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1.
JAMIA Open ; 7(3): ooae065, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38983845

ABSTRACT

Objectives: Artificial intelligence tools such as Chat Generative Pre-trained Transformer (ChatGPT) have been used for many health care-related applications; however, there is a lack of research on their capabilities for evaluating morally and/or ethically complex medical decisions. The objective of this study was to assess the moral competence of ChatGPT. Materials and methods: This cross-sectional study was performed between May 2023 and July 2023 using scenarios from the Moral Competence Test (MCT). Numerical responses were collected from ChatGPT 3.5 and 4.0 to assess individual and overall stage scores, including C-index and overall moral stage preference. Descriptive analysis and 2-sided Student's t-test were used for all continuous data. Results: A total of 100 iterations of the MCT were performed and moral preference was found to be higher in the latter Kohlberg-derived arguments. ChatGPT 4.0 was found to have a higher overall moral stage preference (2.325 versus 1.755) when compared to ChatGPT 3.5. ChatGPT 4.0 was also found to have a statistically higher C-index score in comparison to ChatGPT 3.5 (29.03 ± 11.10 versus 19.32 ± 10.95, P =.0000275). Discussion: ChatGPT 3.5 and 4.0 trended towards higher moral preference for the latter stages of Kohlberg's theory for both dilemmas with C-indices suggesting medium moral competence. However, both models showed moderate variation in C-index scores indicating inconsistency and further training is recommended. Conclusion: ChatGPT demonstrates medium moral competence and can evaluate arguments based on Kohlberg's theory of moral development. These findings suggest that future revisions of ChatGPT and other large language models could assist physicians in the decision-making process when encountering complex ethical scenarios.

2.
BMC Anesthesiol ; 24(1): 227, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982350

ABSTRACT

PURPOSE: We aimed to evaluate the ability of the peripheral perfusion index (PPI) to predict reintubation of critically ill surgical patients. METHODS: This prospective observational study included mechanically ventilated adults who were extubated after a successful spontaneous breathing trial (SBT). The patients were followed up for the next 48 h for the need for reintubation. The heart rate, systolic blood pressure, respiratory rate, peripheral arterial oxygen saturation (SpO2), and PPI were measured before-, at the end of SBT, 1 and 2 h postextubation. The primary outcome was the ability of PPI 1 h postextubation to predict reintubation using area under the receiver operating characteristic curve (AUC) analysis. Univariate and multivariate analyses were performed to identify predictors for reintubation. RESULTS: Data from 62 patients were analysed. Reintubation occurred in 12/62 (19%) of the patients. Reintubated patients had higher heart rate and respiratory rate; and lower SpO2 and PPI than successfully weaned patients. The AUC (95%confidence interval) for the ability of PPI at 1 h postextubation to predict reintubation was 0.82 (0.71-0.91) with a negative predictive value of 97%, at a cutoff value of ≤ 2.5. Low PPI and high respiratory rate were the independent predictors for reintubation. CONCLUSION: PPI early after extubation is a useful tool for prediction of reintubation. Low PPI is an independent risk factor for reintubation. A PPI > 2.5, one hour after extubation can confirm successful extubation.


Subject(s)
Critical Illness , Intubation, Intratracheal , Perfusion Index , Humans , Male , Female , Prospective Studies , Middle Aged , Intubation, Intratracheal/methods , Aged , Airway Extubation/methods , Heart Rate/physiology , Oxygen Saturation/physiology , Respiration, Artificial/methods , Respiratory Rate/physiology , Predictive Value of Tests , Adult
3.
Drug Dev Ind Pharm ; : 1-14, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38963406

ABSTRACT

BACKGROUND: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins, as FDA approved anti-hyperlipidemic drugs, still pose some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity. AIM: This work aimed to study the hypolipidemic effect of Lepidium sativum garden cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin. METHODS: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed. RESULTS: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post-treatment for one month. CONCLUSION: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.

4.
Luminescence ; 39(7): e4824, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39004773

ABSTRACT

Dabigatran (DBG), marketed as Pradaxa, is an anticoagulant medication prescribed for the treatment and mitigation of blood clots and to lower the risk of stroke in individuals with the heart condition known as atrial fibrillation. This medication is specifically indicated for preventing blood clots post hip or knee replacement surgeries and in patients with a prior history of clots. Compared to warfarin, dabigatran serves as a viable alternative that does not necessitate routine blood monitoring tests. The complimentary benefits associated with SALL (salting-out assisted liquid-liquid extraction) and the fluorogenic capabilities of benzofurazan. These methods were combined to provide an affordable and sensitive DBG assaying method. The spectral strength of the yellow luminous product was examined at 533.8 nm and by adjustment of a wavelength of 474.7 nm for excitation. To assess its linearity, the calibration chart was tested across a DBG concentration range of 30-500 ng/ml. Via accurate computation based on ICH, the detection limit (LD) was determined to be 9.5 ng/ml, and the strategy can quantify the DBG to a limit of 28 ng/ml. To ensure success, various crucial parameters for method implementation have been extensively studied and adapted. The validation of the strategy adhered to the policies outlined by ICH, affirming its precision in quantifying DBG in capsules. Furthermore, the inclusion of SALLE steps facilitated accurate monitoring of DBG in plasma samples, introducing a unique and advanced methodology for analyzing this compound in biological samples.


Subject(s)
Anticoagulants , Capsules , Dabigatran , Dabigatran/blood , Dabigatran/chemistry , Dabigatran/pharmacology , Humans , Anticoagulants/chemistry , Anticoagulants/blood , Anticoagulants/pharmacology , Fluorescent Dyes/chemistry , Liquid-Liquid Extraction , Spectrometry, Fluorescence , Limit of Detection , 4-Chloro-7-nitrobenzofurazan
5.
Chem Biodivers ; : e202400831, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005105

ABSTRACT

5-(Cyanomethyl)-3-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-1H-pyrazole-4-carbonitrile (3) is used as a key for the synthesis of arylidenes 5a-fvia its reaction with some aldehydes 4a-f. 5-[(5,5-Dimethyl-3-oxocyclohex-1-en-1-yl)amino]-3-(2-imino-2H-chromen-3-yl)-1H-pyrazole-4-carbonitrile (7) was synthesized via the reaction of compound (3) with 2-hydroxybenzaldehyde in EtOH/piperidine. The target compounds were tested against cotton leafworm larvae in their second and fourth instar. The available data demonstrated that the LC50 values for commercial phenylpyrazole were 3.37 mg/L and 4.55 mg/L for the most affected synthesized compound, 5b. The chemical structure of compound 5b has two cyano moieties, a pyrazole ring and a chlorophenyl, which may be increasing it efficiency. Evaluation of the latent effects of the examined synthesized compounds on various biological parameters, including adult longevity, pupal weight, proportion of normal, deformed pupae, adult emergency, fecundity, and egg hatchability, was done in an additional effort to slightly improve insecticidal compounds. Twelve synthesized compounds were subjected to a molecular docking analysis against glutamate-activated chloride channels. Twelve artificial compounds with the PDB ID of 4COF were subjected to a molecular docking study against the gamma-aminobutyric acid receptor (GABA).

6.
bioRxiv ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39005279

ABSTRACT

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remains less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called 'vanishing microbiomes' potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations. RESULTS: Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the United States within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain source. CONCLUSION: Our findings demonstrate that by controlling for geography, we can isolate an important role for lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes.

7.
Arch Environ Occup Health ; : 1-9, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993119

ABSTRACT

Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators (n = 206) and non-applicators (n = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function. Samples were collected over 7 months in 2016. Logistic regression was used to model the odds of reporting wheeze symptoms based on urinary TCPy concentrations while controlling for age and smoking in the household. Ordinal multinomial logistic regression was used to model the percent reference for forced expiratory volume in one second (rFEV1) based on urinary TCPy concentration (µg/g creatinine). Wheezing increased with increasing pesticide exposure (OR = 1.74 (1.32 - 2.31)). There was no statistically significant relationship between rFEV1 and TCPy concentration. Efforts to reduce pesticide exposure should be implemented to prevent the potential onset or exacerbation of any linked respiratory complications in adolescents.

8.
Front Psychiatry ; 15: 1351056, 2024.
Article in English | MEDLINE | ID: mdl-38993387

ABSTRACT

Background: Avoidant Restrictive Food Intake Disorder (ARFID) is a newly classified eating disorder that requires further understanding of its presentation. There is no previous report of ARFID in a child post-tonsillectomy. ARFID may be a potential negative outcome for children following oropharyngeal surgery. Case presentation: A female child aged 10 years and 2 months presented with ARFID associated with depression, anxiety and nutritional deficiency following tonsillectomy. She had more difficulty in swallowing solids than fluids and had repeated vomiting and spitting food after chewing it. She became dehydrated and malnourished with a BMI of 10.5 and was misdiagnosed with myasthenic gravis. Conclusions: To our knowledge, this is the first case report of ARFID in a child post-tonsillectomy. We discuss the pathophysiology of ARFID, which remains elusive, and recommend psychiatric assessment when evaluating children post operative tonsillectomy.

9.
Cureus ; 16(6): e62164, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38993398

ABSTRACT

BACKGROUND AND AIM: In Erbil, Iraq, the reluctance of young adults to engage with psychiatric services is influenced by a complex array of barriers, including stigma-related, attitudinal, and instrumental factors that hinder effective mental healthcare access. This study aimed to identify these specific barriers to accessing psychiatric care among young adults in Erbil. MATERIALS AND METHODS: The study utilized a cross-sectional online survey conducted between April 5th and May 1st, 2024. Data collection was carried out through purposive sampling and involved a comprehensive questionnaire. Electronic informed consent was obtained from all participants before they started the survey, which collected demographic data and utilized the Barriers to Access to Care Evaluation (BACE v3) tool. Statistical analysis was conducted using SPSS version 27 (IBM Corp., Armonk, NY). Descriptive statistics (frequency and percentage) were used for categorical data, while the mean and standard deviation characterized continuous variables. Chi-square tests, including Fisher's exact test and odds ratio (OR), were used to analyze categorical data, with a significance level set at p < 0.05. RESULTS: A total of 407 participants were enrolled in the study. The study highlighted several barriers to mental health care. Stigma-related barriers were significant, with participants fearing being seen as weak (mean score = 2.14, SD = 0.96) and concerns about being labeled "crazy" (mean score = 1.80, SD = 1.19). Regarding attitudinal barriers, there was a notable preference for dealing with issues independently (mean score = 2.04, SD = 0.98) and a tendency toward resolving problems without professional help (mean score = 1.88, SD = 0.98). Additionally, instrumental barriers were identified, including the rare availability of culturally diverse mental health professionals (mean score = 1.78, SD = 1.09) and practical difficulties such as arranging transportation to appointments (mean score = 0.61, SD = 0.87). CONCLUSION: The study demonstrated that young adults in Erbil face significant stigma and attitudinal and instrumental barriers to accessing psychiatric care. In response to these findings, it is recommended for the government to prioritize mental health awareness, actively destigmatize mental health issues, and improve service accessibility to foster a supportive care environment. Additionally, mental health professionals and educational institutions should collaborate to provide targeted support programs and resources for young adults.

10.
Cureus ; 16(6): e62120, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38993401

ABSTRACT

Epiploic appendagitis is a benign inflammatory condition of the epiploic appendages, small fat-filled structures attached to the colon. Misdiagnosed frequently as more serious conditions like appendicitis or diverticulitis, it usually resolves with minimal treatment. This case report aims to emphasize the importance of recognizing epiploic appendagitis in differential diagnoses, highlighting the role of accurate imaging and surgical intervention in managing unusual presentations. We report a case involving a 27-year-old male who presented with acute, severe pain in the left iliac fossa. Initial assessments showed stable vital signs and negative virology screenings. Ultrasound imaging did not reveal any abnormalities in the abdominal organs but noted multiple gas-filled bowel loops and a 48 x 22 mm collection in the left iliac region. A CT scan with IV contrast further identified a 35 x 26 mm area of fat stranding in the left iliac fossa, indicative of epiploic appendagitis, and a 1 cm area of omental fat necrosis near the hepatic flexure. Persistent symptoms led to a diagnostic laparoscopy, which confirmed and treated gangrenous appendices epiploica. The patient's postoperative recovery was uneventful, highlighting the effectiveness of surgical management. This case underscores the necessity for heightened awareness and diagnostic precision when encountering patients with acute abdominal pain that does not match common ailments. Early and accurate imaging, followed by timely surgical intervention if needed, can significantly improve outcomes by preventing complications from misdiagnosis or delayed treatment.

11.
Cureus ; 16(6): e62174, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38993431

ABSTRACT

INTRODUCTION: Surgical intervention for rectal cancer is widely recognized for its potential to significantly impact quality of life, chiefly due to the high probability of permanent colostomy and the associated postoperative complications. OBJECTIVE: This study aimed to evaluate the short-term outcomes and morbidity associated with total mesorectal excision for middle and lower rectal cancer within an Iraqi cohort, in a prospective setting. METHODS: This study prospectively collected and analyzed data from 89 patients who underwent a standardized radical rectal resection, with a follow-up period extending to one month post-surgery. RESULTS: The mean age of patients was 54.4 ± 12.9 years, with a gender distribution of 46 males and 43 females. A total of 33 patients presented with preoperative comorbidities, which heightened the risk of adverse short-term outcomes by a factor of 7.51. The most prevalent comorbidities were hypertension and diabetes mellitus, affecting 22 and 20 patients, respectively. Patients aged 60 years and above were at a 3.97 times greater risk of developing complications. The overall complication rate was 21.35%, with wound infections (9.0%) and cardiovascular events (3.4%) being the most common. Mortality during the follow-up was 1.1%. CONCLUSION: The findings indicate that increased age and the presence of comorbidities are significant risk factors for morbidity and mortality post-surgery. Neoadjuvant chemoradiotherapy or radiotherapy was shown to reduce morbidity and mortality rates while improving survival. The morbidity and mortality rates observed in this study concur with existing literature.

12.
Cureus ; 16(5): e61307, 2024 May.
Article in English | MEDLINE | ID: mdl-38947653

ABSTRACT

INTRODUCTION: Despite the recognition of the importance of physician knowledge and physician-patient communication about the use of complementary and alternative medicine (CAM), few studies have explored this issue. Therefore, this study aims to assess physicians' knowledge and physician-patient communication regarding CAM. METHODS: A cross-sectional study was conducted among physicians working at governmental hospitals and primary healthcare centers in Madinah, Saudi Arabia. The data collection tool was a validated English language questionnaire distributed using social media platforms. The questionnaire included sections to assess physician knowledge and communication about CAM. RESULTS: Of the 373 completed questionnaires, around 151 (40.5%) of the respondents stated that they have a poor level of knowledge about CAM, and 272 (72.9%) need to gain additional knowledge to properly counsel patients on CAM. Medical journals were the main source of knowledge about CAM. There were 121 (32.4%) physicians who believed that <20% of their patients use some form of CAM, and 180 (48.3%) believed that <20% of their patients spontaneously reported their CAM use without prompting or direct questioning. Around 180 (48.3%) of physicians believed that they asked <20% of their patients about using CAM. Regarding barriers that limit communication with the patient about CAM, the highest percentage was insufficient knowledge about CAM (137, 36.7%). CONCLUSION: The study showed that a significant number of physicians lack the appropriate knowledge about CAM and most of them agreed to gain additional knowledge to properly counsel their patients. Further research is needed to evaluate physicians' knowledge about CAM using a more objective method.

13.
Cureus ; 16(5): e61320, 2024 May.
Article in English | MEDLINE | ID: mdl-38947675

ABSTRACT

Coronary arteriovenous fistulas (CAVFs) are congenital or acquired communications between the coronary arteries and coronary venous system, and they can also include other cardiac structures or vasculature. We discuss a case of a large fistula between the left main coronary artery and the right atrium in a geriatric patient with a history of gastrointestinal arteriovenous malformations (AVM). The occurrence of CAVFs, an uncommon cardiac irregularity, is particularly infrequent among older adults. Typically, it is discovered by chance when investigating symptoms such as shortness of breath or chest pain, where coronary angiography is necessary to determine the most effective treatment strategy. This case highlights the possible utility of evaluating CAVFs in patients with a history of gastrointestinal AVM who similarly present with clinical symptoms of high-output heart failure. Once identified, this could simplify the treatment approach and improve communication between healthcare providers to minimize the risk of harm to the patient.

14.
Integr Pharm Res Pract ; 13: 81-89, 2024.
Article in English | MEDLINE | ID: mdl-38948431

ABSTRACT

Purpose: Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is challenging due to its narrow therapeutic range and variable dose. This study aimed to highlight polypharmacy and drug interactions in patients receiving warfarin therapy at Medani Heart Centre, Sudan. Methods: This retrospective hospital-based study was conducted from May 2017 to October 2018. Each concurrent medication prescribed for 104 patients was collected and checked for drug-drug interactions using Medscape Reference-Drug Interaction Checker. The data were analysed by using SPSS 20, and descriptive statistics were used. Results: The results revealed that 95.2% of patients had more than three medications in their profile, (3-5), (6-9) and more than 10 medications were prescribed for 40.4%, 44.2% and 10.6% of patients, respectively. A total of 93.3% of patients had drug-drug interactions, as follows: (1-5), (6-10), (11-15), (16-20) and more than 20 drug-drug interactions were found in 31.7%, 32.7%, 19.2%, 5.8% and 3.8% of patients, respectively. A total of 178 warfarin-drug interactions were identified in 88.5% of the patients. The INR ranged between 2 and 2.99 in 13.4% of patients, and INR values below 2 and above 5 were found in 44.2% and 21.2% of patients, respectively. Analgesics (n=54; 30.3%), cardiovascular drugs (n=51; 28.6%), and anticoagulants (n=46; 25.8%) were the most common drug classes that interact with warfarin. Significant and serious types of interactions with warfarin were found in 51% and 37.5% of patients, respectively. Conclusion: This study highlights the complexity of managing warfarin therapy amid prevalent polypharmacy. A substantial majority of patients experienced multiple drug interactions. The identification of significant and serious interactions emphasizes the need for vigilant management strategies, including improved communication among healthcare professionals and targeted education for both providers and patients, to enhance the safety and efficacy of warfarin therapy.

15.
Drug Dev Res ; 85(5): e22228, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38952003

ABSTRACT

Chromone-based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone-2-carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Among the tested cell lines, MDA-MB-231, the triple-negative breast cancer cell line, was found to be the most sensitive, where the N-(2-furylmethylene) (15) and the α-methylated N-benzyl (17) derivatives demonstrated the highest growth inhibition with GI50 values of 14.8 and 17.1 µM, respectively. In vitro mechanistic studies confirmed the significant roles of compounds 15 and 17 in the induction of apoptosis and suppression of EGFR, FGFR3, and VEGF protein levels in MDA-MB-231 cancer cells. Moreover, compound 15 exerted cell cycle arrest at both the G0-G1 and G2-M phases. The in vivo efficacy of compound 15 as an antitumor agent was further investigated in female mice bearing Solid Ehrlich Carcinoma. Notably, administration of compound 15 resulted in a marked decrease in both tumor weight and volume, accompanied by improvements in biochemical, hematological, histological, and immunohistochemical parameters that verified the repression of both angiogenesis and inflammation as additional Anticancer mechanisms. Moreover, the binding interactions of compounds 15 and 17 within the binding sites of all three target receptors (EGFR, FGFR3, and VEGF) were clearly illustrated using molecular docking.


Subject(s)
Antineoplastic Agents , Chromones , ErbB Receptors , Molecular Docking Simulation , Receptor, Fibroblast Growth Factor, Type 3 , Triple Negative Breast Neoplasms , Vascular Endothelial Growth Factor A , Humans , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Female , Animals , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Vascular Endothelial Growth Factor A/metabolism , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Mice , Chromones/pharmacology , Chromones/chemical synthesis , Chromones/chemistry , Chromones/therapeutic use , Drug Design , Apoptosis/drug effects , Cell Proliferation/drug effects
16.
Ann R Coll Surg Engl ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38961733

ABSTRACT

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

17.
PLoS One ; 19(7): e0302583, 2024.
Article in English | MEDLINE | ID: mdl-38985703

ABSTRACT

Social media platforms serve as communication tools where users freely share information regardless of its accuracy. Propaganda on these platforms refers to the dissemination of biased or deceptive information aimed at influencing public opinion, encompassing various forms such as political campaigns, fake news, and conspiracy theories. This study introduces a Hybrid Feature Engineering Approach for Propaganda Identification (HAPI), designed to detect propaganda in text-based content like news articles and social media posts. HAPI combines conventional feature engineering methods with machine learning techniques to achieve high accuracy in propaganda detection. This study is conducted on data collected from Twitter via its API, and an annotation scheme is proposed to categorize tweets into binary classes (propaganda and non-propaganda). Hybrid feature engineering entails the amalgamation of various features, including Term Frequency-Inverse Document Frequency (TF-IDF), Bag of Words (BoW), Sentimental features, and tweet length, among others. Multiple Machine Learning classifiers undergo training and evaluation utilizing the proposed methodology, leveraging a selection of 40 pertinent features identified through the hybrid feature selection technique. All the selected algorithms including Multinomial Naive Bayes (MNB), Support Vector Machine (SVM), Decision Tree (DT), and Logistic Regression (LR) achieved promising results. The SVM-based HaPi (SVM-HaPi) exhibits superior performance among traditional algorithms, achieving precision, recall, F-Measure, and overall accuracy of 0.69, 0.69, 0.69, and 69.2%, respectively. Furthermore, the proposed approach is compared to well-known existing approaches where it overperformed most of the studies on several evaluation metrics. This research contributes to the development of a comprehensive system tailored for propaganda identification in textual content. Nonetheless, the purview of propaganda detection transcends textual data alone. Deep learning algorithms like Artificial Neural Networks (ANN) offer the capability to manage multimodal data, incorporating text, images, audio, and video, thereby considering not only the content itself but also its presentation and contextual nuances during dissemination.


Subject(s)
Algorithms , Machine Learning , Social Media , Humans , Support Vector Machine , Bayes Theorem
18.
Nanomaterials (Basel) ; 14(13)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38998769

ABSTRACT

Arsenic (As)-contaminated soil reduces soil quality and leads to soil degradation, and traditional remediation strategies are expensive or typically produce hazardous by-products that have negative impacts on ecosystems. Therefore, this investigation attempts to assess the impact of As-tolerant bacterial isolates via a bacterial Rhizobim nepotum strain (B1), a bacterial Glutamicibacter halophytocola strain (B2), and MgO-NPs (N) and their combinations on the arsenic content, biological activity, and growth characteristics of maize plants cultivated in highly As-contaminated soil (300 mg As Kg-1). The results indicated that the spectroscopic characterization of MgO-NPs contained functional groups (e.g., Mg-O, OH, and Si-O-Si) and possessed a large surface area. Under As stress, its addition boosted the growth of plants, biomass, and chlorophyll levels while decreasing As uptake. Co-inoculation of R. nepotum and G. halophytocola had the highest significant values for chlorophyll content, soil organic matter (SOM), microbial biomass (MBC), dehydrogenase activity (DHA), and total number of bacteria compared to other treatments, which played an essential role in increasing maize growth. The addition of R. nepotum and G. halophytocola alone or in combination with MgO-NPs significantly decreased As uptake and increased the biological activity and growth characteristics of maize plants cultivated in highly arsenic-contaminated soil. Considering the results of this investigation, the combination of G. halophytocola with MgO-NPs can be used as a nanobioremediation strategy for remediating severely arsenic-contaminated soil and also improving the biological activity and growth parameters of maize plants.

19.
Molecules ; 29(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38999138

ABSTRACT

Cancer remains a leading cause of death worldwide, often resulting from uncontrolled growth in various organs. Protein kinase inhibitors represent an important class of targeted cancer therapies. Recently, the kinases BRAF and VEGFR-2 have shown synergistic effects on tumor progression. Seeking to develop dual BRAF/VEGFR-2 inhibitors, we synthesized 18 amino-benzothiazole derivatives with structural similarities to reported dual inhibitors. Four compounds-4a, 4f, 4l, and 4r-demonstrated remarkable cytotoxicity, with IC50 values ranging from 3.58 to 15.36 µM, against three cancer cell lines. Furthermore, these compounds showed IC50 values of 38.77-66.22 µM in the case of a normal cell line, which was significantly safer than the reference, sorafenib. Subsequent investigation revealed that compound 4f exhibited the capacity to inhibit the BRAF and VEGFR-2 enzymes, with IC50 values similar to sorafenib (0.071 and 0.194 µM, respectively). Moreover, compound 4f caused G2-M- and S-phase cycle arrest. Molecular modeling demonstrated binding patterns compatible with inhibition for both targets, where 4f exerted the critical interactions in the BRAF site and interacted in the VEGFR-2 site in a manner akin to sorafenib, demonstrating affinity similar to dabrafenib.


Subject(s)
Antineoplastic Agents , Benzothiazoles , Cell Proliferation , Molecular Docking Simulation , Protein Kinase Inhibitors , Proto-Oncogene Proteins B-raf , Thiadiazoles , Vascular Endothelial Growth Factor Receptor-2 , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/metabolism , Humans , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Benzothiazoles/chemical synthesis , Thiadiazoles/chemistry , Thiadiazoles/pharmacology , Thiadiazoles/chemical synthesis , Cell Line, Tumor , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Drug Design , Structure-Activity Relationship , Sorafenib/pharmacology , Sorafenib/chemistry , Molecular Structure , Computer Simulation , Drug Screening Assays, Antitumor
20.
Cells ; 13(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38994957

ABSTRACT

Platelet activation is critical for haemostasis, but if unregulated can lead to pathological thrombosis. Endogenous platelet inhibitory mechanisms are mediated by prostacyclin (PGI2)-stimulated cAMP signalling, which is regulated by phosphodiesterase 3A (PDE3A). However, spatiotemporal regulation of PDE3A activity in platelets is unknown. Here, we report that platelets possess multiple PDE3A isoforms with seemingly identical molecular weights (100 kDa). One isoform contained a unique N-terminal sequence that corresponded to PDE3A1 in nucleated cells but with negligible contribution to overall PDE3A activity. The predominant cytosolic PDE3A isoform did not possess the unique N-terminal sequence and accounted for >99% of basal PDE3A activity. PGI2 treatment induced a dose and time-dependent increase in PDE3A phosphorylation which was PKA-dependent and associated with an increase in phosphodiesterase enzymatic activity. The effects of PGI2 on PDE3A were modulated by A-kinase anchoring protein (AKAP) disruptor peptides, suggesting an AKAP-mediated PDE3A signalosome. We identified AKAP7, AKAP9, AKAP12, AKAP13, and moesin expressed in platelets but focussed on AKAP7 as a potential PDE3A binding partner. Using a combination of immunoprecipitation, proximity ligation techniques, and activity assays, we identified a novel PDE3A/PKA RII/AKAP7 signalosome in platelets that integrates propagation and termination of cAMP signalling through coupling of PKA and PDE3A.


Subject(s)
A Kinase Anchor Proteins , Blood Platelets , Cyclic AMP-Dependent Protein Kinases , Cyclic Nucleotide Phosphodiesterases, Type 3 , Epoprostenol , Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 3/genetics , Blood Platelets/metabolism , Blood Platelets/drug effects , Humans , A Kinase Anchor Proteins/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Epoprostenol/metabolism , Epoprostenol/pharmacology , Phosphorylation , Cyclic AMP/metabolism , Signal Transduction
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