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1.
BMC Neurol ; 24(1): 156, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714968

ABSTRACT

BACKGROUND: Posterior Circulation Syndrome (PCS) presents a diagnostic challenge characterized by its variable and nonspecific symptoms. Timely and accurate diagnosis is crucial for improving patient outcomes. This study aims to enhance the early diagnosis of PCS by employing clinical and demographic data and machine learning. This approach targets a significant research gap in the field of stroke diagnosis and management. METHODS: We collected and analyzed data from a large national Stroke Registry spanning from January 2014 to July 2022. The dataset included 15,859 adult patients admitted with a primary diagnosis of stroke. Five machine learning models were trained: XGBoost, Random Forest, Support Vector Machine, Classification and Regression Trees, and Logistic Regression. Multiple performance metrics, such as accuracy, precision, recall, F1-score, AUC, Matthew's correlation coefficient, log loss, and Brier score, were utilized to evaluate model performance. RESULTS: The XGBoost model emerged as the top performer with an AUC of 0.81, accuracy of 0.79, precision of 0.5, recall of 0.62, and F1-score of 0.55. SHAP (SHapley Additive exPlanations) analysis identified key variables associated with PCS, including Body Mass Index, Random Blood Sugar, ataxia, dysarthria, and diastolic blood pressure and body temperature. These variables played a significant role in facilitating the early diagnosis of PCS, emphasizing their diagnostic value. CONCLUSION: This study pioneers the use of clinical data and machine learning models to facilitate the early diagnosis of PCS, filling a crucial gap in stroke research. Using simple clinical metrics such as BMI, RBS, ataxia, dysarthria, DBP, and body temperature will help clinicians diagnose PCS early. Despite limitations, such as data biases and regional specificity, our research contributes to advancing PCS understanding, potentially enhancing clinical decision-making and patient outcomes early in the patient's clinical journey. Further investigations are warranted to elucidate the underlying physiological mechanisms and validate these findings in broader populations and healthcare settings.


Subject(s)
Early Diagnosis , Machine Learning , Stroke , Humans , Male , Female , Middle Aged , Aged , Stroke/diagnosis , Stroke/physiopathology , Registries , Adult
2.
BMC Neurol ; 24(1): 88, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443844

ABSTRACT

BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HT) may increase the risk of stroke. Limited studies have shown that stroke severity and infarction size are smaller in patients with HT. We explored the relationship between triglyceride levels and stroke risk factors, severity and outcome in a large prospective database. DESIGN: Prospective Cross-sectional study. SETTING: We retrospectively interrogated the Qatar Stroke Database in all patients admitted between 2014-2022 with acute ischemic stroke and evaluated the relationship between triglyceride, diabetes, stroke severity (measured on NIHSS), stroke type (TOAST classification) and the short- (mRS at 90 days) and long-term outcomes (MACE at 1 year) in patients with HT. PARTICIPANTS: Six thousand five hundred fifty-eight patients ≥20 years were included in this study RESULTS: Six thousand five hundred fifty-eight patients with ischemic stroke [mean age 54.6 ± 12. 9; male 82.1%) were included. Triglyceride levels upon admission were low-normal (≤1.1 mmol/L) in 2019 patients, high-normal (1.2-1.7 mmol/L) in 2142 patients, borderline-high (1.8-2.2 mmol/L) in 1072 patients and high (≥2.3 mmol/L) in 1325 patients. Higher triglyceride levels were associated with stroke and increased likelihood of having diabetes, obesity, active smoking, and small vessel/lacunar stroke type. An inverse relationship was noted whereby higher triglyceride levels were associated with lower stroke severity and reduced likelihood of poorer outcome (mRS 3-6) at discharge and 90 days. Long-term MACE events were less frequent in patients with higher triglyceride levels. After adjusting age, gender, diabetes, prior stroke, CAD, and obesity, multivariate analysis showed that hypertension and triglyceride levels were higher in mild ischemic strokes patients. CONCLUSIONS: Increasing triglycerides are associated with higher risk of small vessel disease and requires further prospective cohort studies for confirmation.


Subject(s)
Diabetes Mellitus , Ischemic Stroke , Stroke , Humans , Male , Adult , Middle Aged , Aged , Cross-Sectional Studies , Prospective Studies , Retrospective Studies , Prognosis , Stroke/epidemiology , Obesity , Triglycerides
3.
Neurosurg Rev ; 47(1): 674, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316160

ABSTRACT

Multiple prognostic scores have been developed to predict morbidity and mortality in patients with spontaneous intracerebral hemorrhage(sICH). Since the advent of machine learning(ML), different ML models have also been developed for sICH prognostication. There is however a need to verify the validity of these ML models in diverse patient populations. We aim to create machine learning models for prognostication purposes in the Qatari population. By incorporating inpatient variables into model development, we aim to leverage more information. 1501 consecutive patients with acute sICH admitted to Hamad General Hospital(HGH) between 2013 and 2023 were included. We trained, evaluated, and compared several ML models to predict 90-day mortality and functional outcomes. For our dataset, we randomly selected 80% patients for model training and 20% for validation and used k-fold cross validation to train our models. The ML workflow included imbalanced class correction and dimensionality reduction in order to evaluate the effect of each. Evaluation metrics such as sensitivity, specificity, F-1 score were calculated for each prognostic model. Mean age was 50.8(SD 13.1) years and 1257(83.7%) were male. Median ICH volume was 7.5 ml(IQR 12.6). 222(14.8%) died while 897(59.7%) achieved good functional outcome at 90 days. For 90-day mortality, random forest(RF) achieved highest AUC(0.906) whereas for 90-day functional outcomes, logistic regression(LR) achieved highest AUC(0.888). Ensembling provided similar results to the best performing models, namely RF and LR, obtaining an AUC of 0.904 for mortality and 0.883 for functional outcomes. Random Forest achieved the highest AUC for 90-day mortality, and LR achieved the highest AUC for 90-day functional outcomes. Comparing ML models, there is minimal difference between their performance. By creating an ensemble of our best performing individual models we maintained maximum accuracy and decreased variance of functional outcome and mortality prediction when compared with individual models.


Subject(s)
Cerebral Hemorrhage , Machine Learning , Humans , Male , Female , Qatar , Middle Aged , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/diagnosis , Prognosis , Aged , Adult , Retrospective Studies , Stroke/mortality , Stroke/diagnosis , Databases, Factual
4.
Qatar Med J ; 2024(1): 6, 2024.
Article in English | MEDLINE | ID: mdl-38344402

ABSTRACT

INTRODUCTION: Cervicocephalic arterial dissections (CADs) occur in 3 cases per 100,000 individuals across all ages. Multiple simultaneous CADs are found in 13 to 22% of cases, and three or more dissections occur in approximately 2%. CADs might result from multifactorial intrinsic deficiencies of vessel wall integrity and extrinsic factors, e.g., minor trauma. CASE PRESENTATION: A young gentleman presented to the emergency department with a sudden onset of a spinning sensation of surrounding, left side arm weakness, blurring of vision, and an NIHSS score of 4. An urgent CT scan of the head and intracranial angiogram showed bilateral severe stenosis of the distal cervical segment of internal carotid arteries (ICAs) and right vertebral artery moderate stenosis at the V2 segment. He had been given IV TPA (Alteplase) within the 4.5-hour window. After 4 hours, the patient's GCS dropped from 15 to 10, and the NIHSS score increased from 4 to 24, followed by witnessed a generalized tonic-clonic seizure. Repeat urgent CT head showed no evidence of intracerebral hemorrhage (ICH). The patient was arranged for cerebral angiographic catheterization that showed bilateral flame-shaped occlusion of cervical ICA dissection. There is a mild focal narrowing of the right cervical vertebral artery, likely dissection. Routine laboratory blood workup for vasculitis was negative. During MICU admission, he had witnessed the right arm hemichorea-ballism spectrum abnormal movement. After the 6th-month follow-up, intracranial CT angiogram showed reduced caliber of the bilateral distal cervical course of the internal carotid arteries seen with residual dissection and focal outpouching of the right ICA representing pseudoaneurysm. DISCUSSION: The occurrence of multiple CADs suggests the presence of an underlying intrinsic arteriopathy, such as FMD, the presence of pseudoaneurysm, environmental triggers, cervical manipulation, and remote history of head or neck surgery. A study of the most extensive case series of patients with cervical artery dissection showed 15.2% of patients with multiple CAD. In most patients with multiple cervical artery dissections, antithrombotic treatment is effective, complete recanalization, and the outcome is favorable. Outside the window period of acute ischemic stroke, either anticoagulation or antiplatelet therapy is a recognized treatment for secondary ischemic stroke prevention due to extracranial artery dissection. For acute stroke or TIA patients caused by intracranial artery dissection, experts recommend antiplatelet therapy rather than anticoagulation. CONCLUSION: Simultaneous triple-vessel cervicocephalic arterial dissections are rarely reported condition. Multiple CADs are associated with underlying vasculopathy and environmental triggers, and a majority are recanalized with antithrombotic treatment with favorable outcomes. Antithrombotic treatment is effective in most patients with multiple CADs, and most expect complete recanalization. This case report guides physicians in the treatment and outcome of acute stroke due to multiple CAD.

5.
J Vasc Interv Radiol ; 34(10): 1740-1748, 2023 10.
Article in English | MEDLINE | ID: mdl-37302471

ABSTRACT

PURPOSE: To investigate the safety and effectiveness of rescue stent placement in patients who experienced acute stroke in whom mechanical thrombectomy failed. METHODS: This was a retrospective review of a multiethnic stroke database. After stent placement, an aggressive antiplatelet protocol was followed with glycoprotein IIb/IIIa infusion. The primary outcomes were incidence of intracerebral hemorrhage (ICH), recanalization score, and favorable prognosis (modified Rankin score ≤ 2) at 90 days. A comparison was made between patients from the Middle East and North Africa (MENA) region and those from other regions. RESULTS: Fifty-five patients were included, with 87% being men. The mean age was 51.3 years (SD ±11.8); 32 patients (58%) were from South Asia, 12 (22%) from MENA, 9 (16%) from Southeast Asia, and 2 (4%) from elsewhere. Successful recanalization (modified Thrombolysis in Cerebral Infarction score = 2b/3) was achieved in 43 patients (78%), and symptomatic ICH occurred in 2 patients (4%). A favorable outcome at 90 days was seen in 26 of the 55 patients (47%). Apart from significantly older age-mean, 62.8 years (SD ±13; median, 69 years) versus 48.1 years (SD ±9.3; median, 49 years)-and coronary artery disease burden-4 (33%) versus 1 (2%) (P < .05), patients from MENA had risk factors, stroke severity, recanalization rates, ICH rates, and 90-day outcomes similar to those from South and Southeast Asia. CONCLUSION: Rescue stent placement showed good outcomes and a low risk of clinically significant bleeding in a multiethnic cohort of patients from MENA and South and Southeast Asia, similar to that in published literature.


Subject(s)
Ischemic Stroke , Stroke , Male , Humans , Middle Aged , Female , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/therapy , Treatment Outcome , Thrombectomy/adverse effects , Thrombectomy/methods , Stents/adverse effects , Stroke/diagnostic imaging , Stroke/etiology , Stroke/therapy , Retrospective Studies
6.
BMC Plant Biol ; 22(1): 214, 2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35468717

ABSTRACT

Duckweed (Lemna minor L.) is an aquatic macrophyte and grows profoundly on the surface of polluted water reservoirs of Pakistan. The plant can be used as a potential alternative for the fish and poultry industry to meet the promptly growing demand for feed. Our study investigates the effect of varying concentrations (ppm) of nutrients like N, P, and their combination, NP on biomass production, carbohydrate, lipid, protein, and mineral (Ca, Mg, Fe, Mn & Zn) contents of L. minor. The varying concentrations of N and P substantially affected the above-stated parameters. The highest biomass yield was recorded in the 30 ppm NP tank as 172 g/m2 day in comparison with the control tank. Higher protein, lipid, and carbohydrate contents were recorded for 30 ppm NP, 20 ppm NP, and 10 ppm NP respectively. Minerals like Ca, Mg, Fe, Mn & Zn increased in 20 ppm P and all N concentrations. The combined application of NP was more effective in boosting the protein, carbohydrate, and lipid content whereas less effective in increasing the mineral contents. A rise in the concentration of N and P showed a positive correlation with the nutritional composition of L. minor.


Subject(s)
Araceae , Phosphorus , Animals , Biomass , Carbohydrates , Lipids , Minerals/metabolism , Nitrogen/metabolism , Phosphorus/metabolism , Poultry/metabolism
7.
Eur J Clin Pharmacol ; 78(11): 1801-1811, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36121499

ABSTRACT

BACKGROUND AND PURPOSE: Uncertainty remains regarding the impact of enteric-coated aspirin (EC-ASA) on secondary prevention of ischemic stroke compared to plain aspirin (P-ASA). Hence, this study was designed to investigate the effect of EC formulation on ASA response via evaluating thromboxane B2 (TXB2) levels in patients with suspected or newly diagnosed stroke. METHODS: A prospective cohort study on suspected or newly diagnosed ischemic stroke patients who are aspirin-naive was conducted. Patients were received either EC aspirin or plain aspirin for at least 3 days. The primary outcome was the proportion of aspirin non-responsiveness between two groups (level of residual serum TXB2 associated with elevated thrombotic risk (< 99.0% inhibition or TXB2 > 3.1 ng/ml) within 72 h after three daily aspirin doses, while secondary outcomes were the incidence of early gastrointestinal tract (GIT) bleeding with the various aspirin preparations. (Trial registration: Clinicaltrials.gov NCT04330872 registered on 02 April 2020). RESULTS: Of 42 patients, ischemic strokes were confirmed in both P-ASA (81%) and EC-ASA (67%) arms. ASA non-responsiveness showed no significant difference between the two formulations (P-ASA vs. EC-ASA; 28.6% vs 23.8%; P = 0.726). Univariate and multivariate logistic regression analysis showed that patients treated with EC-ASA were more likely to have a lower rate of non-responders compared to P-ASA (unadjusted OR 0.78; 95% CI 0.20, 3.11); with the risk highest in type 2 diabetic patients with HBA1c > 6.5% (adjusted OR 6; 95% CI 1.02, 35.27; P = 0.047). No incidence of GIT bleeding observed throughout the study. CONCLUSION: A significant proportion of ASA non-responsiveness was recorded regardless of ASA formulation administered. The increased risk of ASA non-responsiveness in diabetic patients needs further exploration by larger prospective studies.


Subject(s)
Aspirin , Ischemic Stroke , Aspirin/adverse effects , Gastrointestinal Hemorrhage/chemically induced , Glycated Hemoglobin , Humans , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Thromboxane B2
8.
J Thromb Thrombolysis ; 53(4): 824-828, 2022 May.
Article in English | MEDLINE | ID: mdl-35244832

ABSTRACT

Understanding the relationship of COVID-19 to stroke is important. We compare characteristics of pre-pandemic stroke (PPS), cases in acute COVID infection (CS) and in patients who have recovered from COVID-19 infection (RCS). We interrogated the Qatar stroke database for all stroke admissions between Jan 2020 and Feb 2021 (PPS) to CS and RCS to determine how COVID-19 affected ischemic stroke sub-types, clinical course, and outcomes prior to, during and post-pandemic peak. There were 3264 cases admitted (pre-pandemic: 3111, stroke in COVID-19: 60 and recovered COVID-19 stroke: 93). Patients with CS were significantly younger, had more severe symptoms, fever on presentation, more ICU admissions and poor stroke recovery at discharge when compared to PPS and RCS. Large vessel disease and cardioembolic disease was significantly higher in CS compared to PPS or RCS. There was a significant decline in stroke mimics in CS. Stroke in RCS has characteristics similar to PPS with no evidence of lasting effects of the virus on the short-term. However, CS is a more serious disease and tends to be more severe and have a poor prognosis.


Subject(s)
COVID-19 , Ischemic Stroke , Stroke , COVID-19/epidemiology , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Pandemics , Qatar/epidemiology , Stroke/diagnosis , Stroke/epidemiology
9.
Int J Mol Sci ; 23(22)2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36430952

ABSTRACT

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.


Subject(s)
Extracellular Traps , Ischemic Stroke , Stroke , Thrombosis , Humans , Extracellular Traps/metabolism , Neutrophils/metabolism , von Willebrand Factor/metabolism , Histones , Stroke/pathology , Thrombosis/pathology , Fibrin/metabolism , DNA
10.
Int J Mol Sci ; 24(1)2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36613546

ABSTRACT

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. Understanding the differences in molecular pathways in AIS and TIA has merit for deciphering the underlying cause for neuronal deficits with long-term effects and high risks of morbidity and mortality. In this study, we performed comprehensive investigations into the circulating microRNA (miRNA) profiles of AIS (n = 191) and TIA (n = 61) patients. We performed RNA-Seq on serum samples collected within 24 hrs of clinical diagnosis and randomly divided the study populations into discovery and validation cohorts. We identified a panel of 11 differentially regulated miRNAs at FDR < 0.05. Hsa-miR-548c-5p, -20a-5p, -18a-5p, -484, -652-3p, -486-3p, -24-3p, -181a-5p and -222-3p were upregulated, while hsa-miR-500a-3p and -206 were downregulated in AIS patients compared to TIA patients. We also probed the previously validated gene targets of our identified miRNA panel to highlight the molecular pathways affected in AIS. Moreover, we developed a multivariate classifier with potential utilization as a discriminative biomarker for AIS and TIA patients. The underlying molecular pathways in AIS compared to TIA may be explored further in functional studies for therapeutic targeting in clinical translation.


Subject(s)
Circulating MicroRNA , Ischemic Attack, Transient , Ischemic Stroke , MicroRNAs , Stroke , Humans , Biomarkers , Circulating MicroRNA/genetics , Ischemic Attack, Transient/genetics , Ischemic Stroke/genetics , MicroRNAs/metabolism , Stroke/therapy
11.
Int J Mol Sci ; 23(6)2022 Mar 21.
Article in English | MEDLINE | ID: mdl-35328807

ABSTRACT

Ischemic strokes are associated with significant morbidity and mortality, but currently there are no reliable prognostic or diagnostic blood biomarkers. MicroRNAs (miRNAs) regulate various molecular pathways and may be used as biomarkers. Using RNA-Seq, we conducted comprehensive circulating miRNA profiling in patients with ischemic stroke compared with healthy controls. Samples were collected within 24 h of clinical diagnosis. Stringent analysis criteria of discovery (46 cases and 95 controls) and validation (47 cases and 96 controls) cohorts led to the identification of 10 differentially regulated miRNAs, including 5 novel miRNAs, with potential diagnostic significance. Hsa-miR-451a was the most significantly upregulated miRNA (FC; 4.8, FDR; 3.78 × 10-85), while downregulated miRNAs included hsa-miR-574-5p and hsa-miR-142-3p, among others. Importantly, we computed a multivariate classifier based on the identified miRNA panel to differentiate between ischemic stroke patients and healthy controls, which showed remarkably high sensitivity (0.94) and specificity (0.99). The area under the ROC curve was 0.97 and it is superior to other current available biomarkers. Moreover, in samples collected one month following stroke, we found sustained upregulation of hsa-miR-451a and downregulation of another 5 miRNAs. Lastly, we report 3 miRNAs that were significantly associated with poor clinical outcomes of stroke, as defined by the modified Rankin scores. The clinical translation of the identified miRNA panel may be explored further.


Subject(s)
Circulating MicroRNA , Ischemic Stroke , MicroRNAs , Stroke , Biomarkers , Circulating MicroRNA/genetics , Gene Expression Profiling , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/genetics , MicroRNAs/genetics , ROC Curve , Stroke/genetics
12.
J Stroke Cerebrovasc Dis ; 31(6): 106452, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35390731

ABSTRACT

INTRODUCTION: Stroke in air travelers is being increasingly recognized. We report on stroke among passengers arriving at or transiting through a busy air travel hub. METHODS: The stroke database of the sole tertiary care center for stroke in a large busy international hub was interrogated. Demographic data of transit passengers, their stroke risk factors, stroke severity, National Institutes of Health Stroke Scale (NIHSS), acute stroke interventions, discharge status and outcome utilizing the Modified Raking scale (mRS) were retrieved and compared between passengers and non-passenger controls. RESULTS: Forty-three flight-related stroke patients were compared to 2564 non-passenger stroke patients. The mean age in the flight-related stroke group was 59.53±10.83 years, 30/43 (69.8%) were males. The stroke subtypes were ischemic in 30 (69.8%) patients, hemorrhagic in 9 (20.9%), and transient ischemic attack in 3 (7.0%), with one cerebral sinus venous thrombosis (2.3%). The mean NIHSS score was 7.79±6.44 in passengers, demonstrating moderate severity. Ten patients (23.3%) received thrombolysis, one (2.3%) received thrombectomy, and one (2.3%) received both thrombolysis and thrombectomy. Outcomes, 54.8% had a good outcome (mRS 0-2), and 45.2% had dependence/death (mRS 3-6). CONCLUSION: Air passengers with stroke were found to be older with more severe strokes and a higher probability of receiving acute stroke treatment compared to non-passengers. Increased awareness with appropriate and timely recognition and triaging of transit passengers with stroke is warranted.


Subject(s)
Brain Ischemia , Stroke , Aged , Aircraft , Brain Ischemia/diagnostic imaging , Brain Ischemia/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Stroke/diagnostic imaging , Stroke/epidemiology , Thrombectomy/adverse effects , Treatment Outcome
13.
Molecules ; 27(13)2022 Jun 25.
Article in English | MEDLINE | ID: mdl-35807344

ABSTRACT

NIMA-related kinase7 (NEK7) plays a multifunctional role in cell division and NLRP3 inflammasone activation. A typical expression or any mutation in the genetic makeup of NEK7 leads to the development of cancer malignancies and fatal inflammatory disease, i.e., breast cancer, non-small cell lung cancer, gout, rheumatoid arthritis, and liver cirrhosis. Therefore, NEK7 is a promising target for drug development against various cancer malignancies. The combination of drug repurposing and structure-based virtual screening of large libraries of compounds has dramatically improved the development of anticancer drugs. The current study focused on the virtual screening of 1200 benzene sulphonamide derivatives retrieved from the PubChem database by selecting and docking validation of the crystal structure of NEK7 protein (PDB ID: 2WQN). The compounds library was subjected to virtual screening using Auto Dock Vina. The binding energies of screened compounds were compared to standard Dabrafenib. In particular, compound 762 exhibited excellent binding energy of -42.67 kJ/mol, better than Dabrafenib (-33.89 kJ/mol). Selected drug candidates showed a reactive profile that was comparable to standard Dabrafenib. To characterize the stability of protein-ligand complexes, molecular dynamic simulations were performed, providing insight into the molecular interactions. The NEK7-Dabrafenib complex showed stability throughout the simulated trajectory. In addition, binding affinities, pIC50, and ADMET profiles of drug candidates were predicted using deep learning models. Deep learning models predicted the binding affinity of compound 762 best among all derivatives, which supports the findings of virtual screening. These findings suggest that top hits can serve as potential inhibitors of NEK7. Moreover, it is recommended to explore the inhibitory potential of identified hits compounds through in-vitro and in-vivo approaches.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Deep Learning , Lung Neoplasms , Drug Discovery , Early Detection of Cancer , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , NIMA-Related Kinases
14.
J Psycholinguist Res ; 51(3): 455-472, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34499286

ABSTRACT

Critical discourse analysis aims to explore the dialectical relationship between discourse and ideology. Based on psycholinguistic research, this paper analyzes the Chinese and American media's news reports and comments on the COVID-19. It aims to expose the hidden psychological messages and ideologies behind the words. The corpus in this paper is mainly from the official media of China Daily and Time from December 2019 to January 2021 in China and the United States. This paper uses Wang Zhenhua's Appraisal Theory and Halliday's Systemic Functional Grammar as tools to make a comparative analysis of the corpus. At the textual level, languages are classified and lexical choices are analyzed followed by the analysis of the reporter's ideology after reviewing the motivation of the reporters of two countries. On the level of social responsibility expression and discourse, the paper analyzes the news reports, which are characterized by the combination of the reporter's views on the news. In the aspect of social practice, the social and cultural factors and background of news reports are analyzed. China calls for strengthening cooperation and exchanges with other countries to jointly fight the epidemic. The Chinese government has actively shared its experience and made corresponding contributions to international economic recovery. However, the US government shirks its responsibility by claiming that the effective implementation of Chinese methods and experience in China does not mean that it can achieve corresponding results in Europe and the US. At the same time, the United States provides medical supplies to other countries. This study hopes to help awaken readers' critical thinking and increase their awareness of the anti-control of mass discourse. At the same time, it is hoped that readers can view the epidemic from a more scientific perspective, understand the facts and reject the unwarranted panic. It will also help reshape Chinese and American discourse.


Subject(s)
COVID-19 , Asian People , China , Humans , Language , Social Responsibility , United States
15.
Pak J Pharm Sci ; 35(4(Special)): 1173-1179, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36218095

ABSTRACT

Current study was designed to determine the skin elasticity potential of tested emulgel formulations. One emulgel containing Pyrus communis fruit extract and the other had Cydonia oblonga fruit extract. For this purpose 26 female subjects were selected and divided into two batches. Each batch has 13 volunteers, who used tested formulations and their base for 90 days. Skin elasticity were observed by using Cutometer MPA 580. From Cutometer skin mechanical parameters were calculated. From the results it was noted that emulgel formulations containing extracts of Pyrus Communis and Cydonia oblonga showed marked effect on the facial skin mechanical properties during 90 days study period. Statistically observed skin mechanical parameters of tested formulations had significant difference from base. After distention from Cutometer both formulations enhance the retraction ability of the skin as compared to base. Moreover it was also noted that Cydonia oblonga had more pronounced results than Pyrus communis loaded emulgel. From the results it has been interpreted that although both formulations has good potential to hydrate the skin resulting in intensification of its elasticity. As both fruits are rich source of phytonutrients like Vitamin C, Sugar, organic acids which might be the reason of their enhancement potential of skin pliancy.


Subject(s)
Pyrus , Rosaceae , Ascorbic Acid , Female , Fruit , Humans , Phytochemicals , Plant Extracts , Sugars
16.
J Stroke Cerebrovasc Dis ; 30(1): 105435, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33171425

ABSTRACT

OBJECTIVES: The presence of COVID-19 infection may increase the risk of thrombotic events including ischemic strokes. Whilst a number of recent reports suggest that COVID-19 associated stroke tends to be severe, there is limited data on the effects of COVID-19 in prospective registries. MATERIAL AND METHODS: To determine how COVID-19 infection may affect cerebrovascular disease, we evaluated the ischemic stroke sub-types, clinical course and outcomes prior to and during the pandemic in Qatar. The Hamad General Hospital (HGH) stroke database was interrogated for stroke admissions during the last 4 months of 2019 and January-May 2020. RESULTS: In Qatar the number of confirmed cases of COVID-19 increased from only 2 in February to 779 in March, 12,628 in April and 45,501 in May. Stroke admissions to HGH declined marginally from an average of 97/month for six pre-COVID months to 72/month in March-May. There were 32 strokes that were positive for COVID-19. When compared to non-COVID-19 stroke during the three months of the pandemic, COVID-19 patients were younger with significantly lower rates of hypertension, diabetes and dyslipidemia. COVID-19 positive patients had more cortical strokes (34.4% vs 5.6%; p = 0.001), severe disease (NIHSS >10: 34.4% vs 16.7%; p = 0.001) prolonged hospitalization and fewer with good recovery (mRS 0-2: 28.1% vs 51.9%; p = 0.001). CONCLUSIONS: When compared to six pre-COVID-19 months, the number of ischemic stroke admissions during the three months of the pandemic declined marginally. COVID-19 positive patients were more likely to have a large cortical stroke with severe symptoms and poor outcome.


Subject(s)
Brain Ischemia/etiology , COVID-19/complications , Stroke/etiology , Adult , Aged , Brain Ischemia/diagnosis , Brain Ischemia/therapy , COVID-19/diagnosis , COVID-19/therapy , Databases, Factual , Female , Humans , Male , Middle Aged , Patient Admission , Prognosis , Qatar , Risk Factors , Severity of Illness Index , Stroke/diagnosis , Stroke/therapy , Time Factors
17.
AAPS PharmSciTech ; 22(5): 181, 2021 Jun 15.
Article in English | MEDLINE | ID: mdl-34129154

ABSTRACT

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (ß-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-ßCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-ßCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.


Subject(s)
Acrylamides/chemical synthesis , Acyclovir/chemical synthesis , Alkanesulfonates/chemical synthesis , Hypromellose Derivatives/chemical synthesis , Polymerization , beta-Cyclodextrins/chemical synthesis , Acrylamides/administration & dosage , Acyclovir/administration & dosage , Administration, Oral , Alkanesulfonates/administration & dosage , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/chemical synthesis , Drug Evaluation, Preclinical/methods , Hypromellose Derivatives/administration & dosage , Male , Particle Size , Polymers/administration & dosage , Polymers/chemical synthesis , Rabbits , Solubility , Spectroscopy, Fourier Transform Infrared/methods , X-Ray Diffraction/methods , beta-Cyclodextrins/administration & dosage
18.
Pak J Pharm Sci ; 34(3): 981-986, 2021 May.
Article in English | MEDLINE | ID: mdl-34602422

ABSTRACT

Skin care formulations with antioxidants are being widely explored for their benefits to human skin. The purpose of this study was to formulate a stable w/o emulsion containing anthocyanin derived from Malus dosmestica fruit extract and to further explore its beneficial effects on normal human skin. Anthocyanin was extracted using various solvents from the peel of Malus dosmestica fruit. w/o creams containing anthocyanin has been prepared and systematically characterized for various physiochemical properties in terms of stability at varying conditions of storage. An efficacy study has been carried out on 12 male healthy Asian subjects to determine effects of anthocyanin on skin melanin, erythema, skin moisture, trans-epidermal water loss (TEWL) and on skin sebum. Solvent system containing methanol/acetone/water (3.5: 3.5: 3 v/v/v) including 1% formic acid established a best recovery of anthocyanin from fruit peel. W/O emulsions presented promising stability profile when kept at different storage conditions over 90 days period. All skin parameters studied, anthocyanin has been found more efficacious (p<0.05) for its effects on skin melanin and erythema content of skin. It has been shown that a topical application of anthocyanin derived from Malus domestica has substantial potential for human skin system and needs some patient oriented studies could warrant its potential for damaged skin.


Subject(s)
Anthocyanins/pharmacology , Fruit , Malus , Plant Extracts/pharmacology , Sebum/drug effects , Skin/drug effects , Adult , Anthocyanins/chemistry , Chromatography, High Pressure Liquid , Emulsions , Humans , In Vitro Techniques , Male , Melanins/metabolism , Plant Extracts/chemistry , Silicones , Skin/metabolism , Skin Cream , Water Loss, Insensible/drug effects
19.
Eur Neurol ; 83(2): 154-161, 2020.
Article in English | MEDLINE | ID: mdl-32434193

ABSTRACT

BACKGROUND: Sex differences may determine presentation, utility of treatment, rehabilitation, and occurrences of major adverse cardiovascular events (MACEs) in acute stroke (AS). OBJECTIVE: The purpose of the study was to evaluate the short-term prognosis and long-term outcomes in MACEs in Qatari nationals admitted with AS. METHODS: All AS patients admitted between January 2014 and February 2019 were included. We evaluated the preadmission modified Rankin scale (mRS) score, etiology and severity of symptoms, complications, and functional recovery at discharge and 90 days. MACEs were recorded for 5 years. RESULTS: There were 891 admissions for AS (mean age 64.0 ± 14.2 years) (male, n = 519 [mean age ± SD 62.9 ± 14.1 years]; female, n = 372 [mean age ± SD 65.6 ± 14.2 years] p = 0.005). There were no differences in the preadmission mRS and severity of symptoms as measured on National Institute of Stroke Scale. At discharge, the outcome was better (mRS 0-2) in men (57.8 vs. 46.0%), p = 0.0001. This difference persisted at the 90-day follow-up (mRS 0-2, male 69.4% vs. female 53.2%, p = 0.0001). At the 90-day follow-up, more women died (total deaths 70; women 38 [10.2%] versus men 32 [6.2%], p = 0.03). MACEs occurred in 25.6% (133/519) males and 30.9% (115/372) females over the 5-year follow-up period (odds ratio 0.77, 95% confidence interval 0.57-1.0, p = 0.83). CONCLUSIONS: Female patients have a poor short-term outcome following an AS when corrected for age and comorbidities. While our study cannot explain the reasons for the discrepancies, higher poststroke depression and social isolation in women may be important contributory factors, and requires further studies are required to confirm these findings.


Subject(s)
Recovery of Function , Sex Characteristics , Stroke , Adult , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Odds Ratio , Prognosis , Qatar , Stroke/mortality , Stroke/psychology
20.
J Stroke Cerebrovasc Dis ; 29(10): 105110, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32912536

ABSTRACT

BACKGROUND AND PURPOSE: Mimics comprise a third of patients presenting with an acute stroke. There is limited information on their natural history. METHODS: We evaluate long term major cardiovascular events (MACE) in stroke mimics in a prospective database from Qatar. RESULTS: Between Feb 2014 and Jan 2019, 481 patients (male: 238; female: 243) mean age 57.5 years (±18.0), with 399 (83%) medical mimics and 82 (17%) functional mimics were evaluated. Imaging revealed previous old stroke in 26.6% and small vessel disease in 5%. MACE occurred in 57 (11.9%) and there were 31 deaths (6.4%) with majority of deaths (5.6%) from cardiovascular causes. MACE was significantly higher in patients with previous stroke, p < 0.0001), coronary artery disease, p = 0.002), diabetic, p = 0.01), and hypertensive on admission, p < 0.0001. MACE were also significantly higher in patients where imaging showed a previous stroke, p = 0.006). CONCLUSION: The occurrence of MACE during follow-up suggests that patients with existing vascular disease require aggressive management of vascular risk factors.


Subject(s)
Stroke/epidemiology , Adult , Aged , Databases, Factual , Diagnosis, Differential , Female , Humans , Incidence , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Qatar/epidemiology , Risk Factors , Stroke/diagnosis , Stroke/mortality , Stroke/therapy
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