The association between growth differentiation factor-15, erythroferrone, and iron status in thalassemic patients.

BACKGROUND: Iron overload can result in grave consequences in thalassemic patients, despite the availability of iron chelators. Therefore, alternative pathways aiming to reduce iron toxicity are currently investigated. Among which, reduction of iron absorption through control of hepcidin production appears to be promising. In this study, we investigated growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) as potential suppressors of hepcidin. METHODS: This cross-sectional study was conducted on 61 thalassemic patients and 60 healthy controls. The frequency of GDF15 gene polymorphism (rs4808793) (-3148C/G), serum level of GDF15 and erythroferrone were measured and correlated with those of hepcidin and serum ferritin. RESULTS: The presence of GDF15 gene mutations were significantly higher in the patients' group compared to controls (P value 0.035). Also, thalassemia patients had significantly higher levels of GDF15 and ERFE and lower hepcidin levels than controls (P value < 0.001). Serum hepcidin level showed significantly negative correlations with GDF15, ERFE, reticulocyte count, LDH level, and serum ferritin. Contrarily, it had highly significant positive correlation with hemoglobin. CONCLUSIONS: High level of GDF15 and/or ERFE may inhibit hepcidin production and increase iron load in patients with thalassemia; therefore, medications that suppress their actions may provide new therapeutic potentials for iron toxicity. IMPACT: Iron overload continues to be a major contributor to high morbidity and mortality in patients with thalassemia. New strategies together with proper chelation, need to be developed to minimize the effect of iron toxicity. Growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) inhibit hepcidin production and increase iron levels in conditions with ineffective erythropoiesis. Medications that suppress the production or interfere with the action of GDF15 or ERFE may represent new therapeutic potentials for iron toxicity. Prevention of iron toxicity will significantly reduce morbidity and mortality and improve the quality of life of thalassemia patients.

Identification of Gut Microbiota Profile Associated with Colorectal Cancer in Saudi Population.

Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression. This study aims to analyze the gut microbiota composition and the enriched metabolic pathways in patients with late-stage CRC. In this study, a cohort of 25 CRC patients diagnosed at late stage III and IV and 25 healthy participants were enrolled. The fecal bacterial composition was investigated using V3-V4 ribosomal RNA gene sequencing, followed by clustering and linear discriminant analysis (LDA) effect size (LEfSe) analyses. A cluster of ortholog genes' (COG) functional annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify enrichment pathways between the two groups. The findings showed that the fecal microbiota between the two groups varied significantly in alpha and beta diversities. CRC patients' fecal samples had significantly enriched populations of Streptococcus salivarius, S. parasanguins, S. anginosus, Lactobacillus mucosae, L. gasseri, Peptostreptococcus, Eubacterium, Aerococcus, Family XIII_AD3001 Group, Erysipelatoclostridium, Escherichia-Shigella, Klebsiella, Enterobacter, Alistipes, Ralstonia, and Pseudomonas (Q < 0.05). The enriched pathways identified in the CRC group were amino acid transport, signaling and metabolism, membrane biogenesis, DNA replication and mismatch repair system, and protease activity (Q < 0.05). These results suggested that the imbalance between intestinal bacteria and the elevated level of the predicated functions and pathways may contribute to the development of advanced CRC tumors. Further research is warranted to elucidate the exact role of the gut microbiome in CRC and its potential implications for use in diagnostic, prevention, and treatment strategies.

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

Shear wave elastography of the tibial nerve in healthy subjects.

ABSTRACT: The purpose of this study is to investigate sonoelastographic features of the tibial nerve.The study included 72 tibial nerves in 36 healthy subjects. High resolution ultrasound and Shear wave elastography were used to evaluate the tibial nerve. Cross sectional area and stiffness were measured.The mean cross sectional area of the tibial nerve was 13.4 mm2. The mean shear elastic modulus of the tibial nerve in the short axis was 23.3 kPa. The mean shear elastic modulus of the tibial nerve in long axis was 26.1 kPa. The tibial nerve elastic modulus also showed no correlation with cross sectional area neither in the long axis nor short axis. Age, height, weight, and body mass index showed no correlation with tibial nerve elastic modulus in short or long axes.The elastic modulus of the tibial nerve has been determined in healthy subjects and can serve as a reference for future assessment of polyneuropathy.

Shear wave elastography of the submandibular gland in healthy individuals.

OBJECTIVES: Shear wave elastography is a rapidly evolving new technique. The purpose of the present study was to determine the sonoelastographic features of the submandibular glands in healthy individuals. METHODS: We conducted a cross-sectional study of 45 healthy individuals, whose submandibular glands were studied using shear wave elastography. The stiffness of both submandibular glands was measured and its relationships with the age, sex, body mass, body mass index (BMI), and height of the participants were assessed. RESULTS: The participants had a mean age of 31.82 ± 5.53 years, a mean height of 158.30 ± 7.16 cm, a mean body mass of 57.83 ± 8.84 kg, and a mean BMI of 22.99 ± 2.72 kg/m2. The mean shear elastic modulus of the right and left submandibular glands were 18.02 kPa and 19.09 kPa, respectively. Positive correlations were found between the elasticity of the right submandibular gland and the anthropometric parameters. CONCLUSION: The elastic modulus of the submandibular glands has been determined in healthy individuals and the data generated can serve as a reference for future studies of pathological conditions of these structures.

Evaluation of infrapatellar tendon plication in spastic cerebral palsy with crouch gait pattern: a pilot study.

OBJECTIVE: In order to substantially improve crouch pattern in cerebral palsy, the existent patella alta needs to be addressed. This pilot study evaluates the effectiveness of a previously described infrapatellar tendon plication for the treatment of patella alta in crouch gait pattern in skeletally immature spastic cerebral palsy patients. METHODS: In 10 skeletally immature patients (20 knees) with spastic diplegia and crouch gait, the previously described technique by Joseph et al. for infrapatellar tendon plication was evaluated within the setting of single event multilevel surgery (SEMLS). Outcome measures included knee extension lag, Koshino's radiological index for patella alta, and the occurrence of complications. Patients were followed-up for a minimum of 12 months. RESULTS: The extensor lag improved and was statistically significant in all cases of the study with no incidence of tibial apophyseal injury at the latest follow-up. Radiographic Koshino index normalized and was maintained all through the follow-up period except in one patient (5%) who was overcorrected. Two patients (4 knees, 20%) showed postoperative knee stiffness due to casting which resolved with physiotherapy within six weeks. One knee (5%) developed a superficial infection which also resolved uneventfully with repeated dressings. CONCLUSION: The described infra-patellar plication technique in skeletally immature spastic diplegics appears effective, safe, and reproducible.

Shear wave elastography of the saphenous nerve.

The purpose of this study is to study sonoelastographic features of the saphenous nerve.The study included 72 saphenous nerves in 36 healthy subjects. High resolution ultrasound and Shearwave elastography were used to evaluate the saphenous nerve. Cross sectional area (CSA) and stiffness were measured.The mean CSA of the saphenous nerve was 5.7 mm. The mean shear elastic modulus of the saphenous nerve in the short axis was 29.5 kPa. The mean shear elastic modulus of the saphenous nerve in long axis was 29.9 kPa. The saphenous nerve elastic modulus also showed no correlation with CSA in neither the long axis nor short axis. Positive correlation between elasticity measurements in the long and short axes. Age, height, weight, and BMI showed no correlation with saphenous nerve elastic modulus in short or long axes.The elastic modulus of the saphenous nerve has been determined in healthy subjects and can serve as a reference for future assessment of the saphenous nerve before different procedures.

Angiotensin converting enzyme DD genotype is associated with development of rheumatic heart disease in Egyptian children.

Angiotensin converting enzyme (ACE) gene polymorphism was previously studied in some cardiovascular diseases. There are only few studies which investigated this polymorphism in patients with rheumatic heart disease (RHD). The results of these investigations are inconsistent. Furthermore, gene polymorphism distribution is different in various ethnic populations. We conducted this study to demonstrate this gene polymorphism in Egyptian children with RHD. Leukocytes DNA was extracted from 139 patients with RHD and 79 healthy control children. After amplification by the PCR, the products were separated by electrophoresis in 6% polyacrylamide gel and visualized after ethidium bromide staining with UV light. The PCR product is a 190-bp fragment in the absence of the insertion (D allele) and a 490-bp fragment in the presence of the insertion (I allele). Gene polymorphism was as follows: DD gene when lane contains only 190-bp fragment, II gene when lane contains only 490-bp fragment and ID gene when lane contains both fragments. We found that gene polymorphism in both control and patients groups followed the following order of distribution from highest to lowest: ID, II, DD gene. The frequency in control group was 49.4, 36.7, and 13.9%, respectively. In patients groups, the gene frequency was 42.5, 30.9, and 26.6%, respectively. DD gene frequency differs significantly between the two groups. We concluded that patients with RHD have a higher ACE-DD genotype than normal control. ACE-DD genotype may be a risk factor for RHD in Egyptian children.