Metabolic profiling during COVID-19 infection in humans: Identification of potential biomarkers for occurrence, severity and outcomes using machine learning.

BACKGROUND: After its emergence in China, the coronavirus SARS-CoV-2 has swept the world, leading to global health crises with millions of deaths. COVID-19 clinical manifestations differ in severity, ranging from mild symptoms to severe disease. Although perturbation of metabolism has been reported as a part of the host response to COVID-19 infection, scarce data exist that describe stage-specific changes in host metabolites during the infection and how this could stratify patients based on severity. METHODS: Given this knowledge gap, we performed targeted metabolomics profiling and then used machine learning models and biostatistics to characterize the alteration patterns of 50 metabolites and 17 blood parameters measured in a cohort of 295 human subjects. They were categorized into healthy controls, non-severe, severe and critical groups with their outcomes. Subject's demographic and clinical data were also used in the analyses to provide more robust predictive models. RESULTS: The non-severe and severe COVID-19 patients experienced the strongest changes in metabolite repertoire, whereas less intense changes occur during the critical phase. Panels of 15, 14, 2 and 2 key metabolites were identified as predictors for non-severe, severe, critical and dead patients, respectively. Specifically, arginine and malonyl methylmalonyl succinylcarnitine were significant biomarkers for the onset of COVID-19 infection and tauroursodeoxycholic acid were potential biomarkers for disease progression. Measuring blood parameters enhanced the predictive power of metabolic signatures during critical illness. CONCLUSIONS: Metabolomic signatures are distinctive for each stage of COVID-19 infection. This has great translation potential as it opens new therapeutic and diagnostic prospective based on key metabolites.

CPE-Na-Based Hole Transport Layers for Improving the Stability in Nonfullerene Organic Solar Cells: A Comprehensive Study.

Organic photovoltaic (OPV) cells have experienced significant development in the last decades after the introduction of nonfullerene acceptor molecules with top power conversion efficiencies reported over 19% and considerable versatility, for example, with application in transparent/semitransparent and flexible photovoltaics. Yet, the optimization of the operational stability continues to be a challenge. This study presents a comprehensive investigation of the use of a conjugated polyelectrolyte polymer (CPE-Na) as a hole layer (HTL) to improve the performance and longevity of OPV cells. Two different fabrication approaches were adopted: integrating CPE-Na with PEDOT:PSS to create a composite HTL and using CPE-Na as a stand-alone bilayer deposited beneath PEDOT:PSS on the ITO substrate. These configurations were compared against a reference device employing PEDOT:PSS alone, as the HTL increased efficiency and fill factor. The instruments with CPE-Na also demonstrated increased stability in the dark and under simulated operational conditions. Device-based PEDOT:PSS as an HTL reached T80 after 2500 h while involving CPE-Na in the device kept at T90 in the same period, evidenced by a reduced degradation rate. Furthermore, the impedance spectroscopy and photoinduced transient methods suggest optimized charge transfer and reduced charge carrier recombination. These findings collectively highlight the potential of CPE-Na as a HTL optimizer material for nonfluorine OPV cells.

Can shear wave elastography predict the success of shock­wave lithotripsy used in renal stones treatment? A prospective study.

OBJECTIVE: To evaluate the usage of shear wave elastography (SWE) in the prediction of the success rate of shock­wave lithotripsy (SWL) treatment of renal stones. PATIENTS AND METHODS: In the present study, SWL was performed for 100 patients presented with renal stones in the duration from May 2022 to August 2023. The patients were divided into 2 groups SWL responders and non-responders. The study compared between the 2 groups in terms of baseline parameters of the patients as age, sex, body mass index (BMI), stone size, stone location, stone density (HU), skin-to-stone distance (SSD), the degree of hydronephrosis and the stone elastography values. RESULTS: There was no statistically significant relation between stone-free rate and degree of obstruction (p = 0.628), stone size (p = 0.390) upper calyceal location (p = 0.17), middle calyceal location (p = 0.66), and renal pelvis location (p = 1.0). Nevertheless, a statistically significant relation was found as regards lower calyceal location, stone density (HU), and stone Elastography values using multivariate analysis. CONCLUSIONS: Measurement of stone density by shear wave elastography (SWE) can be used as an alternative to HU in decision-making before SWL. SWL success depends mainly on stone site, HU, and SWE values.

Two-year follow-up comparing Rezum therapy versus bipolar transurethral resection of the prostate for treating benign prostatic hyperplasia. A prospective randomized study.

OBJECTIVE: Comparison of the efficacy and safety of Rezum therapy and bipolar transurethral resection of prostate (B-TURP) for the management of benign prostatic hyperplasia (BPH) of 50-120 g size. METHODS: One hundred patients with BPH who met the inclusion criteria were included and split into two equal groups to undergo Rezum therapy or B-TURP. The two groups were compared for efficacy using international prostate symptom score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), operative time, catheter time, hospital stay, post-void residual urine (PVR), prostate-specific antigen (PSA), and residual prostate size and safety using the incidence of complications. RESULTS: Rezum significantly ameliorated IPSS from the baseline score by 55.3%, QoL by 50%, Qmax by 62.5%, International Index of Erectile Function (IIEF) by 7.1%, PVR by 50%, residual prostate size by 28.1% and PSA by 42% at 2 years. Meanwhile, the improvement in B-TURP was significantly higher than Rezum group, Rezum therapy had a significantly shorter duration of operative time and hospital stay. Also, it had fewer complications in comparison with B-TURP. CONCLUSIONS: Rezum is a minimally invasive procedure that provides significantly improved symptomatic relief of BPH and quality of life with preservation of erectile and ejaculatory functions. However, it is not as effective as B-TURP.

Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination.

Background and study aims Gut infection is common during acute COVID-19, and persistent SARS-CoV-2 gut infection has been reported months after the initial infection, potentially linked to long-COVID syndrome. This study tested the incidence of persistent gut infection in patients with a history of COVID-19 undergoing endoscopic examination. Patients and methods Endoscopic biopsies were prospectively collected from patients with previous COVID-19 infection undergoing upper or lower gastrointestinal endoscopy (UGE or LGE). Immunohistochemistry was used to detect the presence of persistent SARS-CoV-2 nucleocapsid proteins. Results A total of 166 UGEs and 83 LGE were analyzed. No significant differences were observed between patients with positive and negative immunostaining regarding the number of previous COVID-19 infections, time since the last infection, symptoms, or vaccination status. The incidence of positive immunostaining was significantly higher in UGE biopsies than in LGE biopsies (37.34% vs. 16.87%, P =0.002). Smokers showed a significantly higher incidence of positive immunostaining in the overall cohort and UGE and LGE subgroups ( P <0.001). Diabetic patients exhibited a significantly higher incidence in the overall cohort ( P =0.002) and UGE subgroup ( P =0.022), with a similar trend observed in the LGE subgroup ( P =0.055). Conclusions Gut mucosal tissues can act as a long-term reservoir for SARS-CoV-2, retaining viral particles for months following the primary COVID-19 infection. Smokers and individuals with diabetes may be at an increased risk of persistent viral gut infection. These findings provide insights into the dynamics of SARS-CoV-2 infection in the gut and have implications for further research.

Left ventricle mass index in paediatric intensive care unit acquired hypertension.

BACKGROUND: Hypertension acquired in paediatric critical patients is a recognised challenge, with variable reported frequency. Pain, agitation, and/or medications such as beta stimulants and corticosteroids are well-known risk factors. Sympathomimetics in septic patients can cause high blood pressure, especially with unobserved haemodynamic monitors. Beyond haemodynamic factors, several endocrinal-metabolic factors - including catecholamines, insulin, renin, angiotensin, the aldosterone system, and sodium consumption - may contribute to the left ventricular growth. It is well known that the sympathetic tone has a trophic effect on the heart muscle. METHOD: A prospective cohort study was conducted during the year 2021. The children were divided into two groups: those who were critically ill with paediatric intensive care unit-acquired hypertension (n = 59) and those without paediatric intensive care unit-acquired hypertension (n = 62). We used the American Academy of Pediatrics' 2017 definition of hypertension to diagnose paediatric intensive care unit-acquired hypertension. Measurement of cardiac output and systemic vascular resistance was performed by cardiometry. Left ventricular myocardial performance and left ventricular mass index were measured by bedside echocardiography at the onset of hypertension diagnosis. RESULTS: Critically ill children with acquired hypertension had a higher cardiac index (p = 0.0001), systemic vascular resistance index (<0.0001), myocardial performance (0.037), and left ventricular mass index (0.009). The longer duration of stay observed in the hypertension group had no observable effect on mortality (<0.0001). CONCLUSION: Both myocardial performance and left ventricle mass index increased in critically ill children with paediatric intensive care unit-acquired hypertension.

Does the duration of catheterization have an impact on the outcome of trial without catheter in patients with acute urine retention (AUR) due to benign prostatic hyperplasia (BPH)? A prospective randomized study.

BACKGROUND: To study the impact of early in comparison to late catheter removal following acute urine retention (AUR) secondary to benign prostatic hyperplasia (BPH) using silodosin therapy on the outcome of trial without catheter (TWOC). METHODS: Two hundred sixty patients with AUR 2ry to BPH were catheterized then were randomly divided to receive silodosin 8 mg either for three or 7 days followed by catheter removal and successful voiding unaided was assessed. RESULTS: Out of the 260 men (mean age 64.8 ± 6.5 years) treated, 74 men who were receiving 3 days of silodosin and 88 patients who were receiving 7 days of silodosin didn't require re-catheterization on the day of TWOC (57% and 68% respectively, p = 0.096). Complications like urinary leakage, acute urinary tract infection, hematuria, or catheter blockage recorded in 21 men (16.2%) who received 3 days of silodosin, and in 63 men (48.5%) who received 7 days of silodosin (p ⩽ 0.001). CONCLUSION: Patients catheterized after AUR 2ry to BPH can spontaneously void following catheter removal if treated by silodosin, independent of the catheterization duration, while side effects have increased with prolonged catheterization.

Management of Leak by Intraoperative Megastent Insertion During Revisional Bariatric Metabolic Surgery: a Case Report.

We describe gastric tube continuity restoration (gastrogastrostomy) in a patient who underwent revisional laparoscopic one-anastomosis gastric bypass (OAGB) due to weight recurrence after laparoscopic sleeve gastrectomy (SG). The patient sought restoration to SG due to poor quality of life. A postoperative 11-mm leak at the site of the gastrogastrostomy, attributed to adhesions and edema from a marginal ulcer, complicated the procedure. As a result, laparoscopic exploration was performed, followed by insertion of a megastent. We hereby present video documentation of this case report as well as megastent insertion technique for the treatment of such complications.

Does mirabegron have a potential role as a medical expulsive therapy in the treatment of distal ureteral stones? A prospective randomized controlled study.

BACKGROUND: The existence of ß3 receptors in the bladder and ureter was documented in many studies on animals and humans, it was documented that relaxation of the lower ureteral segment is achieved by the stimulation of these receptors. Our aim was to assess the efficacy and safety of mirabegron as a medical expulsive therapy (MET) for distal ureteral stones in comparison with silodosin and placebo. METHODS: One hundred eighty patients with distal ureteral stone of 5-10 mm size were included in our study. They were divided into three groups, and each one consisted of 60 patients. Group I was given silodosin 8 mg, group II mirabegron 50 mg and group III placebo once daily. The treatment was prescribed for all the cases till stone expulsion or a maximum duration of 4 weeks. Primary outcome was the stone expulsion rate (SER). While secondary outcomes were stone expulsion time, side effects of the used drugs, hospital visits number for pain, and amount of analgesic taken. RESULTS: We found that the SER was significantly higher in silodosin than mirabegron and placebo groups (61%, 38.6%, and 36.7%, respectively) (p = 0.013). Also, the stone expulsion interval was significantly shorter in silodosin than mirabegron and control groups (p < 0.001). While hospital visits number for pain, and amount of analgesic taken were comparable. There was no difference between the studied medications in terms of the adverse effects except for retrograde ejaculation (silodosin = 63.3%, mirabegron = 0%, and placebo = 0%; p < 0.001). CONCLUSION: Mirabegron has no medical expulsive effect. While silodosin improves SER and stone expulsion time. However, retrograde ejaculation was its main side effect and occurred in 63.3% of the male patients. Therefore, more research is needed to discover a more tolerable MET.

Effect of pre-treatment of melatonin on superovulation response, circulatory hormones, and miRNAs in goats during environmental heat stress conditions.

Environmental heat stress has a deleterious impact on farm animal reproductive performance. The purpose of this study was to see how the addition of melatonin affected the efficacy of the superovulation regimen in goats in hot climatic conditions. Sixteen Shiba goats were synchronized and divided into two equal groups (n = 8, each): the melatonin group, which received a single S/C dose of melatonin, and a control group, treated with one ml of corn oil only. Ultrasonographic assessment of ovarian structures (Graafian follicles; GFs and corpus lutea; CLs) morphometry and hemodynamics were performed during the estrous phase of the superovulation (D0) and at day7 after ovulation (D7) of the superovulation regimen. The peripheral reproductive hormones were measured, and microRNAs were characterized. The mean diameter and the total-colored area of GFs during the D0 were significantly (P˂0.05) higher in the melatonin group (5.42 ± 0.11 mm and 1592.20 ± 45.26 pixels, respectively) compared to the control group (4.62 ± 0.12 mm and 1052.55 ± 29.47 pixels, respectively). Concentrations of LH and E2 increased significantly (P˂0.05) in the melatonin group (1.06 ± 0.06 ng/ml and 46.34 ± 2.77 pg/ml, respectively) compared to the control group (0.75 ± 0.12 ng/ml and 29.33 ± 1.89 pg/ml, respectively). At D7, the melatonin-received goats attained greater values in the mean count (6.75 ± 0.33, P˂0.005), diameters (6.08 ± 0.12 mm, P˂0.01), and total-colored area (17137.30 ± 128.53 pixels, P˂0.01) of detected CLs and progesterone concentrations (4.08 ± 0.24 ng/ml) compared to control goats (4.00 ± 0.28, 4.50 ± 0.19 mm, 11156.87 ± 117.90 pixels, and 2.90 ± 0.18 ng/ml respectively). MiRNA expression analysis was identified during both stages denoting several up and downregulated miRNA candidates among the studied groups. In conclusion, incorporating melatonin enhanced the efficiency of the superovulation regimen in goats under hot climatic conditions.

Effect of lactoferrin on enamel characteristics of primary and permanent teeth: an in-vitro study.

BACKGROUND: Lactoferrin, a glycoprotein naturally found in breast milk, is known for its bactericidal and antiviral properties, as well as its capacity to modulate the immune system; therefore, pediatricians routinely recommend it as dietary support. The objective of this study was to determine how lactoferrin oral suspension could affect the enamel surface characteristics of primary and permanent teeth. METHODS: This research was conducted on 40 unidentified extracted teeth, including primary and permanent teeth. Experimental teeth were free of cracks or enamel defects, as confirmed by careful examination using a dental operating microscope. The crowns were bisected into 80 specimens and assorted into two groups based on the type of dentition. Group DM included 40 specimens of second deciduous molars, while Group PM contained 40 samples of first premolars. Each of the DM and PM specimens was subsequently split based on the type of dispersion medium into two subgroups: a control subgroup (artificial saliva) and a test subgroup (lactoferrin suspension). The specimens were immersed in lactoferrin suspension for two minutes, then kept in artificial saliva for the rest of the 24 h for 30 successive days. This is a pioneering study about the effect of orally supplemented lactoferrin on teeth; therefore, we examined enamel hardness, ultra-morphology, and mineral contents. RESULTS: Our findings indicated a highly significant decrease (p < 0.01) in the microhardness of the lactoferrin subgroup in Group DM (second deciduous molars) and a significant reduction (p < 0.05) in the microhardness of the lactoferrin subgroup in Group PM (premolars). Calcium weight% was not statistically different (p > 0.05) compared with a significant decline (p < 0.05) in phosphorus weight% in lactoferrin subgroups in both DM and PM groups. The enamel surface of lactoferrin subgroups in both DM and PM groups was demineralized and porous, with the enamel of deciduous teeth being more affected by lactoferrin than permanent teeth. CONCLUSION: Lactoferrin suspension decreased the microhardness of enamel and both calcium and phosphorus weight percentages. Both dentitions exhibited erosions in the enamel surface, with primary teeth being more affected than the permanent teeth.

Staple Line Reinforcement Using SEAMGUARD® versus Suture Over Sewing During Laparoscopic Sleeve Gastrectomy for Super Morbidly Obese Patients: A Prospective Randomized Clinical Trial.

Itroduction: Although theoretically a simple procedure, laparoscopic sleeve gastrectomy (LSG) can be followed by life-threatening complications. Early postoperative complications include staple line bleeding and leakage. Staple line reinforcement (SLR) has been used to decrease these complications. There are various methods for reinforcement of staple line such as suture over sewing, placing omental flap, using buttressing material, and spraying fibrin glue along the staple line. However, it is controversial whether SLR reduces the rate of staple line complications or not. MATERIALS AND METHODS: A prospective randomized clinical trial included 200 super morbidly obese patients randomized into two groups: Group 1 with reinforcement of the staple line by SEAMGUARD® (Gore Medical, Newark, Delaware) and Group 2 with reinforcement of the staple line using suture over sewing. RESULTS: The mean operative time was significantly shorter in Group 1 than Group 2 (62.6 ± 14.5 vs. 84.7 ±15.8 min, p=0.02). Intraoperative blood loss was significantly lower in Group 1 than Group 2 (17.1± 19.1 vs. 56.8 ± 27.9ml, p=0.00). Staple line hematomas were significantly higher in Group 2. There was no difference in postoperative bleeding between the two groups. No leak was reported in both groups. The cost was higher in Group 1. CONCLUSION: Reinforcing the staple line in laparoscopic sleeve gastrectomy using suturing is equal to SEAMGUARD® in all aspects except shorter operative time and lower intraoperative blood loss with SEAMGUARD®.

Pathognomonic features of Pasteurella multocida isolates among various avian species in Sharkia Governorate, Egypt.

The present study aimed to isolate Pasteurella multocida (P. multocida) from pulmonary cases in several avian species and then investigate the histopathological features, antimicrobial resistance determinants, virulence characteristics, and risk factors analysis of the isolates in each species in correlation with epidemiological mapping of pasteurellosis in Sharkia Governorate, Egypt. The obtained data revealed a total occurrence of 9.4% (30/317) of P. multocida among the examined birds (chickens, ducks, quails, and turkeys). The incidence rate was influenced by avian species, climate, breed, age, clinical signs, and sample type. Antimicrobial susceptibility testing revealed that all isolates were sensitive to florfenicol and enrofloxacin, while 86.6 and 73.3% of the isolates displayed resistance to amoxicillin-clavulanic acid and erythromycin, respectively. All of the P. multocida isolates showed a multiple-drug resistant pattern with an average index of 0.43. Molecular characterization revealed that the oma87, sodA, and ptfA virulence genes were detected in the all examined P. multocida isolates. The ermX (erythromycin), blaROB-1 (ß-lactam), and mcr-1(colistin) resistance genes were present in 60, 46.6, and 40% of the isolates, respectively. Ducks and quails were the most virulent and harbored species of antimicrobial-resistant genes. These results were in parallel with postmortem and histopathological examinations which detected more severe interstitial pneumonia lesions in the trachea and lung, congestion, and cellular infiltration especially in ducks. Epidemiological mapping revealed that the Fakous district was the most susceptible to pasteurellosis infection. Thus, farmers are recommended to monitor their flocks for signs of respiratory disease, seek veterinary care promptly if any birds are sick, and avoid the random usage of antibiotics. In conclusion, this study presents a comprehensive picture of the risk factors in correlation to the pathognomonic characteristics of P. multocida infection in poultry sectors to help in developing more effective strategies for prevention and control.

An Analysis of the Literature and a Case Study on the Successful Surgical Treatment of a Crohn's Patient Using a Kono-S Anastomosis.

Background: Crohn's disease (CD) is a chronic inflammatory bowel disease affecting the gastrointestinal tract. Treatment involves immunosuppression, and surgical intervention is sometimes necessary for patients who do not respond to medical treatment. However, recurrence of the disease is a common complication after surgery. Aim: This case report focuses on a patient with CD who underwent ileocecal resection with Kono-S anastomosis, a surgical technique aimed at reducing recurrence rates. Case description: A 43-year-old male with a known history of CD for 13 years presented with recurring moderate-to-severe lower abdominal pain associated with belching, nausea, subjective fever, and sweats. The patient was on infliximab and azathioprine. Investigations confirmed irregular skip mural thickening of ileal loops with significant luminal narrowing along with stenotic fibrostrictures of the ileum, and mild bilateral sacroiliitis. The patient was treated surgically with an ileocecal resection and a Kono-S anastomosis operation. This case report highlights the advantages and disadvantages of the Kono-S anastomosis technique in treating patients with recurrent CD. Clinical significance: Kono-S anastomosis demonstrates a relative safety profile and carries several potential benefits. However, its wider adoption is limited due to insufficient familiarity among surgeons and the possibility of complications. Nevertheless, embracing Kono-S as the standard anastomosis method holds the promise of significant advantages for individuals with CD. Conclusion: This case report highlights the potential benefits of Kono-S anastomosis in reducing CD recurrence and provides valuable insights for further research and clinical practice. How to cite this article: Saeed M, Algahiny AT, Elmitwalli OSMMS, et al. An Analysis of the Literature and a Case Study on the Successful Surgical Treatment of a Crohn's Patient Using a Kono-S Anastomosis. Euroasian J Hepato-Gastroenterol 2023;13(1):36-39.

Does bacterial colonization influence ureteral stent-associated morbidity? A prospective study.

Objective: to evaluate the effect of bacterial colonization on ureteral stent-associated morbidity. Methods: This was a prospective study that took place between February 2019 and March 2022. We examined one hundred fifteen patients for ureteric stents application. On the same day of stent removal, the Arabic version of Ureteral Stent Symptoms Questionnaire (USSQ) was used to assess stent-associated morbidity. The stent-associated morbidity and the specificity and sensitivity of culture in the stent and midstream urine were recorded. Results: In 15.6% of the patients stent colonization was positive; E. coli was the most common isolated organism. There was no statistically significant difference between sex, age, irrigation fluid volume and duration of operation for stent colonization. However, stent indwelling time was significantly higher in patients with stents with positive cultures. In the colonized stents, there was a statistically significant difference with regards to the total score of USSQ, pain, urinary symptoms, work performance and additional problems of USSQ. Meanwhile, there was no statistically significant difference in the general health and sexual matter. Conclusions: stent colonization may be a contributing factor in stent-related morbidity. Stent bacterial colonization increases with the time of stent retention. Stent cultures are not needed as the same microorganisms are detected in urine cultures.

Design, synthesis and molecular docking study of new pyrimidine-based hydrazones with selective anti-proliferative activity against MCF-7 and MDA-MB-231 human breast cancer cell lines.

Efforts were directed on the design, synthesis and evaluation of the anticancer activity of some pyrimidine-based hydrazones against two breast cancer cell lines, MCF-7 and MDA-MB-231. Preliminary screening results revealed that some candidates scrutinized for their antiproliferative activities exhibited IC50 values of 0.87 µM-12.91 µM in MCF-7 and 1.75 µM-9.46 µM in MDA-MB-231 cells, indicating almost equal activities on both cell lines and better growth inhibition activities than those of the positive control 5-fluorouracil (5-FU) which displayed IC50 values of 17.02 µM and 11.73 µM respectively. Selectivity of the significantly active compounds was estimated against MCF-10A normal breast cells when compounds 7c, 8b, 9a and 10b exhibited superior activity for cancerous cells than for normal cells when compound 10b presented the best selectivity Index (SI) with respect to both MCF-7 and MDA-MB-231 cancer cells in comparison to the reference drug 5-FU. Mechanisms of their actions were explored by inspecting activation of caspase-9, annexin V staining and cell cycle analysis. It was noticed that compounds 7c, 8b, 8c 9a-c and 10b produced an increase in caspase-9 levels in MCF-7 treated cells with 10b inducing the highest elevation (27.13 ± 0.54 ng/mL) attaining 8.26-fold when compared to control MCF-7 which was higher than that of staurosporine (19.011 ± 0.40 ng/mL). The same compounds boosted caspase-9 levels in MDA-MB-231 treated cells when an increase in caspase-9 concentration reaching 20.40 ± 0.46 ng/mL (4.11-fold increase) was observed for compound 9a. We also investigated the role of these compounds for their increasing apoptosis ability against the 2 cell lines. Compounds 7c, 8b and 10b tested on MCF-7 cells displayed pre-G1 apoptosis and arrested cell cycle in particular at the S and G1 phases. Further clarification of their effects was made by modulating their related activities as inhibitors of ARO and EGFR enzymes when 8c and 9b showed 52.4% and 58.9% inhibition activity relative to letrozole respectively and 9b and 10b showed 36% and 39% inhibition activity of erlotinib. Also, the inhibition activity was verified by docking into the chosen enzymes.

Genetic Variations of ferroportin-1(FPN1-8CG), TMPRSS6 (rs855791) and Hemojuvelin (I222N and G320V) Among a Cohort of Egyptian ß-Thalassemia Major Patients.

Iron overload remains a major cause of morbidity and mortality among ß-thalassemia major (ß-TM) patients. Iron regulatory proteins and their genetic variants together with changes in hepcidin levels in thalassemic patients could affect the disease manifestations. This work aimed to study genetic variations of ferroportin-1 (FPN1-8CG), Transmembrane Serine Protease 6 (TMPRSS6 rs855791) and hemojuvelin (HJV I222N and G320V) genes within a cohort of 97 ß-TM Egyptian patients by Polymerase chain reaction Restriction Fragment Length Polymorphism (PCR-RFLP) in comparison to fifty normal control subjects. Among ß-TM patients; the CG variant of FPN1 was significantly higher, while the TT and TC variants of TMPRSS6 were significantly lower in comparison to controls. Liver Iron Concentration (LIC) was significantly higher among ß-TM patients harboring the FPN1 (GG) genotype and we found that FPN1gene mutation acts as independent predictor of MRI LIC (p = 0.011), Pulmonary artery pressure (PAP) was significantly higher in patients harboring the mutant FPN1 (GG and CG) genotypes (p value 0.04). ß-TM patients having the HJV I222N (AA) genotype were having significantly higher cardiac iron overload (p value = 0.026). The studied genetic variants of iron regulatory proteins could alter the manifestations of iron overload thus resulting in different clinical phenotypes of thalassemic patients, these findings need to be confirmed by larger cohorts of patients with longer follow-up periods. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01580-8.