The Effect of Clopidogrel and Ticagrelor on Human Adipose Mesenchymal Stem Cell Osteogenic Differentiation Potential: In Vitro Comparative Study.

Ticagrelor (TICA) and clopidogrel (CLP) are extensively used antiplatelet drugs that act by antagonizing the P2Y12 receptors that are found on platelets in addition to bone cells. Aim. The purpose of this study was to investigate the effect of clopidogrel and ticagrelor on stem cells osteogenic differentiation in vitro. Methods. Human adipose-derived mesenchymal stem cells (hAd-MSCs) were divided into (1) control group, (2) osteogenic group (osteo group), (3) clopidogrel group (CLP group), and (4) ticagrelor group (TICA group). The osteogenic differentiation potential was determined by mineralization nodule formation using Alizarin Red S staining, measuring ALP enzyme activity by alkaline phosphatase assay. Quantitative determination for osteogenic markers included osteocalcin (OC); runt-related transcription factor 2 (RUNX2) performed using western blot; osteoprotegerin (OPG) using enzyme-linked immunosorbent assay (ELISA) and inflammatory markers; and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) measured using real-time polymerase chain reaction quantitative (RT-PCR) and ELISA. Results. In comparison to all study groups, the TICA group showed significant increase in the mineralized extracellular matrix, ALP enzyme activity, and bone markers expression as RUNX2 (P < 0.0001), OC, and OPG (P < 0.05). The expression of IL-6 and TNF-α was determined by RT-qPCR and ELISA techniques. TICA and CLP significantly decreased both markers compared to the control group. The TICA group showed statistically significant lower levels of both markers (P < 0.0001) than the CLP and control groups via the ELISA technique. Conclusion. TICA may possess a positive effect on hAd-MSCs osteogenic differentiation compared to CLP.

Thrombocytopenia and disease outcomes in a cohort of patients with systemic lupus erythematosus. A post hoc analysis of the COMOSLE-EGYPT study.

BACKGROUND: Thrombocytopenia ranges from 20% to 40% in patients with systemic lupus erythematosus (SLE). It is usually associated with severe disease manifestations and worse disease outcomes. AIM OF THE STUDY: To identify the frequency of thrombocytopenia in a cohort of Egyptian patients with SLE and to examine the relationship of thrombocytopenia with various disease manifestations and disease outcomes. METHODS: Data on 902 SLE patients were collected, including demographics, clinical, laboratory, immunological findings, and medications. SLE Disease Activity Index (SLEDAI) at baseline, last visit, and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC) were calculated. A comparison was done between patients with thrombocytopenia (group I) and patients without (group II) regarding different disease parameters. Regression analysis was done to examine if thrombocytopenia is a predictor of worse disease outcomes. RESULTS: Thrombocytopenia was found in 33% of our cohort. Longer disease duration was observed in group I compared to group II (p value = .01). As regards clinical manifestations, significantly higher frequencies of constitutional manifestations, anemia, arterial thrombosis, pulmonary hypertension, cardiac manifestations, neurological manifestations, gastrointestinal tract (GIT), and hepatic manifestations were detected in group I compared to group II. The disease damage index was detected to be significantly higher in group I as compared to group II (p value < .001). Mortality was higher in group I (p value < .001). Although it was found that antiphospholipid antibodies (APL) were associated with thrombocytopenia and their presence resulted in higher damage (p value: .001), the presence of thrombocytopenia even in patients with negative APL antibodies was associated with higher damage and mortality. Apart from thrombocytopenia, the male gender was also found to be an independent risk factor for mortality. CONCLUSION: Thrombocytopenia was associated with more organ damage and higher mortality in SLE patients with or without APL antibodies. SLE patients with thrombocytopenia have a 3.4 times higher risk of mortality than patients without thrombocytopenia. Apart from thrombocytopenia, the male gender was also found to be an independent risk factor for mortality.

Microglia are not protective against cryptococcal meningitis.

Microglia provide protection against a range of brain infections including bacteria, viruses and parasites, but how these glial cells respond to fungal brain infections is poorly understood. We investigated the role of microglia in the context of cryptococcal meningitis, the most common cause of fungal meningitis in humans. Using a series of transgenic- and chemical-based microglia depletion methods we found that, contrary to their protective role during other infections, loss of microglia did not affect control of Cryptococcus neoformans brain infection which was replicated with several fungal strains. At early time points post-infection, we found that microglia depletion lowered fungal brain burdens, which was related to intracellular residence of C. neoformans within microglia. Further examination of extracellular and intracellular fungal populations revealed that C. neoformans residing in microglia were protected from copper starvation, whereas extracellular yeast upregulated copper transporter CTR4. However, the degree of copper starvation did not equate to fungal survival or abundance of metals within different intracellular niches. Taken together, these data show how tissue-resident myeloid cells may influence fungal phenotype in the brain but do not provide protection against this infection, and instead may act as an early infection reservoir.

Flexosomes as a promising nanoplatform for enhancing tolnaftate ocular delivery: Formulation, in vitro characterization, statistical optimization, ex vivo and microbial in vivo studies.

The eye is a complex organ with a unique physiology and anatomy. Using novel nanosystems is expected to enhance ocular drug permeation and retention. Hence, this work aimed to study the potential of flexosomes as an ocular delivery system to enhance the corneal permeation and antifungal activity of Tolnaftate (TOL). Different flexosomes formulae were formulated using ethanol injection method, employing a 31.22 full factorial design. The studied formulation variables were: X1: amount of stearyl amine, X2: hydration volume and X3: type of edge activator. Encapsulation efficiency, particle size and zeta potential were selected as dependent variables. FX5 was selected as the optimal TOL flexosomes and showed encapsulation efficiency of 66.08 ± 11.38%, particle size of 154.99 ± 29.11 nm and zeta potential of 42.95 ± 0.64 mV. FX5 was subjected to further ex vivo and in vivo studies which showed that TOL flux was significantly increased through FX5 compared to TOL suspension. Draize test and histopatholoigal tests assured that FX5 is safe to be used for eye.. The in vivo fungal susceptibility testing using Aspergillus niger demonstrated the superior and more durable antifungal activity of FX5 than TOL suspension. Hence, FX5 can be considered as promising nanocarrier for safe and efficient ocular TOL delivery.

Ultra-deformable free fatty acid based nano-carriers for topical delivery of Luteolin: A potential paradigm for management of Methicillin-Resistant Staphylococcus aureus skin infections.

The incidences of antimicrobial resistance in particular, Methicillin-Resistant Staphylococcus aureus (MRSA) have increased during the last two decades. However, conventional dosage forms are unable to evade the barrier effect of the stratum corneum to permit deep penetration of the skin to resolve deep skin infections. There is, therefore, an urgent need for an advanced drug delivery system. Thus the study reported herein was aimed to fabricate a novasome-loaded luteolin (LUT) to improve its topical delivery and to enhance its antibacterial activity. The system was investigated for the impact of the type of surfactant, stearic acid concentration (g %), cholesterol amount (mg) and Brij 52 amount (mg) on the percent entrapment efficiency, particle size, poly-dispersity index and zeta potential. Statistical optimization of these factors was conducted using the Design-Expert® software. The optimum formulation was further in-vitro characterized by release study, differential scanning calorimetry, transmission electron microscope, x-ray diffraction and antibacterial activity. Formulation F2 composed of Span 60, 0.4 g % of stearic acid, 100 mg cholesterol and 30 mg Brij 52 was selected as the optimum formula based on the highest desirability value (0.634). F2 demonstrated enhanced antimicrobial activity with lower minimum inhibitory concentrations against a panel of MRSA clinical isolates when compared to LUT dispersion. Furthermore, the F2 formula exhibited higher anti-virulence activity by effectively inhibiting biofilm formation and suppressing α-hemolysin activity in MRSA isolates. It also demonstrated improved biosafety based on cytotoxicity assessment on human skin fibroblasts (HSF). Finally, when assessed in an in vivo skin infection mouse model, the F2 formula and commercially available fusidic acid preparation significantly reduced the microbial load of infected skin lesions compared to both the negative control and LUT dispersion-treated groups. Based on the aforementioned results, the validity of novasomes as a nano-carrier to boost in vitro and in vivo anti-MRSA activity of LUT could be affirmed.

miRNAs as potential game-changers in renal cell carcinoma: Future clinical and medicinal uses.

Renal cell carcinoma (RCC) has the highest mortality rate of all genitourinary cancers, and its prevalence has grown over time. While RCC can be surgically treated and recurrence is only probable in a tiny proportion of patients, early diagnosis is crucial. Mutations in a large number of oncogenes and tumor suppressor genes contribute to pathway dysregulation in RCC. MicroRNAs (miRNAs) have considerable promise as biomarkers for detecting cancer due to their special combination of properties. Several miRNAs have been proposed as a diagnostic or monitoring tool for RCC based on their presence in the blood or urine. Moreover, the expression profile of particular miRNAs has been associated with the response to chemotherapy, immunotherapy, or targeted therapeutic options like sunitinib. The goal of this review is to go over the development, spread, and evolution of RCC. Also, we emphasize the outcomes of studies that examined the use of miRNAs in RCC patients as biomarkers, therapeutic targets, or modulators of responsiveness to treatment modalities.

COVID-19 outcomes in patients with and without autoimmune rheumatic diseases: A multicenter comparative study.

BACKGROUND AND OBJECTIVE: People with rheumatic diseases are particularly concerned with the coronavirus disease 2019 (COVID-19) pandemic. Our work aimed to study the impact of pre-existing autoimmune rheumatic disease (AIRD) and its immunosuppressive drugs on COVID-19 severity and outcome. PATIENTS AND METHODS: This is a multicenter case-control study performed between September 2020 and February 2021 on 130 adults with COVID-19, including 66 patients with AIRD and 64 without AIRD, who served as a control group. RESULTS: Regarding COVID-19 clinical manifestations; diarrhea, fatigue, and headache were found with significantly higher frequency in the AIRD group while a higher frequency of cough was found in the control group. Comparing COVID-19 complications, only septic shock was significantly higher in the AIRD group (P = 0.013). Both groups were treated with similar COVID-19 drugs except for tocilizumab and anticoagulants, which were statistically significantly more frequently used in the control group (P < 0.001 for both). No statistically significant difference was found between the groups in the outcome or severity of COVID-19. There was no impact of previous immunosuppressive drugs before COVID-19 on the severity of the disease except for a longer duration of recovery in patients on steroids (P < 0.001). Patients with hypertension had severe COVID-19 compared with those without (odds ratio 2.8, 95% confidence interval 1.2-6.9; P = 0.020). CONCLUSION: AIRD may not affect COVID-19 severity and outcome. Similarly, immunosuppressive medications had no effect; except that patients on systemic steroids had longer duration for recovery. Comorbid conditions, such as hypertension, may be associated with more severe COVID-19 disease course.

Pregnancy outcomes among Egyptian women with systemic lupus erythematosus: A prospective cohort study.

Pregnant patients with systemic lupus erythematosus (SLE) represent a high-risk group. The aim of this study is to describe the pregnancy outcomes among SLE patients who were followed prospectively at a conjoint high-risk pregnancy/rheumatology clinic from 2007 to 2021 and to identify predictors of adverse maternal and fetal outcomes. This study included 201 singleton pregnancies of 123 women with SLE. Their mean age was 27.16 ± 4.80 years, and their mean disease duration was 7.35 ± 5.46 years. Secondary antiphospholipid syndrome (APS) was diagnosed in 77 (38.3%) pregnancies. The pregnancy was planned in 104 (51.7%) pregnancies. Flares occurred in 83 (41.3%) and pre-eclampsia in 15 (7.5%) pregnancies. Full-term pregnancy occurred in 93 (46.3%), fetal loss (miscarriage and intra-uterine fetal death) in 41 (20.4%), and prematurity in 67 (33.3%) of the pregnancies, respectively. Seven neonates died from complications of prematurity, and another one died from cardiac congenital anomalies. In the multivariate analyses, unplanned pregnancy was associated with eight times higher risk of disease flare OR = 7.92 (p < 0.001), lupus nephritis flare during pregnancy increased the odds of pre-eclampsia occurrence four times OR = 3.98 (p = 0.02), while disease flares during pregnancy predicted prematurity OR = 2.49, p = 0.049. Patients with secondary APS had three times increased risk of fetal loss OR = 2.97, p = 0.049. To conclude, unplanned pregnancy, disease flares, and APS have been identified as predictors for adverse maternal and/or fetal outcomes. Pregnancy planning is necessary to reduce maternal and fetal complications.

Origanum vulgare Essential Oil Modulates the AFB1-Induced Oxidative Damages, Nephropathy, and Altered Inflammatory Responses in Growing Rabbits.

The current study was performed to investigate the toxic effects of aflatoxin B1 (AFB1) through the evaluation of kidney function tests and histopathological examination of renal tissues, targeting the therapeutic role of Marjoram (Origanum vulgare essential oil-OEO) in improving health status. Forty-eight New Zealand Whites growing rabbits (four weeks old) weighing on average 660.5 ± 2.33 g were randomly and equally distributed into four groups, each of which had four replicas of three animals as the following: Control group (only basal diet), AFB1 group (0.3 mg AFB1/kg diet), OEO group (1 g OEO/kg diet) and co-exposed group (1 g OEO/kg + 0.3 mg AF/kg diet). Our study lasted eight weeks and was completed at 12 weeks of age. The results revealed that OEO decreased the toxic effects of AFB1 in rabbit kidneys by substantially reducing the cystatin C levels in the AFB1 group. Additionally, OEO decreased oxidative stress and lipid peroxidation levels in the co-exposed group. Moreover, OEO reduced DNA damage and inflammatory response in addition to the down-regulation of stress and inflammatory cytokines-encoding genes. Besides, OEO preserved the cytoarchitecture of rabbits' kidneys treated with AFB1. In conclusion, O. vulgare essential oil supplementation ameliorated the deleterious effects of AFB1 on the rabbits' kidneys by raising antioxidant levels, decreasing inflammation, and reversing oxidative DNA damage.

Comorbidities among Egyptian systemic lupus erythematosus: The COMOSLE-EGYPT study.

OBJECTIVE: To study the prevalence and impact of comorbidities among a cohort of patients with systemic lupus erythematosus (SLE). METHODS: This study is retrospective, multicenter including 902 Egyptian patients with SLE. Medical records were reviewed for demographic data, clinical characteristics, routine laboratory findings, immunological profile, and medications. Moreover, SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College Rheumatology Damage Index scores were calculated. RESULTS: Comorbidities were found in 75.5% of the studied group with hypertension and dyslipidemia as the most frequent comorbidities (43.1% and 40.1%, respectively), followed by sicca features, avascular necrosis, diabetes, osteoporosis and renal failure (11.5%,9%, 9%,8.9%, and 7.1%, respectively). Multivariate regression model showed statistically significant relation between the presence of comorbid condition and each of age (P = 0.006), disease duration (P = 0.041), SLEDAI at onset (P < 0.001), cyclophosphamide intake (P = 0.001), and cumulative pulse intravenous methylprednisone (P < 0.001). Also, when adjusted to age and sex, those with multiple comorbid conditions had 18.5 increased odds of mortality compared to those without comorbidities (odds ratio (OR), 95% confidence interval (CI) = 18.5 (6.65-51.69)]. CONCLUSION: Patients with SLE suffer from several comorbidities, with an increasing risk with age, longer disease duration, higher SLEDAI at onset, cyclophosphamide intake and cumulative pulse intravenous methylprednisone. Risk of mortality is exponentiated with multiple comorbidities.

Olive Leaf Extract Attenuates Chlorpyrifos-Induced Neuro- and Reproductive Toxicity in Male Albino Rats.

Chlorpyrifos (CPF) is a common organophosphorus insecticide. It is associated with negative consequences such as neurotoxicity and reproductive injury. This study aimed to observe the ability of olive leaf extract to attenuate chlorpyrifos toxicity, which induced neuro- and reproductive toxicity in male albino rats. Olive leaf extract (OLE) exhibits potent antioxidant and antiapoptotic properties. Twenty-two mature male rats were divided into four groups: control (saline), CPF (9 mg/kg), OLE (150 mg/kg), and CPF + OLE. Treatment was administered orally for 80 days. The CPF significantly reduced serum sex hormones, sperm counts and motility, high oxidants (MDA), and depleted antioxidants (GSH, SOD, TAC) in the brain and testes homogenate; additionally, it decreased serum AChE and brain neurotransmitters, increased Bax, decreased Bcl-2, and boosted caspase-3 immune expression in neural and testicular cells. Immunological expression of Ki 67 in the cerebrum, cerebellum, choroid plexus, and hippocampus was reduced, and α-SMA in testicular tissue also decreased. Histopathological findings were consistent with the above impacts. OLE co-administration significantly normalized all these abnormalities. OLE showed significant protection against neural and reproductive damage caused by CPF.

Enhanced Ocular Anti-Aspergillus Activity of Tolnaftate Employing Novel Cosolvent-Modified Spanlastics: Formulation, Statistical Optimization, Kill Kinetics, Ex Vivo Trans-Corneal Permeation, In Vivo Histopathological and Susceptibility Study.

Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 32 factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 31.21 factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of -32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery.

Implementing polymeric pseudorotaxanes for boosting corneal permeability and antiaspergillus activity of tolnaftate: formulation development, statistical optimization, ex vivo permeation and in vivo assessment.

Fungal keratitis (FK) is a devastating ocular disease that can cause corneal opacity and blindness if not treated effectively. Tolnaftate (TOL) is a selective fungicidal drug against Aspergillus spp. which are among the most common causes of mycotic keratitis. TOL is lipophilic drug with low water solubility and permeation which act as obstacles for its clinical ocular efficacy. Hence, this study aimed to statistically optimize a novel polymeric pseudorotaxanes (PSRs) containing TOL for enhancing its ocular permeability and antifungal effect. For achieving this goal, a full 31.22 factorial design was fashioned for preparing and optimizing TOL-PSRs using film hydration technique. Three formulation variables were studied: drug amount (X1), weight ratio of Pluronics to HPßCD (X2) and Pluronic system (X3). Entrapment efficiency percent (EE%) (Y1), particle size (PS) (Y2) and zeta potential (ZP) (Y3) were set as dependent variables. The selected optimal TOL-PSRs (PSR1) showed EE% of 71.55 ± 2.90%, PS of 237.05 ± 12.80 nm and ZP of -32.65 ± 0.92 mV. In addition, PSR1 was compared to conventional polymeric mixed micelles (PMMs) and both carriers significantly increased the drug flux and resulted in higher amount permeated per unit area in 8 h compared to drug suspension. The histopathological studies assured the safety of PSR1 for ocular use. The in vivo susceptibility testing using Aspergillus niger confirmed that PSR1 displayed sustained antifungal activity up to 24 h. The obtained results revealed the admirable potential of PSR1 to be used as novel nanocarriers for promoting TOL ocular delivery.

Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, Cryptococcus neoformans, is only partially understood. IFNγ producing CD4+ T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against C. neoformans infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa.

Probiotics-loaded nanoparticles attenuated colon inflammation, oxidative stress, and apoptosis in colitis.

Promising therapy is needed for treating inflammatory bowel diseases (IBD) to overcome current treatment that inefficient and associated with unnecessary health risks. Recently, the concept of incorporating natural products into nanocarriers has been intended as a promising therapy for treating IBD via modulating their stability and bioavailability. Thus, we aimed to explore the potential alleviating effects of dietary nano-supplement combined with bacillus strains (Bacillus amyloliquefaciens; BANPs) in colitis model. Rats were orally gavaged by 5% DSS and the efficacy and mechanistic actions of BANPs were evaluated by assessing the severity of clinical signs and inflammatory and apoptosis response, histopathological and immunohistochemistry examination in colonic tissues. The severity of clinical signs was successfully alleviated and fecal Lcn-2 levels, an important colitic marker, were decreased in BANPs then free BA treated groups. In contrast, inflammatory markers overexpression IL-6, IL-1ß, TNFα, COX-2, and iNOS in the colitic group were reduced more prominently in BANPs treated group, unlike free BA. The amelioration of BANPs to colon injury was also correlated with oxidative stress suppression along with restoring total antioxidant capacity. Interestingly, BANPs treatment modulated apoptotic markers as proved by downregulation of cytochrome c, and caspase-3 and upregulation of Bcl-2 and Bax than free BA. The severity of the histopathological alterations in the colon was greatly reduced in BANPs than free BA groups. Remarkably, over-expression of ki67 and IL-6 in colonic tissues were suppressed in BANPs group. These findings together highlighted the beneficial efficacy of BANPs in IBD treatment which are evidenced by colonic inflammation alleviation. Taken together, these results recommend that BANPs is a promising agent that encourages its possible therapeutic role in colitis treatment.

Diode laser versus bipolar diathermy for turbinate reduction in cases of inferior turbinate hypertrophy.

This study was designed to assess the surgical outcomes of two commonly used techniques for turbinate reduction (diode laser and bipolar diathermy) in selected group of patients with chronic nasal obstruction which resulted from inferior turbinate hypertrophy. The current study was conducted on adult patients with a diagnosis of inferior turbinate hypertrophy. 42 patients (21 in each group) with an age range of 21-38 years (mean = 26.0 ± 4.1) were included in this work and were randomly distributed in 2 groups: one group was scheduled for diode laser turbinectomy (DLT) while the other group was managed by bipolar diathermy (BDT). In DLT, the machine was on a continuous mode with intermittent loading, with laser energy level set to 6 W (0.3-s pulse, 0.1-s break). Pre- and postoperative assessments were statistically compared via tests from SPSS 19.0 (IBM, Chicago, Illinois; USA). Percentage of categorical variables were compared using the Chi-square (χ2) test. P < 0.05 was considered significant, P˃0.05 was considered non-significant, and P < 0.001 was considered highly significant. At 6 months postoperatively, in cases of DLT, there was high significant improvement as regards nasal obstruction and headache (χ2 = 64.78 and 39 respectively; P < 0.0001). There was insignificant difference as regards rhinorrhea (χ2 = 5.524; P = 0.137). In comparison to the postoperative data of both groups, significant difference was reported as regards nasal obstruction and headache (P < 0.001) and rhinorrhea (P < 0.05). This study demonstrated that both laser and bipolar cautery are effective in improving nasal obstruction and rhinorrhea. Preservation of the nasal mucociliary function was better in the diode laser group.

GST T1, M1, and IRS-1 G972R Genetic Variants Association to Gestational Diabetes Mellitus (GDM) in Egyptian Women: Linkage to Maternal Hyperglycemia.

BACKGROUND: Gestational Diabetes Mellitus (GDM) shares in part the pathogenic mechanisms of multiple genetic interactions. Some of the T2D susceptibility genes are encountered in association with GDM. OBJECTIVE: We aimed to investigate GST T1, M1, and G972R IRS-I gene polymorphisms with the risk of developing GDM. METHODS: In this randomized case-control study, pregnant women with GDM were genotyped by PCR analysis for glutathione s-transferase-T1, M1 variant polymorphisms. RFLP was done for the G972R IRS 1 gene. Their newborns were additionally assayed for the whole of the clinical, laboratory, and genetic aspects. RESULTS: The T allele IRS-1rs1801278 TT genotype was more frequently detected in GDM mothers in comparison to healthy control ones [for TT homozygous variant; OR(CI 95%): 2.05(1.09-3.87, p: 0.025)]. Furthermore, GST T1 null was significantly presented in GDM mothers than those of control mothers [OR (CI95%: 0.29 (0.084-1.02), p:0.04]. Added to the significant correlation of glycemic indices to clinical parameters of infants born to GDM, the M1-null genotype of GST was significantly correlated (p<0.05) to abnormal values of respiratory rates and 1 minute-APGAR score noted for extra NICU care. CONCLUSION: Our results suggested that GST T1null and IRS-1 TT genotypic variants were claimed for GDM development among Egyptian women with a possible impact on their newly born infants.

Consensus evidence-based recommendations for treat-to-target management of immunoglobulin A vasculitis.

IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common cause of systemic vasculitis in childhood. Given its potential life-threatening systemic complications, early and accurate diagnosis as well as management of IgAV represent a major challenge for health care professionals. This study was carried out to attain an evidence-based expert consensus on a treat-to-target management approach for IgAV using Delphi technique. The preliminary scientific committee identified a total of 16 key clinical questions according to the patient, intervention, comparison, and outcomes (PICO) approach. An evidence-based, systematic, literature review was conducted to compile evidence for the IgAV management. The core leadership team identified researchers and clinicians with expertise in IgAV management in Egypt upon which experts were gathered from different governorates and health centers across Egypt. Delphi process was implemented (two rounds) to reach a consensus. An online questionnaire was sent to expert panel (n = 26) who participated in the two rounds. After completing round 2, a total of 20 recommendation items, categorized into two sections were obtained. Agreement with the recommendations (rank 7-9) ranged from 91.7-100%. Consensus was reached (i.e. ⩾75% of respondents strongly agreed or agreed) on the wording of all the 20 clinical standards identified by the scientific committee. Algorithms for the diagnosis and management have been suggested. This was an expert, consensus recommendations for the diagnosis and treatment of IgAV and IgA vasculitic nephritis, based on best available evidence and expert opinion. The guideline presented a strategy of care with a pathway to achieve a state of remission as early as possible. PLAIN LANGUAGE SUMMARY: Given its potential life-threatening systemic complications, early and accurate diagnosis of immunoglobulin A vasculitis represents a major challenge for health care professionals. This work provided cornerstone principles for the management of the condition. Adopting PICO approach and implementing Delphi process a consensus was reached on evidence-based treat-to-target treatment recommendations. This will endorse enhancement and consistency of care of this cohort of patients in standard practice.

Promising Role of Growth Hormone-Boosting Peptide in Regulating the Expression of Muscle-Specific Genes and Related MicroRNAs in Broiler Chickens.

Appropriate skeletal muscle development in poultry is positively related to increasing its meat production. Synthetic peptides with growth hormone-boosting properties can intensify the effects of endogenous growth hormones. However, their effects on the mRNA and miRNA expression profiles that control muscle development post-hatching in broiler chicks is unclear. Thus, we evaluated the possible effects of synthetic growth hormone-boosting peptide (GHBP) inclusion on a chicken's growth rate, skeletal muscle development-related genes and myomiRs, serum biochemical parameters, and myofiber characteristics. A total of 400 one-day-old broiler chicks were divided into four groups supplied with GHBP at the levels of 0, 100, 200 and 300 µg/kg for 7 days post-hatching. The results showed that the highest levels of serum IGF-1 and GH at d 20 and d 38 post-hatching were found in the 200 µg/kg GHBP group. Targeted gene expression analysis in skeletal muscle revealed that the GHBP effect was more prominent at d 20 post-hatching. The maximum muscle development in the 200 µg/kg GHBP group was fostered by the upregulation of IGF-1, mTOR, myoD, and myogenin and the downregulation of myostatin and the Pax-3 and -7 genes compared to the control group. In parallel, muscle-specific myomiR analysis described upregulation of miR-27b and miR-499 and down-regulation of miR-1a, miR-133a, miR-133b, and miR-206 in both the 200 and 300 µg/kg GHBP groups. This was reflected in the weight gain of birds, which was increased by 17.3 and 11.2% in the 200 and 300 µg/kg GHBP groups, respectively, when compared with the control group. Moreover, the maximum improvement in the feed conversion ratio was achieved in the 200 µg/kg GHBP group. The myogenic effects of GHBP were also confirmed via studying myofiber characteristics, wherein the largest myofiber sizes and areas were achieved in the 200 µg/kg GHBP group. Overall, our findings indicated that administration of 200 µg/kg GHBP for broiler chicks could accelerate their muscle development by positively regulating muscle-specific mRNA and myomiR expression and reinforcing myofiber growth.

Lupus-related vasculitis in a cohort of systemic lupus erythematosus patients.

Objectives: This study aims to examine the frequency and clinical association of lupus-related vasculitis in patients with systemic lupus erythematosus (SLE). Patients and methods: We retrospectively analyzed medical records of a total of 565 SLE patients (42 males, 523 females; mean age: 32.7±9.5 years; range, 13 to 63 years) between January 2017 and February 2020. Demographic, clinical data, and laboratory data and treatment modalities applied were recorded. Lupus-related vasculitis and its different types were documented, and the patients with vasculitis were compared with those without vasculitis. Results: The mean disease duration was 8.9±6.3 years. Vasculitis associated with lupus was found in 191 (33.45%) patients. Cutaneous vasculitis was found in 59.2%, visceral vasculitis in 34.0%, and both in 6.8% of total vasculitis patients. The patients with vasculitis had a longer disease duration (p=0.01), were more likely to have juvenile onset (p=0.002), livedo reticularis (p<0.001), Raynaud's phenomenon (RP) (p<0.001), digital gangrene (p<0.001), thrombosis (p=0.003), and cranial neuropathy (p=0.004). The patients with vasculitis showed a higher prevalence of hypercholesterolemia (p=0.045), diabetes mellitus (p=0.026), higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at disease onset (p<0.001), and Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (p=0.003) scores. They had more prevalent hematological manifestations (p<0.001), hypocomplementemia (p=0.007), received a higher cumulative dose of intravenous methylprednisolone (p<0.001), and had also more frequent cyclophosphamide (p=0.016) and azathioprine intake (p<0.001). In the logistic regression analysis, SLE vasculitis was independently associated with juvenile disease onset, livedo reticularis, RP, hematological manifestations, and higher scores of SLEDAI at disease onset (p<0.05). Conclusion: Juvenile disease onset, livedo reticularis, RP, hematological manifestations, and higher SLEDAI scores at disease onset may be associated with the development of vasculitis in SLE patients.