The Use of Ultrasound for Detecting the Association Between Endothelial Dysfunction and lp13.3 Genomic Region rs646776 Polymorphism in Patients With Rheumatoid Arthritis From the Suez Canal Region.

Background  Rheumatoid arthritis (RA) is an autoimmune disease associated with endothelial dysfunction (ED) and vascular morbidity. The study aimed to use ultrasound to assess the relationships of lp13.3 genomic region-rs646776 polymorphism with ED and subclinical cardiovascular disease (CVD) in patients with RA from the Suez Canal region in Egypt. Results This case-control study included 66 patients with RA and 66 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism showed that the genotype frequencies for lp13.3 genomic region-rs646776 polymorphism in the RA group were 62.1% (n = 41), 34.8% (n = 23), and 3% (n = 2) for the AA, AG, and GG genotypes, respectively. The prevalence of the G allele was higher in the RA group than in the control group (20.5% and 7.6%, respectively; p < 0.01). Furthermore, ED was more prevalent in G allele carriers than in A allele carriers, suggesting a greater probability of ED and CVD in patients with RA with the GG genotype than in those with other genotypes. Conclusions This study indicated the validity of ultrasound in detecting the association between lp13.3 genomic region-rs646776 polymorphism and ED in Egyptian patients with RA. These findings could help identify high-risk patients with RA who may benefit from active treatment to help prevent CVD.

Radical reform of the undergraduate medical education program in a developing country: the Egyptian experience.

Medical educators are in a continuous quest to close the gap between the needs of medical practice and the rising expectations of the communities in their countries. During the past two decades, competency-based medical education has been evolving as an appealing strategy to close this gap. In 2017, the Egyptian medical education authorities mandated all medical schools to change their curricula to comply with revised national academic reference standards, which changed from outcome-based to competency-based. In parallel, they also changed the timeline of all medical programs for six years of studentship and one-year internship to five years and two years, respectively. This substantial reform involved the assessment of the existing situation, an awareness campaign for the proposed changes and an extensive national faculty development program. Monitoring the implementation of this substantial reform was performed through surveys, field visits and meetings with students, teaching staff and program directors. In addition to the expected challenges, the COVID-19-associated restrictions presented a significant further challenge during the implementation of this reform. This article presents the rationale for and steps of this reform, the challenges faced and how they were addressed.

Effect of Dimethylacetamide Concentration on Motility, Quality, Antioxidant Biomarkers, Anti-Freeze Gene Expression, and Fertilizing Ability of Frozen/Thawed Rooster Sperm.

Sperm cryopreservation is of great importance for the poultry industry but still needs to be optimized. The high susceptibility of poultry sperm to cryodamage leads to low fertility rates after cryopreservation. Therefore, the present study aimed at evaluating the effect of including a cryoprotectant, dimethylacetamide (DMA), in the chicken semen freezing extenders at a final concentration of 3%, 6%, or 9% on the post-thawed sperm motility, quality, antioxidant biomarkers, anti-freeze gene expression, and fertilizing ability. Results showed that the total motile sperm, progressivity, and viability were quadratically increased (p < 0.05) in the 6% DMA group. The antioxidant enzyme activity and lipid peroxidation were negatively (p < 0.05) affected by the increase in DMA concentration. Furthermore, some anti-freeze-associated genes such as heat shock protein 70 (HSP70) and ras homolog family member A (RHOA) were linearly and quadratically down-regulated (p < 0.05) with the high concentration of DMA. Finally, the fertility and hatchability rates did not indicate statistical differences between DMA groups. It can be concluded that using the low concentration of 3−6% DMA in the freezing semen extender is preferable to obtain acceptable results in the post-thawed sperm quality and fertility.

Developing, Validating, and Implementing a Tool for Measuring the Readiness of Medical Teachers for Online Teaching Post-COVID-19: A Multicenter Study.

BACKGROUND: While online education is by no means a new concept, it was recently thrust into the spotlight after school campuses all over the world were forced to close because of the COVID-19 pandemic. The sudden need to shift revealed emerging challenges to online teaching, both logistic and personal. One important challenge is the ability to assess the readiness of educators for online teaching, so that appropriate and specific feedback/training can be offered to those in need. This study aims at developing, validating, and implementing a tool to measure the teachers' readiness for online teaching in three medical schools from three different countries. METHODS: This was a multi-center, cross-sectional study that involved developing a survey through review of literature and previous studies, item development and revision, and pilot testing. The survey was then distributed electronically to a convenient sample of 217 teaching faculty members of different academic ranks from three medical schools in Egypt, Saudi Arabia, and Bahrain. Exploratory factor analysis and reliability study were performed. Descriptive statistics were applied, and the statistical significance level was set at 0.05. RESULTS: Factor analysis produced the following five factors: "Online Teaching and Course Design Skills", "Digital Communication", "Basic Computer Skills", "Advanced Computer Skills" and "Using Learning Management Systems". The tool showed high reliability (alpha = 0.94). Survey results showed highest mean scores for Basic Computer Skills with lower scores for Online Teaching and Course Design Skills and Using Learning Management Systems. ANOVA revealed statistically significant differences between the three studied schools regarding Digital Communication (F=5.13; p=0.007) and Basic Computer Skills (F=4.47; p=0.012) factors. CONCLUSION: The tool proved to be reliable and valid. Results indicated an overall acceptable readiness in the three involved schools, with a need for improvement in "Online Teaching and Course Design" and Using Learning Management Systems.

Best-fitted regression models for profitability of two egg-type commercial pullets.

This study is focused on describing the most important factors which have a great influence on profitability of egg production of two commercial layer flocks under Egyptian conditions, LSL white and brown. The data for each flock has been collected from seven governorates including the Delta and Upper Egypt zones over the period 2005-2012. General linear procedure was generated to get both least square means and separation of means. Application of stepwise regression was carried to predict the most important factors that affect egg production profitability in US dollar. White egg layers had significantly higher net profit per hen than the brown egg type, being as 12.2 vs. 12.1 cents for the white and brown type egg layers, respectively. Closed houses and battery systems were the preferred systems for the white-egg genotype where pullets achieved significantly higher egg income over feed coast by 15.9 and 14.9 cents for closed and battery system, respectively compared to 10.9 and 11.5 cents for the LSL brown one, respectively. Open houses and floor systems were profitable for brown-egg genotype by recording a significantly higher profitability as 13.3 and 12.7 cents, respectively copmared to 8.7 and 9.7 cents for the white-egg genotype.Both white and brown-egg types had recorded significantly higher net profitability under delta zone rather than upper Egypt by 2.2 cents and 2.1 cents, respectively. Application of the stepwise regression procedure was to predict the net profit (Y) from three independent variables, egg weight (X1), egg price (X2), and hen housed egg production (X3). Generally, LSL white layers, egg price (X2) had the highest share in profitability by 44.24% compared to hen housed egg production (X3) that share 29.98%. For LSL brown layers, egg weight (X1) is the most important factor accounting for the profitability in cents. Its relative importance to the profitability is 57.24% followed by egg price (X2) 21.25%. Hen housed egg production (X3) had very little share 0.14%.

Application of Modified Team-Based Learning Approach for Enhancing Undergraduate Medical Educational Seminars.

BACKGROUND: Team-Based Learning (TBL) is an instructor-led, structured form of cooperative learning that promotes self-directed learning and teamwork while equipping students with the problem-solving and collaborative skills needed to meet the demands of their future professions. This study examines the impact of applying a modified TBL approach to enhance educational seminars in a PBL-adopted curriculum. METHODS: A total of 300 students participated in the study. Students' Individual Readiness Assurance Test (IRAT) mean scores were compared with mean scores of the same students' Group Readiness Assurance Test (GRAT). Student satisfaction was determined on a scale with 6 options in response to 13 questions to compare different aspects of traditional and TBL educational seminars. RESULTS: Comparison between IRAT and GRAT scores showed consistently higher GRAT scores. The majority of students expressed their overall satisfaction in favor of the TBL seminar, especially regarding seminar organization, knowledge acquisition, and team work skills. CONCLUSION: Application of the TBL approach in educational seminars increased second- and third-year medical students' engagement and satisfaction and improved their test performance.

Non-invasive Oxygen-Ozone therapy in treating digital ulcers of patients with systemic sclerosis.

BACKGROUND: Digital ulcers (DUs) in Systemic sclerosis (SSc) result from recurrent Raynaud's phenomenon (RP) and microtrauma with high impact on quality of life. Medical use of ozone (triatomic oxygen) was initiated in the 19th century. Ozone has multiple therapeutic effects in wound healing due to the property of releasing nascent oxygen, which has been shown to stimulate antioxidant enzymes. We aimed to assess the effects of ozone therapy on the healing of scleroderma DUs and determine levels of expression of vascular endothelial growth factor (VEGF), and endothelin-1 type A receptor (ETAR) autoantibodies in the wounds after treatment. SUBJECTS AND METHODS: Fifty SSc female patients with DUs, were randomized into ozone group (I) (n=25) treated by calcium channel blockers plus oxygen-ozone treatment and control group (II) (n=25) treated by calcium channel blockers only. Ozone group received noninvasive oxygen-ozone treatments for 30 minutes per day for 20 days using the ozone generator device. Therapeutic effects were graded into 4 levels according to Zhang and other researchers. The wounds sizes were measured at baseline and day 20, respectively. Expressions of VEGF and ETAR autoantibodies proteins were determined by immune-histochemical examination. RESULTS: Demographics and clinical characteristics of the 2 groups showed no significant differences. At day 20, the effective healing rate was significantly higher in group (I) than in group (II), where it represented 96% (24/25) in ozone group versus 44% (11/25) in control group, and (𝑃 = 0.007). After treatment, the wound sizes in both groups were significantly smaller than before treatment. In group (I), the wound size reduction was significantly more than in group (II) (0.75 ± 0.30 versus 2.44 ± 0.80 mm), (𝑃 = 0.00). At day 20, VEGF was significantly higher in ozone group (I), than in control group (II), (83.96±9.68) versus (67.92±6.55), (𝑃 = 0.00) while, ETAR was significantly lower in ozone group (I), than in control group (II), (3.14±1.12 versus 4.59±1.24), (𝑃 = 0.00). CONCLUSION: Ozone therapy may be beneficial tool in the treatment of DUs in SSc patients, where it promotes the wound healing through a potential induction of VEGF and down-regulation of ETAR at sites of the ulcers.

CD4+CD25-Foxp3+ T cells as a marker of disease activity and organ damage in systemic lupus erythematosus patients.

INTRODUCTION: T regulatory cells (Treg) play an important role in the maintenance of immune cell homeostasis, as it has been reported that CD4+CD25+ T cells suppress the auto-reactive responses in autoimmune diseases such as systemic lupus erythematosus (SLE). The clinical significance of the recently identified population of CD4+CD25-Foxp3+ T cells and whether they are associated with particular organ involvement is still not clear. So, the aim of our study was to evaluate the presence of CD4+CD25-Foxp3+ cells in SLE patients in comparison to healthy controls and to determine whether their frequency is associated with disease activity and particular clinical manifestations in these SLE patients. MATERIAL AND METHODS: The frequency of CD4+CD25-Foxp3+ T cells was analyzed in 56 female SLE patients and 30 healthy female control subjects, using flow cytometry (FACS). CD4+CD25-Foxp3+ T cells were correlated with clinical and laboratory data and the SLE Disease Activity Index (SLEDAI). RESULTS: The level of CD4+CD25-Foxp3+ T cells was significantly increased in SLE patients (15.57 ±4.32%) as compared with the control group (2.46 ±0.65%). A significant correlation was observed for the percentage of CD4+CD25-Foxp3+ T cells with clinical disease activity scores and disease duration (r = 0.6, p < 0.001; r = 0.3, p = 0.02 respectively). It was also positively correlated with renal impairment and hematological involvement. CONCLUSIONS: Systemic lupus erythematosus patients exhibited an altered level of their CD4+Foxp3+ T cells with increased levels of CD4+CD25-Foxp3+ cells.

CD5+ B lymphocytes in systemic lupus erythematosus patients: relation to disease activity.

B cells are essential players in the pathogenic mechanisms of systemic lupus erythematosus (SLE). Although CD5+ B cells have been considered to play a paradoxical role in preventing, rather than inducing autoimmunity, there is no consensus agreement about the proportions of CD5+ B cells population in SLE patients. So, the aim of the present study was to assess blood concentration of CD5+ B cells in patients with SLE and to evaluate their relationship with disease activity and organ damage. We recruited 100 SLE patients and 100 healthy control subjects. Based on SLE disease activity index (SLEDAI), patients were divided into two groups: active SLE (n = 50) and inactive SLE (n = 50). SLE was active when SLEDAI was ≥ 4. The expression of CD5+ B cells was evaluated using flow cytometry to measure the proportions and absolute numbers of the cells. The proportions of CD5+ B cells of total lymphocytes were significantly lower in SLE patients versus controls (4.1 ± 3.9 vs 10.8 ± 5.2%, P = <0.001). CD5+ B cells were significantly decreased in active SLE patients (3.1 ± 2.7%) in comparison to inactive patients (5.2 ± 3.7%) (P = 0.013). CD5+ B cells correlated positively with C3 (r = 0.328, P = 0.020) and C4 (r = 0.355, P = 0.011). CD5+ B cells were significantly decreased in SLE patients compared to healthy controls and they were significantly decreased in active SLE patients in comparison to inactive ones.

Serum Interleukin-37: a new player in Lupus Nephritis?

INTRODUCTION: Interleukin-37 (IL-37) has been proved to be a fundamental natural suppressor of innate immunity and inflammatory responses in autoimmune diseases such as systemic lupus erythematous (SLE). The purpose of this study was to assess serum IL-37 level in SLE patients and its correlation with disease activity and clinical and laboratory manifestations of SLE patients. PATIENTS/METHODS: The serum level of IL-37 was assessed and analyzed in 100 SLE patients and 50 healthy controls by using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory manifestations and disease activity using SLE Disease Activity Index (SLEDAI) were also assessed. RESULTS: IL-37 serum level was significantly higher among SLE patients than controls. It has statistically significant correlation with disease activity, renal and mucocutaneous involvement in SLE patients. CONCLUSION: IL-37 level is elevated in SLE patients in comparison to healthy controls and is correlated to high disease activity, mucocutaneous and renal involvement.

Characterization of Copy Number Variation's Potential Role in Marek's Disease.

Marek's Disease (MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. Chicken Lines 63 and 72, as well as their recombinant congenic strains (RCS) with varied susceptibility to MD, are ideal models to study the complex mechanisms of genetic resistance to MD. In this study, we investigated copy number variation (CNV) in these inbred chicken lines using the Affymetrix Axiom HD 600 K SNP genotyping array. We detected 393 CNV segments across all ten chicken lines, of which 12 CNVs were specifically identified in Line 72. We then assessed genetic structure based on CNV and observed markedly different patterns. Finally, we validated two deletion events in Line 72 and correlated them with genes expression using qPCR and RNA-seq, respectively. Our combined results indicated that these two CNV deletions were likely to contribute to MD susceptibility.

Vitamin D receptor Fok1 & Bsm 1 Gene Polymorphisms in Systemic Lupus Erythematosus and Osteoarthritis: Autoimmune Inflammatory versus Degenerative Model.

Vitamin D deficiency has been described in SLE and OA. Low vitamin D level is prevalent in Egyptian SLE patients while controversial studies are present regarding its level in OA patients in Egypt. We investigated whether vitamin D receptor (VDR) genes Bsm1 and Fok1 polymorphisms could be used as genetic markers for the susceptibility to SLE and /or OA in a sample of Egyptian population. The study was carried out on 100 SLE patients, 100 osteoarthritic patients and 100 normal controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Our results showed a statistically significant difference in Fok1 genotype distribution between SLE and OA patients (p=0.001). In SLE group, the "f" allele was significantly over-represented where 30% had "f" allele compared to 0% in OA (P = 0.03). Fok1 ff genotypes showed a significant association with disease activity in SLE patients. In addition, the fb haplotype frequency was significantly higher in SLE patients than controls (P=0.01). In conclusion Fok1 genotype and f allelic frequencies may be susceptible risk factors for SLE rather than OA in Egyptian patients.

Assessment of left atrial mechanical functions and atrial electromechanical delay in Juvenile idiopathic arthritis by tissue Doppler echocardiography.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a systemic chronic inflammatory disease. Studies using tissue Doppler imaging (TDI) for the evaluation of cardiac functions of children with JIA are limited. Thus, this study was conducted to evaluate Left ventricular function, left atrial mechanical functions and atrial electromechanical delay in JIA. METHODS: This study was carried out as a across sectional study. A total of 34 patients with active JIA and 34 controls were included. Atrial electromechanical delay and left atrial (LA) mechanical functions in addition to systolic and diastolic left ventricular (LV) functions were measured by using conventional echocardiography and TDI. Assessment of disease activity was done using Juvenile arthritis disease activity score (JADAS-27). RESULTS: JIA patients had abnormal atrial electromechanical coupling as established from prolonged lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), inter-atrial and intra-atrial electromechanical delays compared with healthy controls. Left ventricular filling abnormalities were found characterized by a reduced E/A ratio (1.07 ± 0.56 vs. 1.48 ± 0.16, p = 0.01). E/Em was significantly higher in patients with JIA (7.58 ± 1.79 vs. 4.74 ± 1.45, p = 0.003) denoting impaired diastolic function. Left atrial mechanical functions assessment showed significantly decreased LA passive emptying fraction, increased LA active emptying fraction and LA total emptying volume in JIA patients (p = 0.01, p = 0.01, p = 0.03 respectively). CONCLUSION: Atrial electromechanical coupling intervals, and LA mechanical functions were impaired which can be considered as an early form of subclinical cardiac involvement in JIA patients. Significant diastolic functional abnormalities exist in JIA.

Testis-enriched heat shock protein A2 (HSPA2): Adaptive advantages of the birds with internal testes over the mammals with testicular descent.

The molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, plays an important role in spermatogenesis and male fertility. Although HSPA2 is evolutionarily highly conserved across the metazoan lineages, the observation of striking differences in temperature-sensitive expressions, testicular physiology, spermatogenesis, as well as its role in male fertility indicates that avian and mammalian HSPA2 may exhibit distinct evolutionary trajectory. The present study reports that while mammalian HSPA2 is constrained by intense purifying selection, avian HSPA2 has been subjected to positive selection. The majority of the positively selected amino acid residues fall on the α-helix and ß-sheets of the peptide-binding domain located at the carboxyl-terminal region of the avian HSPA2. The detection of positively selected sites at the helix and ß-sheets, which are less tolerant to molecular adaptation, indicates an important functional consequence and contribution to the structural and functional diversification of the avian HSPA2. Collectively, avian HSPA2 may have an adaptive advantage over the mammals in response to heat stress, and therefore, mammals with testicular descent may be at a greater risk in the event of scrotal temperature rise.

Is our medical school socially accountable? The case of Faculty of Medicine, Suez Canal University.

BACKGROUND: Faculty of Medicine, Suez Canal University (FOM/SCU) was established as community oriented school with innovative educational strategies. Social accountability represents the commitment of the medical school towards the community it serves. AIMS: To assess FOM/SCU compliance to social accountability using the "Conceptualization, Production, Usability" (CPU) model. METHODS: FOM/SCU's practice was reviewed against CPU model parameters. CPU consists of three domains, 11 sections and 31 parameters. Data were collected through unstructured interviews with the main stakeholders and documents review since 2005 to 2013. RESULTS: FOM/SCU shows general compliance to the three domains of the CPU. Very good compliance was shown to the "P" domain of the model through FOM/SCU's innovative educational system, students and faculty members. More work is needed on the "C" and "U" domains. CONCLUSION: FOM/SCU complies with many parameters of the CPU model; however, more work should be accomplished to comply with some items in the C and U domains so that FOM/SCU can be recognized as a proactive socially accountable school.

Teaching evidence-based medicine using a problem-oriented approach.

BACKGROUND: Faculty of Medicine, Suez Canal University is adopting an innovative curriculum. Evidence-based medicine (EBM) has been integrated into problem based learning (PBL) sessions as a responsive innovative paradigm for the practice and teaching of clinical medicine. AIMS: To integrate EBM in the problem based sessions of the sixth-year students, and to assess students' and tutor satisfaction with this change. METHODS: EBM training was conducted for sixth-year students (196) including four theoretical, and eight practical sessions. Sixteen EBM educational scenarios (problems) were formulated, according to sixth-year curriculum. Each problem was discussed in two sessions through steps of EBM, namely: formulating PICO questions, searching for and appraising evidence, applying the evidence to the clinical scenario and analysing the practice. Students and tutors satisfaction were evaluated using a 3-point ratings questionnaire. RESULTS: The majority of students and faculty expressed their satisfaction about integrating EBM with PBL and agreed that the problems were more stimulating. However, 33.6% of students indicated that available time was insufficient for searching literatures. CONCLUSION: Integrating EBM into PBL sessions tends to be more interesting and stimulating than traditional PBL sessions for final year students and helps them to practice and implement EBM in clinical context.

Human umbilical cord mesenchymal stem cells as treatment of adjuvant rheumatoid arthritis in a rat model.

AIM: To investigate the effect of human umbilical cord stem cells, both mesenchymal and hematopoietic (CD34+), in the treatment of arthritis. METHODS: Mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells (HSC) were isolated from human umbilical cord blood obtained from the umbilical cord of healthy pregnant donors undergoing full-term normal vaginal delivery. MSC, HSC, methotrexate (MTX) and sterile saline were injected intra-articularly into the rat hindpaw with complete freunds adjuvant (CFA) induced arthritis after the onset of disease (day 34), when arthritis had become well established (arthritis score ≥ 2). Arthritic indices were evaluated and the levels of interleukin (IL)-1, tumor necrosis factor (TNF)-α and interferon (IFN)-γ and anti-inflammatory cytokine IL-10 in serum were determined using enzyme-linked immunosorbent assay. Animals of all groups were sacrificed 34 d after beginning treatment, except positive control (PC) which was sacrificed at 10, 21 and 34 d for microscopic observation of disease progression. We used hematoxylin, eosin and Masson's trichrome stains for histopathological examination of cartilage and synovium. RESULTS: The mean arthritis scores were similar in all groups at 12 and 34 d post immunization, with no statistical significant difference. Upon the injection of stem cells (hematopoietic and mesenchymal), the overall arthritis signs were significantly improved around 21 d after receiving the injection and totally disappeared at day 34 post treatment in MSC group. Mean hindpaw diameter (mm) in the MSC rats was about half that of the PC and MTX groups (P = 0.007 and P = 0.021, respectively) and 0.6 mm less than the HSC group (P = 0.047), as indicated by paw swelling. Associated with these findings, serum levels of TNF-α, IFN-γ and IL-1 decreased significantly in HSC and MSC groups compared to PC and MTX groups (P < 0.05), while the expression of IL-10 was increased. Histopathological examination with H and E stain revealed that the MTX treated group showed significant reduction of leucocytic infiltrate and hypertrophy of the synovial tissue with moderate obliteration of the joint cavity. Stem cells treated groups (both hematopoietic CD34+ and mesenchymal), showed significant reduction in leucocytic infiltrate and hypertrophy of the synovial tissue with mild obliteration of the joint cavity. With Masson's trichrome, stain sections from the PC group showed evidence of vascular edema of almost all vessels within the synovium in nearly all arthritic rats. Vacuoles were also visible in the outer vessel wall. The vessel became hemorrhagic and finally necrotic. In addition, there was extensive fibrosis completely obliterating the joint cavity. The mean color area percentage of collagen in this group was 0.324 ± 0.096, which was significantly increased when compared to the negative control group. The mean color area percentage of collagen in hematopoietic CD34+ and mesenchymal groups was 0.176 ± 0.0137 and 0.174 ± 0.0197 respectively, which showed a marked decrement compared to the PC group, denoting a mild increase in synovial tissue collagen fibers. CONCLUSION: MSC enhance the efficacy of CFA-induced arthritis treatment, most likely through the modulation of the expression of cytokines and amelioration of pathological changes in joints.