Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder.

Despite potent suppression of HIV-1 viral replication in the central nervous system (CNS) by antiretroviral therapy (ART), between 15% and 60% of HIV-1-infected patients receiving ART exhibit neuroinflammation and symptoms of HIV-1-associated neurocognitive disorder (HAND) - a significant unmet challenge. We propose that the emergence of HIV-1 from latency in microglia underlies both neuroinflammation in the CNS and the progression of HAND. Recent molecular studies of cellular silencing mechanisms of HIV-1 in microglia show that HIV-1 latency can be reversed both by proinflammatory cytokines and by signals from damaged neurons, potentially creating intermittent cycles of HIV-1 reactivation and silencing in the brain. We posit that anti-inflammatory agents that also block HIV-1 reactivation, such as nuclear receptor agonists, might provide new putative therapeutic avenues for the treatment of HAND.

A novel functionalized CuTi hybrid nanocomposites: facile one-pot mycosynthesis, characterization, antimicrobial, antibiofilm, antifouling and wastewater disinfection performance.

BACKGROUND: The continuous progress in nanotechnology is rapid and extensive with overwhelming futuristic aspects. Through modernizing inventive synthesis protocols, a paradigm leapfrogging in novelties and findings are channeled toward fostering human health and sustaining the surrounding environment. Owing to the overpricing and jeopardy of physicochemical synthesizing approaches, the quest for ecologically adequate schemes is incontestable. By developing environmentally friendly strategies, mycosynthesis of nanocomposites has been alluring. RESULTS: Herein, a novel architecture of binary CuO and TiO2 in nanocomposites form was fabricated using bionanofactory Candida sp., for the first time. For accentuating the structural properties of CuTi nanocomposites (CuTiNCs), various characterization techniques were employed. UV-Vis spectroscopy detected SPR at 350 nm, and XRD ascertained the crystalline nature of a hybrid system. However, absorption peaks at 8, 4.5, and 0.5 keV confirmed the presence of Cu, Ti and oxygen, respectively, in an undefined assemblage of polygonal-spheres of 15-75 nm aggregated in the fungal matrix of biomolecules as revealed by EDX, SEM and TEM. However, FTIR, ζ-potential and TGA reflected long-term stability (- 27.7 mV) of self-functionalized CuTiNCs. Interestingly, a considerable and significant biocide performance was detected at 50 µg/mL of CuTiNCs against some human and plant pathogens, compared to monometallic counterparts. Further, CuTiNCs (200 µg/mL) ceased significantly the development of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans biofilms by 80.3 ± 1.4, 68.7 ± 3.0 and 55.7 ± 3.0%, respectively. Whereas, 64.63 ± 3.5 and 89.82 ± 4.3% antimicrofouling potentiality was recorded for 100 and 200 µg/ml of CuTiNCs, respectively; highlighting their destructive effect against marine microfoulers cells and decaying of their extracellular polymeric skeleton as visualized by SEM. Moreover, CuTiNCs (100 and 200 µg/ml) exerted significantly outstanding disinfection potency within 2 h by reducing the microbial load (i.e., total plate count, mold & yeast, total coliforms and faecal Streptococcus) in domestic and agricultural effluents reached >50%. CONCLUSION: The synergistic efficiency provided by CuNPs and TiNPs in mycofunctionalized CuTiNCs boosted its recruitment as antiphytopathogenic, antibiofilm, antimicrofouling and disinfectant agent in various realms.

Effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological profiles during transition period in dromedary camels.

BACKGROUND: Nutrition has a primary role for optimum expression of genetic potential, and most of the farmers have limited resources of green fodder. Hence, a fat-soluble vitamin, especially vitamin A and E and trace elements remained most critical in the animal's ration and affects their productive and reproductive performance adversely. Animals cannot be able to produce these vitamins in their bodies; hence, an exogenous regular supply is needed to fulfil the physiological needs and to maintain high production performance. This study elucidated effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological parameters in dromedary camels during transition period. RESULTS: At 0 day, there were no appreciable differences in the expression patterns of the metabolic (IGF-I, ACACA, SCD, FASN, LPL, and BTN1A1) genes between the control and treatment groups, despite lower levels. A substantial variation in the mRNA levels of SOD1, SOD3, PRDX2, PRDX3, PRDX4, PRDX6, and AhpC/TSA was observed between the control and treatment groups, according to the antioxidant markers. In comparison to the control group, the treatment group displayed a significant up-regulation at 0 and 21 days. The treatment and control groups exhibited substantial differences in the mRNA values of IL-1α, IL-1ß, IL-6, and TNFα, as indicated by immunological markers. In comparison to the control group, there was a noticeable down-regulation in the treatment group at 0 and + 21 days. But IL10 produced the opposite pattern. No significant difference was observed in glucose, cholesterol, triglyceride, HDL, total protein, NEFA, BHBA, cortisol and IGF-1 levels between control and treatment group. The activity of serum GPx, SOD and TAC was significantly affected by time and treatment x time in supplemented groups as compared with control group. IL-1, IL-1, IL-6, and TNF were noticeably greater in the control group and lower in the treatment group. Additionally, in all groups, the concentration of all pro-inflammatory cytokines peaked on the day of delivery and its lowest levels showed on day 21 following calving. The IL-10 level was at its peak 21 days prior to calving and was lowest on calving day. CONCLUSION: The results demonstrated a beneficial effect of antioxidant vitamins and trace elements on the metabolic, antioxidant and immunological markers in dromedary camels throughout their transition period.

Metabolic profile and gene expression pattern of cytokines and antioxidants markers during different physiological stages in Barki ewes.

BACKGROUND: In livestock, identifying the physiological and reproductive stages is valuable in guiding management decisions related to nutrition, veterinary procedures, and breeding programs. To achieve this goal, a cohort of Barki ewes in this research underwent observation across three pivotal physiological conditions: pre-pregnancy, late pregnancy, and early lactation. Blood samples were collected to investigate the changes in serum metabolic profile as well as gene expression pattern of cytokines and antioxidants markers during these stages. RESULTS: Our results showed that during late pregnancy, there was a significant (P < 0.05) increase in red blood cells (11.9 ± 0.5 1012/L), hemoglobin (10.8 ± 0.4 g/dl) and neutrophils count (7 ± 0.1 109/L) with significant decrease (P < 0.05) of total white blood cell count (9.1 ± 0.05 109/L). The packed cell volume (%) and monocyte count showed a significant (P < 0.05) decrease during both late pregnancy and early lactation stages. The serum concentrations of glucose, cholesterol, GSH, GPx, SOD and catalase displayed significant (P < 0.05) decrease during late pregnancy and early-lactation. Notably, during late pregnancy, there was a significant (P < 0.05) increase in the serum concentrations of albumin, globulin, urea, IGF-1, and malondialdehyde with significant decrease (P < 0.05) of total protein (4.9 ± 0.08 g/dl). Additionally, during early lactation, there was a significant (P < 0.05) increase in the serum levels of non-esterified fatty acids, triiodothyronine (T3), and thyroxin (T4). The gene expression profiles of cytokines (IL-4, IL-6, IL-8, and NFKB) were decreased in the ewes during late pregnancy compared to pre-pregnant and early lactation stages. In addition, the expression profile of antioxidant genes (SOD, CAT, GPX, and Nrf2) was significantly upsurged in the non-pregnant ewes compared to late pregnancy and early lactation ones. CONCLUSIONS: The results concluded that different physiological status significantly affects the blood metabolic profile and gene expression pattern in Barki sheep. Our findings can be helpful in monitoring animal health and applying in breeding programs of Barki sheep under harsh environmental conditions.

Assessment of vitamin status; A, E and D in Egyptian neonates with IUGR: a cross sectional study.

BACKGROUND: Neonates with intrauterine growth retardation (IUGR) may present with fatal complications and permanent serious consequences. Vitamin status may influence fetal development. In this study we assessed vitamin A, E and D concentrations in umbilical cord blood in newborns with IUGR. METHODS: Maternal data were obtained. Neonatal assessment included; age of gestation calculated from last menstrual period, Ultrasound (U/S), new Ballard, Apgar scores and anthropometric measurements including; Head circumference, length and weight. WHO growth percentile curves were used. Vitamin A, E and D in cord blood samples were measured by high performance liquid chromatography (HPLC) and ELISA consecutively. RESULTS: A total of 86 full term newborns were enrolled in this study, 42 (48.8%) with IUGR with gestational age (33.59 ± 1.20) week by U/S and 44 (51.2%) appropriate for gestational age neonates with gestational age (38.70 ± 1.50). Ballard and Apgar scores (p < 0.05) and Z scores for weight, length and head circumference (p < 0.001) at birth were significantly lower in neonates with Intrauterine growth retardation (IUGR) than appropriate for gestational age (AGA) neonates. The levels of Vitamin A, E and D were significantly lower in the IUGR group than the AGA (p < 0.05) for all. Significant positive correlations of weight with vitamin A, and E cord blood levels were found (p < 0.05), while length was significantly positively correlated only with vitamin A (p < 0.05). Head circumference showed significant positive correlations with the three vitamins (p < 0.05) for all. CONCLUSION: Neonates with IUGR had significantly lower levels of Vitamin A, E and D than AGA neonates. Significant positive correlations of weight with vitamin A, and E cord blood levels was detected, while neonatal length was associated only with vitamin A level. The present study highlights the significance of nutritional policies for inhibiting deficiency of these vitamins during pregnancy and childhood.

Evaluation of Pyrazolyl-Indolizine Derivatives as Antimicrobial Agents: Synthesis, In vitro, In silico ADMET and Molecular Docking Studies.

Herein, we report analogues of s-indacene by the synthesis of novel indolizine derivatives. Using chloroform as an appropriate solvent, sixteen derivatives of pyrazolyl-indolizine (4-19) were prepared by the reaction of 3-(dimethylamino)-1-(1H-pyrrol-2-yl)prop-2-en-1-one with hydrazonoyl chloride derivatives in the presence of triethylamine in good to excellent yields. We used NMR spectra, IR, mass spectrometry, as well as elemental analyses to prove the chemical structures and the purity of the synthesized compounds. Among all tested compounds 5, 9, 13 and 19 had a potent antimicrobial efficiency against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aerginousea, Sallmonella typhemerium, and Candida albicans. Furthermore, a significant increase in lipid peroxidation (LPO) toward the Gram-negative bacteria, Pseudomonas aeruginosa when treated with compound 9 was observed, while compound 13 remarkably increased the cell membrane oxidation of Salmonella typhimurium. Additionally, we utilized docking studies and in silico methods to evaluate the drug-likeness, physicochemical properties, and ADMET profiles of the compounds. The results of the molecular docking simulation revealed that the synthesized compounds displayed decreased binding energy when interacting with the active sites of important enzymes, including Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of S. typhimurium, and Gyrase B of B. subtilis.

Design, synthesis, structure elucidation, antimicrobial, molecular docking, and SAR studies of novel urea derivatives bearing tricyclic aromatic hydrocarbon rings.

The targeted compounds were prepared using both (9H-fluoren-9-ylidene)hydrazine (1) and 10H-phenothiazine (2) as starting materials. The treatment of 1 or 2 with different isocyanates afforded the title compounds 7a-d, 8a, and 8b in excellent yield. All compounds were characterized and ascertained by infrared, nuclear magnetic resonance, and elemental analyses as well as single-crystal X-ray diffraction. The antimicrobial efficiency of all was tested in vitro, and a noticeable inhibition activity against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans was obtained by compounds 7a, 7b, 8a, and 8b. Moreover, the biofilm mechanism activity was strongly inhibited by compounds 7b and 8b for all bacterial pathogens, with a percentage ratio of more than 55%. The findings from the molecular docking simulation revealed that compounds 7a, 7b, 8a, and 8b exhibited favorable binding energies and interacted effectively with the active sites of sterol 14-demethylase, dihydropteroate synthase, gyrase B, LasR (major transcriptional activator of P. aeruginosa), and carbapenemase for C. albicans, S. aureus, B. subtills, K. pneumoniae, and P. aeruginosa, respectively. These results suggest that the compounds have the potential to inhibit the activity of these enzymes and demonstrate promising antimicrobial properties. Moreover, the in silico evaluation of drug likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles for compounds 7a, 7b, 8a, and 8b demonstrated their compatibility with Lipinski's, Ghose's, Veber's, Muegge's, and Egan's rules. These findings suggest that these compounds possess favorable physicochemical properties, making them promising candidates for continued drug development efforts.

Perceived stress, coping strategies, symptoms severity and function status among carpal tunnel syndrome patients: a nurse-led correlational Study.

BACKGROUND: Carpal tunnel syndrome (CTS) is a prevalent condition characterized by hand pain, tingling, and numbness. The severity of symptoms and functional status in CTS patients may be influenced by perceived stress and how individuals cope with it. However, scarce knowledge exists about the role of coping strategies as moderators in this relationship. Unfolding the role of perceived stress and coping strategies for CTS management will help the nurse to provide comprehensive and tailored nursing care. This will ultimately improve patient comfort, functionality, and quality of life. PURPOSES: This study aimed to examine the role of coping strategies (adaptive and maladaptive) in the relationship between perceived stress and both symptoms severity and function status among those patients. METHOD: We employed a multisite, correlational study design with moderation analysis. The study included 215 patients with CTS from neurosurgery outpatient clinics at three hospitals in Egypt. After obtaining their consent to participate, eligible participants completed anonymous, self-reported measures of perceived stress, the brief COPE inventory, and the Boston Carpal Tunnel Questionnaire. Demographic and biomedical data were also collected. The questionnaire took about 20 min to be completed. The data was collected over six months, starting in February 2023. RESULTS: The results showed that perceived stress, adaptive coping, and maladaptive coping were significant predictors of symptoms severity and functional status. Adaptive coping moderated the relationships between perceived stress and both symptoms severity and function status, while maladaptive coping did not. The interaction between perceived stress and adaptive coping explained a moderate effect on symptoms severity and function status after controlling for the main effects and the covariates. CONCLUSION: This study explored the relationship between perceived stress, coping strategies, and outcomes in patients with CTS. The results indicate that nurses play a vital role in assessing and assisting patients to adopt effective coping strategies to manage perceived stress and alleviate symptoms and functional impairment. Moreover, the findings support the need for psychological interventions that address both perceived stress and coping strategies as a way to enhance the functioning status and quality of life of patients with CTS.

Collaborative leadership and productive work performance: The mediating role of nurses' innovative behavior.

AIM: This study aims to explore the relationship between collaborative leadership and nurses' productive work performance as well as the mediating role of nurses' innovative behavior in this relationship. BACKGROUND: Collaborative leadership is an imperative necessity in the contemporary turbulent healthcare environment as it provides a collaborative atmosphere where innovative behavior and productive performance of nurses are fostered, hence moving healthcare organizations toward competitiveness and sustainability. METHOD: A cross-sectional descriptive correlational exploratory research design was used to conduct the study. Data were collected from 550 nurses recruited from three large university hospitals in Alexandria, Egypt, using three instruments, namely, interprofessional collaborative leadership in healthcare teams scale, productive work performance questionnaire, and innovative behavior inventory. The instruments of the study are Likert-type questionnaires through which nurses' perspectives regarding study variables were investigated. We used descriptive statistics, inferential statistics as well as structured equation modeling (SEM). RESULTS: SEM revealed that collaborative leadership accounted for 83% of the variance of individual productive work performance and 77% of the variance of nurses' innovative behavior. Moreover, nurses' innovative behavior partially mediates the relationship between collaborative leadership and their productive work performance. CONCLUSION: Collaborative leadership practices are powerful strategies to enhance the innovative behavior of nurses and sustain their productive work performance. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Fostering a collaborative atmosphere in workplace is mandatory for nurses' innovativeness. Replacing hierarchal leadership styles with collaborative ones is a promising strategy to enhance the productive performance of nurses. Healthcare managers and leaders could cultivate an interprofessional collaborative culture in the workplace in order to sustain productivity and eradicate counterproductive work behaviors among healthcare providers.

Fully Characterized Effective Bacteriophages Specific against Antibiotic-Resistant Enterococcus faecalis, the Causative Agent of Dental Abscess.

Background and Objectives: Enterococcus faecalis (E. faecalis) is a primary pathogen responsible for dental abscesses, which cause inflammation and pain when trapped between the crown and soft tissues of an erupted tooth. Therefore, this study aims to use specific phages as an alternative method instead of classical treatments based on antibiotics to destroy multidrug-resistant E. faecalis bacteria for treating dental issues. Materials and Methods: In the current study, twenty-five bacterial isolates were obtained from infected dental specimens; only five had the ability to grow on bile esculin agar, and among these five, only two were described to be extensive multidrug-resistant isolates. Results: Two bacterial isolates, Enterococcus faecalis A.R.A.01 [ON797462.1] and Enterococcus faecalis A.R.A.02, were identified biochemically and through 16S rDNA, which were used as hosts for isolating specific phages. Two isolated phages were characterized through TEM imaging, which indicated that E. faecalis_phage-01 had a long and flexible tail, belonging to the family Siphoviridae, while E. faecalis_phage-02 had a contractile tail, belonging to the family Myoviridae. Genetically, two phages were identified through the PCR amplification and sequencing of the RNA ligase of Enterococcus phage vB_EfaS_HEf13, through which our phages shared 97.2% similarity with Enterococcus phage vB-EfaS-HEf13 based on BLAST analysis. Furthermore, through in silico analysis and annotations of the two phages' genomes, it was determined that a total of 69 open reading frames (ORFs) were found to be involved in various functions related to integration excision, replication recombination, repair, stability, and defense. In phage optimization, the two isolated phages exhibited a high specific host range with Enterococcus faecalis among six different bacterial hosts, where E. faecalis_phage-01 had a latent period of 30 min with 115.76 PFU/mL, while E. faecalis_phage-02 had a latent period of 25 min with 80.6 PFU/mL. They were also characterized with stability at wide ranges of pH (4-11) and temperature (10-60 °C), with a low cytotoxic effect on the oral epithelial cell line at different concentrations (1000-31.25 PFU/mL). Conclusions: The findings highlight the promise of phage therapy in dental medicine, offering a novel approach to combating antibiotic resistance and enhancing patient outcomes. Further research and clinical trials will be essential to fully understand the therapeutic potential and safety profile of these bacteriophages in human populations.

The influence of supportive work environment on work-related stress and conflict management style among emergency care nurses: A descriptive correlational study.

BACKGROUND: Stress and conflict in emergency departments are inevitable but can be managed. A supportive work environment is key to helping emergency care providers, especially nurses, constructively manage work-related stress and conflict. AIM: The aim of this study was to assess the influence of supportive work environments on work-related stress and conflict management style among emergency care nurses. METHODS: A descriptive correlational research design was utilized. Data were collected from 221 staff nurses recruited from two university hospital emergency departments in Alexandria, Egypt. Three instruments were used: (1) perceived organizational support scale, (2) nurses' occupational stressors scale, and (3) conflict management style inventory. RESULTS: There was a highly significant correlation between supportive work environments and work-related stress (p = .000) and a significant correlation between supportive work environments and conflict management style (p = .026). Supportive work environments had a significant inverse negative relationship with work-related stress experienced by nurses (p = .001) and accounted for 51% of variance in work-related stress. Meanwhile, supportive work environments had a significant positive relationship with conflict management styles of nurses (p = .026). Work-related stress had a significant relationship with nurses' conflict management style (p = .000) and accounted for 45% of the variance in conflict management style. LINKING EVIDENCE TO ACTION: The style of conflict management modeled by staff within emergency departments can positively or negatively influence the work environment and level of work-related stress. There is a necessity to cultivate a supportive culture for nurses in emergency departments to develop skills for constructive conflict management styles to reduce work-related stress.

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC50 of 0.042 and 1.172 µM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines.In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised.Cytotoxicity, Topo I and Topo II inhibitory assays, and DNA intercalation abilities were evaluated.Compound 7d NPs showed the best Topo I and Topo II inhibition.Cell cycle arrest, apoptosis induction, and molecular docking studies were performed.

Novel pyrimidine Schiff bases and their selenium-containing nanoparticles as dual inhibitors of CDK1 and tubulin polymerase: design, synthesis, anti-proliferative evaluation, and molecular modelling.

Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases (4-9) were employed in the synthesis of selenium nanoparticle forms (4NPs-9NPs). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound 4 showed effective anti-proliferative activity against MCF-7(IC50 3.14 ± 0.04 µM), HepG-2(IC50 1.07 ± 0.03 µM), and A549(IC50 1.53 ± 0.01 µM) cell lines, while its selenium nanoform 4NPs showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, 4NPs outperformed 4 in selectivity against the Vero cell line by 4.5-fold. Furthermore, 4NPs exhibited strong inhibition of CDK1(IC50 0.47 ± 0.3 µM) and tubulin polymerase(IC50 0.61 ± 0.04 µM), outperforming 4 and being comparable to roscovitine (IC50 0.27 ± 0.03 µM) and combretastatin-A4(IC50 0.25 ± 0.01 µM), respectively. Moreover, both 4 and 4NPs arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that 4 and 4NPs were able to inhibit CDK1 and tubulin polymerase binding sites.

Single nucleotide polymorphisms, gene expression and serum profile of immune and antioxidant markers associated with postpartum disorders susceptibility in Barki sheep.

The objective of this study was to explore the immunological and antioxidant alterations associated with ovine postpartum disorders. Blood samples were collected from 90 adult Barki ewes and allocated into three equal-sized groups (30 ewes each): control group (CG), inflammatory postpartum disorders group (IPG) and non-inflammatory postpartum disorders group (NIPG). PCR-DNA sequencing approach was carried out for TLR4 (256-bp) and SOD (456-bp) genes, and nucleotide sequence variations were noticed to be associated with postpartum disorders resistance/susceptibility. Gene expression profile was also evaluated and levels of IL5, IL6, IL1-ß, TNF alpha, TLR4 and Tollip were significantly up-regulated in ewes affected with postpartum disorders than resistant ones, while SOD and CAT genes pattern elicited an opposite trend. Exploring serum profile also showed a significant increase of IL-1α, IL-1ß, IL-6, TNF-α, MDA and NO in IPG compared to their correspond values in NIPG and CG. However, serum levels of IL-10, CAT, GSH and GPx were significantly decreased. This study highlights that SNPs in TLR4 and SOD genes could be genetic markers for postpartum disorders resistance/susceptibility in Barki ewes. Gene expression alongside serum profiles of antioxidant markers could also be used to follow-up the immune status of ewes to build up an effective management protocol.

Synthesis and Molecular Docking Study of Novel Pyrimidine Derivatives against COVID-19.

A novel series of pyrido[2,3-d]pyrimidines; pyrido[3,2-e][1,3,4]triazolo; and tetrazolo[1,5-c]pyrimidines were synthesized via different chemical transformations starting from pyrazolo[3,4-b]pyridin-6-yl)-N,N-dimethylcarbamimidic chloride 3b (prepared from the reaction of o-aminonitrile 1b and phosogen iminiumchloride). The structures of the newly synthesized compounds were elucidated based on spectroscopic data and elemental analyses. Designated compounds are subjected for molecular docking by using Auto Dock Vina software in order to evaluate the antiviral potency for the synthesized compounds against SARS-CoV-2 (2019-nCoV) main protease M pro. The antiviral activity against SARS-CoV-2 showed that tested compounds 7c, 7d, and 7e had the most promising antiviral activity with lower IC50 values compared to Lopinavir, "the commonly used protease inhibitor". Both in silico and in vitro results are in agreement.

Application of Kano model for optimizing the training system among nursing internship students: a mixed-method Egyptian study.

BACKGROUND: Clinical experience is an important component of nursing education because it translates students' knowledge into practice, which serves as the cornerstone of nursing practice in health care delivery. PURPOSE: The study aims to explore the quality attributes required for optimizing the training system of nursing internship students using Kano model. METHODS: A concurrent exploratory sequential triangulation design was used for mixed-methods research. A total of 295 nursing internship students (Target Population) were recruited (whole-population sampling) from the study settings in Egypt. Of them, 280 (97.2%) agreed to participate in the study and completed the interview and the self-administered questionnaire. Data collection was done over 6 months from February to August, 2022. Inferential statistics and thematic data analysis were used to analyze the results. RESULTS: Findings revealed that there were 35 fundamental attributes required for high-quality nursing students' internship training. Kano model was used to categorize and prioritize the 35 quality attributes. Kano analysis revealed that 22 attributes were categorized as "attractive" and 11 attributes were as categorized as "must be" and two were indifferent attributes. CONCLUSION: Incorporating the voice of nurse interns during their training is the key to providing efficient and high-quality internship training experience. It could give realistic impressions about the drawbacks of training and proposed solutions. IMPLICATIONS OF THE STUDY: Nurse managers and educators in clinical settings and educational institutions should put much emphasis on the training attributes and pillars to ensure that nursing internship students are mastering the skills of competent alumni. Provision of conducive training environment that fulfill the basic needs of internship students to maintain passion for learning as well as commitment of internship students to nursing profession will improve the satisfaction level and quality of education, training, and practice. Also, incorporating internship students support system with motivation strategies are helpful tools to maintain exemplary performance of internship students during the training period.

Job embeddedness and missed nursing care at the operating theatres: the mediating role of polychronicity.

BACKGROUND: Perioperative missed nursing care is a serious issue that can compromise patient safety and quality of care. However, little is known about the factors that influence perioperative missed nursing care. AIM: This study aimed to examine the effects of job embeddedness and polychronicity on perioperative missed nursing care as well as to test the mediating role of polychronicity on the relationship between job embeddeness and perioperative missed nursing care. METHOD: This was a cross-sectional correlational study that used a convenience sample of 210 operating room nurses from nine hospitals in Egypt. Data were collected using self-administered questionnaires that measured job embeddedness, polychronicity, and perioperative missed nursing care. Structural equation modeling was used to test the hypothesized relationships among the variables. RESULTS: The findings demonstrated a significant negative and moderate association between missed perioperative care and both nurses' job embeddedness and polychronicity. Moreover, there was a moderately positive and significant correlation between polychronicity and job embeddedness. Path analysis revealed a significant positive causal effect between job embeddedness and polychronicity. The results of mediation revealed that the indirect effect of job embeddedness on missed care through polychronicity was statistically significant; suggesting that polychronicity partially mediated this relationship. CONCLUSION: This study sheds light on the intricate relationship between nurses' job embeddedness, missed care, and polychronicity in the operating theater context. By enhancing job embeddedness and fostering polychronicity among nurses, healthcare organizations can reduce perioperative missed care and ultimately improve patient care outcomes in this critical healthcare setting.

Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.

BACKGROUND: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. METHODS: We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. RESULTS: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. CONCLUSIONS: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

Packing the donor heart: Is SherpaPak cold preservation technique safer compared to ice cold storage.

INTRODUCTION: The present study aimed to compare the clinical outcomes of heart transplant patients whose donor hearts were preserved with the SherpaPak controlled cold organ system versus the conventional ice storage technique. METHODS: All patients undergoing heart transplantation at our center between January 2019 and April 2021 were divided into two groups according to the technique used during donor heart preservation and transport. The first group consisted of 34 SherpaPak controlled temperature preservation patients, and the second group consisted of 47 patients where the conventional three bags and ice technique was utilized during organ transportation. The two groups were compared based on demographics, operative details, and postoperative outcomes. RESULTS: There were no significant differences between the groups regarding Vasoactive Inotropic Score (VIS), Primary Graft Dysfunction (PGD), and the need for a transient pacer. However, the VIS, PGD, and pacing trends were lower in the SherpaPak patients even though the total ischemic and cardiopulmonary bypass times were significantly longer. Furthermore, SherpaPak patients exhibited a shorter stay in the ICU with no severe PGD and mortality. CONCLUSION: The SherpaPak donor heart preservation provides safe outcomes in heart transplant patients. Further research is needed to utilize this method for longer durations of ischemic time and expand travel distances for organ transportation.