Mycobacteroides abscessus (Previously Mycobacterium abscessus) is an emerging microorganism of the newly defined genera Mycobacteroides that causes mainly skin and tissue diseases in humans. The recent availability of total 34 fully sequenced genomes of different strains belonging to this species has provided an opportunity to utilize this genomics data to gain novel insights and guide the development of specific antimicrobial therapies. In the present study, we collected collectively 34 complete genome sequences of M. abscessus from the NCBI GenBank database. Pangenome analysis was conducted on these genomes to understand the genetic diversity and to obtain proteins associated with its core genome. These core proteins were then subjected to various subtractive filters to identify potential antigenic targets that were subjected to multi-epitope vaccine design. Our analysis projected the open pangenome of M. abscessus containing 3443 core genes. After applying various stepwise filtration steps on the core proteins, a total of four potential antigenic targets were identified. Utilizing their constituent CD4 and CD8 T-cell epitopes, a multi-epitope based subunit vaccine was computationally designed. Sequence-based analysis as well as structural characterization revealed the immunological effectiveness of this designed vaccine. Further molecular docking, molecular dynamics simulation and binding free energy estimation with Toll-like receptor 2 indicated strong structural associations of the vaccine with the immune receptor. The promising results are encouraging and need to be validated by additional wet laboratory studies for confirmation.

Proteus mirabilis is a common opportunistic pathogen causing severe illness in humans and animals. To determine the prevalence, antibiogram, biofilm-formation, screening of virulence, and antimicrobial resistance genes in P. mirabilis isolates from ducks; 240 samples were obtained from apparently healthy and diseased ducks from private farms in Port-Said Province, Egypt. The collected samples were examined bacteriologically, and then the recovered isolates were tested for atpD gene sequencing, antimicrobial susceptibility, biofilm-formation, PCR detection of virulence, and antimicrobial resistance genes. The prevalence of P. mirabilis in the examined samples was 14.6% (35/240). The identification of the recovered isolates was confirmed by the atpD gene sequencing, where the tested isolates shared a common ancestor. Besides, 94.3% of P. mirabilis isolates were biofilm producers. The recovered isolates were resistant to penicillins, sulfonamides, β-Lactam-β-lactamase-inhibitor-combinations, tetracyclines, cephalosporins, macrolides, and quinolones. Using PCR, the retrieved strains harbored atpD, ureC, rsbA, and zapA virulence genes with a prevalence of 100%, 100%, 94.3%, and 91.4%, respectively. Moreover, 31.4% (11/35) of the recovered strains were XDR to 8 antimicrobial classes that harbored bla_TEM, bla_OXA-1, bla_CTX-M, tetA, and sul1 genes. Besides, 22.8% (8/35) of the tested strains were MDR to 3 antimicrobial classes and possessed bla_TEM, tetA, and sul1genes. Furthermore, 17.1% (6/35) of the tested strains were MDR to 7 antimicrobial classes and harbored bla_TEM, bla_OXA-1, bla_CTX-M, tetA, and sul1 genes. Alarmingly, three strains were carbapenem-resistant that exhibited PDR to all the tested 10 antimicrobial classes and shared bla_TEM, bla_OXA-1, bla_CTX-M, tetA, and sul1 genes. Of them, two strains harbored the bla_NDM-1 gene, and one strain carried the bla_KPC gene. In brief, to the best of our knowledge, this is the first study demonstrating the emergence of XDR and MDR-P.mirabilis in ducks. Norfloxacin exhibited promising antibacterial activity against the recovered XDR and MDR-P. mirabilis. The emergence of PDR, XDR, and MDR-strains constitutes a threat alarm that indicates the complicated treatment of the infections caused by these superbugs.

Background: The clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART.

Material & methods: Two hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured.

Results: P/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn't whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5).

Conclusions: In patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.

Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models via enhancing AMPK activity. Yet, the protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis.

Purpose: This clinical trial compares the functional and radiological outcomes of single-bone fixation to both-bone fixation of unstable paediatric both-bone forearm fractures.
Methods: This individually randomized two-group parallel clinical trial was performed following the Consolidated Standards of Reporting Trials (CONSORT) statement at a single academic tertiary medical centre with an established paediatric ortho- paedics unit. All children aged between nine and 15 years who presented to the emergency department at Assiut university with unstable diaphyseal, both-bone forearm fractures requiring surgical intervention between November 1, 2018, and Feb- ruary 28, 2020, were screened for eligibility against the inclusion and exclusion criteria. Inclusion criteria were diaphyseal unstable fractures defined as shaft fractures between the distal and proximal metaphyses with an angulation of > 10°, and/ or malrotation of > 30°, and/or displacement > 10 mm after attempted closed reduction. Exclusion criteria included open fractures, Galeazzi fractures, Monteggia fractures, radial head fractures, and associated neurovascular injuries. Patients who met the inclusion criteria were randomized to either the single-bone fixation group (intervention) or the both-bone fixation group (control). Primary outcomes were forearm range of motion and fracture union, while secondary outcomes were forearm function (price criteria), radius re-angulation, wrist and elbow range of motion, and surgical time

Results: A total of 50 children were included. Out of these 50 children, 25 were randomized to either arm of the study. All children in either group received the treatment assigned by randomization. Fifty (100%) children were available for final follow-up at six months post-operatively. The mean age of single-bone and both-bone fixation groups was 11.48 ± 1.93 and 13 ± 1.75 years, respectively, with a statistically significant difference (p = 0.006). There were no statistically significant differences in gender, laterality, affection of the dominant hand, or mode of trauma between single-bone and both-bone fixation groups. All patients in both groups achieved fracture union. There mean radius re-angulation of the single-bone fixation groups was 5.36 ± 4.39 (0–20) degrees, while there was no radius re-angulation in the both-bone fixation group, with a statistically significant difference (p < 0.001). The time to union in the single-bone group was 6.28 ± 1.51 weeks, while the time to union in the both-bone fixation group was 6.64 ± 1.75 weeks, with no statistically significant difference (p = 0.44). There were no infections or refractures in either group. In the single-bone fixation group, 24 (96%) patients have regained their full forearm ROM (loss of ROM < 15°), while only one (4%) patient lost between 15 and 30° of ROM. In the both-bone fixation group, 23 (92%) patients have regained their full forearm ROM (loss of ROM < 15°), while only two (8%) patients lost between 15 and 30° of ROM. There was no statistically significant difference between groups in loss of forearm ROM (p = 0.55). All patients in both groups regained full ROM of their elbow and wrist joints. On price grading, 24 (96%) and 23 (92%) patients who underwent single bone fixation and both-bone fixation scored excellent, respectively. Only one (4%) patient in the single-bone fixation group and two (8%) patients in the both-bone fixation group scored good, with no statistically significant difference in price score between groups (p = 0.49). The majority of the patients from both groups had no pain on the numerical pain scale; 22 (88%) patients in the single-bone fixation group and 21 (84%) patients in the both-bone fixation groups, with no statistically significant difference between groups (p=0.38). The single-bone fixation group had a significantly shorter mean operative time in comparison to both-bones plating (43.60 ± 6.21 vs. 88.60 ± 10.56 (min); p < 0.001).
Conclusion: Single-bone ulna open reduction and plate fixation and casting are safe and had a significantly shorter operative time than both-bone fixation. However, single-bone ORIF had a higher risk radius re-angulation, alas clinically acceptable. Both groups had equally excellent functional outcomes, forearm ROM, and union rates with no complications or refractures. Long-term studies are required.