CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Impact of lifestyle modification on glycemic control and cognitive function among Type II diabetes mellitus patients.

Aim: Assessing impact of lifestyle modification on Type 2 diabetes mellitus (T2DM) glycemic control and cognitive function. Subjects & methods: Prospective study was conducted on T2DM patients (92 patients as interventional group and 92 patients conventional therapy). Results: After 6 months, significant improvements of HbA1c, oxidant and antioxidant, lipid profile, and cognitive function among only the interventional group (p < 0.05). Using logistic analysis, conventional therapy, DM duration >10 years, lower education, HbA1c baseline >7 were significant predictive risks for uncontrolled DM (AOR 4.2, 2.9, 2.7 and 2.2, respectively). While, conventional therapy, baseline mild cognitive impairment (MCI) and females were significant risks for MCI (AOR 11.5, 10.8 and 4.8, respectively). Conclusion: Lifestyle modification is a very important for glycemic control and cognitive function.Clinical Trial Registration: NCT04891887 (ClinicalTrials.gov).

The study aimed at assessing the effect of lifestyle modification program on Type 2 diabetes mellitus (T2DM) patients. The program contents include maintaining healthy diet depending on glycemic index and CHO counting, adjusting cholesterol level, regular physical activity for at least 30 minutes; 3­5 days per week, weight loss and maintaining an appropriate weight, controlling the blood pressure, smoking cessation and practicing mental activity. After 6 months, there was a significant improvement in glycemic control, cognitive function, oxidant and antioxidant and lipid profile levels among patients participating in the program but not among those remained on the conventional therapy.

Prevalence of Health Problems Targeted by the National School-Based Screening Program among Primary School Students in Saudi Arabia, 2019.

The Saudi Ministry of Health (MOH) established a National School-Based Screening Program (NSBSP) for health screening of schoolchildren. Students from specific grades were systematically screened for several health problems, including obesity, visual and auditory problems, dental cavities, scoliosis, and attention-deficit/hyperactivity disorder (ADHD). This cross-sectional study aimed to determine the prevalence of these health problems among primary school students based on secondary data obtained from the NSBSP. We included 444,259 screened school children from the first and fourth grades of 50% of the selected schools (both private and public) across the Kingdom of Saudi Arabia (KSA) during the academic year 2018-2019. Among them, the most prevalent health problems identified were dental cavities (38.7%), eye refractory errors (10.9%), and overweight and obesity (10.5%); the less prevalent problems included ADHD (2.81%), auditory problems (0.6%), and scoliosis (0.48%). A greater prevalence of most health problems was observed in girls more than boys. The NSBSP successfully aided the detection of health conditions with high and low prevalence among primary school students in the KSA, and thus, the identification of health problems of specific concern. Implementation of effective school health services for the prevention, early detection, diagnosis, and treatment of these health problems are imperative.

Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage.

The aim of the present study was to investigate different biological prognostic markers to identify high-risk patients with chronic lymphocytic leukemia (CLL) with a higher tumor burden, in order to ensure appropriate management. A total of 81 Egyptian patients with CLL were enrolled in the present study, with 75 healthy subjects serving as the control group. The expression of CD49d, CD38 and ZAP-70 in CLL cells was assessed using flow cytometry. The fluorescence in situ hybridization technique was employed to evaluate TP53 (del17p), ataxia-telangiectasia (del11q) and 13q14 (del13q14) genes and the presence of trisomy 12. The serological markers ß2 microglobulin (B2M) and sCD23 were measured by ELISA. The CD49d gene was highly expressed in 25.9% and cytogenetic aberrations were observed in 66.6% of all recruited CLL patients. The patients were categorized according to the Binet staging system and a significant increase in the expression of sCD23, CD49d and ZAP-70 was detected in group C (P=0.008, 0.034 and 0.017, respectively) when compared to groups A and B. CD49d+ patients exhibited significantly higher expression of CD38 (P=0.002) and trisomy 12 (P=0.015) and lower expression of del13q14 (P=0.001). Patients who were CD49d+ with B2M>3.5 µg/ml exhibited higher total leukocyte count (P=0.048), higher absolute lymphocyte count (P=0.036), higher expression of CD38 (P=0.002) and trisomy 12 (P=0.034) and lower expression of del13q14 (P=0.002). Therefore, sCD23, CD49d and ZAP-70 may be considered as an optimal prognostic marker combination to be evaluated in the early stages of CLL and throughout disease management. Integrating both serological markers and CD49d expression by flow cytometry may add to the prognostic value of each marker alone and help identify high-risk patients with a higher tumor burden.

Correction: Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

[This corrects the article DOI: 10.1371/journal.pone.0236453.].

ITGA4 gene methylation status in chronic lymphocytic leukemia.

BACKGROUND: We aimed to investigate ITGA4 gene expression pattern and to explore its methylation heterogeneity in chronic lymphocytic leukemia (CLL). PATIENTS & METHODS: Eighty one CLL patients and 75 healthy subjects were enrolled and prognostic evaluation of patients was assessed. ITGA4 q-realtime PCR was performed using Applied Biosystems, TaqMan gene expression assay. ITGA4 gene-specific CpG methylation was investigated in real time using pyrosequencing technology. RESULTS: ITGA4 was differentially expressed in CLL patients. The CpG sites-1, 2 and 3 showed significantly higher mean levels than healthy controls (p = <0.001, 0.007 and 0.009). Significant association between CpG site-1 and CLL has been detected using age-adjusted logistic regression (p < 0.001). CONCLUSION: Hypermethylation at ITGA4 gene CpG sites (1,2,3) is a characteristic feature in CLL.

Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. METHODS: This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. RESULTS: MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. CONCLUSION: MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.

Potential Role of New Anthropometric Parameters in Childhood Obesity with or Without Metabolic Syndrome.

BACKGROUND: Obese children and adolescents are more prone to have metabolic syndrome (MS).MS is a cluster of cardiovascular risk factors associated with insulin resistance. Body round index [BRI], visceral adiposity index [VAI] and a body shape index [ABSI] are among the new obesity anthropometric parameters. AIM: To evaluate the new markers for obesity in children and their possible association with other laboratory and clinical variables of MS. METHODS: Eighty nine obese children and 40 controls aged 10-18 years were recruited. Full history taking, thorough clinical examination, anthropometric and biochemical features were performed in the studied groups. Subcutaneous fat thickness (SFT) and visceral fat thickness (VFT) were estimated by ultrasonography. RESULTS: Obese children, exhibited significantly higher values in all anthropometric measurements (P < 0.001). Diastolic and systolic blood pressure were significantly higher (P < 0.001) in the obese group. ABSI, BRI and VAI have been found to be significantly higher in obese subjects (P < 0.001), with no significant gender difference. BMI, WHtR, WC/HR, SBP, DBP, subcutaneous fat thickness and visceral fat thickness, Liver Span, ABSI, BRI, VAI and HOMA_IR were significantly higher among children with MS than those without MS. Positive significant correlations of VAI with BMI, WC/Ht, WC/Hip, SBP, DBP, SFT, VFT, Liver size and HOMA-IR (r = 0.384, 0.239, 0.268, 0.329, 0.516, 0.320, 0.254, 0.251, and 0.278 respectively) are shown. The area under the ROC curve (AUC) of BMI, VAI, ABSI, BRI for predicting MS was 0.802 (0.701-0.902), 0.737 (0.33-0.841), 0.737 (0.620-0.855), 0.816 (0.698-0.934). CONCLUSION: We suggest using the VAI and WHtR indexes, as they are better predictor of MS.

Risk Factors Associated with Mild Cognitive Impairment among Apparently Healthy People and the Role of MicroRNAs.

BACKGROUND: Mild cognitive impairment (MCI) is a stage between the expected cognitive decline of normal ageing and the serious decline of dementia. AIM: To identify risk factors and role of miRNAs associated with mild cognitive impairment (MCI) among employees. SUBJECTS AND METHOD: A cross-sectional study was carried out on 186 employees aged between 40 and 65 years. Cognitive function was evaluated using ACEIII, MoCA, and Quick cognitive tests. Medical history and lifestyle were assessed. Family 132 & 134 miRNA expressions were assessed by real-time PCR. RESULTS: MCI was detected among 14 / 186 (7.5%). miRNA 132 expression was the only significant miRNAs to detect MCI with low sensitivity and specificity (70%). The logistic analysis revealed that higher miRNA132 expressions, low monthly intake of; vegetables, unroasted nuts, low education and higher ALT levels were predicting factors for MCI with AOR 1.1 (1.01-3.3), 1.2 (1.04-1.43), 0.8 (0.8-0.98), 2.7 (1.9-7.4) and 1.6 (1.1-2.3) respectively. CONCLUSION: MiRNAs expression showed low sensitivity and specificity in detecting MCI; only miRNA 132 might be used. Several modifiable factors seem to reduce the risk of MCI.

Intima media thickness as an early predictor of atherosclerosis in Egyptian children with familial Mediterranean fever.

INTRODUCTION: Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent crises of fever and serosal inflammation. Although FMF patients are symptom free in between attacks, subclinical inflammation continues during the attack-free period. Such patients with inflammatory status have an increased risk of atherosclerotic cardiovascular complications. We attempted to elucidate the role of arterial wall thickening as a predictor of early atherosclerosis in children affected by FMF and to clarify the links between carotid intima media thickness and the markers of subclinical inflammation serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR). MATERIAL AND METHODS: It is a case control study. The study comprised 45 Egyptian children diagnosed with FMF and 45 healthy children of matched age and sex who served as controls, without family history or clinical manifestations suggestive of FMF. Laboratory investigations included complete blood count, NLR, PLR, ESR, C-reactive protein and lipid profile. Serum amyloid A levels were determined in both groups using enzyme linked immunosorbent assay. Assessment of the common carotid artery intima media thickness (CIMT) in the FMF patients was carried out. RESULTS: The level of SAA was significantly higher in patients than the control subjects with a mean value of 38.30 ng/ml and 23.43 ng/ml respectively (p < 0.001). Our patients showed significantly higher PLR when compared to controls (p < 0.001). The mean right and left carotid intima media thickness in patient and control groups showed a highly significant difference (p = 0.005 and 0.036 respectively). CONCLUSIONS: The mean carotid intima media thickness is higher in cases than the control group. Hence carotid intima media thickness may be used as a tool in the prediction of any atherosclerotic burden in those children.

FcγRIIa defunctioning polymorphism in paediatric patients with renal allograft.

INTRODUCTION: Fc gamma receptor (FcγR) IIa is considered the most widely distributed of the three classes of Fc receptors, and it expresses an allelic polymorphism. This type of polymorphism may modify the immune response and may be an important factor for some diseases. The aim of the study reported herein was to evaluate the association between the FcγRIIa polymorphism and susceptibility to both end-stage renal disease (ESRD) and acute kidney graft rejection (AR) in children who have undergone renal transplantation. MATERIAL AND METHODS: The study evaluated 70 children who had undergone transplantation and 60 healthy subjects. AR was observed in 25 children. RESULTS: FcγRIIa genotypes and alleles were significantly different between transplantation patients and the control group. The assessment for FcγR of the groups in which AR was present showed that there was only a risk of having an acute rejection in homozygous genotype RR. CONCLUSIONS: FcγRIIa RR genotype and allele frequency was increased in paediatric renal transplant recipients. The present findings showed that FcγRIIa genotype may be related to ESRD disease susceptibility, and FcγRIIa polymorphisms seemed to affect AR.

Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis.

To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.

Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

BACKGROUND: The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. METHODS: Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. RESULTS: A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0.0001). On multiple linear regression, urea was the only variable independently associated with an elevated plasma glutamine level (Beta=0.77, P=0.02). CONCLUSION: This study indicates that the advanced stages of CKD are associated with increased plasma concentrations of glutamine and homocysteine. Glutamine retained in the plasma of children with CRF, possibly producing higher levels of the waste products (urea and NH3). Dialysis alone is insufficient to redress completely the abnormalities in AA metabolism in ESRD children. Careful consideration of dialysis and dietary measures are necessary.