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First report on pesticide sub-chronic and chronic toxicities against dogs using QSAR and chemical read-across

SAR QSAR Environ Res. 2024 Mar;35(3):241-263. doi: 10.1080/1062936X.2024.2320143. Epub 2024 Feb 23.

ABSTRACT

Excessive use of chemicals is the outcome of the industrialization of agricultural sectors which leads to disturbance of ecological balance. Various agrochemicals are widely used in agricultural fields, urban green areas, and to protect from various pest-associated diseases. Due to their long-term health and environmental hazards, chronic toxicity assessment is crucial. Since in vivo and in vitro toxicity assessments are costly, lengthy, and require a large number of animal experiments, in silico toxicity approaches are better alternatives to save time, cost, and animal experimentation. We have developed the first regression-based 2D-QSAR models using different sub-chronic and chronic toxicity data of pesticides against dogs employing 2D descriptors. From the statistical results (ntrain=5362, r2 = 0.614 to 0.754, QLOO2 = 0.501 to 0.703 and QF12 = 0.531 to 0.718, QF22=0.5230.713), it was concluded that the models are robust, reliable, interpretable, and predictive. Similarity-based read-across algorithm was also used to improve the predictivity (QF12=0.5950.813,QF22=0.5730.809) of the models. 5132 chemicals obtained from the CPDat and 1694 pesticides obtained from the PPDB database were also screened using the developed models, and their predictivity and reliability were checked. Thus, these models will be helpful for eco-toxicological data-gap filling, toxicity prediction of untested pesticides, and development of novel, safer & eco-friendly pesticides.

PMID:38390626 | DOI:10.1080/1062936X.2024.2320143

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Nomograms for assessing the rupture risk of anterior choroid artery aneurysms based on clinical, morphological, and hemodynamic features

Front Neurol. 2024 Feb 8;15:1304270. doi: 10.3389/fneur.2024.1304270. eCollection 2024.

ABSTRACT

BACKGROUND AND PURPOSE: A notable prevalence of subarachnoid hemorrhage is evident among patients with anterior choroidal artery aneurysms in clinical practice. To evaluate the risk of rupture in unruptured anterior choroidal artery aneurysms, we conducted a comprehensive analysis of risk factors and subsequently developed two nomograms.

METHODS: A total of 120 cases of anterior choroidal artery aneurysms (66 unruptured and 54 ruptured) from 4 medical institutions were assessed utilizing computational fluid dynamics (CFD) and digital subtraction angiography (DSA). The training set, consisting of 98 aneurysms from 3 hospitals, was established, with an additional 22 cases from the fourth hospital forming the external validation set. Statistical differences between the two data sets were thoroughly compared. The significance of 9 clinical baseline characteristics, 11 aneurysm morphology parameters, and 4 hemodynamic parameters concerning aneurysm rupture was evaluated within the training set. Candidate selection for constructing the nomogram models involved regression analysis and variance inflation factors. Discrimination, calibration, and clinical utility of the models in both training and validation sets were assessed using area under curves (AUC), calibration plots, and decision curve analysis (DCA). The DeLong test, net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed to compare the effectiveness of classification across models.

RESULTS: Two nomogram models were ultimately constructed: model 1, incorporating clinical, morphological, and hemodynamic parameters (C + M + H), and model 2, relying primarily on clinical and morphological parameters (C + M). Multivariate analysis identified smoking, size ratio (SR), normalized wall shear stress (NWSS), and average oscillatory shear index (OSIave) as optimal candidates for model development. In the training set, model 1 (C + M + H) achieved an AUC of 0.795 (95% CI: 0.706 ~ 0.884), demonstrating a sensitivity of 95.6% and a specificity of 54.7%. Model 2 (C + M) had an AUC of 0.706 (95% CI: 0.604 ~ 0.808), with corresponding sensitivity and specificity of 82.4 and 50.3%, respectively. Similarly, AUCs for models 1 and 2 in the external validation set were calculated to be 0.709 and 0.674, respectively. Calibration plots illustrated a consistent correlation between model evaluations and real-world observations in both sets. DCA demonstrated that the model incorporating hemodynamic parameters offered higher clinical benefits. In the training set, NRI (0.224, p = 0.007), IDI (0.585, p = 0.002), and DeLong test (change = 0.089, p = 0.008) were all significant. In the external validation set, NRI, IDI, and DeLong test statistics were 0.624 (p = 0.063), 0.572 (p = 0.044), and 0.035 (p = 0.047), respectively.

CONCLUSION: Multidimensional nomograms have the potential to enhance risk assessment and patient-specific treatment of anterior choroidal artery aneurysms. Validated by an external cohort, the model incorporating clinical, morphological, and hemodynamic features may provide improved classification of rupture states.

PMID:38390597 | PMC:PMC10882079 | DOI:10.3389/fneur.2024.1304270

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Exergames as a rehabilitation tool to enhance the upper limbs functionality and performance in chronic stroke survivors: a preliminary study

Front Neurol. 2024 Feb 8;15:1347755. doi: 10.3389/fneur.2024.1347755. eCollection 2024.

ABSTRACT

INTRODUCTION: Post-stroke hemiplegia commonly occurs in stroke survivors, negatively impacting the quality of life. Despite the benefits of initial specific post-acute treatments at the hospitals, motor functions, and physical mobility need to be constantly stimulated to avoid regression and subsequent hospitalizations for further rehabilitation treatments.

METHOD: This preliminary study proposes using gamified tasks in a virtual environment to stimulate and maintain upper limb mobility through a single RGB-D camera-based vision system (using Microsoft Azure Kinect DK). This solution is suitable for easy deployment and use in home environments. A cohort of 10 post-stroke subjects attended a 2-week gaming protocol consisting of Lateral Weightlifting (LWL) and Frontal Weightlifting (FWL) gamified tasks and gait as the instrumental evaluation task.

RESULTS AND DISCUSSION: Despite its short duration, there were statistically significant results (p < 0.05) between the baseline (T0) and the end of the protocol (TF) for Berg Balance Scale and Time Up-and-Go (9.8 and -12.3%, respectively). LWL and FWL showed significant results for unilateral executions: rate in FWL had an overall improvement of 38.5% (p < 0.001) and 34.9% (p < 0.01) for the paretic and non-paretic arm, respectively; similarly, rate in LWL improved by 19.9% (p < 0.05) for the paretic arm and 29.9% (p < 0.01) for non-paretic arm. Instead, bilateral executions had significant results for rate and speed: considering FWL, there was an improvement in rate with p < 0.01 (31.7% for paretic arm and 37.4% for non-paretic arm), whereas speed improved by 31.2% (p < 0.05) and 41.7% (p < 0.001) for the paretic and non-paretic arm, respectively; likewise, LWL showed improvement in rate with p < 0.001 (29.0% for paretic arm and 27.8% for non-paretic arm) and in speed with 23.6% (p < 0.05) and 23.5% (p < 0.01) for the paretic and non-paretic arms, respectively. No significant results were recorded for gait task, although an overall good improvement was detected for arm swing asymmetry (-22.6%). Hence, this study suggests the potential benefits of continuous stimulation of upper limb function through gamified exercises and performance monitoring over medium-long periods in the home environment, thus facilitating the patient’s general mobility in daily activities.

PMID:38390596 | PMC:PMC10883060 | DOI:10.3389/fneur.2024.1347755

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Failure to reduce the risk of postoperative lower genital tract infection with perioperative antibiotic prophylaxis during induced abortion: a real-world study

Front Med (Lausanne). 2024 Feb 8;11:1296910. doi: 10.3389/fmed.2024.1296910. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aimed to evaluate perioperative antibiotic use for induced abortion and its association with lower genital tract infections (LGTI) two weeks post-surgery in China.

METHODS: We conducted a prospective cohort study of women seeking induced abortion. We interviewed participants on the day of surgery and two weeks after, and evaluated preoperative tests, gynecological exams, perioperative antibiotic usage, postoperative vaginal microbiota, and LGTI diagnosis. Multivariate logistic regression was used to assess the association between the perioperative antibiotic use and LGTI risk.

RESULTS: We recruited 8,190 women undergoing induced abortion at 27 participating hospitals. Of these, 95% had gynecological exams, but over 80% lacked tests for vaginal microbiota, chlamydia, and gonorrhea. Approximately 20% of those examined had increased vaginal discharge and abnormal vaginal cleanliness. The positive rates for gram-positive rods, fungi, and trichomonas were 38.6, 2.4, and 0.3%, respectively. More than three-quarters (78.5%) of participants received antibiotics, mainly second-gen cephalosporins (36.8%) and nitroimidazoles (12.3%). LGTI rates two weeks post-surgery were 2.7% for antibiotic recipients and 3.1% for non-recipients, with no statistically significant difference (p > 0.05). Logistic regression showed no association between perioperative antibiotic use and LGTI risk (OR = 1.01, 95% CI 0.59-1.74). However, this risk increased with abnormal preoperative discharge tests (OR = 1.39, 95% CI 1.04-1.86).

CONCLUSION: Most Chinese women undergoing induced abortion used perioperative antibiotics, but this did not significantly reduce LGTI risk. Instead, this risk was related to abnormal preoperative discharge tests. Standardization of perioperative antibiotic use for induced abortion is recommended, and prophylactic treatment in Chinese abortion services warrants further investigation.

PMID:38390566 | PMC:PMC10882060 | DOI:10.3389/fmed.2024.1296910

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Predicting the submission frequency of periodic safety update reports: development and application of the EURD tool

Front Med (Lausanne). 2024 Feb 8;11:1299190. doi: 10.3389/fmed.2024.1299190. eCollection 2024.

ABSTRACT

INTRODUCTION: Periodic Safety Update Reports (PSURs) are a key pharmacovigilance tool for the continuous evaluation of the benefit-risk balance of a medicinal product in the post-authorisation phase. The PSUR submission frequency for authorised active substances and combinations of active substances across the EU is individually determined. The objective of this research was the development and application of the EURD tool, a statistical method based on readily available safety data to predict PSUR frequencies and to ensure a consistent risk-based approach.

METHODS: First, variables considered relevant in determining the PSUR frequency were identified from data sources available at the European Medicines Agency. A subsequent first survey with National Competent Authorities in Europe lead to a prioritisation of identified variables, while a second survey was carried out to propose the PSUR frequencies for a set of substances. Finally, a regression model was built on the information collected, applied to a larger list of substances and its results tested via a third survey with the same experts.

RESULTS: The developed EURD tool was applied to the 1,032 EURD list entries with a PSUR assessment deferred to 2025 at the time of the creation of the list in 2012. As the number of procedures would have had a significant impact on the workload for the European Medicines Regulatory Network (EMRN), in a second step the workload impact was estimated after allocating the entries according to their proposed frequency. The analysis suggests that all entries could be reviewed by 2038 by increasing the median workload by 15% (from 868 to 1,000 substances/year).

CONCLUSION: The EURD tool is the first data-driven application for supporting decision making of PSUR frequencies based on relevant active substance safety data. While we illustrated its potential for improving the assignment of PSUR submission frequencies for active substances authorised in the EU, other institutions requiring periodic assessment of safety data and balancing of the resulting workload could benefit from it.

PMID:38390565 | PMC:PMC10882634 | DOI:10.3389/fmed.2024.1299190

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A content analysis of YouTube videos on palliative care: understanding the quality and availability of online resources

Palliat Care Soc Pract. 2024 Feb 21;18:26323524241231819. doi: 10.1177/26323524241231819. eCollection 2024.

ABSTRACT

BACKGROUND: Improvement in quality care is an important aspect of palliative care for individuals with serious illnesses. Palliative care is a multidisciplinary strategy that addresses the physical, emotional, social, and spiritual needs of patients and their families. As technology advances, digital media – especially YouTube – has come to serve as a virtual educational platform, offering resources for health-related information, including information about palliative care.

OBJECTIVES: In this research, the main goal was to evaluate the quality and availability of online resources related to palliative care.

DESIGN: Two theoretical frameworks were used: the Health Communication Model and the Information Quality Framework. These frameworks offer a way to understand how YouTube videos contribute to palliative care information and assess the quality of that information.

METHODS: This study utilizes a quantitative analysis approach to assess the quality and accessibility of YouTube videos on palliative care. Specifically, a random sample of 300 YouTube videos addressing palliative care was examined. Descriptive statistics were used to analyze the data, including the frequency and distribution of the different types of content, sources, and quality indicators. Chi-square tests were done to compare the quality of information provided by different sources and types of content.

RESULTS: The results showed a variety of video types, with educational videos being the most common (40%), followed by personal stories (26.7%) and promotional videos (16.7%). We found that healthcare organizations (30%) and individual content creators (46.7%) were the sources for these videos.

CONCLUSION: There were varying scores in terms of accuracy, completeness, and relevance when it came to quality assessment. While many videos received excellent ratings, some received poor ratings. Additionally, this analysis revealed that the majority of these videos were in English (83.3%), which poses a limitation for non-English speakers who may have difficulty understanding them.

PMID:38390558 | PMC:PMC10883131 | DOI:10.1177/26323524241231819

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Effectiveness of Head-and-Neck Molecular Imaging Reporting and Data System Criterion in Head-and-Neck Squamous Cell Carcinoma PostConcurrent Chemoradiotherapy

Indian J Nucl Med. 2023 Oct-Dec;38(4):334-339. doi: 10.4103/ijnm.ijnm_23_23. Epub 2023 Dec 20.

ABSTRACT

PURPOSE: Postconcurrent chemoradiotherapy (CRT) response assessment has been challenging in locally advanced head-and-neck squamous cell carcinoma (LA-HNSCC) due to prevailing postradiation changes. Molecular response methods have been encouraging, although further clarifications and validations were needed. We tested the effectiveness of a proposed semi-quantitative molecular response criterion in these patients.

MATERIALS AND METHODS: Two subspecialty-trained physicians evaluated 18F-fluorodeoxyglucose positron emission tomography/computed tomography of LA-HNSCC patients (n = 83) post 3 months CRT using a five points Head and Neck Molecular Imaging-Reporting and Data System (HAN-MI-RADS) criterion. Where available, histopathology examination with clinical and imaging interpretation was taken as a reference for the disease. A diagnostic accuracy comparison was done with the existing Hopkins score. Further effectiveness was analyzed with disease-free survival (DFI) and overall survival (OS).

RESULTS: Metastasis was developed in 11/83 patients at 3 months of evaluation. Of 72 patients, 39, 2, and 31 patients had a complete response, equivocal response, and partial response as per HAN-MI-RADS. Per patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting loco-regional disease up to 1 and 2 years was 93.3%, 92.5%, 90.3%, 94.9%, 92.9%, and 84.9%, 91.9%, 90.3%, 87.2%, and 88.6% respectively. One year and two years DFI for each HAN-MI-RADS score showed a statistically significant difference while it was not for OS. The receiver operating characteristic curve analysis showed significantly better outcome predictability of HAN-MI-RADS (area under the curve [AUC] 0.884) than Hopkins (AUC 0.699).

CONCLUSIONS: A five points HAN-MI-RADS criterion was found promising for response assessment with less equivocal results and statistically significant higher AUC than Hopkins for loco-regional recurrence prediction.

PMID:38390552 | PMC:PMC10880860 | DOI:10.4103/ijnm.ijnm_23_23

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Three Artemisia pollens trigger the onset of allergic rhinitis via TLR4/MyD88 signaling pathway

Mol Biol Rep. 2024 Feb 23;51(1):319. doi: 10.1007/s11033-024-09350-7.

ABSTRACT

OBJECTIVE: The prevalence of allergic rhinitis is high, making it a relatively common chronic condition. Countless patients suffer from seasonal Allergic rhinitis (AR). The objective of this investigation is to examine the potential involvement of common pollen allergens in seasonal allergic rhinitis, and study the proposed mechanism of Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the induction of AR.

METHOD: A mouse AR model (sensitized group) was constructed with pollen extracts and ovalbumin (OVA) of Artemisia annua (An), Artemisia argyi (Ar) and Artemisia Sieversiana (Si), and thereafter, AR symptom score was performed. After successful modeling, mouse serum and nasal mucosa tissues were extracted for subsequent experiments. The expression levels of immunoglobulin E (IgE), Interleukin (IL)-4, IL-5, IL-13 and Tumor Necrosis Factor-α (TNF-α) in serum were detected using Enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin (H&E) staining methods were used to observe the pathological changes of the nasal mucosal tissue; Utilizing immunohistochemistry (IHC) staining, the expression levels of TLR4, MyD88 and Nuclear factor kappa B (NF-κB) p65 in mouse nasal mucosa were quantified; The mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of sensitized mice were detected with Quantitative reverse transcription PCR (qRT-PCR) and Western Blot. Finally, the in vitro culture of Human nasal mucosal epithelial cells (HNEpC) cells was conducted, and cells were treated with 200 µg/ml Artemisia annua pollen extract and OVA for 24 h. Western Blot assay was used to detect the expression level of TLR4, MyD88 and NF-κB p65 proteins before and after HNEpC cells were treated with MyD88 inhibitor ST-2825.

RESULT: On the second day after AR stimulation, the mice showed obvious AR symptoms. H&E results showed that compared to the control group, the nasal mucosal tissue in the sensitized group was significantly more inflamed. Furthermore, ELISA assay showed increased expression levels of IgE, IL-4, IL-5, IL-13 and TNF-α in serum of mice induced by OVA and Artemisia annua pollen, Artemisia argyi pollen and Artemisia Sieversiana pollen than those of the control group. However, the expression level of IL-2 was lower than that of the control group (P < 0.05). Using Immunohistochemistry staining visually observed the expression levels of TLR4, MyD88 and NF-κB p65 in mouse nasal mucosa tissues and quantitatively analyzed. The expression levels of TLR4, MyD88 and NF-κB p65 in the sensitized group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The results from qRT-PCR and Western Blot showed that the mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of the sensitized group were significantly higher than those in the control group (P < 0.05). Finally, HNEpC cells were cultured in vitro and analyzed using Western Blot. The expression levels of TLR4, MyD88 and NF-κB p65 in OVA and An groups were significantly increased (P < 0.05). After ST-2825 treatment, TLR4 protein expression was significantly increased (P < 0.05) and MyD88 and NF-κB p65 protein expression were significantly decreased (P < 0.05).

CONCLUSION: To sum up, the occurrence and development of AR induced by OVA and pollen of Artemisia annua, Artemisia argyi and Artemisia Sieversiana were related to TLR4/MyD88 signal pathway.

PMID:38388914 | DOI:10.1007/s11033-024-09350-7

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Co-design and evaluation of a digital serious game to promote public awareness about pancreatic cancer

BMC Public Health. 2024 Feb 22;24(1):570. doi: 10.1186/s12889-024-18050-7.

ABSTRACT

BACKGROUND: Pancreatic cancer, ranking seventh in global cancer-related deaths, poses a significant public health challenge with increasing incidence and mortality. Most cases are diagnosed at an advanced stage, resulting in low survival rates. Early diagnosis significantly impacts prognosis, making symptom awareness crucial. Symptoms are often subtle, leading to delayed help-seeking behaviour. Patients and their carers prioritise increased public awareness, indicating a need for innovative approaches to promote awareness of the disease.

METHODS: This study employed a quasi-experimental pre-test/post-test design to assess the relationship between a serious game and pancreatic cancer awareness. Members of the public (N = 727) were recruited internationally, via social media and with signposting by relevant organisations. Participants completed measures of symptom awareness and help-seeking intentions before and after playing the game. The serious game, co-designed with experts by lived experience, patient advocates and healthcare professionals, presented participants with a human anatomy diagram, with each section linked to a question about pancreatic cancer.

RESULTS: The serious game demonstrated a statistically significant improvement on pancreatic cancer awareness based on matched paired t-tests. Due to missing data, paired comparisons were only possible for 489 cases. Symptom awareness scores exhibited a statistically significant increase from pre-test to post-test, with a large effect size (p < 0.001, d = 1.43). Help-seeking intentions also markedly improved, showing a significant increase from pre-test to post-test, with a large effect size (p < 0.001, d = 1.10). Independent-samples t-tests were also conducted to determine if there were any group differences on pre- to post-test changes based on age, gender, and previous knowledge and/or experience of pancreatic cancer. Participants overwhelmingly endorsed the game’s usability and educational value, suggesting its potential as an effective tool for enhancing public awareness and proactive health-seeking behaviour.

DISCUSSION: This study is the first to explore a serious game’s utility in pancreatic cancer awareness. Results suggest that such interventions can effectively increase public awareness and influence help-seeking intentions. The co-design process ensured content relevance, and participant satisfaction was high. Findings highlight the game’s potential as an accessible and convenient tool for diverse populations.

PMID:38388909 | DOI:10.1186/s12889-024-18050-7

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Signs and symptoms of covid - 19 in patients with a history of coronary artery bypass grafting surgery

BMC Infect Dis. 2024 Feb 22;24(1):241. doi: 10.1186/s12879-024-09090-w.

ABSTRACT

BACKGROUND: People who have coronary artery disease are more likely to develop signs and symptoms of COVID-19 due to their special circumstances. Coronary artery bypass grafting surgery (CABG)does not cure the disease but reduces the signs and symptoms, therefore, there is a possibility of severe complications of Covid-19 after it.

MATERIALS AND METHODS: This study is a descriptive and cross-sectional study conducted from June to July 2020 on 200 patients who underwent CABG from February 2018 to February 2020. The instrument consisted of socio-demographic variables and COVID’s signs and symptoms checklist. Data were collected by census method by telephone. Data were analyzed using descriptive statistics, Fisher’s exact test, Mann Whitney U test, and logistic regression model.

RESULTS: The results showed that the majority of the samples were male (67%). The mean age of them was 62.02 ± 9.06 years and 10% of the m had signs and symptoms of Covid 19. Having the symptoms of COVID-19 is significant in terms of the variables of decreased sense of smell (p < 0.002), decreased sense of taste (p < 0.002), and home quarantine (p < 0.01). The logistic regression model showed decreased sense of taste (OR = 6.071, CI95%: 1.621-29.984, p < 0.009) and non-compliance with home quarantine (OR = 0.061, CI95%: 0.005-0.741, p < 0.028) were the related variables to signs and symptoms of Covid 19.

CONCLUSION: The results did not indicate the frequency of COVID signs and symptoms among people with a history of Coronary artery bypass grafting surgery more than healthy people in the Iranian community. Extensive studies are suggested in this regard.

PMID:38388892 | DOI:10.1186/s12879-024-09090-w