Comparative study between fisher anatomical subunit approximation technique and millard rotation- advancement technique in unilateral cleft lip repair

Introduction: The ideal lip repair is characterized by; the symmetrical shape of nasolabial folds and both alae of the nose with a natural-looking philtrum and Cupid’s bow in both static and dynamic states, in addition to a hidden scar.Objective: to compare between Fisher anatomical subunit approximation technique and Millard rotational advancement technique in unilateral cleft lip repair.Methods: Prospective study for 40 patients presented to Alexandria Main University hospital with unilateral cleft lip deformity between March 2019 and October 2020. Twenty patients with unilateral cleft lip deformity were repaired by Fisher anatomical subunit approximation technique, while the other twenty were repaired by Millard rotational-advancement technique. The postoperative photographs of the patients were captured and processed in computer photogrammetry software through which anthropometric parameters including (lip height, lip width, vermilion height, and alar base width) were compared between the normal side and the repaired side. In this software, each anthropometric parameter length on the normal side is taken as a control with a fixed value of (1) then the same parameter on the repaired side was measured as a ratio of this value to avoid bias. Comparison between both groups for assessment of the quality of cleft lip repair was also done based on Steffensen grading criteria.Results: Comparison between both techniques in unilateral cleft lip repair showed that there was no significant difference between them in the anthropometric measurements. While the comparison between the two groups using Steffensen grading criteria showed that Fisher’s technique surpassed Millard’s technique.Conclusion: We recommend the use of the Fisher anatomical subunit approximation technique in unilateral cleft lip repair for its superior results over the Millard rotational advancement technique

Developing a Chromatographic 99mTc Generator Based on Mesoporous Alumina for Industrial Radiotracer Applications: A Potential New Generation Sorbent for Using Low-Specific-Activity 99Mo.

The commercial low-pressure column chromatographic 99Mo/99mTc generator represents a reliable source of onsite, ready-to-use 99mTc for industrial applications. These generators use fission-produced 99Mo of high specific activity, posing serious production challenges and raising proliferation concerns. Therefore, many concepts are aimed at using low-specific-activity (LSA) 99Mo. Nonetheless, the main roadblock is the low sorption capacity of the used alumina (Al2O3). This study investigates the feasibility of using commercial alumina incorporated with LSA 99Mo to develop a useful 99Mo/99mTc generator for industrial radiotracer applications. First, the adsorption profiles of some commercial alumina sorbents for LSA 99Mo were tested under different experimental conditions. Then, the potential materials to develop a 99Mo/99mTc generator were selected and evaluated regarding elution yield of 99mTc and purity. Among the sorbents investigated in this study, mesoporous alumina (SA-517747) presented a unique sorption-elution profile. It demonstrated a high equilibrium and dynamic sorption capacity of 148 ± 8 and 108 ± 6 mg Mo/g. Furthermore, 99mTc was eluted with high yield and adequate chemical, radiochemical, and radionuclidic purity. Therefore, this approach provides an efficient and cost-effective way to supply onsite 99mTc for radiotracer applications independent of fission-produced 99Mo technology

Capability of the Invasive Tree Prosopis glandulosa Torr. to Remediate Soil Treated with Sewage Sludge

Sewage sludge improves agricultural soil and plant growth, but there are hazards associated with its use, including high metal(loid) contents. An experimental study was conducted under greenhouse conditions to examine the effects of sewage sludge on growth of the invasive tree Prosopis glandulosa, as well as to determine its phytoremediation capacity. Plants were established and grown for seven months along a gradient of sewage sludge content. Plant traits, soil properties, and plant and soil concentrations of N, P, K, Cd, Pb, Cu, Ni, Zn, Cr, Co, As, and Fe were recorded. The addition of sewage sludge led to a significant decrease in soil pH, and Ni, Co, and As concentrations, as well as an increase in soil organic matter and the concentrations of N, P, Cu, Zn, and Cr. Increasing sewage sludge content in the growth medium raised the total uptake of most metals by P. glandulosa plants due to higher biomass accumulation (taller plants with more leaves) and higher metal concentrations in the plant tissues. P. glandulosa concentrated more Cd, Pb, Cu, Zn, and Fe in its below-ground biomass (BGB) than in its above-ground biomass (AGB). P. glandulosa concentrated Ni, Co, and As in both BGB and AGB. P. glandulosa has potential as a biotool for the phytoremediation of sewage sludges and sewage-amended soils in arid and semi-arid environments, with a potential accumulation capability for As in plant leaves

Bed utilization pattern of intensive care units affiliated to Ministry of Health: a national study in Egypt prior to the COVID-19 pandemic

BACKGROUND: This study aims to calculate the following bed utilization of intensive care Units (ICU) at the national and regional levels. METHODS: A descriptive retrospective record-based study was done in all ICUs affiliated to Ministry of Health and Population (MOHP). RESULTS: ICU admission rate ranged from 0.09% to 0.41% with 0.19%. BOR ranged from 10% to 72% with 60%. The ALS (Days) ranged from 1.92 days to 5.41 days with 3.61 days. The average ABTI per year ranged from 1.42 days to 25.04 days with 2.46 days. The average ABTR ranged from 13.14 to 101.02 with 60.14. CONCLUSIONS: Utilization of ICUs affiliated to MOHP is not optimal at the national level and there is a room for improvement

Evaluation of the effect of intravitreal ranibizumab injections in patients with neovascular age related macular degeneration on retinal nerve fiber layer thickness using optical coherence tomography

PURPOSE: To evaluate the effect of repeated intravitreal ranibizumab injections for neovascular age related macular degeneration (nAMD) on the retinal nerve fiber layer (RNFL) thickness using optical coherence tomography. DESIGN: A prospective observational cohort study of patients with nAMD. METHODS: Thirty eyes of 30 patients with nAMD were selected. All patients received three ranibizumab injections and underwent scans using the fast RNFL thickness protocol (Stratus optical coherence tomography) before starting the first injection and 1 month after the third injection. The RNFL thickness measurements prior to the injections and after the third injection were used for the analysis. We also evaluated the effect of the lens status as well as the type of choroidal neovascular membrane on RNFL thickness measurements pre- and post-injection. Pre- and post-injection average and individual quadrant RNFL thickness were measured and statistically analyzed. RESULTS: The mean (± standard deviation) pre-injection RNFL thickness was 90.8±18. The mean (± standard deviation) post-injection RNFL thickness was 91.03±15. The pre- and post-injection values of the mean RNFL thickness were not statistically significant. Likewise, the pre- and post-injection values for RNFL thickness in the different quadrants were not statistically significant. There was no statistical significance for the lens status or the type of choroidal neovascular membrane on the RNFL thickness. CONCLUSION: Repeated ranibizumab injections in nAMD appear to have no harmful effect on the RNFL thickness in the short term, in spite of the proven neurotrophic effect of vascular endothelial growth factor. Nevertheless, the safety profile of ranibizumab injections in nAMD needs to be further evaluated in a large multicenter trial with special emphasis on the long-term effects on the retina and optic nerve

Molecular hybridization design and synthesis of novel spirooxindole-based MDM2 inhibitors endowed with BCL2 signaling attenuation:A step towards the next generation p53 activators

Despite the achieved progress in developing efficient MDM2-p53 protein-protein interaction inhibitors (MDM2 inhibitors), the acquired resistance of tumor cells to such p53 activators posed an argument about the druggability of the pathway. Combination studies disclosed that concomitant inhibition of MDM2 and BCL2 functions can sensitize the tumor cells and synergistically induce apoptosis. Herein, we employed a rapid combinatorial approach to generate a novel series of hybrid spirooxindole-based MDM2 inhibitors (5a-s) endowed with BCL2 signaling attenuation. The adducts were designed to mimic the thematic features of the chemically stable potent spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-ones MDM2 inhibitors while installing a pyrrole ring on the core via a carbonyl spacer inspired by the natural product marinopyrrole A that efficiently inhibits BCL2 family functions by various mechanisms. NCI 60 cell-line panel screening revealed their promising broad-spectrum antiproliferative activities. The NCI-selected derivatives were screened for cytotoxic activities against normal fibroblasts, MDA-MB 231, HepG-2, and Caco-2 cells via MTT assay, subjected to mechanistic apoptosis studies for assessment of p53, BCL2, p21, and caspase 3/7 status, then evaluated for potential MDM2 inhibition utilizing MST assay. The most balanced potent and safe derivatives; 5i and 5q were more active than 5-fluorouracil, exhibited low μM range MDM2 binding (KD =1.32 and 1.72 μM, respectively), induced apoptosis-dependent anticancer activities up to 50%, activated p53 by 47-63%, downregulated the BCL2 gene to 59.8%, and reduced its protein level (13.75%) in the treated cancer cells. Further downstream p53 signaling studies revealed > 2 folds p21 upregulation and > 3 folds caspase 3/7 activation. Docking simulations displayed that the active MDM2 inhibitors resided well into the p53 binding sites of MDM2, and shared key interactions with the co-crystalized inhibitor posed by the indolinone scaffold (5i, 5p, and 5q), the halogen substituents (5r), or the installed spiro ring (5s). Finally, in silico ADMET profiling predicted acceptable drug-like properties with full accordance to Lipinski's, Veber's, and Muegge's bioavailability parameters for 5i and a single violation for 5q

Design, Synthesis, Chemical and Biochemical Insights Into Novel Hybrid Spirooxindole-Based p53-MDM2 Inhibitors With Potential Bcl2 Signaling Attenuation

The tumor resistance to p53 activators posed a clinical challenge. Combination studies disclosed that concomitant administration of Bcl2 inhibitors can sensitize the tumor cells and induce apoptosis. In this study, we utilized a rapid synthetic route to synthesize two novel hybrid spirooxindole-based p53-MDM2 inhibitors endowed with Bcl2 signaling attenuation. The adducts mimic the thematic features of the chemically stable potent spiro [3H-indole-3,2′-pyrrolidin]-2(1H)-ones p53-MDM2 inhibitors, while installing a pyrrole ring via a carbonyl spacer inspired by the natural marine or synthetic products that efficiently inhibit Bcl2 family functions. A chemical insight into the two synthesized spirooxindoles including single crystal x-ray diffraction analysis unambiguously confirmed their structures. The synthesized spirooxindoles 2a and 2b were preliminarily tested for cytotoxic activities against normal cells, MDA-MB 231, HepG-2, and Caco-2 via MTT assay. 2b was superior to 5-fluorouracil. Mechanistically, 2b induced apoptosis-dependent anticancer effect (43%) higher than that of 5-fluorouracil (34.95%) in three studied cancer cell lines, activated p53 (47%), downregulated the Bcl2 gene (1.25-fold), and upregulated p21 (2-fold) in the treated cancer cells. Docking simulations declared the possible binding modes of the synthesized compounds within MDM2

A Novel Keratocan Mutation Causing Autosomal Recessive Cornea Plana

PURPOSE: Mutations in keratocan (KERA), a small leucine-rich proteoglycan, have recently been shown to be responsible for cases of autosomal recessive cornea plana (CNA2). A consanguineous pedigree in which cornea plana cosegregated with microphthalmia was investigated by linkage analysis and direct sequencing. METHODS: Linkage was sought to polymorphic microsatellite markers distributed around the CNA2 and microphthalmia loci (arCMIC, adCMIC, NNO1, and CHX10) using PCR and nondenaturing polyacrylamide gel electrophoresis before KERA was directly sequenced for mutations. RESULTS: Positive lod scores were obtained with markers encompassing the CNA2 locus, the maximum two-point lod scores of 2.18 at recombination fraction theta = 0 was obtained with markers D12S95 and D12S327. Mutation screening of KERA revealed a novel single-nucleotide substitution at codon 215, which results in the substitution of lysine for threonine at the start of a highly conserved leucine-rich repeat motif. Structural modeling predicts that the motifs are stacked into an arched beta-sheet array and that the effect of the mutation is to alter the length and position of one of these motifs. CONCLUSIONS: This report describes a novel mutation in KERA that alters a highly conserved motif and is predicted to affect the tertiary structure of the molecule. Normal corneal function is dependent on the regular spacing of collagen fibrils, and the predicted alteration of the tertiary structure of KERA is the probable mechanism of the cornea plana phenotype