Left Atrial Function Assessment By Speckle Tracking Echocardiography In Low-Risk Atrial Fibrillation Patients.

Objectives: To compare the left atrial function utilising speckle tracking echocardiography in patients with low-risk and high-risk non-valvular atrial fibrillation. Method: The descriptive, cross-sectional study was conducted at the cardiology department of Kafrelsheikh University Hospital, Egypt, from January 2021 to January 2022, and comprised low-risk atrial fibrillatin participants in group I, high-risk atrial fibrillatin patients in group II, and healthy controls in group III. After detailed medical history, the subjects underwent 12-lead electrocardigram, and echocardiographic assessment, including two dimensional, M-mode, tissue doppler, and speckle tracking of the left atrium. The association of left atrial strain with Congestive heart failure, hypertension, age ≥75 (doubled), diabetes,stroke (doubled), vascular disease sex category (female)score was explored. Data was analysed using SPSS 28. RESULTS: Of the 90 subjects, there were 30(33.3%) in each of the 3 groups. The mean age among the groups was significantly different among the groups (p=0.014). Left atrial ejection fraction and left atrial strain had an overall significant difference among the groups(p<0.001). Congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease sex category (female)score was negatively correlated with Left atrial ejection fraction and (p<0.001) and left atrial strain (p<0.001). CONCLUSIONS: In individuals with atrial fibrillatin, there was a significant decrease in left atrial strain and left atrial function. The use of speckle tracking echocardiography allowed for a more detailed analysis of left atrial mechanics. The correlation of left atrialstrain and left atrial ejection fraction with Congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease sex category (female) score was significantly negative.

Coronary Plaque Morphology And Characteristics In Patients With Raised Haemoglobin A1c: An Intravascular Ultrasound Study.

Objectives: To identify coronary plaque morphology using grey scale and virtual histology intravascular ultrasound in patients with and without elevated glycated haemoglobin. Method: The cross-sectional study was conducted at the Cardiology Department of Kafrelsheikh University, Egypt, from November 2019 to January 2022, and comprised adult patients of either gender suffering from acute coronary syndrome admitted for catheterisation. The patients were divided into three groups.Diabetic patients were in group A, prediabetic patients with elevated glycated haemoglobin in group B, and patients with normal glycated haemoglobin in group C. All patients were subjected to clinical examination, 12-lead electrocardiogram, coronary angiography and multimodality intravascular ultrasonography scan of proximal segments 3-6cmof non-culprit coronary arteries intra group differences were compared using the analysis of variance (ANOVA) test. RESULTS: Of the 52 patients, 18(34.7%) were females and 34(65.3%) were males. Group A had 18(34.6%)patients; 13(72%) males and 5(28%) females with mean age 57.9±6.9 years. Group B had 17(32.7%) patients;11(64.7%) males and 6(35.3%) females with mean age 56.5±5.5 years. Group C had 17(32.7%) patients; 10(59%) males and 7(41%) females with mean age 59.5±5.1 years(p>0.05). Thin-cap fibroatheroma wassignificantly higher in groups A and B compared to group C (p=0.045). CONCLUSIONS: Patients with raised glycated haemoglobin presenting with acute coronary syndrome were found to have more vulnerable plaque types than those with normal levels.

Clinical Presentation And Outcome In Acute Coronary Syndrome Patients In Relation To Plaque Morphology Identified By Intra Vascular Ultra Sound.

Objectives: To evaluate plaque morphology in non-culprit coronary arteries using intravascular ultrasound in patients with acute coronary syndrome with and without elevated glycated haemoglobin and its assocaition with patient outcome. Method: The cross-sectional study was conducted at the Cardiology Department of Kafrelsheikh University, Egypt, from November 2019 to January 2022, and comprised adult patients of either gender suffering from acute coronary syndrome. The patients were divided into three groups. Diabetic patients were in group A, prediabetic patients with elevated glycated haemoglobin in group B, and patients with normal glycated haemoglobin in group C. The patients were subjected to coronary angiography and percutaneous coronary intervention. Intravascular ultrasound scan was done after succcessful intervention. Lesions were classified according to ultrasound findings. Patients were followed up for one year to observe subsequent events to the morphology of the lesions detected at baseline. Data was analysed using SPSS 20. RESULTS: Of the 52 patients, 18(34.7%) were females and 34(65.3%) were males. Group A had 18(34.6%)patients; 13(72%) males and 5(28%) females with mean age 57.9±6.9 years. Group B had 17(32.7%) patients; 11(64.7%) males and 6(35.3%) females with mean age 56.5±5.5 years. Group C had 17(32.7%) patients; 10(59%) males and 7(41%) females with mean age 59.5±5.1 years(p>0.05). Thin-capped fibro-atheroma wassignificantly higher in groups A and B compared to group C (p=0.045). Significant direct correlation between major adverse cardiac events and prevalence of thin-capped fibro-atheroma wasfound between groups A and C (p=0.033), and between groups B and C (p=0.047) regarding prevalence of necrotic plaque and subsequent myocardial infarction. CONCLUSIONS: Thin-capped fibro-atheroma was the more common plaque type in patients with raised glycated haemoglobin, and the subsequent rate of major adverse cardiac events was significantly higher in such patients compared to the non-diabetic population.

Prevalence of erectile dysfunction in Egyptian males with metabolic syndrome.

Objectives: Determination of the potential effect of metabolic syndrome (MetS) on erectile function in Egyptian men and description of the sociodemographic characteristics of these men.Materials and methods: A cohort of 615 patients presenting to urology department aged between 30 and 75 years were prospectively assessed and divided into two groups. Group I (n = 325) diagnosed with MetS and mean age of 56.07 ± 8.51 years. Group II (n = 290) subjects with no MetS and mean age 54.97 ± 8.14 years. Patients filled the IIEF questionnaire, medical, personal history, and BMI data were tabulated. Metabolic syndrome was determined when three or more of the five risk factors were present according to the NCEP.Results: In Group I (79.4%) of the patients had erectile dysfunction (ED). Of these, 20.3% had mild, 22.5% had moderate, and 36.6% had severe ED and 30% of patients without MetS had ED. Of these, 17.2% had mild, 5.9% had moderate, and 6.9% had severe ED (p < .001; odds ratio 5.549; 95% CI 3.101-9.928). Patients with metabolic syndrome had lower IIEF-EF domain scores. Logistic regression analysis revealed that DM, dyslipidemia, age, and HTN were the most important criteria for ED in the MetS group (p < .01). While in the group without MetS, DM, HTN, HDL, and age were the most important risk factors (p < .01), and TG and BMI were less important.Conclusions: MetS is a potential risk factor for ED in Egyptian men. Patients with MetS should be questioned about ED. The diabetic patients are most risky for ED.

Identification of Genetic Variants Associated With Myocardial Infarction in Saudi Arabia.

The genetic variants associated with various genetic disorders have not been identified decisively in Saudi Arabia. Among these variants, six known for their association with coronary artery disease or myocardial infarction (MI) were studied on Saudi patients. Reference single nucleotide polymorphisms (SNPs) of these variants are rs5174, rs11591147, rs2259816, rs111245230, rs3782886 and rs2259820, referring to genes LRP8, PCSK9, HNF1A, SVEP1, BRAP and HNF1A, respectively. The analysis employed polymerase chain reaction panel coupled with mini-sequencing (SNapShot multiplex system) in order to identify these variants. A total of 100 MI patients and 103 healthy control individuals participated in this study. The six variants (SNPs) were evaluated for the risk of developing MI in the Saudi patients. Analysis of allele frequencies indicated that A allele of rs11591147 variant can be a protective allele, thus, is associated with the decreased risk of MI in Saudi individuals. Rare allele of rs111245230 variant (e.g., C allele) was extremely reduced, while rare allele of rs3782886 variant (e.g., G allele) does not exist in the ethnic signature of the Saudi population. This study elucidates the possible prediction of risk factors associated with severe diseases in Saudi population utilizing SNapShot multiplex system.

Poly-Tobacco Use among Young Adult Waterpipe Smokers: Insights from University Students in Three Eastern Mediterranean Countries.

INTRODUCTION: There is a tendency of waterpipe smokers to advance their practice toward concurrent use (poly-tobacco use) of other tobacco products and nicotine delivery systems. This study investigated poly-tobacco use among waterpipe smokers, and its effect on their quit intention. METHODS: Descriptive cross-sectional design was utilized to recruit a convenience sample of university students who used waterpipe in three East Mediterranean countries. Using an internet-based survey, data were collected regarding participants' demographics, use of alternative tobacco products and nicotine delivery systems, and waterpipe quitting profile. Results: A total of 2290 students agreed to participate, among which 1116 (45.3%) reported using at least one tobacco product beside waterpipe. Poly-tobacco use was highest (61.1%) in Egypt, followed by Jordan (45.1%) and Palestine (33.1%). Across countries, cigarettes were the most common product (45.2%, n = 924) followed by cigar (18.6%, n = 374) and e-shisha (17.5%, n = 353). Conversely, the least reported product was smokeless tobacco (7.5%, n = 151) preceded by regular pipe (9.5%, n = 193). Participants who were males (OR = 2.83, 95% CI: 2.18-3.65), older (22-29 years) (OR = 1.15, 95% CI: 1.09-1.22), unemployed (OR = 1.58, 95% CI: 1.22-2.04), and those who initiated waterpipe at a younger age (OR = 0.87, 95% CI: 0.87-0.91) had higher odds of being poly-smokers. Poly-tobacco users were significantly more resistant to quit waterpipe. Conclusion: This study demonstrates poly-tobacco use as a rising phenomenon among waterpipe smokers and highlights the necessity for initiating advanced interventions to help waterpipe poly-tobacco users quit this dangerous type of addiction. Various country-specific programs are needed considering the various products used by the users.

Expression screening using a Medaka cDNA library identifies evolutionarily conserved regulators of the p53/Mdm2 pathway.

BACKGROUND: The p53 tumor suppressor protein is mainly regulated by alterations in the half-life of the protein, resulting in significant differences in p53 protein levels in cells. The major regulator of this process is Mdm2, which ubiquitinates p53 and targets it for proteasomal degradation. This process can be enhanced or reduced by proteins that associate with p53 or Mdm2 and several proteins have been identified with such an activity. Furthermore, additional ubiquitin ligases for p53 have been identified in recent years. Nevertheless, our understanding of how p53 abundance and Mdm2 activity are regulated remains incomplete. Here we describe a cell culture based overexpression screen to identify evolutionarily conserved regulators of the p53/Mdm2 circuit. The results from this large-scale screening method will contribute to a better understanding of the regulation of these important proteins. METHODS: Expression screening was based on co-transfection of H1299 cells with pools of cDNA's from a Medaka library together with p53, Mdm2 and, as internal control, Ror2. After cell lysis, SDS-PAGE/WB analysis was used to detect alterations in these proteins. RESULTS: More than one hundred hits that altered the abundance of either p53, Mdm2, or both were identified in the primary screen. Subscreening of the library pools that were identified in the primary screen identified several potential novel regulators of p53 and/or Mdm2. We also tested whether the human orthologues of the Medaka genes regulate p53 and/or Mdm2 abundance. All human orthologues regulated p53 and/or Mdm2 abundance in the same manner as the proteins from Medaka, which underscores the suitability of this screening methodology for the identification of new modifiers of p53 and Mdm2. CONCLUSIONS: Despite enormous efforts in the last two decades, many unknown regulators for p53 and Mdm2 abundance are predicted to exist. This cross-species approach to identify evolutionarily conserved regulators demonstrates that our Medaka unigene cDNA library represents a powerful tool to screen for these novel regulators of the p53/Mdm2 pathway.

The effect of RA on the chick Ebf1-3 genes expression in somites and pharyngeal arches.

Expression of chick early B cell factor 1-3 (cEbf1-3) genes in regions of high retinoic acid (RA) activity, such as somites and pharyngeal arches (PAs), and regulation of other EBF members by RA raise the possibility that the internal cue RA may regulate cEbf1-3 expression in these tissues. To check this possibility, RA gain and loss of function experiments were conducted. Ectopic expression of RA led to up-regulation of cEbf2, 3 but did not change cEbf1 expression in somites. Expectedly, inhibition of RA by disulfiram resulted in downregulation of cEbf2, 3, but did not change cEbf1 expression in somites. The same RA gain and loss of function experiments did not change cEbf1-3 expression in PAs. However, ectopic expression of RA in the cranial neural tube before migration of neural crest cells downregulated cEbf1, 3 and up-regulated cEbf2 expression in the PAs. The same experiment, but with application of disulfiram, resulted in downregulation of cEbf2, but did not alter the expression of the other two genes. We conclude that the three cEbf genes act differently in response to RA signals in somitic mesoderm. cEbf1 may be not RA dependant in somites; however, the other two cEbf genes positively respond to RA signalling in somites. Additionally, only the migratory cEbf-expressing cells into the PAs are affected by RA signals.

Citalopram, an antipsychotic agent, induces G1/G0 phase cell cycle arrest and promotes apoptosis in human laryngeal carcinoma HEP-2 cells.

Human laryngeal squamous carcinoma (LSCC) is a common malignant tumor in the head and neck. Despite the recently developed therapies for the treatment of LSCC, patients' overall survival rate still did not enhance remarkably; this highlights the need to formulate alternative strategies to develop novel treatments. The antitumor effects of antidepressant drugs such as citalopram have been reported on several cancer cells; however, they have yet to be investigated against LSCC. The current study was directed to explore the possible antitumor effects of citalopram on human laryngeal carcinoma cell lines (HEP-2). HEP-2 cells were cultured and treated with different doses of citalopram (50-400 µM) for 24, 48, and 72 h. The effects of citalopram on the viability of cancer cells were determined by the MTT assay. In addition, apoptosis and cell cycle analysis were performed by flow cytometry. Moreover, evaluation of the expression of proapoptotic and apoptotic proteins, such as cytochrome c, cleaved caspases 3 and 9, Bcl-2, and BAX, was performed by western blotting analysis. Our results revealed that citalopram significantly suppressed the proliferation of HEP-2 cells through the upregulation of p21 expression, resulting in the subsequent arrest of the cell cycle at the G0/G1 phase. Furthermore, citalopram treatment-induced HEP-2 cell apoptosis; this was indicated by the significant increase of cytochrome c, cleaved caspases 3 and 9, and BAX protein expression. On the contrary, Bcl-2 protein expression was significantly downregulated following treatment with citalopram. The ultrastructure studies were in accordance with the protein expression findings and showed clear signs of apoptosis with ring chromatin condensation upon treatment with citalopram. These findings suggest that citalopram's anti-tumor activities on HEP-2 cells entailed stimulation of the intrinsic apoptotic pathway, which was mediated via Bcl-2 suppression.

Bioinformatics approach for structure modeling, vaccine design, and molecular docking of Brucella candidate proteins BvrR, OMP25, and OMP31.

Brucellosis is a zoonotic disease with significant economic and healthcare costs. Despite the eradication efforts, the disease persists. Vaccines prevent disease in animals while antibiotics cure humans with limitations. This study aims to design vaccines and drugs for brucellosis in animals and humans, using protein modeling, epitope prediction, and molecular docking of the target proteins (BvrR, OMP25, and OMP31). Tertiary structure models of three target proteins were constructed and assessed using RMSD, TM-score, C-score, Z-score, and ERRAT. The best models selected from AlphaFold and I-TASSER due to their superior performance according to CASP 12 - CASP 15 were chosen for further analysis. The motif analysis of best models using MotifFinder revealed two, five, and five protein binding motifs, however, the Motif Scan identified seven, six, and eight Post-Translational Modification sites (PTMs) in the BvrR, OMP25, and OMP31 proteins, respectively. Dominant B cell epitopes were predicted at (44-63, 85-93, 126-137, 193-205, and 208-237), (26-46, 52-71, 98-114, 142-155, and 183-200), and (29-45, 58-82, 119-142, 177-198, and 222-251) for the three target proteins. Additionally, cytotoxic T lymphocyte epitopes were detected at (173-181, 189-197, and 202-210), (61-69, 91-99, 159-167, and 181-189), and (3-11, 24-32, 167-175, and 216-224), while T helper lymphocyte epitopes were displayed at (39-53, 57-65, 150-158, 163-171), (79-87, 95-108, 115-123, 128-142, and 189-197), and (39-47, 109-123, 216-224, and 245-253), for the respective target protein. Furthermore, structure-based virtual screening of the ZINC and DrugBank databases using the docking MOE program was followed by ADMET analysis. The best five compounds of the ZINC database revealed docking scores ranged from (- 16.8744 to - 15.1922), (- 16.0424 to - 14.1645), and (- 14.7566 to - 13.3222) for the BvrR, OMP25, and OMP31, respectively. These compounds had good ADMET parameters and no cytotoxicity, while DrugBank compounds didn't meet Lipinski's rule criteria. Therefore, the five selected compounds from the ZINC20 databases may fulfill the pharmacokinetics and could be considered lead molecules for potentially inhibiting Brucella's proteins.

Assessment of the Anterior Loop and Pattern of Entry of Mental Nerve Into the Mental Foramen: A Radiographic Study of Panoramic Images.

INTRODUCTION: The precise location of the mental foramina is an essential landmark in planning the position of dental implants in the anterior mandible. Injury to inferior alveolar nerve during anterior mandibular implant surgery causes altered sensation which greatly affects patient satisfaction. METHODS: In this study, we assessed the prevalence of anterior loop of mental nerve and the pattern of entry of mental nerve into the mental foramen. Three hundred panoramic radiographs (600 hemimandibles) obtained from records maintained in the Department of Oral Medicine and Radiology were randomly selected for the study. The radiographs were evaluated by two independent observers for the pattern of entry of mental nerve into the mental foramen on either side of the mandible and for the presence or absence of anterior loop of mental nerve. RESULTS: The most prevalent pattern of mental nerve observed was Straight pattern which totals to 67.5% followed by Anterior loop pattern (18.8%) and then the Perpendicular pattern (13.7%). There was no significant association between the gender and subtypes of looping pattern on the left and right side and a highly significant association between the side of the mandible and loop pattern was observed by Chi square test. CONCLUSION: The Anterior loop pattern of mental nerve has been found in 18.8% of the population suggesting to accurate planning with three-dimensional imaging techniques to avoid injury to mental nerve during dental implant placement and other surgical procedure involving the interforaminal region of the mandible.

Novel phloretin-based combinations targeting glucose metabolism in hepatocellular carcinoma through GLUT2/PEPCK axis of action: in silico molecular modelling and in vivo studies.

Hepatocellular carcinoma (HCC) is commonly associated with disturbances in glucose metabolism and enhanced glycolysis. However, a controversial role for gluconeogenesis was reported to be tumor-promoting and tumor-suppressive. We investigated novel anti-HCC treatments through either the simultaneous inhibition of glycolysis and gluconeogenesis by "phloretin" and "sodium meta-arsenite", respectively (Combination 1); or the concurrent inhibition of glycolysis and induction of gluconeogenesis by phloretin and dexamethasone, respectively, (combination 2). A total of 110 Swiss albino mice were divided into eleven groups, HCC was induced by N, N-dimethyl-4-aminoazobenzene. We have measured the expression of the glucose transporter 2 (GLUT2), Phosphoenolpyruvate carboxykinases (PEPCK), Caspase-3, Beclin 1, Cyclin D1, and cytokeratin 18 genes; blood glucose and ATP levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Furthermore, in silico molecular docking was performed to investigate the potential drug-receptor interactions. Histologically, the phloretin-based combinations resulted in a significant regression of malignant tissue compared to various treatments. GLUT2 and PEPCK mRNA analysis indicated successful off/on modulation of glycolysis and gluconeogenesis. Docking confirmed the potent binding between phloretin, sodium meta-arsenite, and dexamethasone with GLUT2, PEPCK, and Retinoid X Receptor Alpha, respectively. Molecularly, Combination 2 resulted in the highest reduction in cyclin D1, cytokeratin 18, and Beclin 1 expression contemporaneously with the upregulation in Caspase-3 levels. Biochemically, both combinations caused a significant reduction in ATP levels, ALT, and AST activity compared to the other groups. In conclusion, we propose two novel phloretin-based combinations that can be used in treating HCC through the regulation of glucose metabolism and ATP production.

Effect of short-term high fat diet on resistin levels and expression of autophagy-related genes in the cartilage of male rats.

Obesity is a significant risk factor for the development of knee osteoarthritis (KOA). However, the precise molecular mechanisms linking obesity to OA remain unclear. In the present study, we investigated the effect of short-term high-fat diet (HFD) on the development of OA and the possible role of the adipokine resistin and autophagy-related genes in mediating this effect. Thirty adult male Wistar rats were equally divided into 2 groups: control and obese groups. Body mass index (BMI), levels of lipid profile, glucose, insulin and HOMA-IR index were significantly higher in the obese group compared with control. Our results revealed significantly higher serum and cartilage resistin levels with a significant increase in the mRNA expressions of toll-like receptor 4 (TLR4), matrix metalloproteinase-9 (MMP-9) and interleukin-1ß (IL-1ß) as well as protein levels of IL-1ß, matrix metalloproteinase-13 (MMP-13), ADAMTS 5 (aggrecanase-2) and caspase-3 in the cartilage of obese rats. The HFD induced a significant upregulation of autophagy related 5 (ATG5), beclin-1 and light chain 3 (LC3) mRNA expressions and a significant downregulation of mammalian target of rapamycin (mTOR) expression in cartilage. The protein levels of cartilage ATG5 were also significantly elevated in HFD-fed group. In conclusion, we suggested that increased levels of resistin and expression of autophagy-related genes may contribute in part, to OA development in HFD-fed rats. This provides a novel insight into the early molecular changes in the cartilage associated with obesity.

Mathematical and deep learning analysis based on tissue dielectric properties at low frequencies predict outcome in human breast cancer.

BACKGROUND: The early detection of human breast cancer represents a great chance of survival. Malignant tissues have more water content and higher electrolytes concentration while they have lower fat content than the normal. These cancer biochemical characters provide malignant tissue with high electric permittivity (ε´) and conductivity (σ). OBJECTIVE: To examine if the dielectric behavior of normal and malignant tissues at low frequencies (α dispersion) will lead to the threshold (separating) line between them and find the threshold values of capacitance and resistance. These data are used as input for deep learning neural networks, and the outcomes are normal or malignant. METHODS: ε´ and σ in the range of 50 Hz to 100 KHz for 15 human malignant tissues and their corresponding normal ones have been measured. The separating line equation between the two classes is found by mathematical calculations and verified via support vector machine (SVM). Normal range and the threshold value of both normal capacitance and resistance are calculated. RESULTS: Deep learning analysis has an accuracy of 91.7%, 85.7% sensitivity, and 100% specificity for instant and automatic prediction of the type of breast tissue, either normal or malignant. CONCLUSIONS: These data can be used in both cancer diagnosis and prognosis follow-up.

Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2.

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2's receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN's potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

TagSNP approach for HLA risk allele genotyping of Saudi celiac disease patients: effectiveness and pitfalls.

BACKGROUND: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human leukocyte antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA), DQ2 and/or DQ8 alleles. Therefore, the present study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag single nucleotide polymorphisms (SNP). METHODS: HLA-tag SNPs showing strong linkage value (r2>0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using real-time polymerase chain reaction technique. Genotype calls were further validated by Sanger sequencing method. RESULTS: A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs. CONCLUSION: The present study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared with the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.

Gas chromatographic determination of amino acid enantiomers in bottled and aged wines.

Free L- and D-amino acids were determined by chiral GC-MS in 26 wines, comprising white wines, red wines, ice wines and sparkling wines. The aim of the work was to investigate whether quantities and pattern of D-amino acids, in particular D-proline, correlate with the storage time of bottled wines. The relative quantities with respect to the corresponding L-enantiomer ranged in white wines from 0.4 to 3.9% D-Ala, 0.9-8.3% D-Asx, and 0.5-8.9% D-Glx, in red wines from 2.9 to 10.6% D-Ala, 2.2-10.9% D-Asx, and 3.9-7.4% D-Glx, and in sparkling wines from 2.2 to 9.8% D-Ala, 2.1-4.4% D-Asx and 1.3-6.1% D-Glx. Low relative quantities of 0.3-0.7% D-Pro were detected in three white wines stored for more than 20 years and did not exceed 0.2% D-Pro in two red wines stored for 10 and 20 years, respectively. An ice wine stored for 24 years contained 0.9% D-Pro, 6.4% D-Glx, 3.0% D-Asp and 1.5% D-Ala. The data confirm the presence of D-amino acids in wines. They do not provide evidence for a correlation between the storage time of bottled wines and quantities of D-amino acids.

Prevalence and Clinical Significance of Latent Brugada Syndrome in Atrial Fibrillation Patients Below 45 Years of Age.

Aim: This study aims to describe prevalence and clinical significance of latent Brugada syndrome (BrS) in a young population with atrial fibrillation (AF). Methods: Between September 2015 and November 2017, among 111 AF patients below 45 years of age, those without pre-existing pathologies and/or known risk factors were selected for the study. Based on baseline 12-lead-24-h Holter electrocardiogram (ECG), previous class 1C antiarrhythmic drug therapy, or ajmaline testing, patients were stratified as latent type 1 BrS or not. Results: Within the 78 enrolled patients, 13 (16.7%; group 1) revealed a type 1 BrS ECG pattern, while 65 (83.3%; group 2) did not. Mean age was 37 ± 8 vs. 35 ± 7 (p = 0.42), and males were 7 (54%) vs. 54 (83%) (p = 0.02) in the two groups, respectively. Family history of BrS was significantly more common within group 1 patients (2, 15% vs. 0; p = 0.03), and 4 (31%) patients experienced syncope in group 1 vs. 5 (8%) in group 2 (p = 0.02). After a mean follow-up of 42 ± 18 months from the index AF event, more than 80% of the patients, in both study groups, were in sinus rhythm. Conclusion: In young patients with AF without pre-existing pathologies and/or known risk factors, latent BrS should be suspected. Syncope and a family history of BrS emerge as easily identifiable factors related to BrS. Long-term sinus rhythm maintenance appears satisfactory, either in the presence or not of BrS.

Association of Four Missense SNPs with Preeclampsia in Saudi Women.

OBJECTIVE: The objective of this study was to investigate the association of rs1051740, rs2234922 (in microsomal epoxide hydrolase 1; EPHX1), rs268 (in lipoprotein lipase; LPL) and rs6025 (in Factor V Leiden; F5) genetic variants with the risk of preeclampsia development in Saudi women. MATERIALS AND METHODS: This case-control study recruited 233 Saudi women (94 preeclampsia cases and 139 healthy controls) who visited the Gynecology and Obstetrics Departments of two hospitals in Jeddah, Saudi Arabia, for routine postpregnancy clinical follow-ups. All the women underwent thorough clinical and biochemical investigations conducted according to the standard clinical guidelines. Genotyping of the study participants was done using real-time polymerase chain reaction-based TaqMan allelic discrimination assay. The strength of the association between genetic variants and disease development was assessed using chi-square, odds ratio, 95% confidence interval and multifactor dimensionality reduction tests. RESULT: The minor alleles "G" in rs268 (LPL) and "A" in rs6025 (F5) were absent in Saudi women. The frequencies of rs1051740 and rs2234922 of EPHX1, both in the homozygous and allelic forms, were not significantly different between preeclampsia patients and healthy controls (for all tests, P > 0.05). The multifactor dimensionality reduction analysis also indicated that the interaction between the four studied single-nucleotide polymorphisms (SNPs) had no significant association with preeclampsia risk. CONCLUSION: This study found that none of the studied genetic variants (neither the single SNP nor the SNP-SNP interactions) explain the development of preeclampsia in the Saudi population. These findings not only underscore the disease heterogeneity but also highlight the need to develop population-specific diagnostic genetic biomarkers for preeclampsia.

Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes.

BACKGROUND: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D. METHODS: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC. RESULTS: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely "glucagon signaling", "glycine, serine and threonine" and "bile secretion". Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study. CONCLUSION: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.