Negative Side Effects Research Articles

YouTube and the implementation and discontinuation of the oral contraceptive pill: A mixed-method content analysis.

Women living in high-quality healthcare systems are more likely to use oral contraceptives at some point in their lives. Research findings have sparked controversial discussions about contraception in the scientific community and the media, potentially leading to higher rates of method discontinuation. Understanding the underlying motives for method discontinuation is crucial for reproductive health equity and future programming interventions. To address this question, this study aims to explore women's experiences of oral contraceptive use and discontinuation on YouTube. A concurrent explanatory mixed-methods design was used to conduct content analysis of German YouTube videos. The information from 175 videos of 158 individuals was extracted through quantitative descriptive content analysis. Twenty-one individuals were included in the qualitative content analysis. The body was a recurring theme in the pill biographies. Women described, for example, bodily sensations as reasons for taking and stopping the pill. They also described positive and negative side effects while taking the pill and after stopping. The most common side effects of taking the pill mentioned by YouTubers were mood swings (76/158), weight gain (45/158), headaches (33/158), and depressed mood (45/158). The symptoms after discontinuation reported most were facial skin impurities (108/158), decreased mood swings (47/158), hair loss (42/158), and weight loss (36/158). Overall, women overwhelmingly rated their discontinuation experience as positive (87/91). The study identified key symptoms of oral contraceptive initiation and discontinuation by portraying the experiences of female YouTubers, adding valuable insights to the understanding of method initiation and discontinuation. Further research is needed to explore women's personal experiences with method discontinuation beyond the YouTube platform.

Media coverage of COVID-19 vaccination-associated cerebral venous sinus thrombosis was followed by a surge in emergency presentations due to headache – observations from a university hospital in Germany

Nocebo effects describe all negative outcomes for well-being brought about by negative health-related expectations. Media coverage of drug side effects can fuel nocebo effects and lead to increased symptom reports. This retrospective observational analysis of emergency reports at the neurological emergency room at University Hospital Essen, Germany, examines whether media communication about a cumulation of very rare cases of cerebral venous sinus thrombosis (CVST) after COVID-19 vaccination with the AstraZeneca compound (ChAdOx-1 nCoV-19) was followed by an increase in weekly presentation rates of patients with the main complaint of headache, a symptom commonly occurring as a vaccination reaction but also communicated as a warning symptom for CVST. The rate of headache presentations increased by 171.7% during the five weeks after the first announcement of CVSTs in Germany on 11 March 2021, compared to the five weeks immediately prior. Furthermore, more young women sought consultation for headache, reflecting the communicated at-risk profile for CVST. The increased rate of headache presenters contributed to a 32.1% rise in total neurological emergency cases, causing an increased strain on the emergency facility after the side effect risk was publicized. We discuss a causal role of negative side effect expectations after vaccination with AstraZeneca as a driver for this increase. While transparent communication about benefits and potential side effects is crucial for vaccination acceptance, increased vigilance toward nocebo effects in health-related media communication is needed due to its potential harm to the individual and society, especially when emergency medical resources are stretched thin.

Upregulation of iNOS/NO in Cancer Cells That Survive a Photodynamic Challenge: Role of No in Accelerated Cell Migration and Invasion.

Anti-tumor photodynamic therapy (PDT) is a unique modality that employs a photosensitizer (PS), PS-exciting light, and O2 to generate cytotoxic oxidants. For various reasons, not all malignant cells in any given tumor will succumb to a PDT challenge. Previous studies by the authors revealed that nitric oxide (NO) from inducible NO synthase (iNOS/NOS2) plays a key role in tumor cell resistance and also stimulation of migratory/invasive aggressiveness of surviving cells. iNOS was the only NOS isoform implicated in these effects. Significantly, NO from stress-upregulated iNOS was much more important in this regard than NO from preexisting enzymes. Greater NO-dependent resistance, migration, and invasion was observed with at least three different cancer cell lines, and this was attenuated by iNOS activity inhibitors, NO scavengers, or an iNOS transcriptional inhibitor. NO diffusing from PDT-targeted cells also stimulated migration/invasion potency of non-targeted bystander cells. Unless counteracted by appropriate measures, all these effects could seriously compromise clinical PDT efficacy. Here, we will review specific examples of these negative side effects of PDT and how they might be suppressed by adjuvants such as NO scavengers or inhibitors of iNOS activity or expression.

INCREASE OF THE LUBRICATING PROPERTIES OF WATER-CLAY DRILLING MUDS DURING INCLINED AND HORIZONTAL DRILLING

The paper presents the results of experimental studies of the antifracturing properties of natural oils: castor, hemp, rapeseed, soybean, mustard, sunflower, and corn. The results of the experiments are presented, which allow to evaluate the effect of the studied natural oils on the parameters of fresh, mineralized and saline-saturated water-clay drilling mud (density, rheological and structural-mechanical properties, pH level, filtration index, thickness and stickiness of the clay crust, lubrication coefficient). The experiment was conducted using the methodology of the American Petroleum Institute (according to API standards). It was established that in the fresh solution, rapeseed oil in concentrations of 1 and 3 % and sunflower oil in a concentration of 1 % showed the most effective lubricating properties, in a mineralized solution - sunflower oil with a concentration of 0.5 % and rapeseed oil with a concentration of 3 %, in a saline-saturated solution - rapeseed oil with a concentration of 1 %. Sunflower oil additives showed satisfactory test results only for fresh and mineralized water-clay drilling mud. Compared to sunflower oil, rapeseed oil showed itself when added to all the tested samples. It can be concluded that the introduction of rapeseed oil provides satisfactory anti-fracture and technological indicators for all types of solutions, therefore rapeseed oil was chosen as the basis of the lubricant additive. Technologically appropriate concentrations of oils are in the range from 1 to 3 %. At these oil concentrations, the negative side effect, in particular on the foaming of the solution, is to a lesser extent, the solutions are characterized by a stable consistency over time, and their lubricating properties are improved. The composition of a lubricating additive based on rapeseed oil was developed for the treatment of various types of water-clay drilling mud.

Intermediate-term impact on corneal endothelial cells and efficacy of Preserflo MicroShunt implantation in patients with open-angle glaucoma - a prospective study over two years.

Preserflo MicroShunt is a novel microinvasive bleb forming device for the treatment of primary open-angle glaucoma. The intermediate- and long-term success and the impact of this procedure on corneal endothelial cell density remain to be investigated. In this prospective observational study, 62 eyes of 55 glaucoma patients (mean age ± SD: 67.0 ± 15.0years) receiving a Preserflo MicroShunt were included. Corneal endothelial cell density, intraocular pressure and best corrected visual acuity were assessed preoperatively and at 3, 6, 9, 12, 18 and 24months postoperatively. Success rates, bleb revision rates and complications were analysed. Complete success was defined as an intraocular pressure reduction of ≥ 20% and achieving a target pressure of ≤ 18, ≤ 15 or ≤ 12mmHg without antiglaucoma medication. Qualified success indicated that the criteria were reached with or without medication. Corneal endothelial cells showed no significant decline over 24months (p > 0.05). Intraocular pressure showed a substantial reduction postoperatively (p < 0.001), decreasing from 29.6 ± 8,3mmHg to 13.0 ± 4.3mmHg after 24months (p < 0.001). Complete and qualified success with a target pressure ≤ 15mmHg was achieved in 52.9% and 54.6% of cases after 24months, respectively. Best corrected visual acuity did not change after 24months. Preserflo MicroShunt had no negative side effects on corneal endothelial cells and showed favourable success rates after 2years in patients with open-angle glaucoma.

Development and Evaluation of a Novel Herbal Anti-Ulcer Gel Formulation Incorporating Bauhinia Racemosa Extract

This research paper focuses on the development and testing of an anti-ulcer gel containing Bauhinia Racemosa extract that is specifically designed for the treatment of mouth ulcers. The study's goal is to overcome the limits of current treatment choices by offering a natural and effective alternative for people suffering from mouth ulcers. The research aims include developing an anti-ulcer gel based on Bauhinia Racemosa extract, assessing its efficacy and safety, and adding to existing knowledge on ulcer treatment. The gel formulation combines Bauhinia Racemosa's distinct phytochemical composition, including flavonoids, tannins, and saponins, which are thought to have anti-inflammatory, antibacterial, and wound-healing activities. The anti-ulcer gel's efficacy will be evaluated using a variety of criteria, including pain reduction, ulcer healing promotion, and relief of oral discomfort associated with mouth ulcers. Safety and tolerability will be extensively investigated to guarantee that there are no negative side effects. The study will also investigate the probable processes by which the gel exerts its anti-ulcer properties. The anti-ulcer gel's effectiveness will be determined by comparing it to existing conventional therapies for mouth ulcers. The long-term impact and recurrence rates of mouth ulcers treated with the gel will also be studied. The purpose of this research is to contribute to the scientific literature on natural products for the treatment of mouth ulcers by making evidence-based recommendations for the use of anti-ulcer gel in clinical practice. The study will also highlight topics for future research and development of natural products for treating mouth ulcers. This research report aims to improve the quality of life for those suffering from mouth ulcers by offering a safe, effective, and natural treatment option.

Exploring the Therapeutic Potential of Baicalin: Mitigating Anxiety and Depression in Epileptic Rats.

Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting. The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model. Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1β (IL-1β) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding. Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1β signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1β. This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA.

Disrupted one-carbon metabolism in heifers negatively affects their health and physiology.

The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ± 12.6kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming.

Can magnetic nanoparticles enhance adoptive cell therapy via driving migration of lymphocytes into tumors?

Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors.

AN OVERVIEW OF SOME HERBAL ANTIDEPRESSANT PLANTS

There are numerous ways to categorize and treat depression, which is a diverse mood disease. The illness is caused by factors such as 5-HT, NA, and MAO-A inhibition and stimulation. Reduced curiosity about pleasure, feelings of inappropriate guilt or worthlessness, a drop in hunger and sexual desire, sleeplessness, and persistent suicidal thoughts are some of the symptoms. There are several synthetic medications used to treat depression, but not all of them make patients happy, and some of them may have negative side effects. Many have turned to well-liked traditional herbal remedies to avoid the negative effects of allopathic therapy. Due to their broad application, therapeutic efficacy, and little to negligible adverse effects, herbal medications are currently used worldwide. Several medicinal plants and medicines derived from these plants have shown antidepressant properties by the combined effect of their medicinal constituents. We discuss promising novel medicinal products targets for the management of major depressive illness in this review. We address the potential antidepressant benefits of selectively targeting receptors, including opioid, G-protein-coupled, and metabotropic glutamate receptors. Since they may also have therapeutic value, we also talk about substances that target biological processes, including inflammation, the gut microbiota, the cholesterol biosynthesis pathway, and the hypothalamic-pituitary-adrenal axis. Lastly, we offer a synopsis of all the plants displayed in graphical format, together with an overview of the antidepressant plants which currently are widely accessible.

Health Risk Associated with Conventional Skin Lighteners and Female Civil Servants’ Comprehension of Skin Lightening Ingredient Information in Anambra State

Skin-lightening products have been in use for many years to lighten skin colour. However, these products contain chemicals that can alter the skin's chemical structure and inhibit the production of melanin. Therefore, users of these products need to understand the ingredients and the potential health risks associated with their use. A study was conducted to assess the health risks associated with conventional skin-lightening products and to determine how well female civil servants understood the ingredient information on the product packaging. The study aimed to determine how many women read the ingredient information on these products, how many understood the information, and how many were aware of the health risks associated with their use. The study was conducted as a survey of 348 civil servants from 21 Ministries in Anambra State using an online sample size calculator. The study was anchored on the Individual Difference theory and selective perception media effect. The survey found that a significant number of female civil servants in Anambra state do not read the ingredient information on skin-lightening products. It was also discovered that the majority of female civil servants in Anambra State do not comprehend the product ingredient information because of its technical nature. Despite this, the study found that most women were aware of the health risks associated with the use of these products. The study concluded that female civil servants in Anambra State were aware of the ingredient information composition on skin-lightening products, but did not read it, making it difficult for them to understand and interpret the information. However, most of these women were still aware of the health risks associated with the use of skin-lightening products but still used them because of the benefits they claimed to have experienced. The study recommended that manufacturers and brand designers should simplify the technical language used to describe the product ingredients to make it easier for users to understand. Additionally, regulatory agencies like NAFDAC and SON should ensure that manufacturers produce skin products that do not contain harmful chemicals like hydroquinone, corticosteroids, and mercury. If these chemicals are used, users should be informed of the negative side effects.

Minimizing Negative Side Effects in Cooperative Multi-Agent Systems using Distributed Coordination

Autonomous agents operating in real-world environments frequently encounter undesirable outcomes or negative side effects (NSEs) when working collaboratively alongside other agents. Even when agents can execute their primary task optimally when operating in isolation, their training may not account for potential negative interactions that arise in the presence of other agents. We frame the challenge of minimizing NSEs as a lexicographic decentralized Markov decision process in which we assume independence of rewards and transitions with respect to the primary assigned tasks, but recognize that addressing negative side effects creates a form of dependence among the agents. We present a lexicographic Q-learning approach to mitigate the NSEs using human feedback models while maintaining near-optimality with respect to the assigned tasks---up to some given slack. Our empirical evaluation across two domains demonstrates that our collaborative approach effectively mitigates NSEs, outperforming non-collaborative methods.

Natural variant of Rht27, a dwarfing gene, enhances yield potential in wheat.

Discovery of Rht27, a dwarf gene in wheat, showed potential in enhancing grain yield by reducing plant height. Plant height plays a crucial role in crop architecture and grain yield, and semi-dwarf Reduced Height (Rht) alleles contribute to lodging resistance and were important in "Green Revolution." However, the use of these alleles is associated with some negative side effects in some environments, such as reduced coleoptile length, low nitrogen use efficiency, and reduced yield. Therefore, novel dwarf gene resources are needed to pave an alternative route to overcome these side effects. In this study, a super-dwarf mutant rht27 was obtained by the mutagenesis of G1812 (Triticum urartu, the progenitor of the A sub-genome of common wheat). Genetic analysis revealed that the dwarf phenotype was regulated by a single recessive genetic factor. The candidate region for Rht27 was narrowed to a 1.55Mb region on chromosome 3, within which we found two potential candidate genes that showed polymorphisms between the mutant and non-mutagenized G1812. Furthermore, the natural variants and elite haplotypes of the two candidates were investigated in a natural population of common wheat. The results showed that the natural variants affect grain yield components, and the dwarf haplotypes show the potential in improving agronomic traits and grain yield. Although the mutation in Rht27 results in severe dwarf phenotype in T. urartu, the natural variants in common wheat showed desirable phenotype, which suggests that Rht27 has the potential to improve wheat yield by utilizing its weak allelic mutation or fine-tuning its expression level.

Nutraceuticals Health Benefits in Cancer

Abstract: Cancer is one of the leading causes of death worldwide, with multiple pathological components. Genetic abnormalities, infection or inflammation, poor diet, radiation exposure, work stress, and/or ingestion of toxic substances have all been associated with cancer development and progression. Early detection and treatment of cancer have been shown to increase the chances of survival and recovery and reduce the side effects of anticancer drugs. Anticancer drugs continue to cause negative side effects that negate treatment benefits in terms of hospitalization and survival. Many naturally occurring bioactive compounds are shown to have anticancer properties. That is, they can eliminate altered and cancer cells without harming their healthy counterparts. In particular, the following activities have been reported to support nutrition during cancer treatment: cell growth inhibition, antioxidant activity, anti-inflammatory activity, and minimized negative effects due to natural antioxidants. Keeping the side effects minimum helps patients adhere to anticancer therapy. Among currently available anticancer agents, dietary supplementation can be considered in conjunction with current chemotherapy to improve response and compliance in cancer patients. However, it should be noted that before discussing data from studies on bioactive plant supplements, it is important to ensure that the tests were performed according to protocol.

Tamarix aphylla derived metabolites ameliorate indomethacin-induced gastric ulcers in rats by modulating the MAPK signaling pathway, alleviating oxidative stress and inflammation: In vivo study supported by pharmacological network analysis.

Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1β, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.

Determination of synergic antioxidant interactions of Ellagic acid, cemotherapy drugs (Docetaxel and Mitoxantron) and their combinations

Chemotherapy drugs are commonly used in cancer treatment, despite their numerous negative side effects. Today, there are studies to reduce the side effects of these drugs and to increase their benefits by combining them with natural substances. Our study investigated the antioxidant and antiradical activities of Ellagic acid (EA), a natural substance, DOC and MIX, commonly used chemotherapeutics, as well as their combinations (EA+DOC, EA+MIX). For this purpose, the methods of DPPH• and ABTS•+ scavenging activity, Fe3+-Fe2+ and Cu2+-Cu1+ reduction capacity were used. After the study, the interactions were analysed with the combination index using Compusyn software. Concentrations with maximum synergy in combinations have been identified. For this purpose, firstly, the combination concentrations used in the antioxidant activity methods and the absorbance values were entered into the Compusyn programme. When DPPH• and ABTS•+ scavenging activity results were entered into the programme, more effective synergistic effect was observed for EA+DOC at lower concentrations (7:7µg/mL), (0.125:1µg/mL) respectively. For EA+MIX, no synergistic effect was observed with the application of DPPH scavenging activity results to the programme, while for ABTS•+ scavenging activity, more effective synergistic effect was observed at higher concentrations within the applied doses (0.750:6µg/ml). When Fe3+-Fe2+ and Cu2+-Cu1+ reduction results were applied to the programme; synergistic effect was observed at higher concentrations (17:17µg/mL) for both EA+DOC and EA+MIX and even strong synergistic effect was observed in many of them. The obtained results provide guidance for the use of these combinations in further studies, such as anticancer and enzyme studies.

Development of biocomposite films incorporated with the extract from pitcher associated bacteria for the postharvest protection from fungi.

Pythium aphanidermatum is known to cause diseases likedamping-off, root rot, stem rot and fruit rot in a wide range of plants. Eventhough many chemical methods have been demonstrated to have the potential to manage these diseases, their benefits are being offset equally by the negative side effects. Therefore, the control of Pythium spp. using natural antifungal agents is of immense significance due to its environmental safety. Here, the plant associated microorganisms with antifungal metabolites have significant promises to be explored both as sustainable biocontrol agents and also as active constituents of antifungal materials. Antimicrobial packaging films prepared using such components can have significant applications to meet the requirements to prevent postharvest loss of agricultural produce by inhibiting the fungal growth. Eventhough there are reports on the development of antimicrobial packaging films for such applications, the use of bacterial extracts with antifungal activity for the same is least investigated. Hence, the present study demonstrates the development of biocomposite films prepared using polyvinyl alcohol (PVA) incorporated with the extracts prepared from bacterial isolates (Serratia sp. NhPB1, Kocuria sp. NhPB49, and Pantoea dispersa NhPB54) previously isolated from the pitcher plant. Here, the individual films were prepared by incorporating 1mL of bacterial extract in 40mL of 3% PVA solution and the developed films were then subjected to antifungal activity screening against P. aphanidermatum. The antifungal activity analysis of the films prepared with the incorporation of extracts from Serratia sp. NhPB1, Kocuria sp. NhPB49, and Pantoea dispersa NhPB54 showed remarkable activity against the tested pathogen. The application of biocomposite films on Solanum lycopersicum and Capsicum annuum fruits for its protection from P. aphanidermatum by dip coating method further indicates the promises of developed biocomposite films for active packaging applications.

Macrophage Targeted Dendrimer-Tesaglitazar Therapy for Atherosclerosis

Background: Atherosclerosis is a leading contributor to cardiovascular disease, the number one cause of death globally. Although atherosclerosis is clearly a multicellular disease that also affects endothelial cells as well as smooth muscle cells of arteries, it is increasingly recognized as an inflammatory disease. Our goal is to determine if targeting immune cells implicated in atherosclerosis can halt plaque accumulation and resulting derangement of vascular cells in the aorta. Peroxisome proliferator activated receptors (PPARs) within macrophages present a promising therapeutic target as PPAR-α and PPAR-γ agonists have been shown to improve lipid metabolism and inhibit macrophage foam cell formation. However, due to high doses required and associated side effects, clinical translation was halted. We target anti-atherogenic pathways in immune cells using the novel treatment D-Tesa, a dendrimer conjugate of a dual PPAR-α/γ agonist, Tesaglitazar. Methods: 25-week-old, male, apolipoprotein E knockout (ApoE−/−) mice were fed high fat diet (HFD) for 16 weeks to induce atherosclerosis and randomized into two groups: 1) treatment group: D-Tesa for 6 weeks (20μg/kg twice weekly by oral gavage and 2) untreated group. HFD was continued for the duration of the study. Pulse wave velocity (PWV: Doppler), blood pressure (BP: tail cuff on trained, conscious mice), and body weight were monitored. Dendrimer mediated delivery of drug payload to plaque macrophages was studied using D-Cy5, a fluorescently labeled dendrimer, in an atherosclerotic mouse. Aortas were isolated and used for vasoreactivity studies and western blot analysis. THP-1 cell derived foam cells were used to study D-Tesa’s mechanism of action in vitro. Results: Immunofluorescence staining and confocal microscopy revealed that D-Cy5 localized in macrophages within the atherosclerotic plaque in ApoE−/− mice on HFD, indicating that the dendrimer can deliver drugs specifically into the plaque. D-Tesa slowed plaque progression, preserved endothelial function, and decreased arterial stiffness. BP was similar and unchanged between groups. D-Tesa surprisingly decreased body weight, which was the opposite effect observed from the free drug in clinical trials. Western blotting of aorta revealed that D-Tesa treated mice experienced an upregulation of PPAR-α, PPAR-γ, and ABCA1. The in vitro studies with THP-1 derived foam cells confirmed the upregulation of the cholesterol efflux pathway and anti-inflammatory benefit of D-Tesa. Conclusion: D-Tesa offers a novel therapy to ameliorate multiple damaging consequences of atherosclerosis on the cardiovascular system including improvements in plaque burden, endothelial function, arterial stiffness, and body weight in an ApoE−/− model of atherosclerosis. Excitingly, these effects were seen at 2-15 times lower doses despite continued HFD than those reported in literature with a combination of free Tesa and low-fat diet. Thus, D-Tesa offers great translational relevance because of potential reduction in negative side effects and higher patient benefit due to noted lack of compliance with dietary changes in the clinic. Further research is ongoing to evaluate sex differences, dose response, and long-term effects of this highly promising therapy. This work was supported by a NHLBI grant R01HL148112 01 (L.S.) and the Traystman Endowment (S.K.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Measuring the Influence of Side Effect Expectations, Beliefs, and Incident Side Effects on the Risk for Drug Discontinuation Among Individuals Starting New Medications, a Cross-sectional Study.

To measure the impact of beliefs, expectations, side effects, and their combined effects on the risk for medication nonpersistence. Using a cross-sectional design, individuals from Saskatchewan, Canada who started a new antihypertensive, cholesterol-lowering, or antihyperglycemic medication were surveyed about risk factors for nonpersistence including: (a) beliefs measured by a composite score of three questions asking about the threat of the condition, importance of the drug, and harm of the drug; (b) incident side effects attributed to treatment; and (c) expectations for side effects before starting treatment. Descriptive statistics and logistic regression models were used to quantify the influence of these risk factors on the outcome of nonpersistence. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Among 3,029 respondents, 5.8% (n=177) reported nonpersistence within four months after starting the new drug. After adjustment for numerous covariates representing sociodemographics, health-care providers, medication experiences and beliefs, both negative beliefs (OR: 7.26, 95%CI: 4.98-10.59) and incident side effects (OR: 8.00, 95%CI: 5.49-11.68) were associated with the highest odds of nonpersistence with no evidence of interaction. In contrast, expectations for side effects before starting treatment exhibited an important interaction with incident side effects following treatment initiation. Among respondents with incident side effects (n=741, 24.5%), the risk for early nonpersistence was 11.5% if they indicated an expectation for side effects before starting the medication compared to 23.6% if they did not (adjusted OR: 0.38, 95%CI: 0.25-0.60). Expectations for side effects may be a previously unrecognized but important marker of the probability to persist with treatment. A high percentage of new medication users appeared unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur.

COMPARING THE EFFECTS OF AROMATASE INHIBITORS AND SELECTIVE OESTROGEN RECEPTOR MODULATORS ON BODY COMPOSITION, EXERCISE TOLERANCE AND MARKERS OF CARDIOVASCULAR RISK IN FEMALES WITH BREAST CANCER

INTRODUCTION Adjuvant endocrine therapy (AET) blocks the action of estrogens and is commonly prescribed in hormone receptor-positive breast cancer. Given the putative cardioprotective role of estrogens in females, AET may exacerbate the negative metabolic side-effects of anthracycline chemotherapy. This study examined the early effects of combined anthracycline chemotherapy and AET on body composition, exercise tolerance and markers of cardiovascular risk in a cohort of females with breast cancer. METHODS This was a secondary analysis of the BReast cancer EXercise InTervention (BREXIT) Trial. Females with breast cancer (n=105, aged 51 ± 8 years, BMI 27.4 ± 5.1, mean ± SD) scheduled for anthracycline chemotherapy participated in this study. Aerobic exercise capacity, body composition, physical function, and blood pressure were measured before anthracycline treatment and after 4- and 12-months follow-up. Linear mixed models assessed whether aromatase inhibitors (AI) or selective estrogen receptor modulators (SERMS) affected exercise tolerance, body composition and markers of cardiovascular risk compared to non-endocrine breast cancer treatments. RESULTS Twelve months of anthracycline treatment combined with AI or SERMs decreased total body lean mass by 1.4 kg (2%; interaction p=0.01) and 1kg (1%; interaction p=0.16) respectively, when compared to non-endocrine therapies. There were trends for AET to decrease total fat (-1.5%, interaction p=0.05) and android fat (-2.3%, interaction p=0.07) mass compared to non-endocrine therapy after 12 months. AIs significantly increased both systolic (5.8mmHg, interaction p=0.05) and diastolic (4.0mmHg, interaction p=0.05) blood pressure after 12 months of treatment compared to SERMs or non-endocrine therapies. There was no effect of either AET or SERMS on VO2peak, leg press or seated row 1RM, 30 second sit to stand or handgrip strength. DISCUSSION AND CONCLUSION Short-term treatment with adjuvant endocrine therapies may accelerate muscle loss and increase blood pressure compared to non-endocrine therapies. However, these changes were not associated with worsening of physical function.