Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Background and Objectives: Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Methods: Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. Results: 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Conclusion: Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Isolation and identification of multidrug resistance bacterial agents implicated in duck enteritis with first record of Salmonella enterica subspecies arizonae in Egypt.

Background: Bacterial infections causing digestive problems are among the most serious threats to Egypt's duck industry, owing to their effects on feed utilization and body weight gain. Aim: As a result, the goal of this study was to identify bacterial pathogens causing enteritis in ducks as well as testing their antimicrobials resistance capabilities. Methods: Forty-two duck flocks from different localities at four Egyptian Governorates (El-Sharkia, El-Gharbia, El-Dakahlia, and El-Qaliobia) have been subjected to clinical and postmortem examination as well as bacterial isolation and identification. The liver samples have been collected aseptically from freshly euthanized ducks for bacterial isolation followed by identification using conventional biochemical tests, VITEK 2 system, and confirmatory polymerase chain reaction (PCR) for detection of the uid A gene (beta-glucuronidase enzyme) of Escherichia coli. In addition, antimicrobial sensitivity testing for the isolates against different antimicrobials by the VITEK 2 system was used. Results: Forty-six positive bacterial isolates were identified using conventional methods and the VITEK 2 system including Staphylococcus spp. (52.17%), E. coli (41.30%), and 2.17% for each of Enterococcus casseli lavus, Salmonella enterica subspecies arizonae, and Enterobacter cloacae. PCR was positive for E. coli uid A gene at 556 bp. The antibiogram patterns of isolated pathogens from naturally infected ducks in our work demonstrated 87% multidrug resistance with varying results against different antimicrobial drugs tested. Such findings supported the fact of the upgrading multidrug resistance of Staphylococci and Enterobacteriacae. Conclusion: The most prevalent bacterial pathogens associated with duck enteritis were Staphylococcus spp. and E. coli with the first report of S. enterica subspecies arizonae causing duck enteritis in Egypt.

Safety and efficacy of transjugular intrahepatic portosystemic shunts vs endoscopic band ligation plus propranolol in patients with cirrhosis with portal vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to assess the efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) against the combined treatment of endoscopic band ligation (EBL) and propranolol in managing patients with cirrhosis diagnosed with portal vein thrombosis (PVT). METHODS: A literature search from inception to September 2023 was performed using MEDLINE, the Cochrane Library, Web of Science, and Scopus. Independent screening, data extraction, and quality assessment were performed. The main measured outcomes were the incidence and recurrence of variceal bleeding (VB), hepatic encephalopathy, and overall survival. RESULTS: A total of 5 studies were included. For variceal eradication, there was initially no significant difference between the groups; however, after sensitivity analysis, a significant effect emerged (risk ratio [RR], 1.55; P < .0001). TIPS was associated with a significant decrease in the incidence of VB (RR, 0.34; P < .0001) and a higher probability of remaining free of VB in the first 2 years after the procedure (first year: RR, 1.41; P < .0001; second year: RR, 1.58; P < .0001). TIPS significantly reduced the incidence of death due to acute GI bleeding compared with EBL + propranolol (RR, 0.37; P = .05). CONCLUSION: TIPS offers a comprehensive therapeutic advantage over the combined EBL and propranolol regimen, especially for patients with cirrhosis with PVT. Its efficacy in variceal eradication, reducing rebleeding, and mitigating death risks due to acute GI bleeding is evident.

The Effect of an Education Program on School Children Oral Health in Khartoum, Sudan.

Background: Oral health education programs have long been considered an essential part of oral health policies. This is important for reducing the risk of oral diseases through health enhancement and voluntary behavioral changes due to learning opportunities. This study aimed to evaluate the effects of school-based oral health education program on oral health in school children in Sudan. Methods: A quasi-experimental study was conducted at four governmental schools in Khartoum, Sudan, between August 2018, and March 2022. A total of 423 school children were randomly allocated into the control (n = 211) and study (n = 212) groups. An adapted questionnaire was administered to students before and after the intervention to assess their knowledge and practice of oral health. The study group participated in oral health education activities. Data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 21. Results: The findings revealed that the mean knowledge at the pre-educational program was 9.3066 (SD = 3.91078) and the mean knowledge after the educational program was 21.2736 (SD = 2.13982). The scores indicated that the school children had significantly higher knowledge and practice scores after the oral health education program. Conclusion: The study concluded that education program on oral health improved students' oral health knowledge and practices. Imposing theoretical and practical lessons on oral and dental health in school curricula can motivate students to maintain oral health care, and this improves oral health status.

Insight into the Epidemiology of the Adult-onset Systemic Autoimmune Rheumatic Diseases in Egypt: A Descriptive Study of 8690 Patients.

BACKGROUND/OBJECTIVE: Although systemic autoimmune rheumatic diseases (SARDs) seem to be ubiquitous, Africa and the Middle East seem to be a remarkable exception with scarcity of data compared with the developed countries. Furthermore, most of the studies addressed a particular disease. This work aimed to shed light on the relative frequency and epidemiology of the different adult-onset SARDs in Egypt. METHODS: This is a retrospective hospital-based study including six university hospitals providing free health care services: Cairo, Alexandria, Tanta, Ismailia, Beni-Suef and Assiut University Hospitals. All available files for patients attending the outpatient clinics or admitted to the inpatient departments between January 2000 and December 2021 were retrospectively reviewed. Data about the patient's diagnosis, gender, age at disease onset, year of disease onset and residence were collected. RESULTS: The study included 8690 patients. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behçet's disease (BD) and spondyloarthropathies (SPA) represented the main SARDs in Egypt. They mainly affect young patients below the age of 40 years. RA and SLE mainly affect females; males are mainly affected by axial SPA and BD. There is an increasing incidence of SARDs during the study period. CONCLUSION: The study revealed the high burden of SARDs in Egypt, helping better allocation of economic resources for the management of diseases of the highest prevalence and those affecting the young reproductive age groups. Increased public and medical staff awareness about SARDs is recommended to help early referral of patients to rheumatologists and, hence, better estimation of their epidemiology.

In Vitro and In Vivo testing of 3D-Printed Amorphous Lopinavir Printlets by Selective Laser Sinitering: Improved Bioavailability of a Poorly Soluble Drug.

The aim of this paper was to investigate the effects of formulation parameters on the physicochemical and pharmacokinetic (PK) behavior of amorphous printlets of lopinavir (LPV) manufactured by selective laser sintering 3D printing method (SLS). The formulation variables investigated were disintegrants (magnesium aluminum silicate at 5-10%, microcrystalline cellulose at 10-20%) and the polymer (Kollicoat® IR at 42-57%), while keeping printing parameters constant. Differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared analysis confirmed the transformation of the crystalline drug into an amorphous form. A direct correlation was found between the disintegrant concentration and dissolution. The dissolved drug ranged from 71.1 ± 5.7% to 99.3 ± 2.7% within 120 min. A comparative PK study in rabbits showed significant differences in the rate and extent of absorption between printlets and compressed tablets. The values for Tmax, Cmax, and AUC were 4 times faster, and 2.5 and 1.7 times higher in the printlets compared to the compressed tablets, respectively. In conclusion, the SLS printing method can be used to create an amorphous delivery system through a single continuous process.

Patient In-Use Stability Testing of FDA-Approved Metformin Combination Products for N-Nitrosamine Impurity.

Between February 2020 and January 2022, the Food and Drug Administration (FDA) recalled 281 metformin extended-release products due to the presence of N-nitrosodimethylamine (NDMA) above the acceptable daily intake (ADI, 96 ng/day). Our previous studies indicated presence of NDMA levels above ADI in both metformin immediate and extended-release products. When metformin products have NDMA impurities, it is indispensable to check for the same impurities in metformin combination products. Therefore, the objective of the present study was to evaluate in-use stability of commercial metformin combination products for NDMA. For this purpose, metformin products in combination with glyburide (GB1-GB12), glipizide (GP1-GP8), pioglitazone (P1-P3), alogliptin (A1, A2), and linagliptin (L1, L2) were repacked in pharmacy vials, stored at 30°C/75% RH for 3 months, and monitored for NDMA impurity. The NDMA level varied from 0 to 156.8 ± 32.8 ng/tablet initially and increased to 25.4 ± 5.1 to 455.0 ± 28.4 ng/tablet after 3 months of exposure to in-use condition. Initially, 18 products have NDMA level below ADI limit before exposure which decreased to 7 products (GB5, GP3, GP5, A1, A2, L1, and L2) meeting specification. In conclusion, in-use stability study provides quality and safety risk assessment of drug products where nitroso impurities are detected in the probable condition of use.

User Perceptions and Use of Decision Support Medical Apps Among Medical Students: Cross-Sectional Study.

We aimed to assess medical students' use of decision-support medical apps and evaluate their perception of app use. A cross-sectional multi-center observational study was conducted among medical students with and without a medical informatics course as part of their undergraduate medical curriculum. We assessed trust, perceptions, patient impression, reliability, and comfort using an online survey. A total of 439 responses were received. There were significant differences between the two groups when indicating which apps, they trust. Students agreed that using apps enhanced knowledge (91%), saved time (88%), improved patient care (85%), and increased diagnostic accuracy (82%). Students indicated that patients would think that students didn't know what they were doing (63%) or students were fresh out of training (53%) when using apps in the presence of patients. Incorporating medical app usage as part of learning may increase trust and comfort with using medical apps in medical practice.

Hsa-miR-21-5p reflects synovitis and tenosynovitis components of musculoskeletal ultrasonography Seven-joint scores in rheumatoid arthritis disease and predicts the disease flare.

Rheumatoid arthritis (RA) is characterized by progressive joint destruction with subsequent serious disability. Objective biomarkers of RA course progression are lacking, which necessitates the discovery of activity indicators and predictors of the disease outcome. Musculoskeletal Ultrasound Seven-joint Score (MSUS7) is proposed as a reliable technique to evaluate radiographic RA progression. Homo sapiens-microRNA-21-5p (hsa-miR-21-5p) plays an important role during joint remodeling and the pro-inflammatory process driving RA progression. We aimed to evaluate plasma hsa-miR-21-5p as a noninvasive RA activity biomarker and to investigate if hsa-miR-21-5p is linked to MSUS7 components in the context of RA activity. This cross-sectional study included 71 RA patients classified into inactive (n = 36) and active (n = 35) groups according to the Disease Activity Score 28-joint count with ESR (DAS28-ESR). Joints were assessed by MSUS7. Gray-scale ultrasound (GSUS) and power Doppler ultrasound (PDUS) were used to rate the synovitis, tenosynovitis, and erosion in the joints. Plasma hsa-miR-21-5p expression was measured by real-time PCR. The absolute count of regulatory T cell (Treg) was calculated after Treg frequency was assessed by flow cytometry. Results: Hsa-miR-21 expression was significantly up-regulated in the active RA group with a median fold change of 51.6 in comparison to the inactive cases with a median fold change of 7.7 (p < 0.001). Hsa-miR-21-5p was positively correlated with DAS28-ESR, C reactive protein (CRP), and rheumatoid factor (r = 0.7, p < 0.001, r = 0. 0.6, p < 0.001, and r = 0.4, p = 0.002, respectively), while negatively correlated with Treg absolute count (r = -0.4, p < 0.001). Hsa-miR-21-5p levels were correlated with synovitis and tenosynovitis in GSUS (r = 0.4, p < 0.001, r = 0.3, p = 0.025, respectively) and in PDUS (r = 0.5, p < 0.001 and 0.4, p = 0.001, respectively). The hsa-miR-21-5p accurately distinguished RA activity [AUC 0.933, 94.3% sensitivity, and 86.1% specificity]. Logistic regression analysis revealed hsa-miR-21-5p as an independent predictor for RA flare (OR = 1.228, p = 0.004). Hsa-miR-21-5p was linked to synovitis and tenosynovitis components of the MSUS7. Up-regulated hsa-miR-21-5p can be utilized as a predictor for RA disease flare.

Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product.

PURPOSE: Intramammary (IMM) formulations are locally acting and delivered intracisternally into the udder. No pharmacopeial in-vitro release method is available to differentiate between the IMM formulations. Our research aim is to develop in-vitro release methods that discriminate different IMM formulations (SPECTRAMAST® LC and in-house formulations). METHODOLOGY: Different in-house formulations were developed to simulate SPECTRAMAST® LC generics. SPECTRAMAST® LC and the in-house formulations were characterized for physicochemical attributes, such as particle size, rheology, drug content, sedimentation rate, and flocculation rate. The in-vitro release method was optimized by evaluating drug release using USP apparatuses 1, 2 (with and without enhancer/customized cells), and 4. Various test parameters, including medium effect (whole homogenized bovine milk versus aqueous buffer), medium volume (200-900 mL), and rotational speed (50-200 rpm) were investigated. RESULTS: Two potential in-vitro systems can be used as discriminatory methods for IMM formulations: USP apparatus 2 with the IMM formulation loaded into two containers a) customized formulation container (83.1 cm in height and 56.4 cm in width) or b) enhancer cells with their top adapted with mesh #40 (rotation speed:125 rpm and 900 mL of whole homogenized bovine milk). The release profile of SPECTRAMAST® LC at 1 h (99.8%) was not significantly different from formulations with similar physicochemical characteristics F-01 (99.1%) and F-02 (100.5%). Formulation with different physicochemical characteristics F-03 (44.3%) and F-04 (57.2%) showed slower release (1 h) than SPECTRAMAST® LC (98.8%). CONCLUSION: The developed in-vitro release methods can be used as a potential tool for in-vitro comparability evaluations for IMM formulations.

Linking Cognitive Impairment with Amyloid-ß Accumulation in Alzheimer's Disease: Insights from Behavioral Tests and FTIR Spectroscopy.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that progresses over time. Fourier Transform Infrared Spectroscopy (FTIR) analysis gives identification of the main metabolic changes that happen during neurodegeneration, by monitoring biochemical and molecular structure alterations that can help in AD diagnosis or treatment approach. Objective: The aim of the present work is to assess AD hallmarks in molecular structure of retina and monitor accumulation of amyloid beta42(Aß42) in brain and retina during disease progression. Methods: AD induced in rats by Aluminum Chloride (AlCl3). Retinal molecular structure during disease progression for 2,4,6 and 8 weeks was assessed by Fourier-transform infrared spectroscopy (FTIR) and the incidence of the disease was confirmed by a behavioural assessment; the Morris Water Maze test. Aß42 levels in the brain and retina were also measured. Results: The results indicated that cognitive impairment starting from 6 weeks of AlCl3 administration. Retinal concentration of Aß42 was significant increase (p < 0.05) from 2 weeks that precedes the observed increase of Aß42 in the brain which appeared after 4 weeks of AlCl3 administration. Multivariate principal component analysis discovers that the variance noticed in the infrared spectra due to AD condition and it is time dependent for progression of the disease. Conclusions: The accumulation of Aß42 is a sensitive early biomarker in retina for AD. FTIR analysis of the retina revealed changes in hydrogen bond formation or destruction, alterations in lipid chain length and branching accompanied by depleted lipid content and carbonization, as well as degeneration of the retinal tissue due to AD.

Unsupervised cluster analysis of clinical and ultrasound features reveals unique gout subtypes: Results from the Egyptian College of Rheumatology (ECR).

BACKGROUND: Gout comprises a heterogeneous group of disorders; however, comorbidities have been the focus of most efforts to classify disease subgroups. OBJECTIVES: We applied cluster analysis using musculoskeletal ultrasound (MSUS) combined with clinical and laboratory findings in patients with gout to identify disease phenotypes, and differences across clusters were investigated. PATIENTS AND METHODS: Patients with gout who complied with the ACR/EULAR classification criteria were enrolled in the Egyptian College of Rheumatology (ECR)-MSUS Study Group, a multicenter study. Selected variables included demographic, clinical, and laboratory findings. MSUS scans assessed the bilateral knee and first metatarsophalangeal joints. We performed a K-mean cluster analysis and compared the features of each cluster. RESULTS: 425 patients, 267 (62.8 %) males, mean age 54.2 ± 10.3 years were included. Three distinct clusters were identified. Cluster 1 (n = 138, 32.5 %) has the lowest burden of the disease and a lower frequency of MSUS characteristics than the other clusters. Cluster 2 (n = 140, 32.9 %) was mostly women, with a low rate of urate-lowering treatment (ULT). Cluster 3 (n = 147, 34.6 %) has the highest disease burden and the greatest proportion of comorbidities. Significant MSUS variations were found between clusters 2 and 3: joint effusion (p < 0.0001; highest: cluster 3), power Doppler signal (p < 0.0001; highest: clusters 2), and aggregates of crystal deposition (p < 0.0001; highest: cluster 3). CONCLUSION: Cluster analysis using MSUS findings identified three gout subgroups. People with more MSUS features were more likely to receive ULT. Treatment should be tailored according to the cluster and MSUS features.

Naringin-Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation.

Nanotechnology has proven advantageous in numerous scientific applications, one being to enhance the delivery of chemotherapeutic agents. This present study aims to evaluate the mechanisms underlying the chemopreventive action of naringin-dextrin nanocomposites (Nar-Dx-NCs) against diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced lung carcinogenesis in male Wistar rats. DEN was administered intraperitoneally (i.p.) (150 mg/kg/week) for two weeks, followed by the oral administration of 2AAF (20 mg/kg) four times a week for three weeks. Rats receiving DEN/2AAF were concurrently treated with naringin or Nar-Dx-NCs orally at a dose of 10 mg/kg every other day for 24 weeks. Naringin and Nar-Dx-NCs treatments prevented the formation of tumorigenic cells within the alveoli of rats exposed to DEN/2AAF. These findings were associated with a significant decrease in lipid peroxidation, upregulation of antioxidant enzyme (glutathione peroxidase and superoxide dismutase) activity, and enhanced glutathione and nuclear factor erythroid 2-related factor 2 expression in the lungs. Naringin and Nar-Dx-NCs exerted anti-inflammatory actions manifested by a decrease in lung protein expression of tumor necrosis factor-α and interleukin-1ß and mRNA expression of interleukin-6, interferon-γ, nuclear factor-κB, and inducible nitric oxide synthase, with a concurrent increase in interleukin-10 expression. The anti-inflammatory effect of Nar-Dx-NCs was more potent than naringin. Regarding the effect on apoptosis, both naringin and Nar-Dx-NCs significantly reduced Bcl-2 and increased Bax and P53 expressions. Moreover, naringin or Nar-Dx-NCs induced a significant decrease in the expression of the proliferator marker, Ki-67, and the effect of Nar-Dx-NCs was more marked. In conclusion, Nar-Dx-NCs improved naringin's preventive action against DEN/2AAF-induced lung cancer and exerted anticarcinogenic effects by suppressing oxidative stress and inflammation and improving apoptotic signal induction and propagation.

A study on the therapeutic potential of graphene titanate nanocomposite for treating chemically induced arthritis in rats.

Nanotechnology holds substantial promise in the innovative therapies for rheumatoid arthritis (RA). The current study was designed to synthesize and characterize a new graphene titanate nanocomposite (GTNc) and explore its anti-arthritic, anti-inflammatory, and antioxidant potencies against Complete Freund's adjuvant (CFA)-induced arthritis in rats, as well as investigate the underlying molecular mechanisms. Our characterization methods included XRD, FT-IR, SEM, EDX, zeta potential, practical size, and XRF to characterize the novel GTNc. Our findings revealed that arthritic rats treated with GTNc exhibited lower levels of RF, CRP, IL-1ß, TNF-α, IL-17, and ADAMTS-5, and higher levels of IL-4 and TIMP-3. In arthritic rats, GTNc reduced LPO levels while increasing GSH content and GST antioxidant activity. Additionally, GTNc decreased the expression of the TGF-ß mRNA gene in arthritic rats. Histopathological investigation showed that GTNc reduced inflammatory cell infiltration, cartilage degradation, and bone destruction in joint injuries caused by CFA in the arthritic rats. Collectively, the anti-arthritic, anti-inflammatory, and antioxidant properties of GTNc appear promising for future arthritis treatments and bone disability research.

Anti-inflammatory and anti-oxidant activities of mesenchymal stem cells in chemically induced arthritic rats.

BACKGROUND: Mesenchymal stem cells (MSCs) have been extensively used as cell-based treatments for decades due to their anti-inflammatory, immunomodulatory, and healing abilities. The intent of our study was to determine the efficacy of MSCs in alleviating rheumatoid arthritis (RA) induced by Complete Freund's adjuvant (CFA) and to investigate the anti-inflammatory and antioxidant characteristics of MSCs. METHODS AND RESULTS: Intrapedally injecting 0.1 ml of CFA directly into the footpad of the right hind paw daily for 2 days was used to induce RA. Arthritic rats received four doses of MSCs (1 × 106 cells/rat/dose) intravenously through the lateral tail vein. Our results showed that arthritic rats treated with MSCs exhibited reduced levels of paw edema. Furthermore, arthritic rats treated with MSCs exhibited a significant decrease in the levels of RF, CRP, IL-1ß, TNF-α, IL-17 and ADAMTS-5, along with a significant increase in the levels of IL-4 and TIMP-3. Additionally, MSCs significantly reduced the expression of TGF-ß. Both the glutathione (GSH) content and antioxidant activity of GST were enhanced by MSCs, while LPO levels were suppressed. CONCLUSION: These findings provide further evidence that MSCs are valuable in treating RA, possibly due to their anti-inflammatory and anti-oxidative properties. Thus, MSCs have potential as a more effective therapeutic strategy for treating RA.

Lidocaine Infusion Versus Duloxetine for Prevention and Management of Taxane-Induced Peripheral Neuropathy among Breast Cancer Patients-A Randomized Controlled Study.

BACKGROUND: Taxane-induced peripheral neuropathy (TIPN) among breast cancer patients is considered one of the most devastating side effects affecting compliance to chemotherapy protocol and patients' quality of life (QOL). OBJECTIVES: This trial aimed to evaluate the effect of lidocaine infusion vs oral duloxetine on the incidence and severity of TIPN and QOL in patients with breast cancer scheduled for neoadjuvant taxane therapy (TT). STUDY DESIGN: Prospective, randomized, single-blinded, controlled trial. SETTING: This study was carried out on 60 patients with breast cancer scheduled for 12 weeks of TT at the Medical Research Institute Hospital, Alexandria University after obtaining local Ethics Committee approval (IORG008812) and getting a written informed consent from each patient. It was registered in the "clinical trials library for protocol registration and results system" with the number NCT04732455. METHODS: Sixty women scheduled for TT weekly for 12 weeks, were randomly allocated to receive intravenous saline infusion in the control group (GC), or lidocaine 2mg/kg with saline infusion in the lidocaine group (GL), or saline infusion and 30 mg duloxetine in the duloxetine group (GD). All infusions were administered over 40 minutes before each TT. Oral duloxetine was prescribed once daily starting from the night before commencing TT and continued for 12 weeks. Douleur Neuropathique en 4 Questions (DN4) questionnaire was filled weekly to detect the incidence of neuropathic pain (NP). The nerve conduction study (NCS) aimed to detect and measure the degree of neuropathy before starting the chemotherapy protocol and post-12 weeks of Taxol Therapy. NP Scale was measured weekly to assess the severity of NP symptoms. Patients' QOL was evaluated by the European Organization for Research and Treatment of Cancer QOL Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale. RESULTS: Thirty-five percent of patients reported DN4 > 4 points in GC after 6 weeks of TT in comparison to 5% in GL and 0% in GD (P = .005). Moreover, the incidence rose to 75% in GC compared to 20% in GL and 25% GD at the end of TT (P < 0.001). The severity of symptoms, global pain intensity, and patients' unpleasantness were significantly more in GC than GL and GD in the last 4 weeks of TT (P < 0.05). NCS showed that 55% and 25% of patients developed mild and moderate axonal neuropathy, respectively, in GC. In contrast, mild neuropathy was developed in 20% and 25% of patients in GL and GD, respectively, and moderate neuropathy in 5% in both groups. The negative impact of TT on QOL was more significant in GC than GL and GD at weeks 8 and 12 of TT (P < 0.001). LIMITATIONS: Limited reference data for all treatment regimens to include in the Discussion section. CONCLUSIONS: Lidocaine and duloxetine have a comparable effect to decrease the incidence and severity of TIPN. Moreover, patients' QOL was significantly better in both groups. KEY WORDS: Lidocaine infusion, duloxetine, taxane-induced peripheral neuropathy, breast cancer, DN4.

Preparation and Characterization of 3D-Printed Dose-Flexible Printlets of Tenofovir Disoproxil Fumarate.

The aim of this work was to design pediatric-friendly, dose-flexible orally disintegrating drug delivery systems (printlets) of the antiviral drug tenofovir disoproxil fumarate (TDF) by selective laser sintering (SLS) for potential use in hospitals along with other antiviral drugs. In order to obtain a consistent quality of printlets with desired properties, it is important to understand certain critical quality attributes for their main and interactions effect. The printlets were optimized by Box-Behnken's design of the experiment by varying process variables while keeping the composition constant. The composition contained 16.3% TDF, 72.7% polyvinyl pyrrolidone K16-18, 8% magnesium aluminum silicate, 3% Candurin® NXT Ruby Red, and 0.3% colloidal silicon dioxide. The process variables studied were surface (X1), chamber temperatures (X2), and laser scanning speed (X3). The range of variable levels was 75-85°C for X1, 50-70°C for X2, and 200-240 mm/s for X3, respectively. The responses studied were hardness, disintegration time, dissolution, physiochemical, and pharmacokinetic characterization. X-ray powder diffraction indicated partial or complete conversion of the crystalline drug into amorphous form in the printlets. Comparative pharmacokinetics between Viread® (generic) and printlets in rats were superimposable. Pharmacokinetic parameters showed statistically insignificant differences between the two formulations in terms of Tmax, Cmax, and AUC of (p > 0.05). Printlets were bioequivalent to Viread® as per FDA bioequivalence criteria. Thus, the SLS printing method showed the fabrication of dose-flexible printlets with quality, and in vivo performance equivalent to commercial tablets.

Antibacterial and anti-biofilm activities of probiotic Lactobacillus plantarum against Listeria monocytogenes isolated from milk, chicken and pregnant women.

Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen that poses significant risks to public health and food safety. The present study aimed to identify the presence of Listeria spp. in various samples, including pasteurized milk, chicken fillets, and stool samples from pregnant women in Sharkia Governorate, Egypt. Additionally, the study identified the serotypes, virulence-associated genes, antimicrobial resistance patterns, and biofilm formation in L. monocytogenes isolates. Moreover, the antibacterial and anti-biofilm activity of Lactobacillus plantarum ATCC 14917 (L. plantarum) against L. monocytogenes isolates was investigated. A cross-sectional study was conducted from August 2021 to January 2022 to collect 300 samples of pasteurized milk, chicken fillets, and stool from pregnant women admitted to outpatient clinics of hospitals. The results showed that 32.7% of the samples were positive for Listeria spp., including L. innocua (48.9%), L. monocytogenes (26.5%), L. ivanovii (14.3%), L. grayi (5.1%), and L. welshimeri (5.1%). Among all L. monocytogenes isolates, hlyA, actA, inlC, and inlJ virulence-associated genes were detected. However, the virulence genes plcB, iap, and inlA were found in 10 (38.5%), 8 (30.8%), and 25 (96.2%) isolates, respectively. The L. monocytogenes isolates classified into four serotypes (1/2a, 1/2b, 1/2c, and 4b), with 1/2a and 4b each identified in 30.8% of the isolates, while 1/2b and 1/2c were identified in 19.2% of the isolates. All L. monocytogenes isolates showed 100% resistance to streptomycin, kanamycin, and nalidix acid, and 92.3% of isolates showed gentamicin resistance. However, all isolates were susceptible to ampicillin and ampicillin/sulbactam. Multidrug resistance (MDR) was observed in 20 (76.9%) L. monocytogenes isolates. The biofilm formation ability of 26 L. monocytogenes isolates was evaluated at different incubation temperatures. At 4°C, 25°C, and 37°C, 53.8, 69.2, and 80.8% of the isolates, respectively, were biofilm producers. Furthermore, 23.1% were strong biofilm producers at both 4°C and 25°C, while 34.6% were strong biofilm formers at 37°C. Treating L. monocytogenes isolates with L. plantarum cell-free supernatant (CFS) reduced the number of biofilm-producing isolates to 15.4, 42.3, and 53.8% at 4°C, 25°C, and 37°C, respectively. L. plantarum's CFS antibacterial activity was tested against six virulent, MDR, and biofilm-forming L. monocytogenes isolates. At a concentration of 5 µg/mL of L. plantarum CFS, none of the L. monocytogenes isolates exhibited an inhibition zone. However, an inhibition zone was observed against L. monocytogenes strains isolated from pasteurized milk and pregnant women's stools when using a concentration of 10 µg/mL. Transmission electron microscopy (TEM) revealed that L. plantarum CFS induced morphological and intracellular structural changes in L. monocytogenes. In conclusion, this study identified virulent MDR L. monocytogenes isolates with strong biofilm-forming abilities in food products in Egypt, posing significant risks to food safety. Monitoring the prevalence and antimicrobial resistance profile of L. monocytogenes in dairy and meat products is crucial to enhance their safety. Although L. plantarum CFS showed potential antibacterial and anti-biofilm effects against L. monocytogenes isolates, further research is needed to explore its full probiotic potential.

Development of carboxymethyl cellulose-graphene oxide biobased composite for the removal of methylene blue cationic dye model contaminate from wastewater.

Utilizing Glutaraldehyde crosslinked sodium carboxymethyl cellulose (CMC-GA) hydrogel and its nanographene oxide composite (CMC-GA-GOx), an effective carboxymethyl cellulose-graphene oxide biobased composites adsorbent was developed for the adsorption removal of methylene blue (MB) cationic dye contaminate from industrial wastewater. The CMC-GA-GOx composites developed were characterized using FTIR, RAMAN, TGA, SEM, and EDX analysis instruments. Through batch experiments, several variables affecting the removal of MB dye, including the biocomposites GO:CMC composition, adsorption time, pH and temperature, initial MB concentration, adsorbent dosage, and NaCl concentration, were investigated under different conditions. The maximum dye removal percentages ranged between 93 and 98%. They were obtained using biocomposites CMC-GA-GO102 with 20% GO weight percent, adsorption time 25 min, adsorption temperature 25 °C, MB concentrations 10-30 ppm, adsorption pH 7.0, and 0.2 g adsorbent dose. The experimental data of the adsorption process suit the Langmuir isotherm more closely with a maximal monolayer adsorption capacity of 76.92 mg/g. The adsorption process followed the kinetic model of pseudo-second order. The removal of MB was exothermic and spontaneous from a thermodynamic standpoint. In addition, thermodynamic results demonstrated that adsorption operates most effectively at low temperatures. Finally, the reusability of the developed CMC-GA-GO102 has been proved through 10 successive cycles where only 14% of the MB dye removal percentage was lost. These results suggest that the developed CMC-GA-GO102 composite may be an inexpensive and reusable adsorbent for removing organic cationic dyes from industrial wastewater.

Determination of immunological biomarkers in sarcoidosis and their relation to disease activity.

Sarcoidosis is a multisystem granulomatous disease of unknown origin. Ninety percent of patients with sarcoidosis have lung involvement. The onset can be acute or non-acute and the severity of sarcoidosis ranges widely from asymptomatic patients with accidental radiographic findings to patients with severe organ involvement. This case control analytic prospective study was conducted at the Chest Clinic, Al Zahraa hospital, to assess the diagnostic value of serum soluble interleukin 2 receptor (sIL-2R), cluster of differentiation 4 (CD4)/CD8 ratio and CD103 in sarcoidosis. We investigated the value of serum sIL-2R using ELISA and blood CD103, blood CD4/CD8 ratio using flow cytometry for 30 cases of sarcoidosis in different stages and 30 control persons to detect their use as a marker for diagnosis. We found a significant increase in sIL-2R in the sarcoidosis group as compared to the control group (p˂0.0001), while there was a significant decrease in CD103/CD4 in sarcoidosis group as compared to the control group (p < 0.001). In conclusion, sIL-2R and CD103 can be used as diagnostic markers for sarcoidosis.