This study aimed at assessing the effect of gum arabic (Acacia senegal) oral treatment on the metabolic profile of chronic renal failure (CRF) patients. A total of 36 CRF patients (under regular haemodialysis) and 10 normal subjects participated in this study. The patients were randomly allocated into three groups-group A: 12 CRF patients under low-protein diet (LPD) (<40 g day(-1)) and gum arabic (50 g day(-1)) treatment; group B: 14 CRF patients under LPD and gum arabic, iron (ferrous sulphate, 200 mg day(-1)) and folic acid (5 mg day(-1)) treatment; group C (control group): 10 CRF patients under LPD and iron and folic acid treatment and group D: 10 normal volunteers (on normal diet) under daily dose of 50 g gum arabic. Each of the above treatments was continued for three consecutive months. Blood samples were collected from each subject before treatment and twice per month "pre-dialysis" for 3 months. Biochemical parameters measured were: serum urea, serum creatinine, serum uric acid, serum calcium and serum phosphorus. By the end of the 3 months of treatment, serum urea levels significantly decreased by 31.2 and 44.18% for group A and B, respectively, compared with the baseline (0.01 < p < 0.001) and control group (p < 0.05). Serum creatinine levels significantly decreased in the groups of gum users (A, B and D) by 9.94, 12.65 and 11.7%, respectively, compared with the control group (p < 0.001). There was a significant decrease (p < 0.05) in serum uric acid levels by 14 and 19.9% for group A and B, respectively, compared with the baseline. Serum calcium levels increased by 12.64, 15.75 and 8.75% for group A, B and D, respectively, and these increases were significantly different (0.05 < p < 0.001) from baseline and control group for groups A and B. Serum phosphorus levels significantly decreased by 22.54% for group A, 17.69% for group B and 7.71% for group D, compared with the baseline (0.05 < p < 0.001). From this study, we conclude that oral administration of gum arabic could conceivably alleviate adverse effects of CRF.

SIK1 syndrome is a newly described developmental epilepsy disorder caused by heterozygous mutations in the salt-inducible kinase SIK1. To better understand the pathophysiology of SIK1 syndrome, we studied the effects of SIK1 pathogenic sequence variations in human neurons. Primary human fetal cortical neurons were transfected with a lentiviral vector to overexpress wild-type and mutant SIK1 protein. We evaluated the transcriptional activity of known downstream gene targets in neurons expressing mutant SIK1 compared with wild type. We then assayed neuronal morphology by measuring neurite length, number and branching. Truncating SIK1 sequence variations were associated with abnormal MEF2C transcriptional activity and decreased MEF2C protein levels. Epilepsy-causing SIK1 sequence variations were associated with significantly decreased expression of ARC (activity-regulated cytoskeletal-associated) and other synaptic activity response element genes. Assay of mRNA levels for other MEF2C target genes NR4A1 (Nur77) and NRG1, found significantly, decreased the expression of these genes as well. The missense p.(Pro287Thr) SIK1 sequence variation was associated with abnormal neuronal morphology, with significant decreases in mean neurite length, mean number of neurites and a significant increase in proximal branches compared with wild type. Epilepsy-causing SIK1 sequence variations resulted in abnormalities in the MEF2C-ARC pathway of neuronal development and synapse activity response. This work provides the first insights into the mechanisms of pathogenesis in SIK1 syndrome, and extends the ARX-MEF2C pathway in the pathogenesis of developmental epilepsy.

Background Following cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long‐term implantable cardiac monitoring. Methods and Results We studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long‐term monitoring. At 36 months of follow‐up, the cumulative rate of implantable cardiac monitor–detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow‐up (hazard ratio, 2.28 [95% CI, 1.39–3.76]; P =0.001). Replacing age with the CHA 2 DS 2 ‐VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1‐point increment in the CHA 2 DS 2 ‐VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00–1.38; P =0.047). Consistent results were shown using Kaplan–Meier analysis by age and by the CHA 2 DS 2 VASc score. Conclusions Cryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.

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The aim of this study was to determine the Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotype frequency in Rheumatoid Arthritis (RA) in the Sudanese population. The frequency of HLA-DRB1 and -DQB1 alleles and DRB1-DQB1 haplotypes were determined in 122 RA patients and 100 controls. HLA alleles were genotyped by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. In RA patients, HLA-DRB1*04 and *10 alleles were high in frequency (9.6% vs 14.2%, P = 0.038 and P = 0.042, respectively), and dependently on anti-citrullinated protein antibodies (ACPAs) seropositivity (P = 0.044 and P = 0.027, respectively). In contrast, the frequency of the HLA-DRB1*07 allele was significantly low in patients than in controls (11.7% vs 5.0%, P = 0.010). Moreover, the HLA-DQB1*03 allele was strongly associated with RA risk (42.2%, P = 2.2x10-8), whereas, HLA-DQB1*02 and *06 showed protective effects against RA (23.1% and 42.2%, P = 0.024 and P = 2.2x10-6, respectively). Five different HLA haplotypes, DRB1*03-DQB1*03 (P = 0.00003), DRB1*04-DQB1*03 (P = 0.00014), DRB1*08-DQB1*03 (P = 0.027), DRB1*13-DQB1*02 (P = 0.004), and DRB1*13-DQB1*03 (P = 3.79x10-8) were significantly associated with RA risk, while 3 protective haplotypes, DRB1*03-DQB1*02 (Pc = 0.008), DRB1*07-DQB1*02 (Pc = 0.004), and DRB1*13-DQB1*06 (Pc = 0.02) were identified. This is the first study determining the association between HLA class II alleles and haplotypes and RA risk in our population.