Outcomes of an All-Soft Tissue Fixation Technique for Reconstruction of the Medial Patellofemoral Complex Using Double-Bundle Quadriceps Tendon Autograft for Recurrent Patellar Dislocation in Skeletally Immature Patients.

Background: Patellar fracture, femoral physis injury, and recurrent instability are concerning complications in medial patellofemoral ligament (MPFL) reconstruction (MPFLR) techniques for recurrent patellar dislocation in children and adolescents. Purpose: To evaluate the outcomes of an anatomic all-soft tissue fixation technique for reconstruction of the medial patellofemoral complex (MPFC) using a double-bundle quadriceps tendon (QT) autograft for recurrent patellar dislocation in skeletally immature patients. Study Design: Case series; Level of evidence, 4. Methods: This retrospective study involved 24 skeletally immature patients (24 knees; 16 women and 8 men; age range, 9.5-15 years) with recurrent patellar dislocation who underwent MPFC reconstruction using a double-bundle QT autograft between September 2018 and January 2021. Only soft tissue suture fixation was used on the femoral and patellar sides of the 2 bundles of the QT. Radiographs, computed tomography, and magnetic resonance imaging were used to evaluate physeal status, lower limb alignment, patellar height and tilt, trochlear morphology, tibial tubercle-trochlear groove distance, and any associated knee pathology. Functional outcomes were assessed with the Kujala score, the visual analog scale (VAS) for pain, and the grading system of Insall et al.22. Results: The mean follow-up time was 40 ± 9.6 months (range, 28-56 months). At the final follow-up, the Kujala and VAS pain scores showed a significant improvement versus preoperative scores (P < .001), and the passive lateral patellar glide showed a significant reduction (P < .001). All patients had negative apprehension and J signs. Of the 24 patients, 23 regained full range of motion, while 1 patient had a knee flexion deficit. The patellar tilt angle improved significantly at the final follow-up (P < .001). There was no patellar fracture, femoral physis injury, or recurrence of patellar dislocation. According to the grading system of Insall et al, the results were excellent in 15 knees (62.5%), good in 8 knees (33.3%), fair in 1 knee (4.2%), and no knees showed poor results. Conclusion: Reconstruction of the MPFC using a double-bundle QT autograft with an all-soft tissue fixation technique was an effective method for treating patellar instability in skeletally immature patients.

Outcomes of surgical treatment of patellar instability in children with Down syndrome.

BACKGROUND: patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed). MATERIALS AND METHODS: This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score. RESULTS: The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39-56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31-74), and at final follow-up, it was 92.2 ± 4.4 (range: (88-98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39-62), and at final follow-up it was 92.4 ± 5.3 (range: 82-96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury. CONCLUSIONS: Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved. LEVEL OF EVIDENCE: IV; retrospective case series.

Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAFV600E.

Thiazole and thiazolidinone recur in a wide range of biologically active compounds that reach different targets within the context of tumors and represent a promising starting point to access potential candidates for treating metastatic cancer. Therefore, searching for new lead compounds that show the highest anticancer potency with the fewest adverse effects is a major drug-discovery challenge. Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring. In this study, cycloalkylidenehydrazinecarbothioamides (cyclopentyl, cyclohexyl, cyclooctyl, dihydronapthalenylidene, flurine-9-ylidene, and indolinonyl) reacted with 2-bromoacetophenone and diethylacetylenedicarboxylate to yield thiazole and 4-thiazolidinone derivatives. The structure of the products was confirmed by using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray analyses. The antiproliferative activity of the newly synthesized compounds was evaluated. The most effective inhibitory compounds were further tested in vitro against both epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAFV600E) targets. Additionally, molecular docking analysis examined how these molecules bind to the active sites of EGFR and BRAFV600E.

Impact of the SARS-CoV-2 pandemic on the overall respiratory viruses' transmission in a cancer care setting.

INTRODUCTION AND OBJECTIVE: The emergence of the COVID-19 pandemic raised questions about the interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. The objective of this study is to validate the impact of the SARS-CoV-2 pandemic and its interventional measures on the respiratory viruses' transmission/infection rates. METHODS: A retrospective chart review was conducted for cancer patients who underwent laboratory-confirmed respiratory virus polymerase chain reaction (PCR) testing from January 2018 to June 2022. COVID-19 PCR tests from March 2020 to June 2022 were also included. Joinpoint regression analysis was applied to evaluate trends in respiratory virus rates. Statistical analysis was performed using Statistical Package for Social Science software. RESULTS: A total of 6298 respiratory virus PCRs and 40,000 COVID-19 PCRs were performed. Data showed a significant decrease in respiratory viruses' positive cases, total respiratory tests, and respiratory viruses' activity during the pandemic period compared with the pre-pandemic period (p = .0209, .026, and .028, respectively). The joinpoint regression analysis showed a significant decrease of 13.85% in the tested positive cases of respiratory viruses between the years 2018 and 2022. Monthly, the analysis indicated a significant decrease in the positive cases by 13.46% from December 2019 to May 2021. Weekly analysis following lockdown initiation showed a reduction in respiratory virus cases. CONCLUSION: This study provides valuable insights into the interplay between COVID-19 and other respiratory viruses, suggesting that the measures taken for COVID-19 were effective in reducing the spread of viral respiratory infections, aiding future infection control strategies to protect vulnerable populations, including cancer patients, from seasonal respiratory infections.

Clinical Pharmacogenetics of Angiotensin II Receptor Blockers in Iraq.

Background: Clinical pharmacogenetics is a rapidly growing field that focuses on the study of genetic variations and their impact on drug metabolism, efficacy, and safety. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension in Iraq but not all patients respond equally to these drugs. Aim: This article aims to review the current evidence on the clinical pharmacogenetics of ARBs in Iraq and its implications for personalized medicine. Materials and Methods: We conducted a literature review of studies on the genetic variations that affect the response to ARBs in Iraq. We also reviewed the prevalence of these genetic variants in the Iraqi population and discussed the potential clinical implications for personalized medicine. Results: The most studied genetic variations associated with ARB response in Iraq are the angiotensin-converting enzyme gene insertion/deletion polymorphism and the angiotensin II type 1 receptor gene A1166C polymorphism. The angiotensin-converting enzyme gene insertion/deletion polymorphism is associated with variability in response to ARBs, while the angiotensin II type 1 receptor A1166C polymorphism is associated with an increased risk of cardiovascular events in patients treated with ARBs. The prevalence of these genetic variants in the Iraqi population varies widely depending on the region and ethnic group. Conclusion: The clinical pharmacogenetics of ARBs in Iraq suggests that pharmacogenetic testing could improve the selection and dosing of ARBs in Iraqi patients, leading to better patient outcomes and cost-effective healthcare.

PROSPECTIVE SINGLE CENTER ANALYSIS OF OUTCOME STEM CELLS TRANSPLANTS IN PATIENTS WITH CEREBRAL PALSY.

OBJECTIVE: Aim: To evaluate efficacy and safety of autologous bone marrow-derived mononuclear stem cell transplantation intrathecal in children with cerebral palsy. PATIENTS AND METHODS: Materials and Methods: 35 children have levels I-V cerebral palsy aged 8-months to 8-years-old were enrolled from September (2021-2022) at Iraqi private hospital. Gross Motor Function was assessed by a pediatrician and neurologist specialist, 5 mcg/kg/day of G-CSF subcutaneous single injection daily for three consecutive days. Bone marrow harvested from posterior iliac crest under light general anesthesia. Bone marrow mononuclear cells (BMMNCs) separation was performed using density gradient centrifugation with Ficoll, the cell viability checked by propidium iodide dye in a TALI machine (Invitrogen) in average 98%. The viable BMMNCs injected intrathecal in L4-L5 over a period of 5-10 min. RESULTS: Results: Males accounted for 57.14% (20/35) while female 42.86% (15/35), and main neurological symptoms included spastic disorder spastic disorder (quadriplegia 24 (68.6), tetraplegia 2 (5.7), diplegia 5 (14.28), hemiplegia4 (11.42)). Gross Motor Function Classification System and Gross Motor Function Measure-66 (GMFM-66) showed II 10 (28.58), III 11(31.42) and IV 14 (40). On mean follow-up of 3 months post-stem cell transplant improvement was observed in 80% cases. The improvement showed in gross motor function (6/8) p=0.01, and speech (2/4) p=0.04, neck holding (5/5) p=0.0003, sitting balance (4/4) p=0.04, postural tone (5/5) p=0.0003, as well as significant reduction in seizure frequency (2/3) p=0.04 and improvement in cognition (6/7) p=0.01 were observed. CONCLUSION: Conclusion: Stem cell therapy for cerebral palsy shows a significant positive effect on the gross motor function, without long adverse effects.

Optimizing Process Parameters of Direct Ink Writing for Dimensional Accuracy of Printed Layers.

Direct ink writing (DIW) belongs to extrusion-based three-dimensional (3D) printing techniques. The success of DIW process depends on well-printable ink and optimized process parameters. After ink preparation, DIW process parameters considerably affect the parts' dimensional accuracy, and process parameters optimization for dimensional accuracy of printed layers is necessary for quality control of parts in DIW. In this study, DIW process parameters were identified and divided into two categories as the parameters for printing a line and the parameter from lines to a layer. Then, a two-step method was proposed for optimizing process parameters. Step 1 was to optimize process parameters for printing a line. In Step 1, continuity and uniformity of extruded filaments and printed rectangular objects were observed in screening experiments to determine printability windows for each process parameter. Then, interaction effect tests were conducted and degree of freedom for experiments was calculated followed by orthogonal array selection for the Taguchi design. Next, main experiments of line printing based on the Taguchi method were conducted. Signal-to-noise ratio calculations and analysis of variance were performed to find the optimal combination and evaluate the significance, respectively. Step 2 was to optimize the parameter from lines to a layer. In Step 2, the average width of the printed line under optimal condition was first measured. Then, single-factor tests of rectangular object printing were conducted to find the optimal parameter from lines to a layer. After these two steps, confirmation results were conducted to verify the reliability of the proposed method and the method robustness on other shapes and other materials; parameter adaptability in 3D parts printing from printed layers' analyses for the proposed method; and parameter adaptability in constructs fabricated as 100% infill or with porosities.

Synthesis and Structure Determination of Substituted Thiazole Derivatives as EGFR/BRAFV600E Dual Inhibitors Endowed with Antiproliferative Activity.

2,3,4-trisubstituted thiazoles 3a-i, having a methyl group in position four, were synthesized by the reaction of 1,4-disubstituted thiosemicarbazides with chloroacetone in ethyl acetate/Et3N at room temperature or in ethanol under reflux. The structures of new compounds were determined using NMR spectroscopy, mass spectrometry, and elemental analyses. Moreover, the structure of compound 3a was unambiguously confirmed with X-ray analysis. The cell viability assay of 3a-i at 50 µM was greater than 87%, and none of the tested substances were cytotoxic. Compounds 3a-i demonstrated good antiproliferative activity, with GI50 values ranging from 37 to 86 nM against the four tested human cancer cell lines, compared to the reference erlotinib, which had a GI50 value of 33 nM. The most potent derivatives were found to be compounds 3a, 3c, 3d, and 3f, with GI50 values ranging from 37 nM to 54 nM. The EGFR-TK and BRAFV600E inhibitory assays' results matched the antiproliferative assay's results, with the most potent derivatives, as antiproliferative agents, also being the most potent EGFR and BRAFV600E inhibitors. The docking computations were employed to investigate the docking modes and scores of compounds 3a, 3c, 3d, and 3f toward BRAFV600E and EGFR. Docking computations demonstrated the good affinity of compound 3f against BRAFV600E and EGFR, with values of -8.7 and -8.5 kcal/mol, respectively.

Synthesis of bis-thiohydantoin derivatives as an antiproliferative agents targeting EGFR inhibitory pathway.

(R)/(S)-the two enantiomers of 3-substituted-1-[2-(5)-3-substituted-4-benzyl-5-oxo-4-phenyl-2-thioxoimid-azolidin-1-yl]ethyl/propyl-5-benzyl-5-phenyl-2-thioxoimidazolidin-4-ones were formed during the diastereoselective reaction between N,N″-1,ω-alkanediylbis[N'-organylthiourea] derivatives and 2,3-diphenylcyclopropenone in refluxing ethanol. The structures of the isolated compounds were confirmed by NMR, IR, mass spectra and elemental analyses. Moreover, single-crystal X-ray structure analysis was also used to elucidate the structure of the isolated compounds. The mechanism describes the reaction was also discussed. The tested compounds showed EGFR inhibitory activity with IC50 values ranging from 90 to 178 nM in comparison to the erlotinib as a reference with IC50 value of 70 nM. Compound 4c (R = allyl, n = 3) was found as the most potent antiproliferative, had the highest inhibitory effect on EGFR with an IC50 value of 90 nM, compared to erlotinib's IC50 value of 70 nM. The second and third-most active compounds were 4e (R = phenyl, n = 3) and 4d (R = ethyl, n = 3) and with IC50 values of 107 nM and 128 nM. These findings imply that the compounds tested had a significant antiproliferative effect as well as the ability to act as an EGFR inhibitor. Docking studies showed that compound 4c showed high affinity to EGFR based on its docking score (S; kcal/mol) within five test compounds.

Double-Bundle Quadriceps Tendon Autograft for Reconstruction of the Medial Patellofemoral Complex to Manage Recurrent Patellar Dislocation in Patients With Open Physes.

Management of chronic patellar instability in patients with open physis requires special reconstruction techniques to minimize the risks of femoral growth plate injury due to the close proximity of the open physis to the native femoral origin of the medial patellofemoral ligament (MPFL). Children and adolescents have a relatively smaller patella than the adult group, so, there is a higher risk of patellar fracture when tunnels are performed in the patella. It is wise to mimic the normal anatomy of the medial patellofemoral complex (MPFC) by reconstruction of both of the medial quadriceps tendon femoral ligament (MQTFL) and MPFL, so as to restore the normal fan-shaped MPFC, with its wide anterior attachment to both of the patella and quadriceps tendon (QT). This article describes a simple, safe, reproducible, and cost effective technique for surgical management of chronic patellar instability in patients with open physis by reconstruction of the MPFC using a double-bundle QT autograft.

Novel quinoline/thiazinan-4-one hybrids; design, synthesis, and molecular docking studies as potential anti-bacterial candidates against MRSA.

In an attempt to develop effective and safe antibacterial agents, we synthesized novel thiazinanones by combining the quinolone scaffold and the 1,3-thiazinan-4-one group by reaction between ((4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)methylene)hydrazinecarbothioamides and 2,3-diphenylcycloprop-2-enone in refluxing ethanol in the presence of triethyl amine as a catalyst. The structure of the synthesized compounds was characterized by spectral data and elemental analysis, IR, MS, 1H and 13C NMR spectroscopy which showed two doublet signals for CH-5 and CH-6 and four sharp singlets for the protons of thiazinane NH, CH[double bond, length as m-dash]N, quinolone NH and OH, respectively. Also, the 13C NMR spectrum clearly showed the presence of two quaternary carbon atoms which were assigned to thiazinanone-C-5 and C-6. All the 1,3-thiazinan-4-one/quinolone hybrids were screened for antibacterial activity. Compounds 7a, 7e and 7g showed broad spectrum antibacterial activity against most of the tested strains either G +ve or G -ve. Compound 7e is the most potent antibacterial agent against MRSA with the minimum inhibitory concentration against MRSA found to be 48 µg mL-1 compared to the drug ciprofloxacin (96 µg mL-1). Additionally, a molecular docking study was performed to understand the molecular interaction and binding mode of the compounds on the active site of S. aureus Murb protein. In silico docking assisted data strongly correlated with the experimental approach of antibacterial activity against MRSA.

Color Stability of Rhodium-Coated Archwire after Immersion in Mouthwashes.

Background: Is to evaluate the color stability of rhodium-coated aesthetic archwires after immersion in two types of mouthwashes (fluoridated and nonfluoridated), study the effect of immersion time, and to compare the effect of these solutions on color stability of the aesthetic archwires. Materials and Methods: 35 rhodium-coated aesthetic archwires were prepared and divided two halves, arranged in seven strips (each strip contains 10 wires) and immersed in Deionized water, Sidrazac and Biofresh solution. The measurements of the color have been carried out through a computed spectrophotometer based on Commission Internationale de I'Eclairage L ∗ a ∗ b ∗ system, and color variations (ΔE ∗ ), color measurements were repeated 7 and 21 days after immersion in the solution. Statistical analyses include mean, standard deviation, minimum, maximum, and inferential statistics which include ANOVA and Tukey (HSD) for testing for any statistically significant differences in light reflection of the groups; t-test was used to test for differences in immersion time intervals. The significance level has been set at P ≤ 0.05. Results: Both types of mouthwashes resulted in color changes in different degrees and a higher color instability amount has been noted with Sidrazac-fluoridated mouthwashes, The color change amount has been increased with the time being statistically higher in 3 weeks of immersion, while there is nonsignificant color change after immersion in the Biofresh mouthwash. Conclusion: Rhodium-coated archwire shows high color changes in Sidrazac-fluoridated mouthwashes and nonsignificant color change after immersion in the Biofresh mouthwash.

Synthesis of novel amidines via one-pot three component reactions: Selective topoisomerase I inhibitors with antiproliferative properties.

Novel series of amidines were synthesized via the interaction between alicyclic amines, cyclic ketones, and a highly electrophilic 4-azidoquinolin-2(1H)-ones without any catalyst or additive. All the obtained products were elucidated based on NMR spectroscopy, mass spectrometry, and elemental analysis. The reaction conditions were optimized using cyclohexanone (2), piperidine (3a), and 4-azido-quinolin-2(1H)-one (1a) under an air atmosphere. The new compounds 4a-l and 5a-c were tested for antiproliferative activity against four cancer cell lines using doxorubicin as a reference drug. The most potent derivatives were compounds 4b, 4d, 4e, 4i, and 5c, with GI50 ranging from 1.00 µM to 1.50 µM. Compound 5c was the most effective derivative against the four cancer cell lines, outperforming doxorubicin. The compounds 4b, 4d, 4e, 4i, and 5c were studied further as topoisomerase I and IIα inhibitors. The compounds tested showed selective inhibition of topo I over topo IIα. Finally, docking studies explain why these compounds prefer topo I over topo IIα.

Biological Bone Plate and Iliac Bone Autograft for Proximal Tibial Slope Changing Osteotomy in Genu Recurvatum.

Genu recurvatum (GR) is defined as knee hyperextension greater than 5°, with the normal physiological accepted limits of up to 10 to 15° of extension. Physiological GR is commonly bilateral, symmetrical, and mostly asymptomatic. Pathologic GR is usually asymmetric, symptomatic, and can be congenital or acquired. Acquired GR can be classified according to the origin of the deformity into pure osseous, soft tissue, and combined types. Symptomatic GR can present with anterior knee pain and/or instability. Surgery is generally indicated in symptomatic (pain, instability), pathologic GR with an associated causative correctible deformity (bony, soft tissue, or a combination of both). Tibial slope-reversing osteotomy is indicated for the osseous or mixed types where there is inverted tibial slope. Varu-correcting osteotomy is indicated in the posttraumatic soft-tissue type (posterior and lateral soft-tissue injury as in knee dislocation), the aim of osteotomy is to protect the reconstructed ligaments. No role for osteotomy in the nontraumatic soft tissue type (gradual stretching of the posterior structures). In this article, we describe a technique to correct a unilateral genu recurvatum deformity with inverted tibial slope, mostly due to Osgood-Schlatter disease. Correction is done by performing an anterior open-wedge osteotomy of the proximal tibia and impaction of 2 wedges of autogenous iliac bone grafts within the osteotomy. The proximal portion of the tibia is cut in the coronal plan and is used as a biologic plate for fixation with no need for additional hardware (e.g., plate or staples) for fixation of the osteotomy.

Heterocycles from cyclopropenones.

Great attention has been paid to cyclopropenones as they are present in many natural sources. Various synthesized cyclopropenone derivatives also show a wide range of biological activities. The cyclopropenone derivatives undergo a variety of reactions such as ring-opening reactions, isomerization reactions, C-C coupling reactions, C-H activation, cycloaddition reactions, thermal and photo-irradiation reactions, and acid-base-catalyzed reactions under the influence of various chemical reagents (electrophiles, nucleophiles, radicals, and organometallics) and external forces (heat and light). Many previous reviews have dealt with the chemistry and reactions of cyclopropenones. However and to the best of our knowledge, the utility of cyclopropenones in the synthesis of heterocycles has not been reported before. Therefore, it would be interesting to shed light on this new topic. The present review article provides, for the first time, a comprehensive compilation of synthetic methods for the synthesis of various heterocyclic ring systems, as a significant family in the field of organic chemistry.

Autoxidation of 4-Hydrazinylquinolin-2(1H)-one; Synthesis of Pyridazino[4,3-c:5,6-c']diquinoline-6,7(5H,8H)-diones.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c']diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (1H and 13C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.

Novel Benzyloxyphenyl Pyrimidine-5-Carbonitrile Derivatives as Potential Apoptotic Antiproliferative Agents.

BACKGROUND: Pyrimidine-5-carbonitrile has a broad spectrum of biological activities such as antiviral, antioxidant, and anticancer activities. Among similar compounds, monastrol is the most prominent cell-permeant inhibitor of mitosis; therefore, we investigated the new Pyrimidine-5-carbonitrile as a cytotoxic agent for the p53 pathway. OBJECTIVE: Several new benzyloxyphenyl pyrimidine-5-carbonitrile derivatives were designed, synthesized, and characterized, and their cytotoxicity was evaluated. The most active compounds were tested for their activity against p53 as a mechanistic target for antiproliferative action. METHODS: The key intermediate tetrahydropyrimidine-5-carbonitrile derivative 4 was prepared by a multicomponent reaction (MCR) of the Biginelli type. S-alkylation of the key intermediate with the required alkyl or aralkyl halides or refluxing 4 with POCl3 followed by an amino acid yielded the target compounds. The cytotoxicity of 5c-e, 7a-c, 9, 10a, b, and 11 was evaluated using the A549 cell line of human lung adenocarcinoma, HepG2 liver cell line, and MDAMB- 231 cell line of breast cancer using the MTT assay. The transcription effects of 7a, 7c, and 11 on the p53 were assessed and compared with the reference doxorubicin. RESULTS: Compounds 7a, 7c, and 11 have the highest cytotoxic effect when applied to most cancer cells. The tested compounds with 5-FU showed a significant increase in the anticancer activity more than 5-FU alone. Compounds 7a, 7c, and 11 increased the level of active caspase 3 by 4-6-fold compared to untreated control cells in the human liver cancer cell line (HepG2). Compounds 7a, 7c, and 11 increased the levels of caspase 8 and 9, indicating activation of both intrinsic and extrinsic pathways and showing potent induction of Bax, down-regulation of Bcl-2 protein levels, and over-expression of Cytochrome C levels in HepG2 cell lines. Compound 11 exhibited cell cycle arrest at the Pre- G1 and G2/M phases in the cell cycle analysis of the HepG2 cell line. The results revealed an increase of 12.40-19.10 in p53 level compared to the test cells and that p53 protein level of 7a, 7c, and 11 was significantly inductive (636, 861, and 987 pg/mL, respectively) in relation to doxorubicin (1263 pg/mL). CONCLUSION: Pyrimidine-5-carbonitrile derivatives have potent apoptotic and antiproliferative properties.

Challenges in Steroid and Anticoagulant Therapy in Severe COVID-19 Pneumonia: A Prospective Study.

BACKGROUND: As COVID-19 has neither a standard treatment protocol nor guidelines, there are many treatment protocols for anti-inflammatory corticosteroids and anti-coagulations for severe COVID-19 pneumonia patients. This study aimed to assess the most suitable modality in this high-risk group. METHODS: A prospective, experimental study design was adopted that included 123 severe COVID-19 pneumonia patients admitted at Assiut University Hospital. Patients were divided into three groups according to a combined corticosteroid and anticoagulants therapy protocol. Group A included 32 patients, group B included 45 patients, and group C included 46 patients. Assessment of cases was conducted according to the treatment type and duration, weaning duration from oxygen therapy, length of hospital and ICU stay, and complications during treatment. Three months follow-up after discharge was performed. RESULTS: the three patient groups showed significant differences regarding the 3-month outcome, whereas Group C showed the highest cure rate, lowest lung fibrosis, and lowest mortality rate over the other two groups. The in-hospital outcome, the development of pulmonary embolism, bleeding, hematoma, acute kidney disease, and myocardial infarction showed a significant difference between groups (p values < 0.05). Mortality predictors among severe COVID-19 patients by multivariable Cox hazard regression included treatment modality, history of comorbid diseases, increased C reactive protein, high neutrophil-lymphocyte ratio, and shorter ICU and hospital stay. CONCLUSION: the use of combined methylprednisolone and therapeutic Enoxaparin, according to a flexible protocol for COVID-19 patients with severe pneumonia, had two benefits; the prevention of disease complications and improved clinical outcome.

Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications.

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths. COVID-19 complications are mainly induced by low-grade inflammation-causing vascular degeneration. There is an increasing body of evidence that suggests that oral dysbiotic taxa are associated with worse prognosis in COVID-19 patients, especially the Prevotella genus, which was retrieved from nasopharyngeal and bronchoalveolar lavage samples in affected patients. Oral dysbiosis may act by increasing the likelihood of vascular complications through low-grade inflammation, as well as impairing respiratory mucosal barrier mechanisms against SARS-CoV-2. Salivary markers can be used to reflect this oral dysbiosis and its subsequent damaging effects on and the lungs and vasculature. Salivary sampling can be self-collected, and is less costly and less invasive, and thus may be a superior option to serum markers in risk stratification of COVID-19 patients. Prospective studies are needed to confirm such hypothesis. Video Abstract: http://links.lww.com/CAEN/A28.

Accuracy and precision of pulse oximeter at different sensor locations in patients with heart failure.

BACKGROUND: Despite its wide use in clinical practice, few studies have assessed the role of pulse oximetry in patients with heart failure. We aimed to evaluate the accuracy and precision of the pulse oximeter in patients with heart failure and to determine this accuracy at three different sensor locations. METHODS: Comparison of pulse oximetry reading (SpO2) with arterial oxygen saturation (SaO2) was reported in 3 groups of patients with heart failure (HF); those with ejection fraction (EF) >40%, those with EF <40%, and those with acute HF (AHF) with ST and non-ST segment elevation acute myocardial infarction (STEMI and non-STEMI). RESULTS: A total of 235 patients and 90 control subjects were enrolled. There were significant differences in O2 saturation between control and patients' groups when O2 saturation is measured at the finger and toe, but not the ear probes; p=0.029, p=0.049, and 0.051, respectively. In HF with EF>40% and AHF with O2 saturations >90%, finger oximetry is the most accurate and reliable, while in HF with EF<40% and in patients with AHF with O2 saturations <90%, ear oximetry is the most accurate. CONCLUSION: Pulse oximetry is a reliable tool in assessing oxygen saturation in patients with heart failure of different severity. In HF with EF>40% and in AHF with O2 saturations >90%, finger oximetry is the most accurate and reliable, while in HF with EF<40% and in patients with AHF with O2 saturations <90%, ear oximetry is the most accurate. Further studies are warranted.