Risk Of Toxicity Research Articles

ASO Author Reflections: Young Adults and Racial Minorities May Be at High Risk for Financial Toxicity After Breast Cancer Treatment.

ASO Author Reflections: Young Adults and Racial Minorities May Be at High Risk for Financial Toxicity After Breast Cancer Treatment.

IoT-enabled smart cities towards green energy systems: a review

<span>Integration of internet of things (IoT) in smart city management to improve various functions and living standards due to increasing population growth has dramatically evolved ubiquitous and essential services at various stages of urbanization. Hence, smart cities need to be eco-friendly by improving various sectors like education, health, and transport to provide an urban and sustainable quality of life through solving complicated green energy networks, controlling toxic pollution risks, and public safety. Linking optimized green energy systems with the production and automation of advanced applications is crucial to compose implementation strategies for smart city services. This paper aims to conduct a review on eco-friendly plans and infrastructure of IoT-enabled smart cities by exploiting green energy approaches. This study performs critical observations, ideas, and analyses of recent research in the context of our mentioned research theme. This paper points out the technical and functional challenges of an optimal performance-based green IoT-enabled smart city infrastructure. In this sense, this study organizes observations of relevant initiatives, technologies, and experiences in IoT-enabled smart cities, as well as how to embed it with green energy. Moreover, it can provide significant directions to intellectuals and authorities to develop IoT-enabled smart city applications for prospective research.</span>

Discovery of tetrazole thioethers: An efficient, environmentally friendly and metal-free S-arylation using diaryliodonium salts

An efficient, environmentally friendly, and metal-free method for the synthesis of functionalized tetrazole thioethers via the S-arylation of tetrazole-5-thiones using diaryliodonium salts as aryl transfer reagents has been developed. This novel methodology provides rapid access to tetrazole thioether derivatives under facile conditions. Our study underscores the chemoselectivity of unsymmetrical diaryliodonium salts, emphasizing their preference for the transfer of sterically hindered and electron-deficient aryl groups. Notably, the synthesized compound 3h exhibits antitumor activity against A2789 (ovarian cancer) and MDA-MB-231 (breast cancer) tumor cells. In silico studies predict these compounds to possess good drug-likeness and low toxicity risk. These findings highlight the potential of functionalized tetrazole thioethers as antiproliferative agents and pave the way for further development and optimization in future investigations.

Skin-like dual-network gelatin/chitosan/emodin organohydrogel sensors mediated by Hofmeister effect and Schiff base reaction

Conductive gels have been extensively explored in the field of wearable electronics due to their excellent flexibility and deformability. Traditional gels constructed from synthetic networks pose risks to biosecurity due to residual monomers like acrylamide, while pure biological hydrogels are plagued by inadequate mechanical performance. This study explores an innovative strategy, employing a dual-network (DN) system with purely biological components, as a superior alternative to conventional synthetic networks. By integrating gelatin and chitosan, two natural polymers with inherent biocompatibility and advantageous biomedical properties, this approach successfully avoids the toxic risk of synthetic polymers. By utilizing emodin, a natural extract from Rheum officinale, as a cross-linking agent for chitosan by Schiff base reactions, and Hofmeister effect of gelatin induced by sodium carbonate, the DN gelatin/chitosan/emodin organohydrogels achieve ultrahigh tensile strength (up to 9.45 MPa), tunable moduli (ranging from 0.07 to 3.42 MPa), excellent toughness (~9.64 MJ/m3), and high ionic conductivity (7.63 mS/cm). Remarkably, these conductive organohydrogels also exhibit high sensitivity (gauge factor up to 1.5) and ultrahigh linearity (R2 up to 0.9995), making them promising candidates for soft human-motion sensors capable of accurately detecting and monitoring human movements in real time with high sensitivity and durability.

Do CYP2D6 polymorphisms affect the efficacy and toxicity of flecainide? A cohort study

Abstract Background The CYP2D6 enzyme, coded by the CYP2D6 gene, is the primary metabolic pathway for flecainide.(1,2) Over the years, studies on how different variants of this gene affect flecainide metabolism and efficacy have yielded contradictory results.(3–7) This is likely due to the fact that CYP2D6 pharmacogenetic classifications were not standardized until 2017.(8,9) Purpose To date, there has been no published study using a standardized classification to assess the efficacy and toxicity of flecainide across different CYP2D6 phenotypes; therefore, we decided to study this. Methods We conducted a cohort study with data collected through indirect methods, blinding all parties involved except the statistician. We identified patients with flecainide prescriptions (100 mg/12 h) and follow-up in our health area (n=450,136 people) between 2017 and 2021. A primary combined endpoint composed of initial inefficacy and early toxicity was pre-set, and a secondary combined endpoint of toxicity or inefficacy during follow-up. Results 104 patients met the criteria and agreed to participate: 38 (36.5%) intermediate metabolizers, 52 (50%) normal metabolizers, 2 (1.9%) could not be classified with certainty (compatible with intermediate or normal metabolizers), 7 (6.7%) poor metabolizers, 4 (3.8%) ultra-rapid metabolizers, and 1 (1%) possible hybrid. Intermediate and normal metabolizers showed an almost superimposable incidence of the primary endpoint (28,9% vs 28,8%, p=0.99), early inefficacy (21,6% vs 17,4%, p=0.97) and early toxicity (13,2% vs 13,3%, p=0.72). No significant differences were observed in multivariate analysis (p=0.76, picture 1) or in a combined endpoint of toxicity or inefficacy during follow-up (p=0.58, Kaplan-Meier in picture 2). Differences were seen in the primary endpoint when comparing poor metabolizers to the rest of the sample, although they did not reach statistical significance (p=0.07), likely due to the small number of patients in this group (n=7, absolute risk reduction -32%; 95% confidence interval: -41% to -23%). Conclusions Using the standardized classification for CYP2D6 pharmacogenetics, no statistically significant differences were detected between the two largest groups, intermediate and normal metabolizers. It is possible that better results are achieved in poor metabolizers. Based on these results, it is worth questioning whether, in an attempt to minimize the risk of flecainide toxicity, doses that are subtherapeutic in all groups except slow metabolizers have been used unknowingly.

Cardiac motion in patients with ventricular tachycardia: potential implications for the treatment of patients candidates to stereotactic arrhythmia radio-ablation (STAR)

Abstract Background Stereotactic arrhythmia radio-ablation (STAR) has proven to be a valid alternative treatment for refractory ventricular tachycardia (VT) in patients who are unsuitable to undergo standard catheter ablation (CA). It consists in the application of external beam radiotherapy in a single dose of 25 Gy to the target areas. There is increased research activity on better understanding the complex and fast motion of the heart and on reducing radiation toxicity. Purpose In the context of an in silico study to evaluate the feasibility of STAR with protons in patients with VT, the initial findings related to cardiac motion on the first 10 patients are here presented. Methods Prior to CA, each patient underwent ECG gated CT scans in expiratory breath-hold, with and without contrast and reconstructed at 30% (systole) and 80% (diastole) of the cardiac R-R cycle. Contouring of the ablation target as a clinical target volume (CTV) for proton treatment planning was performed based on a standard electrophysiological study with 3D eletroanatomical mapping. Two different treatment plans were created: the first with only the diastolic CTV as target (gated treatment), the second including both diastolic and systolic CTVs to create an Internal Target Volume (ITV) in the hypothesis of non-gated treatment. Robust optimization was used to create the Planning Target Volume (PTV). Results The target volumes used for treatment planning are given in Table 1. The median CTV was 10.90 (2.93-36.94) cm3 for diastole and 14.26 (1.73-36.31) cm3 for systole. These volumes are somewhat smaller than those reported in patients treated previously with STAR: this difference may be due to the fact that no respiratory motion was included in the target contour and that the study population includes many patients referred for ventricular ectopic beats without structural heart disease, where the ablation target is expected to be smaller as compared to patients with VT in structural heart disease. Despite a small median difference between the diastolic and systolic CTV of 0.53 (0.03-9.61) cm3, the ITV approach resulted in a median increase in volume compared to the largest of the two CTVs of 29 % (1%-44%). When considering the proton range uncertainty and potential errors in patient positioning (PTV), the target is this time enlarged by a factor 2.9 (1.9-3.9). This data indicates that both cardiac motion and uncertainties in patient positioning before treatment will have a large impact on the treatment volume thus affecting the amount of surrounding tissue exposed to radiation. Conclusion The ablation target contour at systole and diastole are of similar magnitude but their non-overlap results in a large increase in treated volume when radiation delivery is not gated for cardiac motion. Further analysis shall investigate on a case-by-case basis the potential reduction in risk of healthy tissue toxicity with cardiac-gated proton delivery.Table 1

How do patients with head and neck cancer and low skeletal muscle mass experience cisplatin-based chemoradiotherapy? A qualitative study

BackgroundPatients with head and neck squamous cell carcinoma (HNSCC) face several physical, emotional, and psychological challenges throughout treatment. Cisplatin-based chemoradiotherapy (CRT) is an effective but toxic treatment, with an increased risk for toxicities in patients with low skeletal muscle mass (SMM). Consequently, these patients are anticipated to experience greater treatment-related difficulties. We aimed to explore the experiences of patients with HNSCC and low SMM regarding cisplatin-based CRT.MethodsA descriptive qualitative study was conducted, interviewing seven patients 3 months after CRT using a topic guide. Thematic analysis of semi-structured interviews was conducted, to create a multi-dimensional understanding of patients’ experiences during and after cisplatin-based CRT.ResultsPrior to CRT themes included pre-treatment information, expectations towards treatment and trial, psychosocial circumstances, and supporting network. During CRT themes included toxicities, psychosocial impact, and supporting network. After CRT themes included reflection on period during CRT, psychosocial circumstances, informal support from networks and healthcare workers, and ongoing toxicities.ConclusionMost patients experience cisplatin-based CRT as a life-changing and distressing life event but cope through various strategies and supporting networks. Tailored counseling, ideally with on-demand consultations, is recommended. No differences were noted in patients’ perceptions of their cisplatin regimen.

Multidisciplinary strategies for cardiotoxicity management in ambulatory care: exploring practices, insights, and prospects for advancement

Abstract Background The management of cardiotoxicity, a significant concern in chemotherapy patients, necessitates a multidisciplinary approach. This study investigates the variability in cardiotoxicity management in outpatient settings across different medical specialties, which may lead to inconsistencies in patient care. Methods An extensive questionnaire-based study was conducted to assess the current practices and viewpoints of cardiologists, oncologists, and gynecologists in the management of cardiotoxicity among patients receiving outpatient chemotherapy in Germany. The survey engaged 1,329 medical professionals through an online platform, with a participation rate of 9.9%, amounting to 132 respondents. Results Respondents reported managing a combined total of 1,905 chemotherapy patients monthly, with individual patient loads ranging from 1 to 200. Notably, only a fraction of these patients – 37% under oncologist care and 48% under gynecologist care – underwent routine cardiological examinations. As shown in Figure 1, the three most common causes of cardiological presentations in patients undergoing chemotherapy were due to acute patient complaints (65.2%), before the start of chemotherapy (91.3%), and after the end of chemotherapy (78.3%). Furthermore, 37% of healthcare providers reported incorporating chemotherapy-induced cardiovascular toxicity risk assessments in their clinical routines. Medical history, ECG, and echocardiography were the most frequent examinations. Notably, 91.3% did not include cardiac biomarker measurements in their follow-up procedures (Figure 2). More than half of the participants (56%) expressed a need for simplified cardio-oncology guidelines. The majority of participants (84% and 83%, respectively) requested tools to assist in cardiovascular toxicity risk assessment and the implementation of appropriate therapeutic measures for patients undergoing chemotherapy. Conclusions The study draws attention to significant interdisciplinary care gaps in managing cardiotoxicity, which may contribute to an increased risk of undiagnosed cardiovascular complications in chemotherapy patients. The evident variability in cardiotoxicity management practices among different medical specialties underscores the critical need for heightened awareness and enhanced collaborative efforts. The implementation of comprehensive interdisciplinary clinical pathways and the establishment of a dedicated cardio-oncology network could potentially address these challenges, particularly in supporting primary care physicians.Figure 1Figure 2

High-Dose Chemotherapy and Autologous or Allogeneic Transplantation in Aggressive B-Cell Lymphoma—Is There Still a Role?

Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, or indefinite maintenance. We discuss the current role of autologous and allogeneic stem cell transplantation in this context. In patients with recurrent diffuse large B-cell lymphoma, CAR-T cell treatment has largely replaced autologous transplant. Autologous transplant should be considered in patients with late relapses and in selected patients with T-cell-rich B-cell lymphoma, where CAR-T cell therapy may be less effective. It also remains the treatment of choice for consolidation of patients with primary CNS lymphoma. In mantle cell lymphoma, intensive chemotherapy combined with BTK inhibitors and rituximab results in excellent outcomes, and the role of autologous transplantation is declining. In Hodgkin’s lymphoma, autologous transplant consolidation remains the standard of care for patients who failed initial chemotherapy. Allogeneic transplantation has lower relapse rates but more complications and higher non-relapse mortality than autologous transplantation. It is usually reserved for patients who fail autologous transplantation or in whom autologous stem cells cannot be collected. It may also have an important role in patients who fail CAR-T therapies. The increasing complexity of care and evolving sequencing of therapies for patients with aggressive B-cell lymphomas only emphasizes the importance of appropriate patient selection and optimal timing of stem cell transplantation.

Skepticism regarding the use of carbon nanotubes as reinforcing agent in ceramics for biomedical applications: A critical review

Recent advancements in composite materials, including ceramics, metals, and polymers, have shown significant promise for biomedical applications. In particular, the use of carbon nanotubes (CNTs) as reinforcement in alumina and zirconia ceramics has garnered attention due to their potential to greatly enhance mechanical properties. CNTs, with their high aspect ratio, mechanical strength, and electrical conductivity, offer unique advantages for improving traditional ceramics used in biomedical applications, such as hip and knee replacements, where alumina and zirconia have been employed since the 1970s for their superior wear resistance and biocompatibility. This review critically examines the mechanical benefits of CNT-reinforced ceramics, focusing on factors such as CNT distribution, reinforcement mechanisms, fracture toughness, and long-term durability. Additionally, it explores the significant challenge of CNT toxicity, cytocompatibility, and potential long-term health risks, particularly their non-biodegradable and carcinogenic nature, which could limit their use in medical implants. While promising, inconsistencies in reported improvements, largely due to dispersion issues and ceramic-CNT interactions, along with unresolved toxicity concerns, indicate the need for further research. This review aims to provide a comprehensive understanding of both the mechanical potential and the biological risks of CNT-reinforced ceramics in biomedical applications.

Update on the treatment of BRAFmut metastatic melanoma and future perspectives

Abstractv‐Raf murine sarcoma viral oncogene homolog B (BRAF) mutations were first identified in melanoma in 2002, leading to increased cell division and proliferation, and resultant tumour growth. The identification and characterisation of BRAF mutations (BRAFmut) led to the development of several highly specific, BRAF‐, then mitogen‐activated kinase enzyme (MEK)‐targeted therapies that have enabled rapid tumour responses and improved treatment outcomes in most patients with metastatic BRAFmut melanoma. The combination of these two drug classes (BRAF inhibitors and MEK inhibitors) has demonstrated improved response rates, progression‐free survival, and overall survival (OS), along with a more tolerable safety profile, compared with BRAF inhibition alone. In parallel, improved knowledge of the immune system has enabled the development of immune checkpoint inhibitors (ICIs), although immune‐related adverse events with ICIs may prove to be problematic in some patients and require careful management. While targeted therapy appears to provide rapid disease control in a relatively high proportion of patients, the development of secondary resistance may limit the overall duration of responses. Acquired resistance, along with primary resistance, has also been reported for ICIs, with a lower overall response rate to that with targeted therapy, although durable responses have been reported in some responding patients. A combination strategy of targeted therapy with ICIs has demonstrated modest increases in efficacy compared with targeted therapy combinations, although data significance varies across studies, there is increased risk of toxicity, and triple combination therapy has not yet received clinical approval in Europe. Thus, there is an ongoing need to establish optimal sequencing of these treatments in patients with advanced BRAFmut melanoma, and this has become the focus of current research. The aim of this narrative review was to provide an update on the treatment of BRAFmut metastatic melanoma, current guideline recommendations, and future clinical perspectives.

Residual Assessment of Emerging Pesticides in Aquatic Sinks of Lahore, Pakistan

In recent decades, the use of pesticides has become fundamental to agricultural growth. However, the persistent and toxic nature of pesticides has led to significant concerns regarding their ecological and human health consequences. Therefore, for a better understanding of pesticide contamination and its potential risks, here we assessed the levels of five emerging pesticides—acetochlor, imidacloprid, MCPA, atrazine, and allethrin—in soil samples from ponds used for irrigation and in drinking water samples from nearby areas in Lahore, Pakistan. Our findings revealed that 100% of the samples were contaminated, posing substantial ecological and human health risks. Based on the toxic units (TUsum), all the soil samples showed higher toxic pressure, exceeding acute and chronic toxicity thresholds for earthworms, while 100% of water samples posed chronic toxicity risks to crustaceans and 10% to algae. Pollution index (PI) analysis further classified 100% of the soil samples and 10% of the water samples as highly polluted. These findings show high-pesticide residues in both soil and water and highlight immediate risk assessment and mitigation measures to protect non-target organisms. This preliminary information can be used to adopt risk assessment monitoring programmes and help higher authorities in making policies and guidelines to mitigate the escalating risk for ecology and humans.

Investigating the sustainable energy generation potential of an invasive weed: Lantana camara.

Lantana camara, one of the world's top ten most invasive species, was initially cultivated for ornamental use. However, it spread uncontrollably across the fallow areas and agricultural lands, threatening approximately 44% of Indian forests. Its invasion disrupts ecosystems by suppressing nearby plant growth through allelopathy and poses toxicity risks to grazing ruminants. It significantly increases forest fire risk by adding large amounts of combustible biomass, particularly dried L. camara. Despite efforts to control it using mechanical, chemical, and biocontrol methods, the results have been largely unsatisfactory, with associated costs estimated at $18,000 per square kilometre. Considering these challenges, recent research explored the potential of L. camara as a bioenergy resource. TheL. camarabriquettes exhibit a heating value of approximately 20MJ/kg with a low sulphur (0.5%), nitrogen (1%), and ash content (2%), making them suitable for decentralised energy production. Furthermore, bioethanol production fromL. camarahydrolysate has shown promising results, yielding 0.33g/g withPichia stipitisand0.47g/g with Saccharomyces cerevisiae, which is comparable to other lignocellulosic feedstocks. Additionally, the gasification of L. camara using a downdraft gasifier produced syngas with a lower heating value (LHV) of 6.4MJ/Nm3. These findings demonstrate that using L. camara for bioenergy production presents a dual solution, addressing the growing demand for renewable energy and managing invasive species. This review aims to critically evaluate the potential and challenges associated with the different energy production pathways for L. camara, highlighting its role in sustainable energy generation.

DNA-PK inhibition shows differential radiosensitization in orthotopic GBM PDX models based on DDR pathway deficits.

Glioblastoma (GBM) remains one of the most therapy-resistant malignancies with frequent local failures despite aggressive surgery, chemotherapy, and ionizing radiation (IR). Small molecule inhibitors of DNA-dependent protein kinase (DNA-PKi's) are potent radiosensitizers currently in clinical trials. Determining which patients may benefit from radiosensitization with DNA-PKi's is critical to avoid unnecessary increased risk of normal tissue toxicity. In this study we used GBM patient derived xenografts (PDXs) in orthotopic murine models to study the relationship between molecular features, pharmacokinetics, and the radiosensitizing potential of the DNA-PKi peposertib. We show that peposertib radiosensitizes established and PDX GBM lines in vitro at 300nM and above, with significant increase in radiosensitization by maintaining post-IR exposure for >12 hours. Radiosensitization by peposertib is mediated by catalytic inhibition of DNA-PK, and knock-down of DNA-PK by short hairpin RNA (shRNA) largely abolished the radiosensitizing effect. Peposertib decreased auto-phosphorylation of DNA-PKcs after IR in a dose-dependent manner with delay in resolution of γH2AX foci at 24 hours. The addition of peposertib to IR significantly increased survival in GBM120 orthotopic xenografts, but not in GBM10. There was no difference in plasma or average tumor concentrations of peposertib in the two cohorts. While the mechanism underpinning this discordant effect in vitro vs. in vivo is not clear, there was an association for greater sensitization in TP53 mutant lines. Transfection of a dominant-negative TP53 mutant in baseline TP53 wildtype GBM lines significantly delayed growth and decreased NHEJ efficiency (but not Homologous Recombination), after peposertib exposure.

Bone allograft impregnated with tobramycin and vancomycin delivers antibiotics in high concentrations for prophylaxis against bacteria commonly associated with prosthetic joint infections.

Local delivery of antibiotics as prophylaxis for prosthetic joint infections (PJIs) is frequently used during total hip replacement surgery. Morselized bone allograft impregnated with vancomycin and tobramycin (TobraVanc) could provide effective prophylaxis against bacteria commonly associated with PJIs. In this study, the concentrations of antibiotics released by bone allograft impregnated with TobraVanc were determined by using an in vitro bioassay system entailing measuring inhibition zone diameters caused by antibiotic-impregnated bone chips cast in agar against standard curves. The concentrations were determined in samples of TobraVanc-impregnated bone graft taken before and after the application of the bone graft in the patients undergoing acetabular revision surgery. Antibiotic-impregnated bone grafts, sampled prior to application in the patient, delivered antibiotics in the concentration ranges of 730-9,800 mg/L for tobramycin and 1,300-11,000 mg/L for vancomycin. Samples taken after application in the patient released lower concentrations of tobramycin (490-1,900 mg/L; P < 0.01) and vancomycin (3,000-5,100 mg/L; P < 0.05); however, these concentrations remained well above the tobramycin minimum inhibitory concentrations (MICs) for investigated, highly tobramycin-resistant Staphylococcus epidermidis strains (MICs > 256 mg/L). At the tested concentrations, bone graft material mixed with TobraVanc delivered antibiotics in potent concentrations above the MICs for bacteria causing PJIs. Clinical trials are needed to evaluate the efficacy and risk of TobraVanc-impregnated bone graft as a prophylactic agent for patients undergoing hip replacement surgery.IMPORTANCEAntibiotic prophylaxis is the cornerstone of successful joint replacement surgery, reducing the risk for the dreaded complication of prosthetic joint infection (PJI) to roughly 0.5%-2% in standard total hip replacement (THR). In addition to systemic antibiotics, antibiotics added locally have the potential to reduce the PJI risk even further, because of the high concentrations that can be achieved in the joint with limited risk for systemic toxicity. The results in the current study show that bone chips impregnated with a combination of tobramycin and vancomycin (TobraVanc) release antibiotics in concentrations that are potent against common bacteria causing PJIs. Especially in high-risk patients, our results support the prophylactic use of TobraVanc in hip replacement surgery requiring the use of a bone graft. A clinical study testing the efficacy of TobraVanc-impregnated bone graft in reducing the incidence of PJI in hip replacement surgery is currently ongoing (EudraCT: 2021-001708-14).

Managing Crohn’s Disease Postoperative Recurrence Beyond Prophylaxis: A Comprehensive Review with Meta-Analysis

Background and Aims: Postoperative recurrence in Crohn’s disease remains a significant clinical challenge, with high recurrence rates despite advancements in medical therapy. This study aims to evaluate the efficacy of various treatments for managing postoperative recurrence following ileocolonic resection in Crohn’s disease. Methods: A comprehensive search of PubMed, Cochrane, and Scopus databases was performed to identify studies reporting on the therapeutic management of postoperative recurrence in Crohn’s disease. Studies encompassing patients with an endoscopic Rutgeerts score of at least I2 were included. Results: Ustekinumab showed promise, achieving significant endoscopic and clinical success in difficult-to-treat patients. Anti-TNF agents demonstrated superior endoscopic and clinical remission rates compared to mesalamine and azathioprine. Retreatment with anti-TNF therapy remained effective even after preoperative failure. Thalidomide showed efficacy in refractory Crohn’s disease, but carries significant toxicity risks, necessitating careful patient selection and monitoring. Combination therapies and non-pharmacologic strategies like enteral nutrition offer additional options, though patient compliance remains challenging. Conclusions: Personalized treatment plans based on individual risk factors and biomarkers are crucial. Infliximab is recommended as the first-line treatment, with ustekinumab and vedolizumab as alternatives in case of anti-TNF failure or intolerance. Early intervention, patient education, and ongoing evaluation are essential for optimizing long-term outcomes in managing postoperative recurrence in Crohn’s disease.

Effects of Decabromodiphenyl Ethane and Cadmium Coexposure on Their Bioaccumulation, Oxidative Stress, Root Metabolism, and Rhizosphere Soil Microorganisms in a Soil-Rice System.

Decabromodiphenyl ethane (DBDPE) and cadmium (Cd) are typical pollutants in e-waste, seriously threatening crop growth. This study investigated the bioaccumulation and toxicity mechanisms of DBDPE and Cd in a soil-rice system. The results showed that 50 mg/kg DBDPE could reduce the level of accumulation of Cd in rice roots. DBDPE and Cd induced the antioxidant system (SOD, POD, and MDA) in rice seedlings. The combined exposure reduced the contents of carbohydrates, lipids, amino acids, and organic acids. Phenylalanine and phenylpropanoid metabolisms were identified as the key detoxification metabolic pathways under combined exposure. DBDPE and Cd disrupted the functional cycling of carbon and nitrogen in rhizosphere soil, while Gemmatimonadetes, Actinobacteria, and Bacteroidetes were the key bacterial groups responding to DBDPE and Cd stress. This work provides data for the toxicity risk evaluation of DBDPE and Cd combined exposure to food crops.

Identifying and modeling the impact of neonicotinoid exposure on honey bee colony profit

Abstract Pollination by the European honey bee, Apis mellifera, is essential for the production of many crops, including highbush blueberries (Vaccinum corymbosum). To understand the impact of agrochemicals (specifically, neonicotinoids, a class of synthetic, neurotoxic insecticides) on these pollinators, we conducted a field study during the blueberry blooms of 2020 and 2021 in British Columbia (B.C.). Forty experimental honey bee colonies were placed in the Fraser Valley: half of the colonies were located within 1.5 km of highbush blueberry fields (“near” colonies) and half were located more than 1.5 km away (“far” colonies). We calculated risk quotients for these compounds using their chronic lethal dietary dose (LDD50) and median lethal concentration (LC50). Pesticide risk was similar between colonies located near and far from blueberry forage, suggesting that toxicity risks are regionally ubiquitous. Two systemic neonicotinoid insecticides, clothianidin and thiamethoxam, were found at quantities that exceeded chronic international levels of concern. We developed a profit model for a pollinating beekeeper in B.C. that was parameterized by: detected pesticide levels; lethal and sublethal bee health; and economic data. For colonies exposed to neonicotinoid pesticides in and out of the blueberry forage radii, there were economic consequences from colony mortality and sublethal effects such as a loss of honey production and compromised colony health. Further, replacing dead colonies with local bees was more profitable than replacing them with imported packages, illustrating that beekeeping management selection of local options can have a positive effect on overall profit.

Artificial intelligence for detection of retinal toxicity in chloroquine and hydroxychloroquine therapy using multifocal electroretinogram waveforms.

Chloroquine and hydroxychloroquine, while effective in rheumatology, pose risks of retinal toxicity, necessitating regular screening to prevent visual disability. The gold standard for screening includes retinal imaging and automated perimetry, with multifocal electroretinography (mfERG) being a recognized but less accessible method. This study explores the efficacy of Artificial Intelligence (AI) algorithms for detecting retinal damage in patients undergoing (hydroxy-)chloroquine therapy. We analyze the mfERG data, comparing the performance of AI models that utilize raw mfERG time-series signals against models using conventional waveform parameters. Our classification models aimed to identify maculopathy, and regression models were developed to predict perimetric sensitivity. The findings reveal that while regression models were more adept at predicting non-disease-related variation, AI-based models, particularly those utilizing full mfERG traces, demonstrated superior predictive power for disease-related changes compared to linear models. This indicates a significant potential to improve diagnostic capabilities, although the unbalanced nature of the dataset may limit some applications.

Impact of Cyclophosphamide on Testis and Sexual Glands of Adult Albino Rats and Probable Recovery After Drug Withdrawal: A Histological and Immunohistochemical study

Background: Cyclophosphamide is a chemotherapy and an immune-suppressive drug which is used for treatment of malignant and immune –related disease. The current work was conducted to evaluate the histological structure of the male gonad and sexual glands during treatment and after discontinuation of cyclophosphamide. Material and Methods: Thirty male albino- rats were classified into three groups. The first one was treated by normal saline, the second and third groups received cyclophosphamide 150 mg/kg intra peritoneal every two days for one week. The third group regarded as recovery group and divided into two subgroups with one- or two-months’ recovery period. At the accomplishment of the work, blood was drowning for hormonal analysis (testosterone) then the animals were sacrificed. The testis, prostate and seminal vesicle were removed and prepare for histological and immunohistochemical staining. Results: The cyclophosphamide treated group (GII) showed reduction of serum testosterone level, the testicular and sexual glands sections revealed atrophic and degenerative changes of their lining epithelium with reduction of their function and changes of their Ki67 expression which indicate abnormal proliferative pattern of the cells. However, the histopathological changes of treated group showed no improvement after one or even two months of drug withdrawal. Conclusion: The present study pointed out the risk of infertility and gonadal toxicity during cyclophosphamide treatment which may be permanent even after termination of the treatment.