Plasma D-Dimer Value Corrected with Some Physiological and Inflammatory Markers (C-Reactive Protein and Ferritin) in Iraqi Patients with COVID-19 Infection

Since the beginning of the COVID-19 pandemic it has been observed that patients have elevated plasma levels of D-dimer and some inflammatory markers (ferritin, interleukine 6, C-reactive protein (CRP) or fibrinogen). Some studies point to the existence of a certain correlation between those markers and D-dimer. CRP is a protein discovered in the 1930s by Tillett and Francis and is an acute phase reactant. It is a pentameric protein which is synthesized by the liver under the action of cytokine interleukin 6 (IL-6). D-dimers are multiple peptide fragments produced as a result of degradation of crosslinked fibrin, mediated by plasmin. A total of 60 patients were recruited and categorized into :1- group1 (controls), 2- group 2 (COVID-19 patients). 5 ml of blood was obtained from each patient by vein puncture, using 5 ml disposable syringes, then centrifuged at 3000 rpm for 10 minutes to collect the serum.  D- dimer, C-reactive protein were measured by using (Roche Diagnostics GmbH, Mannheim, Germany). At the same time, the Ferritin was assessed by using a miniVIDAS analyzer for the fluorescent enzymatic detection of β2-microglobulin (β2M) using the technique. Enzyme Linked Fluorescent Assay (ELFA) (BioMerieux). Our results showed that there was a non- significant difference in the P-values between control and patients males and females. The Mean ± SE of age in control group was 45.90 ± 3.34, while the Mean ± SE of age in patients was 45.35 ± 2.52. There was a non- significant difference between the two groups, the Mean ± SE of CRP in control group was 5.04 ±0.81, while the Mean ± SE of CRP in COVID-19 patients was 37.16 ±3.24, there was a highly Significant differences between them (P≤0.01). The CRP of COVID-19 patients were compared with those of control patients, the results shows significant increased CRP in covid-19 patients group as a compression with the control group, the findings of the study is similar to Jacob Lentner, etal findings. In response to infections, the liver synthesizes significant quantities of acute-phase proteins (APPs), such as CRP. This acute inflammatory protein is a highly sensitive biomarker for inflammation, tissue damage, and infection. It has been shown that CRP levels are correlated with levels of inflammation. CRP levels can promote phagocytosis and activate the complement system. In other words, CRP binds to microorganisms and promotes their removal through phagocytosis. D-dimers are one of the fragments produced when plasmin cleaves fibrin to break down clots. Our study showed that the serum D-dimer concentrations in patients significantly higher than those in control group which is similar to Mamta Soni, etal, 2020 findings. Elevated D-dimer levels have emerged as a consistent finding in severely ill COVID-19 patients, Multiple studies have identified an association between higher D-dimer levels and an increased risk of mortality in the COVID-19 patient population. Ferritin is an iron-storing protein; its serum level reflects the normal iron level and helps the diagnosis of iron deficiency anemia. Circulation ferritin level increases during viral infections and can be a marker of viral replication. Our study showed a significant increase in ferritin level in covid-19 patients group compared to control group, which consider similar to [] results. Although the exact cause for elevated ferritin in COVID-19 infection is unknown, it could be influenced by cytokine release or cellular damage that results in the leakage of intracellular ferritin. It has been previously shown that ferritin is a direct indicator of cellular damage suggestive of an association between organ damage and ferritin production. This could later cause cell death, known as ferroptosis. It is suggested that inflammation associated with sepsis could alter iron metabolism and deficiency to facilitate the immune system, which could be an early sign of COVID

Fracture Resistance and Microleakage of Endocrowns Utilizing Three CAD-CAM Blocks

This study assessed marginal leakage and fracture resistance of computer-aided design/computer-aided manufacturing (CAD/CAM) fabricated ceramic crowns with intracoronal extensions into the pulp chambers of endodontically treated teeth (endocrowns) using either feldspathic porcelain (CEREC Blocks [CB], Sirona Dental Systems GmbH, Bensheim, Germany), lithium disilicate (e.max [EX], Ivoclar Vivadent, Schaan, Liechtenstein), or resin nanoceramic (Lava Ultimate [LU], 3M ESPE, St Paul, MN, USA).). Thirty extracted human permanent maxillary molars were endodontically treated. Standardized preparations were done with 2-mm intracoronal extensions of the endocrowns into the pulp chamber. Teeth were divided into three groups (n=10); each group was restored with standardized CAD/CAM fabricated endocrowns using one of the three tested materials. After cementation with resin cement, specimens were stored in distilled water at 37°C for one week, subjected to thermocycling, and immersed in a 5% methylene-blue dye solution for 24 hours. A compressive load was applied at 35 degrees to long axis of the teeth using a universal testing machine until failure. Failure load was recorded, and specimens were examined under a stereomicroscope for modes of failure and microleakage. Results were analyzed using one-way analysis of variance and Bonferroni post hoc multiple comparison tests (α=0.05). LU showed significantly (p<0.05) higher fracture resistance and more favorable fracture mode (ie, fracture of the endocrown without fracture of tooth) as well as higher dye penetration than CB and EX. In conclusion, although using resin nanoceramic blocks for fabrication of endocrowns may result in better fracture resistance and a more favorable fracture mode than other investigated ceramic blocks, more microleakage may be expected with this material

Exact Ordering

&nbsp;Ordering is an important subject of learning; it has so many applications in day -to - day life. Hence, in this paper exact and general exact ordering methods are reviewed giving sample applications for them. Firstly, the exact ordering method is introduced and few theorems are given to assign the conditions needed to locate the position of a required object among a class of objects to be ordered in a certain manner in three classes. Secondly, the exact ordering method is generalized to any odd number of classes &nbsp;In both cases and if the required object class is put in the middle of other classes, then the required object will be located exactly in the middle of all objects provided that we arrange the objects orderly in three classes in the first case and in ones in the second general case and where certain defined steps are to be followed.In general &nbsp;steps are required to determine the required object exactly and where &nbsp;is the odd number of classes. Making the subject more interesting, deeper, and handled in a sophisticated manner, through the introduction of exact ordering operators, is then exposed to. Finally, few different applications are suggested in physics, operational research, criminal investigation and in sorting files and postal mailing. A practical demonstration with playing cards is also mentioned

Patient Satisfaction and Its Predictors in the General Hospitals of Southwest Saudi Arabia: A Cross-sectional Survey

Background: Patient satisfaction occupies a central position in measuring the quality of care as it provides information on the provider's success, meeting the patient’s values and expectations. Hence, it is an essential tool for assessing health services outcomes. This study aimed to assess patients' satisfaction level and factors influencing healthcare quality of general hospitals in the Jazan region, Saudi Arabia (SA). Methods: This observational cross-sectional study was conducted on a sample of 423 patients selected through stratified random sampling from general hospitals of the Jazan region. Results: The overall satisfaction rate among the study participants was 80.9%. Satisfaction with food services was the highest (91.15%) followed by doctor services (81.0%), reception and entry procedures (80%), and nursing services (78.15%). The various aspects of satisfaction with doctors and nurses included the treatment prescribed by physicians, clarity in communication with patients, compassion and providing clear explanation of what they were doing. However, about 27.3% of the patients were dissatisfied with the length of waiting period before seeing a doctor. Binary logistic regression analysis suggested that uneducated patients and patients with secondary school education were more likely to have higher satisfaction level than university-educated patients (OR = 3.40, 95% C.I. [1.56–7.45], p = 0.002), (OR = 2.66, 95% C.I. [1.28–5.55], p = 0.009), and (OR = 2.29, 95% C.I. [1.40–3.73], p = 0.001), respectively. Conclusion: The health services satisfaction level was high in the Jazan population. However, some aspects of dissatisfaction were reported, such as the long waiting period before seeing a doctor. These aspects are recommended to be improved to ensure that the services provided by general hospitals are of high quality

New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease M Pro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies

New 2-thioxopyrimidinone derivatives (A1–A10) were synthesized in 87–96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6–A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6–A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand–protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations

Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy

Purpose: PTEN, a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in PTEN deficient triple negative breast cancer (TNBC). Methods: PTEN, ATR and pCHK1Ser345 protein level was evaluated in 1650 human breast cancers. ATR blockade by VE-821 was investigated in PTEN-proficient (MDAMB-231) and PTEN-deficient (BT-549, MDA-MB-468) TNBC cell lines. Functional studies included DNA repair expression profiling, MTS cell-proliferation assay, FACS (cell cycle progression & γH2AX accumulation) and FITC-annexin V flow cytometry analysis. Results: Low nuclear PTEN was associated with higher grade, pleomorphism, dedifferentiation, higher mitotic index, larger tumour size, ER negativity, and shorter survival (p values <0.05). In tumours with low nuclear PTEN, high ATR and/or high pCHK1ser345 level was also linked to higher grade, larger tumour size and poor survival (all p values <0.05). VE-821 was selectively toxic in PTEN deficient TNBC cells and resulted in accumulation of double strand DNA breaks, cell cycle arrest, and increased apoptosis. Conclusion: ATR signalling adversely impact survival in PTEN deficient breast cancers. ATR inhibition is synthetically lethal in PTEN deficient TNBC cells

Peripheral Ulcerative Keratitis: A Review

Peripheral ulcerative keratitis (PUK) is a rare but serious ocular condition that is an important clinical entity due to its ophthalmological and systemic implications. It is characterized by progressive peripheral corneal stromal thinning with an associated epithelial defect and can be associated with an underlying local or systemic pro-inflammatory condition, or present in an idiopathic form (Mooren ulcer). Associated conditions include autoimmune diseases, systemic and ocular infections, dermatologic diseases, and ocular surgery. Cell-mediated and autoantibody- mediated immune responses have been implicated in the pathogenesis of PUK, destroying peripheral corneal tissue via matrix metalloproteinases. Clinically, patients with PUK present with painful vision loss, a peripheral corneal ulcer, and often adjacent scleritis, episcleritis, iritis, or conjunctivitis. Diagnostic evaluation should be focused on identifying the underlying etiology and ruling out conditions that may mimic PUK, including marginal keratitis and Terrien marginal degeneration. Treatment should be focused on reducing local disease burden with topical lubrication, while simultaneously addressing the underlying cause with antimicrobials or anti-inflammatory when appropriate. Existing and emerging biologic immunomodulatory therapies have proven useful in PUK due to autoimmune conditions. Surgical treatment is generally reserved for cases of severe thinning or corneal perforation

Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention

© 2018 American Association for Cancer Research. Targeting PARP1 for synthetic lethality is a new strategy for breast cancers harboring germline mutations in BRCA. However, these mutations are rare, and reactivation of BRCA-mediated pathways may result in eventual resistance to PARP1 inhibitor therapy. Alternative synthetic lethality approaches targeting more common sporadic breast cancers and preinvasive ductal carcinoma in situ (DCIS) are desirable. Here we show that downregulation of XRCC1, which interacts with PARP1 and coordinates base excision repair, is an early event in human breast cancer pathogenesis. XRCC1-deficient DCIS were aggressive and associated with increased risk of local recurrence. Human invasive breast cancers deficient in XRCC1 and expressing high PARP1 levels also manifested aggressive features and poor outcome. The PARP1 inhibitor olaparib was synthetically lethal in XRCC1-deficient DCIS and invasive breast cancer cells. We conclude that targeting PARP1 is an attractive strategy for synthetic lethality and chemoprevention in XRCC1-deficient breast cancers, including preinvasive DCIS. Significance: These findings show that loss of XRCC1, which is associated with more malignant DCIS, can be exploited by PARP inhibition, suggesting its application as a promising therapeutic and chemoprevention strategy in XRCC1-deficient tumor cells

Causes of elective cesarean delivery on maternal request in Aljouf, Saudi Arabia

Background: Recently observed there is a steadily higher rate of cesarean delivery worldwide mostly due to the increasing number of women requesting an elective cesarean section on maternal request without valid indication. The aim of the study was to determine the causes of elective cesarean delivery on maternal requests in Aljouf Saudi Arabia.Methods: This was a descriptive cross-sectional study and data was evaluated by completing seven questionnaires and interviews with laboratory reports who were admitted for cesarean delivery at the Obstetrics department of Maternity and Children Hospital (MCH) Aljouf, Saudi Arabia from January 2020 to December 2020. A total of 141 Saudi women of age between 18 and over 35 years were enrolled, including those who have singleton pregnancy, no complications during pregnancy, and no medical indication for cesarean delivery.Results: 141 women reported willingness to request cesarean delivery. The mean systolic 120±6.23, diastolic 75±2.45 blood pressure mm of Hg, and fasting blood sugar level 4.1±1.1 mmol/l have been found within the normal limit. The ultrasound (US) confirmed singleton pregnancy without any abnormalities.  Data reveals that common causes of elective cesarean section on maternal request to avoid the episiotomy 77.3%, fear of labor pain 69.5%, trauma to the vagina 79.4%, uncertainty about timing 61.7%, losing a baby during vaginal delivery 54.6%, experience other members 41.8%, the risk for baby 39%, prolapse or incontinence24.1%, unsatisfactory sexual intercourse 17.7% and the undesirable experience of the previous vaginal delivery 12%.Conclusions: Maternal request for cesarean delivery is considered one of the reasons for increasing the rate of cesarean delivery in Saudi Arabia. To avoid the episiotomy and fear of labor pain may strong causes for choosing cesarean delivery

Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite

Targeting tumour metabolism through glucose transporters is an attractive approach. However, the role these transporters play through interaction with other signalling proteins is not yet defined. The glucose transporter SLC2A3 (GLUT3) is a member of the solute carrier transporter proteins. GLUT3 has a high affinity for D-glucose and regulates glucose uptake in the neurons, as well as other tissues. Herein, we show that GLUT3 is involved in the uptake of arsenite, and its level is regulated by peroxiredoxin 1 (PRDX1). In the absence of PRDX1, GLUT3 mRNA and protein expression levels are low, but they are increased upon arsenite treatment, correlating with an increased uptake of glucose. The downregulation of GLUT3 by siRNA or deletion of the gene by CRISPR cas-9 confers resistance to arsenite. Additionally, the overexpression of GLUT3 sensitises the cells to arsenite. We further show that GLUT3 interacts with PRDX1, and it forms nuclear foci, which are redistributed upon arsenite exposure, as revealed by immunofluorescence analysis. We propose that GLUT3 plays a role in mediating the uptake of arsenite into cells, and its homeostatic and redox states are tightly regulated by PRDX1. As such, GLUT3 and PRDX1 are likely to be novel targets for arsenite-based cancer therapy