signature Biobank: A longitudinal biopsychosocial repository of psychiatric emergency patients.

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit.

Fetal programming effect of rumen-protected methionine on primiparous Angus × Simmental offspring's performance and skeletal muscle gene expression.

Primiparous Angus × Simmental dams (n = 22) with an average body weight (BW) of 449 ±â€…32 kg of BW were divided based on two nutritional treatments: control (CTRL) and rumen-protected methionine (RPM). The control group received bermudagrass hay, corn gluten, and soybean hulls pellets supplementation (base diet); whereas the RPM group received the base diet in addition to 0.07% of DM of RPM at a fixed rate during the last trimester of gestation and the first ~80 d of lactation, in which calves (n = 17) were early weaned. Only male calves were included in this study. After weaning, calves born to RPM dams also received RPM from weaning (day 1) to day 100. Blood sampling and skeletal muscle biopsies for subsequent quantitative polymerase chain reaction (PCR) analysis were conducted on days 1, 25, 50, and 100 on calves. Quantitative PCR data were analyzed using GLIMMIX, and blood metabolites concentrations, BW, and body condition score (BCS) were analyzed using the MIXED procedure of SAS. There was no difference in maternal BW and BCS between treatments. Glucose and blood metabolites that served as biomarkers for liver health (e.g., aspartate transaminase, albumin, alkaline phosphatase, and alanine transaminase) were in the normal levels for all calves (P > 0.40). Calves in the RPM group had a greater expression of adipogenic genes (e.g., PPARG, LPL, and CEBPD) at day 100 compared with CTRL (P < 0.01). In addition, DNA methylation (DNMT1) and oxidative stress-related genes (SOD2 and NOS3) in the RPM group were upregulated at day 100 compared with CTRL (P < 0.01). These results may suggest that calves born to primiparous dams exposed to RPM supplementation are more prone to develop greater adipose tissue than CTRL calves. Furthermore, RPM supplementation may improve methylation processes, as shown by the upregulation of DNMT1. The results shown in our study aim at expanding the knowledge on fetal programming and early-life growth and development of beef cattle under supplementation with RPM.

Plane of nutrition plays a critical role in fetal and postnatal growth in beef cattle offspring. Methionine, a limiting amino acid in ruminants, is also involved in DNA methylation due to its role as S-adenosyl methionine precursor. A complete randomized design experiment was conducted to assess the fetal programming effect of rumen-protected methionine (RPM) supplementation on beef cattle. Calves born to primiparous beef heifers, that individually received RPM during the last trimester of gestation and lactation, had a greater expression of genes related to adipose tissue development, oxidative stress, and DNA methylation compared with those born to dams that did not receive rumen-protected supplementation. No difference in animal performance or blood parameters that serve as biomarkers for liver health status was detected. Our results suggest that maternal supplementation with RPM during the last trimester of gestation and lactation, and supplementation to the offspring after early weaning, could potentially increase adipose tissue development on male calves.

Learning to embrace one's stress: the selective effects of short videos on youth's stress mindsets.

BACKGROUND AND OBJECTIVES: Stress is not inherently negative. As youth will inevitably experience stress when facing the various challenges of adolescence, they can benefit from developing a stress-can-be-enhancing mindset rather than learning to fear their stress responses and avoid taking on challenges. We aimed to verify whether a rapid intervention improved stress mindsets and diminished perceived stress and anxiety sensitivity in adolescents. DESIGN AND METHODS: An online experimental design randomly exposed 233 Canadian youths aged 14-17 (83% female) to four videos of the Stress N' Go intervention (how to embrace stress) or to control condition videos (brain facts). Validated questionnaires assessing stress mindsets, perceived stress, and anxiety sensitivity were administered pre- and post-intervention, followed by open-ended questions. RESULTS: The intervention content successfully instilled a stress-can-be-enhancing mindset compared to the control condition. Although Bayes factor analyses showed no main differences in perceived stress or anxiety sensitivity between conditions, a thematic analysis revealed that the intervention helped participants to live better with their stress. CONCLUSIONS: Overall, these results suggest that our intervention can rapidly modify stress mindsets in youth. Future studies are needed to determine whether modifying stress mindsets is sufficient to alter anxiety sensitivity in certain adolescents and contexts.

The serotonin transporter sustains human brown adipose tissue thermogenesis.

Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT. Serotonin decreases uncoupled respiration and reduces uncoupling protein 1 via the 5-HT2B receptor. SERT inhibition by the selective serotonin reuptake inhibitor (SSRI) sertraline prevents uptake of extracellular serotonin, thereby potentiating serotonin's suppressive effect on brown adipocytes. Furthermore, we see that sertraline reduces BAT activation in healthy volunteers, and SSRI-treated patients demonstrate no 18F-fluorodeoxyglucose uptake by BAT at room temperature, unlike matched controls. Inhibition of BAT thermogenesis may contribute to SSRI-induced weight gain and metabolic dysfunction, and reducing peripheral serotonin action may be an approach to treat obesity and metabolic disease.

Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation.

The objective of our study was to assess the effect of rumen-protected niacin supplementation on the transcriptome of liver tissue in growing Angus × Simmental steers and heifers through RNA-seq analysis. Consequently, we wanted to assess the known role of niacin in the physiological processes of vasodilation, detoxification, and immune function in beef hepatic tissue. Normal weaned calves (~8 months old) were provided either a control diet or a diet supplemented with rumen-protected niacin (6 g/hd/d) for a 30-day period, followed by a liver biopsy. We observed a significant list of changes at the transcriptome level due to rumen-protected niacin supplementation. Several metabolic pathways revealed potential positive effects to the animal's liver metabolism due to administration of rumen-protected niacin; for example, a decrease in lipolysis, apoptosis, inflammatory responses, atherosclerosis, oxidative stress, fibrosis, and vasodilation-related pathways. Therefore, results from our study showed that the liver transcriptional machinery switched several metabolic pathways to a condition that could potentially benefit the health status of animals supplemented with rumen-protected niacin. In conclusion, based on the results of our study, we can suggest the utilization of rumen-protected niacin supplementation as a nutritional strategy could improve the health status of growing beef cattle in different beef production stages, such as backgrounding operations or new arrivals to a feedlot.

Are Physician Assistants Able to Correctly Identify Prescribing Errors? A Cross-Sectional Study.

PURPOSE: (1) To describe how often physician assistant (PA) students correctly identify prescribing errors and (2) examine between-cohort differences on ability to correctly identify prescribing errors. METHODS: This was a cross-sectional study of 2 cohorts of PA students at one institution. Students were presented with 3 hypothetical prescriptions, 2 of which contained a prescribing error. For each prescription, students were asked to (1) identify whether an error occurred and (2) indicate the type of error. A simple Poisson regression model analyzed the data. RESULTS: We received responses from 130 students (72.6% response rate). Approximately 12% (12.3%, n = 16) correctly identified whether all 3 prescriptions were correct. The median number of correctly identified prescriptions was 1 (interquartile range = 1). There was not a statistically significant between-cohort difference identifying the correct number of prescriptions (ß = 0.27, P = .10). CONCLUSION: Physician assistant students' prescribing error identification was similar to previous research in medical and nursing students. Efforts to improve prescribing training are critical to ensure patient safety.

Films for Wound Healing Fabricated Using a Solvent Casting Technique.

Wound healing is a complex process that involves restoring the structure of damaged tissues through four phases: hemostasis, inflammation, proliferation, and remodeling. Wound dressings are the most common treatment used to cover wounds, reduce infection risk and the loss of physiological fluids, and enhance wound healing. Despite there being several types of wound dressings based on different materials and fabricated through various techniques, polymeric films have been widely employed due to their biocompatibility and low immunogenicity. Furthermore, they are non-invasive, easy to apply, allow gas exchange, and can be transparent. Among different methods for designing polymeric films, solvent casting represents a reliable, preferable, and highly used technique due to its easygoing and relatively low-cost procedure compared to sophisticated methods such as spin coating, microfluidic spinning, or 3D printing. Therefore, this review focuses on the polymeric dressings obtained using this technique, emphasizing the critical manufacturing factors related to pharmaceuticals, specifically discussing the formulation variables necessary to create wound dressings that demonstrate effective performance.