Toward robust and high-throughput detection of seed defects in X-ray images via deep learning.

BACKGROUND: The detection of internal defects in seeds via non-destructive imaging techniques is a topic of high interest to optimize the quality of seed lots. In this context, X-ray imaging is especially suited. Recent studies have shown the feasibility of defect detection via deep learning models in 3D tomography images. We demonstrate the possibility of performing such deep learning-based analysis on 2D X-ray radiography for a faster yet robust method via the X-Robustifier pipeline proposed in this article. RESULTS: 2D X-ray images of both defective and defect-free seeds were acquired. A deep learning model based on state-of-the-art object detection neural networks is proposed. Specific data augmentation techniques are introduced to compensate for the low ratio of defects and increase the robustness to variation of the physical parameters of the X-ray imaging systems. The seed defects were accurately detected (F1-score >90%), surpassing human performance in computation time and error rates. The robustness of these models against the principal distortions commonly found in actual agro-industrial conditions is demonstrated, in particular, the robustness to physical noise, dimensionality reduction and the presence of seed coating. CONCLUSION: This work provides a full pipeline to automatically detect common defects in seeds via 2D X-ray imaging. The method is illustrated on sugar beet and faba bean and could be efficiently extended to other species via the proposed generic X-ray data processing approach (X-Robustifier). Beyond a simple proof of feasibility, this constitutes important results toward the effective use in the routine of deep learning-based automatic detection of seed defects.

Hydrocotyle umbellata L.; a natural source of bioactives to mitigate diabetes mellitus and its complications.

Metabolomics study of Hydrocotyle umbellata L. revealed the richness of its aerial parts in phenolics primarily; quercetin and its glycoside derivatives, which are well-reported to exert antidiabetic activity owing to their powerful antioxidant capacity. Hence, the antioxidant and antidiabetic potentials of the quercetin standardized ethanolic extract of H. umbellata aerial parts were investigated. The antioxidant activity was examined by using in-vitro 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, while the antidiabetic activity was examined by using in-vitro α-glucosidase inhibitory assay and further confirmed by in-vivo experiments using streptozotocin-induced diabetes in rat model. Interestingly, the standardized ethanolic extract showed significant in-vitro antioxidant activity, and effectively inhibited Saccharomyces cerevisiae α-glucosidase enzyme activity. Moreover, it significantly reduced fasting blood glucose, triglycerides, and cholesterol levels. Thus, H. umbellata is a potential natural candidate to attenuate diabetes mellitus and its altered lipid profile complications, which could be attributed to its quercetin and quercetin glycosides content.

Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Catalytic potential of a fungal indole prenyltransferase toward ß-carbolines, harmine and harman, and their prenylation effects on antibacterial activity.

The prenylation of compounds has attracted much attention, since it often adds bioactivity to non-prenylated compounds. We employed an enzyme assay with CdpNPT, an indole prenyltransferase from Aspergillus fumigatus with two naturally occurring ß-carbolines, harmine (3) and harman (4) as prenyl acceptors, in the presence of dimethylallyl diphosphate (DMAPP) as the prenyl donor. The enzyme accepted these two prenyl acceptor substrates to produce 6-(3',3'-dimethylallyl)harmine (5) from 3 and 9-(3',3'-dimethylallyl)harman (6) and 6-(3',3'-dimethylallyl)harman (7) from 4. The X-ray crystal structure analysis of the CdpNPT (38-440) truncated mutant complexed with 4, and docking simulation studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant, suggested that CdpNPT could employ the two-step prenylation mechanism to produce 7, while the enzyme produced 6 with either one- or two-step prenylation mechanisms. Furthermore, the antibacterial assays revealed that the 3',3'-dimethylallylation of 3 and 4, as well as harmol (1), at C-6 enhanced the activities against Staphylococcus aureus and Bacillus subtilis.

Enzymatic formation of a prenyl ß-carboline by a fungal indole prenyltransferase.

CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a ß-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the "regular-type" dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His6-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.

Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study.

BACKGROUND: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. METHODS: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. RESULTS: The patients' mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18-4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48-5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). CONCLUSIONS: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

Impact of Ramadan fasting on disease activity in patients with multiple sclerosis: a multicenter study.

BACKGROUND: The safety of Ramadan fasting for Muslim patients suffering from multiple sclerosis (MS) is still a matter of debate. This work aimed to study the clinical course of MS during Ramadan fasting and to clarify the predictors of relapses and symptoms exacerbation. METHODS: This retrospective study included 153 Muslim patients with MS. Data related to the disease course before Ramadan were obtained from patients' files, whereas data related to the disease activity during Ramadan, were collected from patients over the two months following Ramadan. RESULTS: Patients with MS who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant longer disease duration compared to those who did not experience (P < 0.001, <0.001, 0.01 respectively). Also, patients who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant higher expanded disability status scale (EDSS) compared to those who did not experience (P <0.001, <0.001,0.01, respectively). The occurrence of relapses, exacerbation of symptoms and development of new symptoms during Ramadan, were significantly higher in patients who experienced relapses in the preceding year compared to those who did not (P= 0.002, 0.002, 0.01, respectively). Binary logistic regression revealed that each score elevation of EDSS increased the odds of relapse during Ramadan by 1.02 (P-value = 0.04). Also, each month's increase in disease duration increased the odds of relapse during Ramadan by 1.87 (P-value = 0.046). CONCLUSION: High EDSS and long disease duration are independent predictors of relapse during Ramadan.

The MuSC-19 study: The Egyptian cohort.

OBJECTIVE: This study aimed to report the severity of COVID-19 in a cohort of Egyptian patients with multiple sclerosis (MS) with particular attention on the impact of disease modifying drugs (DMDs). METHODS AND STUDY POPULATION: We included 119 MS patients recruited from two centers, Ain-Shams university and Cairo university with confirmed or suspected COVID-19 during the period from May to September 2020 as a part of the MuSC-19 project. Univariate logistic regression was fitted to assess risk factors for severe COVID-19 (at least one outcome among hospitalization, ICU admission and death). RESULTS: Females were 77%, mean age was 34 years, mean duration of MS was 5.28 years, median EDSS was 3, most of the patients (83%) had RRMS, while 15% and 2% had respectively SPMS and PPMS. Only eleven patients (9% of study population) had a severe outcome and 3 patients (3%) died. Headache was the only symptom significantly associated with the severity of COVID-19 (OR=10.85, P = 0.001). There was no association between any of the DMDs and severe COVID-19 outcome. CONCLUSION: This study showed an acceptable safety profile of DMDs in Egyptian MS patients who developed COVID-19, as 91% of the cohort had a favorable outcome. Headache as a symptom associated with severe outcome in Egyptian patients' needs further validation.

Utilization of Multiple Sclerosis Therapies in the Middle East Over a Decade: 2009-2018.

BACKGROUND: The multiple sclerosis (MS) landscape has changed over the past two decades across the world and in the Middle East. The Middle East is an ethnically diverse region located between 12° and 42° of latitude and 35° and 54° of longitude and varying altitudes. The magnitude of the shifts observed in the epidemiology and management of MS differ in each region and from country to country. OBJECTIVES: The aim of this study was to provide a clinicodemographic overview of the cohorts of patients contributed to MSBase, a large international MS registry, in the Middle East and describe disease-modifying treatment (DMT) utilization in the different countries within the region. Understanding the differences between these cohorts is integral to interpretation of the studies conducted using registry data and provides insight into clinical practice in these cohorts. METHODS: The MSBase registry was searched for patients with MS or clinically isolated syndrome from the Middle Eastern countries with data captured between 2009 and 2018. In 2-year epochs, and with special focus on the most recent epoch (2017-2018), we explored the demographic, clinical characteristics and treatment exposures of the studied cohorts and reported the results using standard descriptive statistics. RESULTS: Over the 10-year study period, 13,356 patients from 17 centers in 8 Middle Eastern countries fulfilled the inclusion criteria. The represented countries were Egypt, Iran, Kuwait, Lebanon, Oman, Saudi Arabia, Turkey and the United Arab Emirates. Overall, the represented cohort was young (median 36 years, quartiles 29-45) and captured relatively early after the onset of MS (median disease duration < 10 years, quartiles 3-12). The relapsing-remitting phenotype was the most prevalent phenotype in all countries (73-97%) and the highest proportion of progressive MS was reported in Saudi Arabia (12%). Median Expanded Disability Status Scale (EDSS) ranged from 0 to 3, depicting a mildly disabled cohort, with the exception of Saudi Arabia where the median EDSS was 4 (quartiles 1.5-6.5). The median relapse frequency was highest in Lebanon (median 1.03, 95% CI 0.94-1.16) followed by Egypt (median 1.02, 95% CI 0.89-1.24) and lowest in Saudi Arabia (median 0.70, 95% CI 0.58-0.95) and Kuwait (median 0.75, 95% CI 0.71-0.80). The treatment landscape greatly varied between different countries. Platform injectable therapies were mostly utilized in Egypt, Iran and Turkey (86%, 79% and 53%, respectively), while oral therapies and monoclonal antibodies were more commonly used in Kuwait, Lebanon and the United Arab Emirates (87.2%, 67.3% and 58.7%, respectively). CONCLUSION: Patients in the Middle East enrolled in a large multinational registry are representative of the general MS population. The spectrum of therapies used in the individual countries, however, is highly variable. Further studies that include rural and non-academic practices are needed to enhance our understanding of the MS cohorts in the Middle East.

Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era.

The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.

3D characterization of walnut morphological traits using X-ray computed tomography.

BACKGROUND: Walnuts are grown worldwide in temperate areas and producers are facing an increasing demand. In a climate change context, the industry also needs cultivars that provide fruits of quality. This quality includes satisfactory filling ratio, thicker shell, ease of cracking, smooth shell and round-shaped walnut, and larger nut size. These desirable traits have been analysed so far using calipers or micrometers, but it takes a lot of time and requires the destruction of the sample. A challenge to take up is to develop an accurate, fast and non-destructive method for quality-related and morphometric trait measurements of walnuts, that are used to characterize new cultivars or collections in any germplasm management process. RESULTS: In this study, we develop a method to measure different morphological traits on several walnuts simultaneously such as morphometric traits (nut length, nut face and profile diameters), traits that previously required opening the nut (shell thickness, kernel volume and filling kernel/nut ratio) and traits that previously were difficult to quantify (shell rugosity, nut sphericity, nut surface area and nut shape). These measurements were obtained from reconstructed 3D images acquired by X-ray computed tomography (CT). A workflow was created including several steps: noise elimination, walnut individualization, properties extraction and quantification of the different parts of the fruit. This method was applied to characterize 50 walnuts of a part of the INRAE walnut germplasm collection made of 161 unique accessions, obtained from the 2018 harvest. Our results indicate that 50 walnuts are sufficient to phenotype the fruit quality of one accession using X-ray CT and to find correlations between the morphometric traits. Our imaging workflow is suitable for any walnut size or shape and provides new and more accurate measurements. CONCLUSIONS: The fast and accurate measurement of quantitative traits is of utmost importance to conduct quantitative genetic analyses or cultivar characterization. Our imaging workflow is well adapted for accurate phenotypic characterization of a various range of traits and could be easily applied to other important nut crops.

Managing Disease-Modifying Therapies and Breakthrough Activity in Multiple Sclerosis Patients During the COVID-19 Pandemic: Toward an Optimized Approach.

The emergence of the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health challenge of global concern since December 2019, when the virus was recognized in Wuhan, the capital city of Hubei province in China and epicenter of the COVID-19 epidemic. Given the novelty of COVID-19 and the lack of specific anti-virus therapies, the current management is essentially supportive. There is an absence of consensus on guidelines or treatment strategies for complex disorders such as multiple sclerosis (MS), in which the risk of infections is higher than in the general population. This is due to the overall impairment of the immune system typical of autoimmune diseases, in addition to accumulation of disabilities, and the iatrogenic effect generated by corticosteroids and the recommended disease-modifying therapies (DMTs). DMTs have different modes of action, but all modulate and interfere with the patient's immune response, thereby raising concerns about adverse effects, such as an increased susceptibility to infections. In this review, we analyze the evidence for use of DMTs during the current critical period and ratify an algorithmic approach for management to optimize care between keeping DMTs, with their infection hazards, or coming off them, with the risk of disease activation. We also provide an algorithmic approach to the management of breakthrough activity during the COVID-19 pandemic.

Interferon-Beta-Induced Headache in Patients with Multiple Sclerosis: Frequency and Characterization.

BACKGROUND: Studies have shown that interferon-beta (IFN-ß) treatment is associated with headaches in patients with multiple sclerosis (MS). Headaches can affect quality of life and overall function of patients with MS. We examined the frequency, relationships, patterns, and characteristics of headaches in response to IFN-ß in patients with relapsing-remitting multiple sclerosis (RRMS). PATIENTS AND METHODS: This study was a prospective, longitudinal analysis with 1-year follow-up. The study comprised 796 patients with RRMS treated with IFN-ß (mean age 30.84±8.98 years) at 5 tertiary referral center outpatient clinics in Egypt between January 2015 and December 2017. Headaches were diagnosed according to the International Classification of Headache Disorders ICHD-3 (beta version), and data were collected through an interviewer-administered Arabic-language-validated questionnaire with an addendum specifically designed to investigate the temporal relationship between commencement of interferon treatment, and headache onset and characteristics. RESULTS: Two hundred seventy-six patients had pre-existing headaches, and 356 experienced de novo headaches. Of 122 patients who experienced headaches before IFN-ß treatment, 55 reported headaches that worsened following onset of IFN-ß treatment. In patients with post-IFN-ß headaches, 329 had headaches that persisted for >3 months, 51 had chronic headaches, and 278 had episodic headaches, and 216 of these patients required preventive therapies. Univariate analysis showed a >6- and an approximately 5-fold increased risk of headache among those treated with intramuscular (IM) INF-ß-1a (OR 6.51; 95% CI: 3.73-10.01; P-value <0.0001) and 44 µg of SC INF-ß-1a (OR 5.44; 95% CI: 3.15-9.37; P-value <0.0001), respectively, compared with that in patients who received 22 µg of SC INF-ß-1a. CONCLUSION: Interferon-ß therapy aggravated pre-existing headaches and caused primary headaches in patients with MS. Headache risk was greater following treatment with IM INF-ß-1a and 44 µg SC INF-ß-1a.

High throughput phenotyping dataset related to seed and seedling traits of sugar beet genotypes.

Several seed and seedling traits are measured to evaluate germination and emergence potential in relation with environmental conditions. More generally, these traits are also measured in the field of ecology as simple traits that can be correlated to other adaptative traits more difficult to measure on adult plants, as for example traits of the rooting system. Methods were developed for deep high throughput phenotyping of hundreds of genotypes from dry seed to the end of heterotrophic growth. The present dataset comes from a project on genotyping and phenotyping of populations of genotypes, with different geographic and genetic origins so as to increase genotypic diversity of sugar beet in terms of germination and early growth traits, evaluated at low temperatures. Data were collected in relation to the creation of the first sugar beet crop ontology. This dataset corresponds to the first automated phenotyping of a population of 198 genotypes and 4 commercial control varieties and is hosted on INRAE public depository under the reference number doi.org/10.15,454/AKNF4Q. The equipment and methods presented here are available on a phenotyping platform opened to collaborative research and adaptable for specific services for characterizing thousands of genotypes on different crops or other species. The phenotyping values can also be linked to genomic information to study the genetic determinism of the trait values.

In-vivo Anti-inflammatory Activity of Hydrocotyle umbellata L. aerial parts and Isolation of the Main Phytochemicals.

Hydrocotyle umbellata L. (Family Araliaceae) populary known as Acaricoba, is indicated in folk medicine for treatment of several inflammatory disorders. The goal of the present study is to evaluate the anti-inflammatory activity of the defatted ethanolic extract (DEE) of the aerial parts using carrageenan-induced rat paw oedema method. The levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and the inflammatory mediator prostaglandin E2 (PGE2) were assessed using ELISA. The DEE at dose level 100 mg/kg showed significant decrease in oedema volume after 2 and 3 h, equivalent to 70.75% and 95.92% of the activity of the standard anti-inflammatory indomethacin, respectively. DEE significantly decreased the concentrations of the excessively produced IL-6 and PGE2 (24 ± 2.1 and 2374 ± 87 pg/mL compared to 16 ± 2 and 2419 ± 95 pg/mL induced by indomethacin). Chemical investigation was carried out to isolate and identify the bioactive compounds that might be responsible for this activity. The total phenolic (79.28 ± 0.1 mg) and total flavonoid (57.99 ± 0.1 mg) contents of the DEE were quantified spectrophotometricaly and expressed as gallic acid and rutin equivalents/g dry weight, respectively. The DEE was subjected to further fractionation using solvents of increasing polarities. Purification of the ethyl acetate fraction using different chromatographic techniques led to the isolation of five compounds, which were identified through 1D and 2D and UV/Vis spectral data. The five compounds were: quercetin, avicularin, quercitrin, hyperoside, and neochlorogenic acid. Several biological studies confirmed the important role of caffeoyl quinic acid and quercetin derivatives as anti-inflammatory bioactive compounds.

Pediatric-onset multiple sclerosis in Egypt: a multi-center registry of 186 patients.

INTRODUCTION: Although the frequency of pediatric-onset multiple sclerosis (POMS) has increased in recent decades, it is still highly uncommon, which creates a need for the involvement of more registries from various clinical centers. OBJECTIVE: To characterize the demographic, clinical, and paraclinical features of Egyptian patients with POMS. PATIENTS AND METHODS: A retrospective chart review study was undertaken on 237 Egyptian patients with demyelinating events which started before the age of 18 years who attended one of five tertiary referral centers in Cairo, Egypt. RESULTS: Multiple sclerosis was diagnosed in 186 patients, 47 (25.27%) patients had disease onset before the age of 12 years; "early-onset pediatric multiple sclerosis (EOPMS)". The mean age of disease onset was (14.13±2.49 years), with a female:male ratio of 1.62:1, none of the enrolled patients had a primary progressive course (PPMS), whereas 10 patients (5.38%) had a secondary progressive form. Approximately two-thirds of the patients had monofocal disease onset, and less than 10% presented with encephalopathy; most of them had EOPMS. Motor weakness was the presenting symptom in half of the patients, whereas cerebellar presentation was detected in 34.95%, mainly in EOPMS. Seizures (not related to encephalopathy) were more frequent in those with EOPMS. Initial brain magnetic resonance images were positive in all patients, with detected atypical lesions in 29.03%, enhanced lesions in 35.48%, black holes in 13.98%, and infratentorial in 34.41%. Cervical cord involvement was found in 68.28%. More than two-thirds of the patients received either immunomodulatory or immunosuppressant (IS) treatment throughout their disease course, and about half of them received their treatment within the first year from symptoms onset, with a more favorable outcome, and patients with highly active disease received natalizumab, fingolimod, or other IS. CONCLUSION: The results from this registry - the largest for MS in the Arab region to date - are comparable to other registries. Immunomodulatory therapies in POMS are well tolerated and efficacious and they can improve the long-term outcome in children.

SNPs in the Insulin-Like Growth Factor Gene and Obesity Impact on Colorectal Cancer in Egyptians

Background and aims: The insulin pathway may play a role in development of colorectal cancer (CRC). In this study, we investigated associations between CRC and obesity in Egyptians with reference to single nucleotide polymorphisms (SNPs) in the insulin-like growth factor-1 (IGF-I) gene. We also studied serum levels of IGF-1in Egyptian CRC patients with different BMI values. Methods: This prospective study included 66 CRC patients and 30 healthy individuals, for whom body mass index (BMI) was estimated, patients and controls being categorized into overweight or obese in one group and average weight in the other. Serum levels of IGF-1 were assessed by ELISA and SNPs in the IGF-I gene at rs6214C/T, rs6220 T/C and rs35767 C/T were examined by PCR- RFLP. Results: Serum levels of IGF-1 were significantly lower in both CRC average weight and overweight cases. IGF-1 could negatively predict CRC at a cut-off of 154 ng/ml with 87.5% sensitivity and 72.6 specificity. IGF-1 rs6214 CT and TT (T allele) genotypes were associated with a significantly increased risk of CRC. Univariate logistic regression showed that CRC risk significantly decreases by 0.14 for each one unit increase in IGF1. Conclusion: BMI could be considered as effect modifier for CRC risk. IGF-1 SNP rs6214 (TT and CT) are significantly associated with risk regardless of the BMI.

Potential Diagnostic and Prognostic Value of Lymphocytic Mitochondrial DNA Deletion in Relation to Folic Acid Status in HCV-Related Hepatocellular Carcinoma

Objective: We assessed the possibility of using mitochondrial (mt) DNA deletion as a molecular biomarker for disease progression in HCV-related hepatocellular carcinoma (HCC) and to identify its association with folic acid status. Methods: Serum folic acid and lymphocytic mtDNA deletions were assessed in 90 patients; 50 with HCC, 20 with liver cirrhosis (LC), and 20 with chronic hepatitis C (CHC) compared to 10 healthy control subjects. The diagnostic accuracy of mtDNA deletions frequency was evaluated using receiver-operating characteristic (ROC) curve analysis Survival analysis was performed using the Kaplan-Meier method. Differences in the survival rates were compared using log-rank test. Result: Our data revealed a significant elevation of mtDNA deletions frequency in the HCC group compared to the other groups (P-value <0.01). Also, our data showed a significant correlation between folate deficiency and high frequency of mtDNA deletions in patients with HCV-related HCC when compared to the other groups (r= -0.094 and P-value <0.05). Moreover, the size of the hepatic focal lesion in the HCC patients was positively correlated with mtDNA deletions (r= 0.09 and P-value <0.01). The median survival time for the HCC patients with high frequency of mtDNA deletions (ΔCt ≥3.9; 5.7+ 0.6 months) was significantly shorter than those with low mtDNA deletions frequency (ΔCt < 3.9; 11.9+ 0.04 months, P-value <0.01). Conclusion: Our data provided an evidence that lymphocytic mtDNA deletion could be used as non-invasive biomarker for disease progression and patients' survival in HCV-related HCC. Also, our findings implied a causal relationship between the folate deficiency and the high mtDNA deletions frequency among Egyptian patients with HCV related HCC.

Characteristics and predictors of progression in an Egyptian multiple sclerosis cohort: a multicenter registry study.

BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease with a heterogeneous presentation and diverse disease course. Recent studies indicate a rising prevalence of MS in the Middle East. OBJECTIVE: To characterize the demographics and disease features of Egyptian patients attending four tertiary referral MS centers in Cairo. MATERIALS AND METHODS: This was a retrospective, observational study on 1,581 patients between 2001 and 2015. Medical records were reviewed and data were identified and extracted in a standardized electronic registry. RESULTS: The mean age of disease onset was 26.6±7.8 years, with the majority being female (2.11:1). Relapsing-remitting MS was the most common type (75.1%). The main presenting symptom was motor weakness (43.9%), which was also the most frequent symptom during the disease course. Family history of MS was found in 2.28%. Higher initial Expanded Disability Status Scale score, black holes, and infratentorial lesions on initial magnetic resonance imaging were independent factors for disease progression by univariate analysis (OR 3.87 [95% CI 1.84-6.51], 4.14 [95% CI 3.08-5.58], 4.07 [95% CI 3.21-4.99], respectively); however, in multivariate analysis, only infratentorial lesions were an independent risk for disease progression (OR 6, 95% CI 2.99-12.02; P=0.0005). CONCLUSION: The results from this registry - the largest for MS in the Arab region to date - are comparable to other registries with slight differences.

Circulating Hypermethylated RASSF1A as a Molecular Biomarker for Diagnosis of Hepatocellular Carcinoma

Background: Detection of circulating DNA can be applied for the diagnosis of many malignant neoplasms, including the hepatocellular carcinoma (HCC). The molecular pathogenesis of HCC is complex, involving different genetic and epigenetic alterations, chromosomal aberrations, gene mutations and altered molecular pathways. RASSF1A is a well-established tumor suppressor gene which suffers frequent inactivation due to promoter hypermethylation of CPG islands in multiple tumors including HCC, resulting in the reduction or loss of gene expression. Objective: To examine the role of circulating RASSF1A as a non-invasive diagnostic marker for HCC. Participant and Methods: A total of 45 HCC patients with a background of HCV infection, 40 cases of HCV infection without tumours and 40 apparently healthy controls were subjected to full history taking, clinical examination, routine laboratory investigations, assessment of serum AFP and detection of circulating hypermethylated RASSF1A gene by methylation-sensitive restriction enzyme digestion and real-time PCR. Results: The level of hypermethylated RASSF1A was significantly elevated in the HCC group as compared to the HCV and control groups (p=0.001 for both). Copy number in serum was associated with increased tumor size (p value <0.001). On the other hand, no significant correlation was observed between RASSF1A and AFP (p=0.5). Using ROC curve analysis, the best cut-off for circulating serum RASSF1A to differentiate the HCC group was 8 copies/µl. Conclusion: The presence of hypermethylated RASSF1A in serum may be a useful and informative biomarker for HCC diagnosis and might be introduced as a screening method for populations at risk of HCC development.