Prevalence and Associated Risk Factors of Cerebral Microbleeds in Egyptian Patients with Acute Ischemic Stroke and Atrial Fibrillation.

BACKGROUND: Few studies addressed the prevalence of cerebral microbleeds (CMB) and associated risk factor profile in Egyptian ischemic cerebral stroke patients with atrial fibrillation (AF). METHODS: The prevalence of CMB was estimated in 150 cases of AF ischemic stroke patients and compared to the prevalence in 150 age- and sex-matched controls of ischemic stroke patients without AF. CMB-associated risk factors were identified by comparing AF ischemic stroke patients with and without CMB. All participants were subjected to complete general, neurological examination, and magnetic resonance imaging. RESULTS: The prevalence of CMBs in ischemic stroke with and without AF was 40.7% and 49.3%, respectively. Age, hypertension, diabetes mellitus, past history of stroke, antiplatelet, anticoagulant, National Institutes of Health Stroke Scale, CHA2DS2VASc, and white matter lesions (WML) were significant risk factors associated with CMB on univariate analysis. On multivariable logistic regression analysis, age (odds ratio [OR] 1.1, confidence interval [CI] 1.02-1.13), hypertension (OR 3.2, CI 1.19-8.81), anticoagulant (OR 3.3, CI 1.17-9.40), and WML (OR 9.6, CI 3.49-26.3) were the only independent risk factors associated with the presence of CMBs. CONCLUSIONS: AF in ischemic stroke patients was not associated with higher prevalence of CMBs. Old age, hypertension, anticoagulant treatment, and WML were the independent risk factors associated with CMB in AF ischemic stroke patients. Our results suggest that elderly hypertensive AF ischemic stroke patients maintained on anticoagulant therapy should be screened for the incidence of CMBs and monitored regularly for the development of intracerebral hemorrhage.

Early post-stroke seizures in a sample of Egyptian patients with first-ever stroke.

BACKGROUND: Cerebrovascular stroke is considered as the most common cause of symptomatic seizures. Post-stroke seizures herald a poor functional outcome, a high mortality rate, and a long in-hospital duration of stay. AIM: To assess the incidence and risk factors responsible for early seizures after the first-ever cerebral stroke, and its relation to the functional outcome and the in-hospital mortality following stroke as well as the duration of stay. PATIENTS AND METHODS: 150 patients with first-ever stroke, who were admitted in an intensive care and stroke unit of the Neurology Department of Zagazig University Hospitals, Egypt, within the first 24 hours of stroke onset were included in the study. Early seizures (within 7 days of stroke onset), stroke severity (National Institutes of Health stroke scale; NIHSS), radiological data, functional outcome (Barthel index), in-hospital mortality and duration of stay were collected and analyzed. RESULTS: The incidence of early seizures associated with first-ever stroke was 9.3%. Risk factors for early seizures were intracerebral hemorrhage (ICH) [odds ratio (OR) = 3.2, P = <0.001), cortical lesions (OR = 2.8, P = <0.05), and a large lesion size (OR = 2, P= <0.05). Patients with early seizures had lower scores on the Barthel index than those without seizures (7.5 ± 4.1 versus 10.5 ± 3.5), had higher discharge National Institutes of Health Stroke scale (NIHSS) scores, had a higher in-hospital mortality rate (35.7% versus 6.6% in patients without seizures) and duration of stay (19.4 ± 6.5 versus 10.7 ± 4.2 days respectively). CONCLUSION: The incidence of early post-stroke seizures was high in our study and was positively associated with a poor functional outcome, a higher in-hospital mortality rate and a longer duration of in-hospital stay. The most important risk factors were ICH, the cortical site of involvement and a large size of the lesion.

Infarction Size, Interleukin-6, and Their Interaction Are Predictors of Short-Term Stroke Outcome in Young Egyptian Adults.

BACKGROUND: A trend of increasing incidence of first-ever cerebral ischemic stroke in young adults has been recently reported. The current study was conducted with the objective of identifying independent predictors of short-term outcome of first-ever cerebral ischemic stroke affecting young Egyptian adults. METHODS: The present hospital-based study included 50 patients, 23 males and 27 females, aged 18-45 years, with first-ever ischemic stroke confirmed by computed tomography (CT) and magnetic resonance imaging. Twenty healthy age- and sex-matched random control subjects were included to set the reference laboratory values. Detailed medical, neurological, and laboratory data were collected. Stroke severity and short-term stroke outcome were assessed using the Canadian Neurological Scale and the National Institutes of Health Stroke Scale (NIHSS), respectively. RESULTS: High prevalence of modifiable risk factors was observed in young Egyptian adults affected with first-ever ischemic cerebral stroke. Although all studied risk factors were significantly correlated with NIHSS score, multiple regression analysis revealed that only infarction size (CT size), interleukin-6 (IL-6), and their synergistic interaction were the most important predictors of NIHSS stroke outcome. CONCLUSIONS: IL-6 and infarction size were independent predictors of short-term stroke outcome in young Egyptian adults. Synergistic interaction of IL-6 with infarction size suggests an investigative value for assessing serum IL-6 level and a therapeutic benefit for its reduction during the course of early ischemic stroke treatment.

Machine learning approach for hemorrhagic transformation prediction: Capturing predictors' interaction.

Background and purpose: Patients with ischemic stroke frequently develop hemorrhagic transformation (HT), which could potentially worsen the prognosis. The objectives of the current study were to determine the incidence and predictors of HT, to evaluate predictor interaction, and to identify the optimal predicting models. Methods: A prospective study included 360 patients with ischemic stroke, of whom 354 successfully continued the study. Patients were subjected to thorough general and neurological examination and T2 diffusion-weighted MRI, at admission and 1 week later to determine the incidence of HT. HT predictors were selected by a filter-based minimum redundancy maximum relevance (mRMR) algorithm independent of model performance. Several machine learning algorithms including multivariable logistic regression classifier (LRC), support vector classifier (SVC), random forest classifier (RFC), gradient boosting classifier (GBC), and multilayer perceptron classifier (MLPC) were optimized for HT prediction in a randomly selected half of the sample (training set) and tested in the other half of the sample (testing set). The model predictive performance was evaluated using receiver operator characteristic (ROC) and visualized by observing case distribution relative to the models' predicted three-dimensional (3D) hypothesis spaces within the testing dataset true feature space. The interaction between predictors was investigated using generalized additive modeling (GAM). Results: The incidence of HT in patients with ischemic stroke was 19.8%. Infarction size, cerebral microbleeds (CMB), and the National Institute of Health stroke scale (NIHSS) were identified as the best HT predictors. RFC (AUC: 0.91, 95% CI: 0.85-0.95) and GBC (AUC: 0.91, 95% CI: 0.86-0.95) demonstrated significantly superior performance compared to LRC (AUC: 0.85, 95% CI: 0.79-0.91) and MLPC (AUC: 0.85, 95% CI: 0.78-0.92). SVC (AUC: 0.90, 95% CI: 0.85-0.94) outperformed LRC and MLPC but did not reach statistical significance. LRC and MLPC did not show significant differences. The best models' 3D hypothesis spaces demonstrated non-linear decision boundaries suggesting an interaction between predictor variables. GAM analysis demonstrated a linear and non-linear significant interaction between NIHSS and CMB and between NIHSS and infarction size, respectively. Conclusion: Cerebral microbleeds, NIHSS, and infarction size were identified as HT predictors. The best predicting models were RFC and GBC capable of capturing nonlinear interaction between predictors. Predictor interaction suggests a dynamic, rather than, fixed cutoff risk value for any of these predictors.

Dietary Supplementation with Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial.

Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.

Neutrophil-lymphocyte ratio as a marker for disability and activity in multiple sclerosis.

BACKGROUND: There is limited data regarding the association of Neutrophil-lymphocyte ratio (NLR) inflammatory marker with multiple sclerosis (MS) disability and activity. OBJECTIVE: The aim of the present study was to evaluate validity of NLR as an inflammatory marker for MS disability and activity. METHODS: A case-control study including 140 MS patients and 140 age, sex and body mass index matched healthy controls was performed. All participants were subjected to detailed history taking, complete general and neurological examination, laboratory and radiological investigations. Assessment of disease disability was performed using Expanded Disability Status Scale. RESULTS: The NLR levels was significantly higher in MS patients compared to the controls and in patients with relapse compared to remission. Logistic regression analyses showed that NLR was significantly associated with disease disability (odds ratio (OR): 2.568; confidence interval (CI): 1.377 - 4.788; P: 0.003) and activity (OR: 3.603; CI: 2.086 - 6.226; P: 0.02). The cutoff value for the NLR to predict MS disability and activity was 3.12. CONCLUSION: NLR was significantly increased in MS patients compared to controls. The significant association of NLR with MS disability and activity suggest that it could be utilized as a simple, rapid and inexpensive inflammatory marker.

Sensitivity to cadmium-chloride-induced forelimb ectrodactyly is independent of the p53 gene-dosage in the C57BL/6J mouse.

BACKGROUND: The p53 pathway plays an important role in the regulation of apoptosis, osteoblast differentiation, skeletal development, and teratogenic sensitivity. The administration of cadmium chloride (CdCl(2)) on gestational day 9 in susceptible mouse strains causes postaxial forelimb ectrodactyly in a percentage of fetuses through unknown mechanisms. In this study, the hypothesis that the p53 gene dosage might affect the incidence or severity of CdCl(2)-induced forelimb ectrodactyly was examined. METHODS: Heterozygous p53-null female mice, on the C57BL/6J background known to be sensitive to CdCl(2)-induced forelimb ectrodactyly, were mated with heterozygous males and then treated with a single intraperitoneal (ip) dose of CdCl(2) (4 mg x kg(-1)) at embryonic day (ED) 9. Embryos and fetuses, genotyped using DNA isolated from the yolk sacs, were collected at ED10 and examined for the pattern of cell death in the limb buds or collected at ED18 and examined for limb malformations. RESULTS: In the wild type and heterozygous p53 embryonic limb buds, CdCl(2)-induced apoptosis involved mesenchymal cells as well as the apical ectodermal ridge (AER), whereas CdCl(2)-induced apoptosis was restricted mainly to the AER in the homozygous p53-null limb buds. No difference in the incidence or severity of forelimb ectrodactyly in the embryos of different p53 genotypes was observed. CONCLUSION: Despite the fact that CdCl(2) induced both p53-dependent (in the mesenchyme) and p53-independent (in the AER) cell death in the developing limb bud, CdCl(2)-induced ectrodactyly was independent of the p53 gene dosage at the studied time point.

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double-blind, placebo-controlled clinical trial.

Aging is associated with a decline in natural killer (NK) and natural killer T (NKT) cell function that may contribute to increased susceptibility to malignancy and infection. A preliminary investigation was conducted examining the hypothesis that arabinoxylan rice bran (Biobran/MGN-3), a denatured hemicellulose with known immunomodulatory activity, could counteract this decline in NK/NKT cell activity in geriatrics. A total of 12 healthy geriatric subjects of both sexes and over 56 years old, participated in a randomized, double-blind, placebo-controlled clinical trial. A total of six subjects served as control and six subjects ingested Biobran/MGN-3 (500 mg/day) for 30 days. The effect of Biobran/MGN-3 supplementation on NK/NKT cell activity was assessed using the degranulation assay. All study subjects were monitored for the development of any inadvertent side effects. In addition, the pharmacological effects of Biobran/MGN-3 on blood cell components and liver and kidney functions were also assessed. Results demonstrated that Biobran/MGN-3 had no effect on the total percentage of NK cells, however it enhanced the cytotoxic activity of induced NK cell expression of cluster of differentiation 107a, when compared with baseline values and with the placebo group (P<0.05). Furthermore, there were no side effects observed, indicating that Biobran/MGN-3 supplementation was safe at the utilized dosage and for the duration of administration. Various additional beneficial effects were observed, including improved mean corpuscular volume and reduced hepatic aspartate aminotransferase enzyme levels, which suggested improved liver function. It was concluded that Biobran/MGN-3 induces a significant increase in NK activity which may increase resistance to viral infections and cancers in the geriatric population. However, additional clinical trials should be conducted in the future to verify these findings.

Differential perturbation of the Fgf/Erk1/2 and Shh pathways in the C57BL/6N and SWV embryonic limb buds after mid-gestational cadmium chloride administration.

The differential susceptibility of inbred mouse strains to teratogen-induced malformations can serve as a model to assess the molecular pathogenesis of dysmorphology. Using such a model, the teratogenic effect of cadmium chloride (CdCl(2)), which results in limb reduction deformities in the C57BL/6N mouse strain, but not in the SWV strain, was found to correlate with reduction of the expression domains of Fgf8/4 (fibroblast growth factor-8 and -4) in the apical ectodermal ridge (AER) and Shh (sonic hedgehog) in the posterior mesenchyme, as well as reduction of MAPK/Erk1/2 (the mitogen-activated protein kinase/extracellular regulated kinase 1/2) phosphorylation (pErk1/2) in the mesenchyme throughout the limb bud. The pattern of pErk1/2 reduction did not consistently reflect the pattern of Fgf8/4 reduction suggesting that CdCl(2) might affect pErk1/2 through an Fgf-independent pathway. Other potential downstream mediators of the Fgf pathway including Mkp3 and Fgf10 as well as pMek (phosphorylated MAPK/Erk1/2 kinase) were not different in limb buds between the two strains at the studied time points. The effect of CdCl(2) on skeletogenesis was traced in time to the early stages of pre-chondrogenic condensation as determined by the Sox9 expression domain. The data of the present study indicate that a differential strain response to CdCl(2)-induced forelimb digital loss may be due to a polymorphic interference with the Fgf/Shh positive feedback loop and Erk1/2 phosphorylation.